Senior Recital: Jonathan Fallin, trumpet

This recital is presented in partial fulfillment of requirements for the degree Bachelor of Music in Music Education. Mr. Fallin studies trumpet with Dr. Douglas Lindsey.https://digitalcommons.kennesaw.edu/musicprograms/1026/thumbnail.jp

Tributyltin exposure alters cytokine levels in mouse serum

Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, keratinocyte chemoattractant (KC), macrophage inflammatory protein 1β (MIP), MIP2 and regulated on activation normal T-cell-expressed and secreted (RANTES) was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40 and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in the serum of mice exposed to TBT for less than 24 h. Levels of IL1β, IL-12 βp40, IL-5 and IL-15 were also modulated in mouse serum, depending on the specific experiment and exposure level. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines

A new photogrammetric method for quantifying corneal topography

Attempts to describe normal corneal shape and to represent corneal topography by an array of discrete points have limited usefulness. A quantitative photogrammetric method that produces indices to describe corneal shape was developed. Four indices depict the departure of keratographic rings from circularity, and two indices express the trends and consistencies of all the rings from one keratograph. This photogrammetric index method (PIM) was evaluated against established measurement techniques. Values for the six indices were computed for groups (10 corneas each) of symmetrical, regularly astigmatic, and keratoconic corneas that had been defined by keratometry and clinical criteria. Predictions of the differences among groups were formulated for each index based on group descriptions and anticipated manual tracing and/or digitization error. Parametric and nonparametric tests of significance supported most predictions. The asymmetry of irregularly astigmatic keratoconic corneas, the variability of their orthogonal principal meridians, and an increasing symmetry toward their peripheries were documented clearly. The circularity of symmetrical group rings and the ellipticity of regularly astigmatic group rings were also evident. Preliminary norms are offered to illustrate the usefulness of the PIM in defining groups of corneas with the same histories and in classifying individual corneas

Effect of tissue fit on corneal shape after transplantation

Postkeratoplasty astigmatism is now a major problem preventing visual recovery. Certain postopertive topographic characteristics are felt to be dictated by the fit of the donor corneal button in its recipient bed. Deficient tissue at the wound is predicted to contribute to the location of the steep meridian and excess tissue to the location of the flat meridian. In an eight-cat sample using our Fit Assessment Method and Photogrammetric Index Method, the authors tested the relationship between button fit in recipient bed and resulting corneal curvature at approximately 42, 161, and 289 postoperative days. Corneal symmetry improved between the first and second postoperative periods. Deficient tissue led to steepened curvature and ample tissue to flattened curvature in the first measurement period. When buttons fit poorly, deficient tissue led to steepness in the first postoperative period, but led to flattened curvature 90 deg away from the deficient tissue meridian in the second and third periods. The relationship between ample tissue and flattest postoperative curvature did not depend on the magnitude of button-bed disparity in any period. Corneal elasticity appeared to influence the way tissue disparity affected postoperative topography. Our findings support Troutman's balloon mode. When there was a large amount of uncompensated tissue disparity, the tissue deficiency exerted a force that shortened the translimbal chord. This produced both steepened curvature parallel to this chord soon after surgery and flattened curvature at 90 deg to the chord in the stable postoperative cornea

Speaker segmentation and clustering

This survey focuses on two challenging speech processing topics, namely: speaker segmentation and speaker clustering. Speaker segmentation aims at finding speaker change points in an audio stream, whereas speaker clustering aims at grouping speech segments based on speaker characteristics. Model-based, metric-based, and hybrid speaker segmentation algorithms are reviewed. Concerning speaker clustering, deterministic and probabilistic algorithms are examined. A comparative assessment of the reviewed algorithms is undertaken, the algorithm advantages and disadvantages are indicated, insight to the algorithms is offered, and deductions as well as recommendations are given. Rich transcription and movie analysis are candidate applications that benefit from combined speaker segmentation and clustering. © 2007 Elsevier B.V. All rights reserved

The proteasome inhibitor bortezomib controls indoleamine 2,3-dioxygenase 1 breakdown and restores immune regulation in autoimmune diabetes

Bortezomib (BTZ) is a first-in-class proteasome inhibitor approved for the therapy of multiple myeloma that also displays unique regulatory activities on immune cells. The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan metabolizing enzyme exerting potent immunoregulatory effects when expressed in dendritic cells (DCs), the most potent antigen-presenting cells capable of promoting either immunity or tolerance. We previously demonstrated that, in inflammatory conditions, IDO1 is subjected to proteasomal degradation in DCs, turning these cells from immunoregulatory to immunostimulatory. In non-obese diabetic (NOD) mice, an experimental model of autoimmune diabetes, we also identified an IDO1 defect such that the DCs do not develop tolerance toward pancreatic islet autoantigens. We found that BTZ rescues IDO1 protein expression in vitro in a particular subset of DCs, i.e., plasmacytoid DCs (pDCs) from NOD mice. When administered in vivo to prediabetic mice, the drug prevented diabetes onset through IDO1- and pDC-dependent mechanisms. Although the drug showed no therapeutic activity when administered alone to overtly diabetic mice, its combination with otherwise suboptimal dosages of autoimmune-preventive anti-CD3 antibody resulted in disease reversal in 70% diabetic mice, a therapeutic effect similar to that afforded by full-dosage anti-CD3. Thus, our data indicate a potential for BTZ in the immunotherapy of autoimmune diabetes and further underline the importance of IDO1-mediated immune regulation in such disease

Argyrin B a non-competitive inhibitor of the human immunoproteasome exhibiting preference for β1i

Inhibitors of the proteasome have found broad therapeutic applications however, they show severe toxicity due to the abundance of proteasomes in healthy cells. In contrast, inhibitors of the immunoproteasome, which is upregulated during disease states, are less toxic and have increased therapeutic potential including against autoimmune disorders. In this project, we report argyrin B, a natural product cyclic peptide to be a reversible, non-competitive inhibitor of the immunoproteasome. Argyrin B showed selective inhibition of the β5i and β1i sites of the immunoproteasome over the β5c and β1c sites of the constitutive proteasome with nearly 20-fold selective inhibition of β1i over the homologous β1c. Molecular modelling attributes the β1i over β1c selectivity to the small hydrophobic S1 pocket of β1i and β5i over β5c to site-specific amino acid variations that enable additional bonding interactions and stabilization of the binding conformation. These findings facilitate the design of immunoproteasome selective and reversible inhibitors that may have a greater therapeutic potential and lower toxicity