Dopamine appears to play a critical role in regulating spatial working memory (SWM) in non-human primates, and SWM deficits are observed in patients with Parkinson�s disease and schizophrenia. Unfortunately, the current experimental literature in humans is marred by inconsistent behavioural findings, and there is a void in neuroimaging studies examining dopaminergic manipulation of SWM-related brain activity. The present thesis used a combination of behavioural neurocognitive testing and brain imaging to further examine dopaminergic manipulation of SWM in healthy humans, using two pharmacological challenges: 1) acute tyrosine depletion (TPD) (to acutely deplete tonic dopamine), and 2) D1/D2 receptor activation using the dopamine receptor agonist pergolide (to stimulate dopamine neurotransmission) under conditions of TPD. The effects of TPD on behavioural performance were examined using three SWM tasks: 1) a delayed-recognition task previously impaired by TPD (Experiment 1) and 2) two delayed-response tasks designed to vary only in response requirements (Experiment 2). The findings demonstrated an apparent failure of TPD to impair performance on any of the tasks. Further, the effects of TPD on SWM-related brain activity during a SWM n-back task were examined using regional Cerebral Blood Flow (rCBF) measured by H2 150 Positron Emission Tomography (Experiment 2), and Steady State Visually Evoked Potentials (SSVEP) measured by Steady State Probe Topography (Experiment 4). TPD failed to produce discernable effects on either neural networks (task-related rCBF) or temporal electrophysiological activity (SSVEP) associated with the SWM n-back task. In contrast, D1/D2 receptor stimulation under dopamine depleted conditions impaired performance on both a SWM delayed-response task (Experiment 1) and SWM n-back task (Experiment 2), and resulted in task-related increases in fronto-temporal SSVEP latency (suggestive of increased inhibition) and decreases in parieto-occipital SSVEP amplitude (suggestive of increased activation) during the early delay period of the SWM n-back task (Experiment 4). These changes are consistent with the undisputed role of frontal and parietal regions in n-back task performance, and with previous evidence of dopaminergic modulation of these regions in animals and humans. In summary, TPD did not modulate SWM behavioural performance on four different SWM tasks with differing task demands, and failed to produce measurable changes to either SWM-related neural networks (task-related rCBF) or cortical electrophysiological activity (SSVEP) associated with the SWM n-back task. The implication of these findings, when taken together with previous studies, is that the degree of dopaminergic depletion achieved with TPD may be insufficient to consistently and robustly modulate SWM networks in healthy humans, questioning the utility of TPD as a probe of dopaminergic function. In addition, these findings demonstrate the complexity of stimulating D1/D2 receptors under dopamine depleted conditions, and highlight the critical importance of baseline dopamine levels in influencing the effects of acute dopamine challenge on SWM performance.

<p> </p><p>I denna studie har jämförelse gjorts mellan Interacoustics Eclipse och GSI Audera i samband med Auditory Steady-State Respons (ASSR) mätningar.</p><p>Syftet med studien var att undersöka ASSR som metod, att utvärdera dess tillförlitlighet i jämfö­relse med tonaudiometri för personer med normal hörsel och personer med hörsel­nedsätt­ning. Avsikten var dessutom att undersöka om elektrod­placering­ på örsnibb eller på mastoid påverkade mät­resultatet, försökspersonens upplevelse av instrumen­­t­ens ljudstimuli, om de estimerade ASSR-värdena påverkades av att mättillfället påbörjades eller avslutades med Interacoustics Eclipse samt undersöka tiden för mätningarna.</p><p>En experimentell studie genomfördes. Mätningarna som utfördes var tonaudiometri och ASSR, den senare uppmättes med Interacoustics Eclipse och GSI Audera på (n=20) vuxna med normal hörsel och (n=4) vuxna med hörselnedsättning.</p><p>För personer med normal hörsel påvisades en god överensstämmelse mellan estimerade ASSR-värden och tonaudiometri för Interacoustics Eclipse, något sämre överensstämmelse för GSI Audera. Genomsnittlig mättid för båda instrumenten var ca 40 min. Resultaten visade att elektrodplaceringen inte har någon påverkan på ASSR-värden för Interacoustics Eclipse. Hälften av försökspersonerna upplevde att Interacoustics Eclipse hade ett behagligare ljudstimuli att slappna av till och den andra hälften upplevde GSI Audera som behagligast. De estimerade ASSR-värdena påverkades minimalt beroende på om mättillfället påbörjades eller avslutades med Interacoustics Eclipse.</p><p> </p>

