A longitudinal pilot study to compare, in children with reduced overbite malocclusions associated with oral habits (finger-sucking and tongue-thrusting), the effects of the experimental Myofunctional Trainer (MFT; Myofunctional Research Co.) and the conventional Bluegrass appliance (BG) on dento-alveolar relations, tongue position, and on speech. Methods: The experimental group received the MFT appliance while the control group received the BG appliance. Dento-alveolar changes were assessed by cephalometry and study models. Longitudinal midsagittal 2-dimensional B-mode ultrasound scans of the tongue surface were performed to determine tongue position. Speech acceptability tests were also performed. Results & Conclusions: The BG appliance was successful in breaking the finger-sucking habit. The MFT appliance showed only partial success which could be attributed to lack of compliance. At the end of treatment, the open bite was reduced in both groups due to dento-alveolar changes. The BG appliance had a deleterious effect on speech acceptability while in place, while there was no such effect with the MFT appliance.

The presence of autoantibodies in systemic lupus erythematosus (SLE) suggests a breach of tolerance. Recently, the IgM-IgD+ naïve B cell population has been shown to be enriched for self-reactive cells that are anergic in healthy subjects. Therefore, to determine whether there is altered selection of self-reactive cells in SLE, this population was examined using multiparameter flow cytometry. SLE patients had increased proportions of IgM-IgD+ cells in mature and transitional B cell compartments that were activated as compared to controls. Comparison of mature and transitional IgM-IgD+ B cell proportions suggested altered selection between the transitional to mature stages in SLE. There was no correlation between altered B cell function or genetic polymorphisms in B cell signalling molecules and the expansion or activation of IgM-IgD+ cells. Thus, selection of self-reactive B cells appears to be abnormal in SLE, but this does not appear to result from altered responses to Ig crosslinking.

An evolutionary geometry parametrization is established to represent aerodynamic configurations. This geometry parametrization technique is constructed by integrating the classical B-spline formulation with the knot insertion algorithm. It is capable of inserting control points to a given parametrization without modifying its geometry. Taking advantage of this technique, a shape design problem can be solved as a sequence of optimizations from the basic parametrization to more refined parametrizations. Owing to the nature of the B-spline formulation, feasible parametrization refinements are not unique; guidelines based on sensitivity analysis and geometry constraints are developed to assist the automation of the proposed optimization sequence. Test cases involving airfoil optimization and induced drag minimization are solved adopting this method. Its effectiveness is demonstrated through comparisons with optimizations using uniform refined parametrizations.

The presence of autoantibodies in systemic lupus erythematosus (SLE) suggests a breach of tolerance. Recently, the IgM-IgD+ naïve B cell population has been shown to be enriched for self-reactive cells that are anergic in healthy subjects. Therefore, to determine whether there is altered selection of self-reactive cells in SLE, this population was examined using multiparameter flow cytometry. SLE patients had increased proportions of IgM-IgD+ cells in mature and transitional B cell compartments that were activated as compared to controls. Comparison of mature and transitional IgM-IgD+ B cell proportions suggested altered selection between the transitional to mature stages in SLE. There was no correlation between altered B cell function or genetic polymorphisms in B cell signalling molecules and the expansion or activation of IgM-IgD+ cells. Thus, selection of self-reactive B cells appears to be abnormal in SLE, but this does not appear to result from altered responses to Ig crosslinking.

An evolutionary geometry parametrization is established to represent aerodynamic configurations. This geometry parametrization technique is constructed by integrating the classical B-spline formulation with the knot insertion algorithm. It is capable of inserting control points to a given parametrization without modifying its geometry. Taking advantage of this technique, a shape design problem can be solved as a sequence of optimizations from the basic parametrization to more refined parametrizations. Owing to the nature of the B-spline formulation, feasible parametrization refinements are not unique; guidelines based on sensitivity analysis and geometry constraints are developed to assist the automation of the proposed optimization sequence. Test cases involving airfoil optimization and induced drag minimization are solved adopting this method. Its effectiveness is demonstrated through comparisons with optimizations using uniform refined parametrizations.

Our laboratory previously found that protein-energy malnutrition (PEM) existing prior to brain ischemia impaired functional outcome measured in an open field test, and one-third of animals showed a marked increase in reactive gliosis. It was hypothesized that PEM worsened stroke outcome by increasing inflammation via increased activation of the transcription factor, nuclear factor kappa B (NFκB). Mongolian gerbils (11-12 wk old) were randomly assigned to a control diet (12.5% protein) or a protein-deficient diet (2%) for 28 days. The control group on average gained 4.9g and the PEM group lost 7.4g. PEM gerbils had significantly decreased food intake (P<0.001; unpaired t-test). Animals were then subjected to global ischemia or sham surgery, resulting in four experimental groups. Global ischemia was achieved by a 5 min bilateral common carotid artery occlusion with tympanic temperature regulated at 36.5 ± 0.2C. PEM independently increased hippocampal NFκB activation by three times higher than control diet animals at 6hr after surgery (p=0.014; 2-factor ANOVA) detected by electrophoretic mobility shift assay (EMSA). There was no significant effect of ischemia on NFκB activation and there was no interaction of diet and ischemia. Serum glucose and serum cortisol were also measured since both variables can be affected by PEM and can influence stroke outcome, but there was no significant effect of diet or ischemia. Because of the increased NFκB activation observed in PEM-Sham animals, a second experiment investigated if PEM also increased NFκB activation in the absence of surgery. Gerbils of the same age were randomly assigned to either control diet or PEM for 28 days but did not receive any surgery. PEM consistently increased NFκB activation. Since PEM exists in 16% of elderly stroke patients at admission, the data suggest that PEM may worsen stroke outcome through increased activation of NFκB. Because increased NFκB activation was also observed in PEM independent of ischemia, the data also have implications for the inflammatory response of protein-energy malnourished elderly in general.

