α-Crystallin B (cryAB) is the most abundant small heat shock protein in cardiomyocytes (CMs), where it has been shown to have potent anti-apoptotic properties. The mechanism by which cryAB prevents apoptosis has not been fully characterized. Therefore, I was interested in elucidating its protective mechanism in CMs. I identified its sub-cellular localization and its binding interactors following H2O2 exposure. I found that cryAB is found in the cytosol under control conditions and that following H2O2 exposure it becomes phosphorylated and translocates to the mitochondria. CryAB silencing resulted in increased apoptosis levels in CMs. Co-immunoprecipitation revealed an apparent increased interaction of cryAB and PcryAB with mitochondrial VDAC, caspase 12 and uncleaved caspase 3 in stressed hearts relative to controls. These results suggest that the cardio-protective effects of cryAB are mediated by its translocation to the mitochondria and its interaction with VDAC, caspase 12 and caspase 3 following exposure to H2O2.

Normal endothelial cell function is controlled in part by a tightly regulated balance between angiopoietin-1 and -2 (Ang-1 and Ang-2). Angiopoietin dysregulation (decreased Ang-1 and increased Ang-2) leads to an activated endothelium that is contractile, adhesive, and prothrombotic. Since an activated endothelial phenotype is seen in invasive group A streptococcal infection, E. coli O157:H7-induced hemolytic-uremic syndrome (HUS), and sepsis, we hypothesized that angiopoietin dysregulation might also be present in these syndromes, and to that end, measured angiopoietin levels in several well-characterized patient cohorts. Decreased Ang-1 and/or increased Ang-2 were found in all three syndromes, and were predictive of clinical outcome in HUS and sepsis. The prognostic utility of Ang-2 in sepsis was further enhanced by combination with biomarkers of inflammation. Angiopoietin dysregulation may therefore represent a shared final common pathway to endothelial activation as well as a clinically useful prognostic biomarker in streptococcal toxic shock, HUS, and sepsis.

<p>In this dissertation work, the aim was to garner better mechanistic understanding of how shock wave lithotripsy (SWL) breaks stones in order to guide design improvements to a modern electromagnetic (EM) shock wave lithotripter. To accomplish this goal, experimental studies were carefully designed to isolate mechanisms of fragmentation, and models for wave propagation, fragmentation, and stone motion were developed. In the initial study, a representative EM lithotripter was characterized and tested for in vitro stone comminution efficiency at a variety of field positions and doses using phantom kidney stones of variable hardness, and in different fluid mediums to isolate the contribution of cavitation. Through parametric analysis of the acoustic field measurements alongside comminution results, a logarithmic correlation was determined between average peak pressure incident on the stone surface and comminution efficiency. It was also noted that for a given stone type, the correlations converged to an average peak pressure threshold for fragmentation, independent of fluid medium in use. The correlation of average peak pressure to efficacy supports the rationale for the acoustic lens modifications, which were pursued to simultaneously enhance beam width and optimize the pulse profile of the lithotripter shock wave (LSW) via in situ pulse superposition for improved stone fragmentation by stress waves and cavitation, respectively. In parallel, a numerical model for wave propagation was used to investigate the variations of critical parameters with changes in lens geometry. A consensus was reached on a new lens design based on high-speed imaging and stone comminution experiments against the original lens at a fixed acoustic energy setting. The results have demonstrated that the new lens has improved efficacy away from the focus, where stones may move due to respiration, fragmentation, acoustic radiation forces, or voluntary patient movements. Using traditional theory of brittle fragmentation and newfound understanding of average peak pressure correlation to stone comminution, the entire set of stone comminution data for lens comparison was modeled using a Weibull-style distribution function. This model linked both the average peak pressure and shock wave dose to efficacy, including their respective threshold parameters, and demonstrated correlation of coefficients to cavitation activity. Subsequently, this model was used in prediction of stone comminution efficiency from mimicked respiratory motions in vitro, which compared favorably to actual simulated motion studies using both the new and original lenses. Under a variety of mimicked respiratory motions, the new lens produced statistically higher stone comminution efficiency than the original lens. These results were confirmed in vivo in a swine model, where the new lens produced statistically higher stone comminution after 1,000 and 2,000 shocks. Finally, a mechanistic investigation into the effects of cavitation with the original lens was conducted using an integrated, self-focusing annular ring transducer specially designed for tandem pulse lithotripsy. It was found that cavitation and stone comminution efficiency are progressively enhanced by tandem pulsing as source energies of both the primary LSW and trailing pressure pulse increase, which suggests cavitation and stress waves act synergistically enhance the efficacy in kidney stone fragmentation.</p> / Dissertation