Recent research shows that human auditory steady-state responses (ASSRs) develop a resonance at 40 Hz and the dramatic amplitude increase of the Pb component of the middle latency response (MLR) accounts for the high amplitude of the ASSR at 40 Hz. The first part of this study aimed to investigate the ASSR resonance characteristics as a function of rate in guinea pigs. A study of the grand average of the peak-to-peak and fundamental frequency amplitudes does indeed show a resonance around 40 Hz in guinea pigs. Unlike human ASSRs, this resonance is very broad (26-52 Hz) and flat. The centrally recorded ASSRs are smaller and tend to have resonances at higher rates compared to temporal signals. The second part of the analysis investigated whether the superposition of transient responses can predict the acquired ASSRs at each corresponding rate. This superposition theory is one of two competing theories on the origin of the ASSRs, with the other centering on the induced phase synchronization of brain waves. In order to test the first theory, transient responses were used to create synthetic ASSRs, which were then compared to the acquired ASSRs via correlation coefficient and phasor analysis. For the 40 Hz ASSR, both temporal and central electrode synthesized ASSRs show a correlation coefficient above 0.80. In the comparison at 20 Hz, the correlation coefficient is very high (about 0.9) in the temporal electrode, yet significantly lower (about 0.7) for the central electrode. Furthermore, at 80 Hz, the correlation coefficient is significantly lower in both temporal and central electrodes (about 0.7). At all rates, the correlation coefficients are highest with low jitter sequences. Finally, phasor analysis was also used to test the superposition theory of the generation of the acquired ASSRs at 20, 40, and 80 Hz. Overall, in the temporal recordings at 40 Hz, the superposition of the MLR responses accurately predicted the acquired 40 Hz ASSR as demonstrated by both magnitude and phase analysis. The recordings made in the central electrode only predicted the acquired ASSR in its phases, with significant differences found in magnitude at its main harmonics. Similarly, at 20 and 80 Hz in both temporal and central electrodes, the synthetic ASSRs did not appear to fully predict the acquired ASSRs. Although the phases were successfully predicted, large magnitude variations were observed. As shown by mean prediction error plots, the acquired ASSRs are best predicted by low jitter sequences, followed by low-medium and medium jitter sequences.

In this paper, we identify sufficient conditions for Lyapunov Mean Square Stability (LMSS) of a contention-based network of first-order systems, with state-based schedulers. The stability analysis helps us to choose policies for adapting the scheduler threshold to the delay from the network and scheduler. We show that three scheduling laws can result in LMSS: constant-probability laws and additively increasing or decreasing probability laws. Our results counter the notions that increasing probability scheduling laws alone can guarantee stability of the closed-loop system, or that decreasing probability scheduling laws are required to mitigate congestion in the network. / <p>QC 20130116</p>

We study diffusion-reaction-advection models describing population dynamics of aquatic organisms subject to a constant drift, with reflecting upstream and outflow downstream boundary conditions. We consider three different models: single logistically growing species, two and three competing species. In the case of a single population, we determine conditions for existence, uniqueness and stability of non-trivial steady-state solutions. We analyze the dependence of such solutions on advection speed, growth rate and length of the habitat. Such analysis offers a possible explanation of the "drift paradox" in our context. We also introduce a spatially implicit ODE (nonspatial approximation) model which captures the essential behavior of the original PDE model. In the case of two competing species, we use a diffusion-advection version of the Lotka-Volterra competition model. Combining numerical and analytical techniques, in both the spatial and nonspatial approximation settings, we describe the effect of advection on competitive outcomes. Finally, in the case of three species, we use the nonspatial approximation approach to analyze and classify the possible scenarios as we change the flow speed in the habitat.

Choline oxidase (E.C. 1.1.3.17) from Arthrobacter globiformis catalyzes the four-electron oxidation of choline to glycine betaine (N,N,N-trimethylglycine) via two sequential, FAD-dependent reactions in which betaine aldehyde is formed as an enzyme-bound intermediate. In each oxidative half-reaction, molecular oxygen acts as electron acceptor and is converted into hydrogen peroxide. Biochemical, structural, and mechanistic studies on the wild-type and a number of mutant variants of choline oxidase have recently been carried out, allowing for the depiction of the mechanism of alcohol oxidation catalyzed by the enzyme. Catalysis by choline oxidase is initiated by the removal of the hydroxyl proton of alcohol substrate by a catalytic base in the enzyme-substrate complex, yielding the formation of the alkoxide species. In this dissertation, the roles of His351 and conserved His466 were investigated. The results presented demonstrate that His351 is involved in the stabilization of the transition state for the hydride transfer reaction and contributes to substrate binding. His466 is likely to be a catalytic base in choline oxidase due to its dramatic effect on enzymatic activity. Comparison of choline oxidase and other enzymes within its superfamily reveals the presence of a conserved His-Asn pair within the active site of enzymes. Therefore, the role of the conserved Asn510 in choline oxidase was examined in this study. The results presented here establish the importance of Asn510 in both the reductive and oxidative half-reactions. The lost of ability to form a hydrogen bond interaction between the side chain at position 510 with neighboring residues such as His466 resulted in a change from stepwise to concerted mechanism for the cleavages of OH and CH bonds of choline, as seen in the Asn510Ala mutant. Finally, the steady-state kinetic mechanism of pyranose 2-oxidase in the pH range from 5.5 to 8.5 was investigated. It was found that pH exerts significant effects on enzyme mechanism. This study has established the involvement of the residues in the initiation of enzyme catalysis and the stabilization of the alkoxide intermediate in choline oxidase. In addition, this work demonstrates the first instance in which the kinetic mechanism of a flavin-dependent oxidase is governed by pH.

