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This project examines the systemic causes of transfer shock, the phenomenon wherein students transitioning onto a university campus from a community college experience a drop in their grade point average (GPA) in their first semester of transfer. Previous research has focused on student characteristics that are predictive of transfer shock, but few researchers have approached this topic from the perspective of the students themselves. This study seeks to understand how transfer students experience the initial transition onto the four-year university campus and the interactions with managerial professionals, and how those interactions impact the likelihood of students experiencing transfer shock or not. I used the work of Tinto (1975) and Deil-Amen (2011), as well as interviews with 15 transfer students, to theorize that students' procedural interactions are significant for their socio-academic integration. This study demonstrates the process of socio-academic integration and highlights the ways that the institution can support or impede student academic performance and success.

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Cancer is an uncontrolled growth of the body's own cells. While cancer rates increase with age, this disease afflicts both young and old. Traditional cancer therapy has had three major facets: 1) chemotherapy, which can non-specifically damage healthy tissue, 2) radiation, which can make some types of cancer more likely in the future, and 3) surgery, which can be physically traumatic and is not effective in removing unseen microtumors or circulating metastases. Immunotherapy, by its very nature, is drastically different. Immunotherapy seeks to employ cells or molecules from the immune system, in their original or a modified form, to augment, assist or replace missing elements of the native functioning immune system. Our immunotherapeutic approach has been to develop novel chimeric antigen receptors (CAR) and deliver the engineered transgene into hematopoietic stem cells (HSC). We have developed a novel single chain TCR (scTCR) in which the TCR V-alpha and V-beta segments are joined by a flexible linker. In addition to our scTCR we developed a single chain antibody molecule (scFv) to increase avidity to the tumor antigen and avoid the potential limitation of MHC restriction. Our lab has previously developed a signaling cassette based on the CD3 zeta chain, CD28 and p56Lck proteins which are prominent in the T-cell signaling pathway. The single chain specificities are linked to the signaling cassette that we have shown to function in T-cells. With specificity and signaling coupled, the chimeric antigen receptor can be transduced into hematopoietic stem cells (HSC) via a lentivirus vector. This adoptive immunotherapy can potentially eliminate malignant cells or supplement traditional therapies by providing engineered specificity and a useful method to transfer and expand tumor specific T-cells. We show in this study that the CAR can be delivered effectively to HSC and that the introduced transgene is expressed in multiple cell lineages. We also have developed a novel method of increasing lentiviral transduction efficiency. Both transduced fraction of cells and overall expression can be increased by proper timing and coordination of cell growth, cell cycle phase, vector addition and treatment with heat shock.

Chaperone proteins such as heat-shock proteins 70, 90 and 110, glucose-related protein 94 and calreticulin have been reported to be effective anti-tumor vaccines when purified from a tumor source. We have developed a procedure utilizing a free-solution-isoelectric focusing technique to obtain vaccines from tumor or normal tissue sources that are rich in multiple immunogenic chaperone proteins, called Chaperone-Rich Cell Lysate (CRCL). Tumor-associated peptides are presumed to be the currency of T-cell mediated anti-cancer immunity, and tumor-derived chaperone vaccines are believed to be purveyors of such peptides. As a novel anti-cancer strategy, we have examined the extent to which the peptide repertoire of CRCL can be manipulated. Here, we explored the concept of creating a designer CRCL, utilizing the adjuvant properties and the carrying capacity of CRCL to deliver exogenous antigenic peptides for DC-based presentation and ultimately demonstrate the anti-tumor efficacy of the designer vaccine in vivo. Designer CRCL allows for the development of personalized vaccines to those afflicted with cancer expressing known antigens.Growing evidence indicates that the stress response, specifically involving HSPs, has a profound impact on tumor immunogenicity. Enhancement of T-cell-mediated immunogenicity correlates with the expression of inducible heat shock protein 70 (iHSP70), the major heat-inducible member of the HSP70 family. In addition, studies have shown tumor-specific cell surface localization of iHSP70 correlates with an increased sensitivity to lysis mediated by human natural killer (NK) cells. Given these findings, investigating novel and effective means of modulating the heat shock response within tumor cells may bear great therapeutic potential and result in potent anti-tumor immune activity. Withaferin A (WA) is a compound isolated from the plant Withania somnifera that has been shown to induce a robust transcriptional heat shock response. In our studies, we found that WA treatment resulted in increased surface expression of iHSP70 in several tumor types leading to significant immunostimulatory effects. These findings indicated that WA-dependent modulation of the heat shock response may enhance tumor immunogenicity. Given the potent immunomodulatory and anti-tumor effects of WA as well as the adjuvanticity and specificity of peptide-complexed CRCL against tumors, these therapies individually have shown profound anti-cancer activity.