This dissertation examined the experiences of African American and Hispanic community college transfers studying in a predominantly White institution (PWI) teacher education program. Extant literature has demonstrated that there is an increasing shortage of public school teachers of color. To address this pervasive crisis, universities must recruit larger numbers of under-represented students from America's community colleges to fill the gap. Additionally, under-represented students in predominantly White institution (PWI) teacher education programs must be retained and graduated in higher numbers to impact teacher production. To understand the needs and experiences of these students, three African American and four Hispanic students successfully studying in the College of Education and Human Development at Texas A & M University were interviewed to examine their experiences as they transitioned into and through the pre-service teacher education program. This study utilized a case study analysis and data collected through interviews, observations, and document analysis were analyzed utilizing constant comparative techniques. Key themes that emerged through data analysis included (1) Student Perceptions of the Transfer Process, (2) The Role of Intimate Support Structures, (3) The Role of Institutional Support Structures, (4) Situational Factors Faced by Under-represented Transfers, and (5) Strategies Employed by Under-represented Transfers in a Predominantly White, Teacher Education Program. Findings from this study suggest that Texas A & M University should improve the marketing of academic support resources and provide narrowly tailored services to meet the needs of under-represented transfer students. Additionally, Schlossberg's Transition Theory is amended to better represent the assets and liabilities utilized by these populations in this particular PWI.

It is proposed in this investigation that the phenomenon of shock is central to the fiction of Mary E. Mann as a premier factor at the heart of its powers of creative constitution. The study highlights Mann’s writing as a system of jolts, fits, and shocks lacking intrinsic meaning. The lack of intrinsic meaning in events is not viewed negatively as a mode of loss, existential meaning not having been posited beforehand as standard for measuring the nature of feelings, acts, or lives. The tendency for shocks to lack meaning in Mann’s writing is not seen as nihilistic. Shock in Mann’s writing needs to be elucidated without a prior meaning-frame or nihilistic loss-of-meaning agenda. The study presents the case that Mann’s fiction is devoted to the business of exhibiting the potential horror of human life in a non-metaphysical, non-theoretic way. In Mann’s literary texts lives fall apart without justification or forewarning. Characters walk straight into darkness and pain—but no loss or gain of metaphysical meaning is to be inferred. Disaster does not mean that life is intrinsically disastrous. Nor does catastrophe imply that we live in a universe where meaning is inevitably withheld. When meaning is given or withheld it happens to be given or withheld. This accidentalness is itself shocking. Like happiness, disaster is non-essential. It is to a large extent ruled by chance. Unlike Thomas Hardy, with whom she is sometimes compared, Mary Mann is accordingly not a pessimistic writer who tends to want to let darkness have the final word in order to immerse the reader in a metaphysics of gloom. In her short stories and novels darkness often has the last word; yet that tells us nothing about the intrinsic nature of reality. Negativity is real but extrinsic and non-essential. In Mann’s tales of Norfolk destinies, lives and characters fail simply because times are sometimes hard, and because adversity is central to fiction and existence.

No description available.

No description available.