We study diffusion-reaction-advection models describing population dynamics of aquatic organisms subject to a constant drift, with reflecting upstream and outflow downstream boundary conditions. We consider three different models: single logistically growing species, two and three competing species. In the case of a single population, we determine conditions for existence, uniqueness and stability of non-trivial steady-state solutions. We analyze the dependence of such solutions on advection speed, growth rate and length of the habitat. Such analysis offers a possible explanation of the "drift paradox" in our context. We also introduce a spatially implicit ODE (nonspatial approximation) model which captures the essential behavior of the original PDE model. In the case of two competing species, we use a diffusion-advection version of the Lotka-Volterra competition model. Combining numerical and analytical techniques, in both the spatial and nonspatial approximation settings, we describe the effect of advection on competitive outcomes. Finally, in the case of three species, we use the nonspatial approximation approach to analyze and classify the possible scenarios as we change the flow speed in the habitat.

No description available.

Tripeptidyl peptidase II (TPPII) is an exopeptidase which cleaves tripeptides from theN-terminus of peptides. The exact functional role of TPPII is still a matter of investigation. Itis believed that the enzyme is primarily involved in intracellular protein degradation, where itcooperates with the proteasome and other peptidases to degrade proteins into free aminoacids. These amino acids can subsequently be used in the production of new proteins. The aimof this work was to express murine wild type TPPII using E. coli and thereafter purify theenzyme from the bacterial lysate. Methods used for the purification included protein andnucleic acid precipitation, anion exchange chromatography, hydrophobic interactionchromatography and gel filtration. The presence of TPPII was determined using activityassay, western blot and SDS-PAGE. Despite the fact that some modification is still needed,the purification yielded a total of 34μg TPPII with a purity of approximately 60%. Thispurified enzyme can be used for future functional characterization.

The recent financial and economic turmoil driven by housing market has led the economists to refocus on the issue about monetary policy and asset price, especially housing price. In this dissertation I investigate the various relationships between monetary policy and asset prices in U.S. economy through steady state Bayesian VAR (SS BVAR) and revised Taylor-typed interest rate rule (Forward-looking rule) based on Generalized Method of Moments (GMM) methodology. In chapter II, steady state Bayesian VAR (SS BVAR) methodology is introduced and multi step-ahead forecasts are executed. Upon usual squared error loss methodology the forecasting performances of SS BVAR are evaluated in comparison with standard BVAR and conventional VAR. Equal predictive ability tests following Giacomini and White (2006) verify that the SS BVAR is superior in forecasting power especially in long-horizons. In chapter III, identification issue involving housing sector is explored through two different ways: economic theory-based approach and algorithms of inductive causations. Despite the different approaches the housing sector’s specifications are somewhat similar. Impulse response analyses demonstrate that monetary shock to housing price is relatively smaller, less significant, and less lasting when compared to Choleski identification. Also historical decomposition and conditional forecast analyses indicate that the housing price shock itself is crucial in accounting the sharp increase and sudden drop of housing price since 2003. Upon the estimated evidences I conjecture that there are much uncertainty between monetary policy and housing price, recalling the consideration of institutional factors when trying to accounting housing sectors. In chapter IV, following Dupor and Conley (2004), I explore how Fed responds to stock price and inflation movements differently across high and low inflation sub-periods. Replicated linear estimation results of Dupor and Conley (2004)’s indicate that Fed raises its target interest rate responding to stock price gap with statistical significance. Linear estimation results, however, are not robust to small change of chosen breakpoint especially in inflation coefficient. So I construct nonlinear model as an alternative way to relax this problem and carry out test of structural change with the nonlinear framework. Consequently both nonlinearity and structural change matter in explanation of Fed’s behavior in this type of reaction function analysis. Given structural change, inflation coefficients movement shows that Fed has responded to expected inflation pressure nonlinearly across sub-period, while stock price gap coefficient shows explicit break around early ’90 in line with Dupor and Conley (2004)’s finding.