Recent epidemiological evidence suggests that many chronic health disorders in the developed world are associated with endogenous toxins formed from the Western diet. The Western diet, which encompasses calorie dense foods, processed foods and increased quantities of red meat, can cause intracellular oxidative stress through increased formation of reactive oxygen species(ROS) and reactive carbonyl species (RCS). A number of micronutrients have been investigated for their protective capacity in in vitro and in vivo models of oxidative stress. This thesis investigated the cytotoxic targets of Fenton-mediated ROS and RCS and the subsequent protective mechanisms of vitamins B1 (thiamin) or B6 (pyridoxal, pyridoxamine or pyridoxine) in an isolated rat hepatocyte model. The approach was to use an “accelerated cytotoxicity mechanism screening” technique (ACMS) to develop an in vitro cell system that mimicked in vivo tissue cytotoxicity. Using this technique, we investigated the protective mechanisms of vitamins B1 and/or B6 against the cytotoxic effects of two endogenous toxins associated with the Western diet: 1) RCS, as exemplified by glyoxal, a glucose/fructose autoxidation product and 2) biological ROS induced by exogenous iron. Firstly, we developed an understanding of the sequence of events contributing to glyoxal-induced oxidative stress, with a focus on protein carbonylation. Next, we determined the mechanisms by which carbonyl scavenging drugs (vitamin B6 included) protected against the intracellular targets of glyoxal-induced toxicity. Our results suggested that the agents used were cytoprotective by multiple mechanisms and glyoxal trapping was only observed when the agents were administered at concentrations equal to glyoxal. We also evaluated the protective capacity of vitamins B1 and B6 against iron-catalyzed cytotoxicity and found that hepatocytes could be rescued from protein and DNA damage when vitamins B1 or B6 were added up to one hour after treatment with iron. The vitamins also varied in their primary mechanisms of protection. Our improved understanding of Western diet-derived endogenous toxins enabled us to identify and prioritize the specific inhibitory mechanisms of vitamins B1 or B6. The ability to delay, inhibit or reverse toxicity using multi-functional B1 or B6 vitamins could prove useful as therapy to minimize oxidative stress in diet-induced chronic conditions.

It is agreed upon by many philosophers that perception represents the world to be in a certain way. However, there is disagreement among those philosophers about whether perceptual content is conceptual or not. The aim of this thesis is to provide a clear presentation of the debate and to propose an account of nonconceptual perceptual content that can tackle many philosophical problems related to the issue. Conceptualism about perceptual content is the view that perceptual content is wholly conceptual. Proponents of this view claim that a subject cannot be in a contentful perceptual state without possessing concepts that fully characterize the content of his experience. The main motivation behind conceptualism is the justificatory role perception is supposed to play in forming perceptual beliefs. It is claimed that if perceptual content provides rational ground or reason for forming perceptual beliefs, it has to be conceptual just like the belief it is a reason for. However, there are several philosophical problems that arise from such an understanding of perceptual content. Most of them mainly derive from the implausibility of the claim that a subject needs to possess every concept that figures in the characterization of the content of his perceptual state. So, nonconceptualism is based on the assumption that a contentful perceptual state can occur albeit the absence of all or some concepts that characterize the content. Therefore, in this thesis I aim to provide a notion of nonconceptual perceptual content that is epistemically relevant, i.e. that can ground perceptual beliefs in spite of its nonconceptual character.

A longitudinal pilot study to compare, in children with reduced overbite malocclusions associated with oral habits (finger-sucking and tongue-thrusting), the effects of the experimental Myofunctional Trainer (MFT; Myofunctional Research Co.) and the conventional Bluegrass appliance (BG) on dento-alveolar relations, tongue position, and on speech. Methods: The experimental group received the MFT appliance while the control group received the BG appliance. Dento-alveolar changes were assessed by cephalometry and study models. Longitudinal midsagittal 2-dimensional B-mode ultrasound scans of the tongue surface were performed to determine tongue position. Speech acceptability tests were also performed. Results & Conclusions: The BG appliance was successful in breaking the finger-sucking habit. The MFT appliance showed only partial success which could be attributed to lack of compliance. At the end of treatment, the open bite was reduced in both groups due to dento-alveolar changes. The BG appliance had a deleterious effect on speech acceptability while in place, while there was no such effect with the MFT appliance.

Using 1.0 fb^{-1} of data collected by the Collider Detector at Fermilab (CDF) from Run II of the Fermilab Tevatron, we measure the top-antitop production cross-section in events with two leptons, significant missing transverse energy, and at least jets, at least one of which is identified as a b-jet. As the Run II dataset grows, more stringent tests of Standard Model predictions for the top quark sector are becoming possible. The dilepton channel, where both top quarks decay t-> W b ->l nu b, is of particular interest due to its high purity. Use of an isolated track as the second lepton significantly increases the dilepton acceptance, at the price of some increase in background, particularly from W + jets events where one of the jets is identified as a lepton. To control the increase in background we add to the event selection the requirement that at least one of the jets be identified as a b-jet, reducing the background contribution from all sources. Assuming a branching ratio of BR(W->l nu) = 10.8% and a top mass of m_top = 175 GeV/c^{2} the measured cross-section is sigma = (10.5 +/- 1.8 stat. +/- 0.8 syst. +/- 0.6 lumi.) pb.