Various genes have evolved to protect the cell against stressor-induced damage or death including the heat shock proteins (HSPs). Stressor-induced HSP gene expression involves the activation of heat shock factor (HSF), which binds to the heat shock element (HSE) found in the promoter region of <em>hsp</em> genes. Previously, our laboratory has examined the expression and function of <em>hsp</em> genes in the South African clawed frog, <em>Xenopus laevis</em>. Amphibians are particularly susceptible to adverse environmental conditions, including high temperatures and toxicants. In contrast to the many known inducers of HSF activation in poikilothermic vertebrates, few inhibitors have been either discovered or described in the literature. The present study has compared for the first time the effect of two heat shock response (HSR) inhibitors, quercetin and KNK437, on <em>hsp</em> gene expression in <em>Xenopus</em> A6 cells, demonstrating their efficacy in poikilotherms. Northern blot and densitometric analysis showed that cells treated with either quercetin or KNK437 decreased the heat shock-induced accumulation of <em>hsp70</em>, <em>hsp47</em>, and <em>hsp30</em> mRNAs. Additionally, constitutive levels of <em>hsp47</em> and <em>hsc70</em> mRNAs were reduced. In comparison, neither quercetin nor KNK437 affected the levels of constitutively expressed <em>ef1&alpha;</em> mRNAs under control or heat shock conditions. Western blot and densitometric analysis in this study showed that under heat shock conditions, exposure to quercetin or KNK437 significantly decreased the accumulation of HSP30, and that KNK437 was more effective in doing so than quercetin. In comparison, levels of actin were not significantly affected by either heat shock or exposure to DMSO, quercetin, or KNK437. These findings suggest that one mechanism by which quercetin and KNK437 inhibits the HSR in <em>Xenopus</em> is through the inhibition of HSF activity. <br /><br /> Results of this study also suggest that KNK437 inhibits the acquisition of thermotolerance in poikilotherms, similar to observations in mammalian systems. In the presence of KNK437, cells given a 2 h heat pretreatment at 33ºC followed by a thermal challenge for 1 h at 37ºC, showed numerous ruffled membrane edges and some aggregates of disrupted stress fibers. In comparison, cells directly challenged for 1 h at 37ºC, showed a marked decrease in HSP30, which was located predominantly at the cellular periphery in conjunction with actin aggregates. These cells showed virtually no intact stress fibers spanning cells and no coherent cell-cell connections. A 3-D analysis of cells given a 1 h thermal challenge at 37ºC (after a prior 2 h heat shock at 33ºC) in the absence of KNK437, showed numerous linear actin bundles transversing the entire cell, even extending into areas of cell-cell contact, and abundant HSP30 concentrated in the perinuclear region surrounding an intact nucleus. However, in the presence of KNK437, there was a significant emergence of membrane ruffles indicating global instability of cellular adhesion. This study has demonstrated that KNK437, which is the more specific and efficient HSR inhibitor, will be an important inhibitor to compare with the well-documented quercetin for future investigations.

We analyze sector specific shocks in productivity and demand in 19 manufacturing sectors of the Austrian economy. Based on a structural vector autoregressive (SVAR) model with long run restrictions developed by Gali (1999) we extract technology and non-technology shocks from sectoral and aggregate data and study their patterns and relationship by means of a principal components analysis. We find a close association of sectoral and macroeconomic non-technology shocks but only a very weak association for technology shocks. Impulse-response analysis indicates that for almost all manufacturing sectors and the Austrian economy productivity growth rates experience an immediate increase to positive technology shocks while the hours worked decline. We therefore confirm Gali's results on the level of manufacturing industries. Finally, we use the identified shocks as explanatory variables in fixed effect regressions on growth rates of employment, output and investment. We find that our shocks are closely associated to employment growth and output growth but not to growth in investment. The effect of technology shocks is different on the level of manufacturing industries and the aggregate economy. (author's abstract) / Series: Working Papers Series "Growth and Employment in Europe: Sustainability and Competitiveness"

Simulating transient compressible flows involving shock waves presents challenges to the CFD practitioner in terms of the mesh quality required to resolve discontinuities and prevent smearing. This document discusses a novel two-dimensional Cartesian anisotropic mesh adaptation technique implemented for transient compressible flow. This technique, originally developed for laminar incompressible flow, is efficient because it refines and coarsens cells using criteria that consider the solution in each of the cardinal directions separately. In this document the method will be applied to compressible flow. The procedure shows promise in its ability to deliver good quality solutions while achieving computational savings. Transient shock wave diffraction over a backward step and shock reflection over a forward step are considered as test cases because they demonstrate that the quality of the solution can be maintained as the mesh is refined and coarsened in time. The data structure is explained in relation to the computational mesh, and the object-oriented design and implementation of the code is presented. Refinement and coarsening algorithms are outlined. Computational savings over uniform and isotropic mesh approaches are shown to be significant.