The thesis is devoted to the investigation of the initial-value problem for linearized Euler equations utilizing an idealized one-reaction detonation model in the case of three-dimensional perturbations in a circular pipe.The problem is solved using the Laplace transform in time, Fourier series in the azimuthal angle, and expansion into Bessel's functions of the radial variable.For each radial and azimuthal mode, the inverse Laplace transform can be presented as an expansion of the solution into the normal modes of discrete and continuous spectra. The dispersion relation for the discrete spectrum requires solving the homogeneous ordinary differential equations for the adjoint system and evaluation of an integral through the reaction zone.The solution of the initial-value problem gives a convenient tool for analysis of the flow receptivity to various types of perturbations in the reaction zone and in the quiescent gas.

Throughout the latter half of the 20th century, many developing economies adopted a set of economic policies in order to transition to market economy. Reforms were introduced either simultaneously or gradually, fuelling the debate over whether the so-called shock-therapy reforms were more beneficial or less beneficial to growth than gradual reforms. This study focuses on the role of the mode of transition in determining the effectiveness of Foreign Direct Investment (FDI) on the growth of the Gross Domestic Product (GDP). FDI is valuable for development in transition economies since it has often been a main source of investment for these types of economies. An empirical analysis was conducted using sixty transitioning countries, examining the growth up to sixteen years after the initial reform. The results indicate that there is some evidence of a difference in the effects of FDI inflows on GDP growth between the shock-therapy and gradual reformers.

We use particle and magnetic field data from the Ion and Neutral Camera (INCA) and the magnetometer (MAG) onboard Cassini to detect and examine an energetic particle event that occurred upstream from the Saturnian bow shock during DOY 229/2007. The energetic (>100 keV) O+ ions are observed only when the Interplanetary Magnetic Field (IMF) connects the spacecraft with the planetary bow shock. We provide strong evidence showing the magnetospheric origin of the observed ions: (1) We detect singly ionized oxygen (O+) which is not resident of the solar wind, (2) the particle pitch angle distribution indicates that the ions travel along the field line connecting the spacecraft to the bow shock and (3) the ion intensity increases are observed only during the periods of magnetic connection to the bow shock. Our results show that the Saturnian dayside magnetosphere is not as sealed as thought to be, but can -under certain circumstances- allow high energy magnetospheric plasma to leak into the nearby solar wind and further in space.

In eukaryotes, the ubiquitin-proteasome system (UPS) degrades most cellular protein. Inhibition of the UPS has been associated with different disease states and can affect various intracellular processes including the activation of heat shock protein (hsp) gene expression. During cellular stress, HSPs act as molecular chaperones by inhibiting protein aggregation and assisting in their refolding once normal conditions are re-established. In the present study, Withaferin A (WA), a steroidal lactone with possible anti-inflammatory and antitumor properties, was found to inhibit proteasome activity and induce the expression of hsp genes in the amphibian model system, Xenopus laevis. Treatment of Xenopus kidney epithelial A6 cells with WA produced an increase in the accumulation of ubiquitinated protein and a significant decrease in chymotrypsin-like activity. Furthermore, immunoblot analysis revealed that WA induced HSP30 and HSP70 accumulation. For example, cells treated with 5 μM WA for 18 h resulted in the optimal accumulation of HSP30 and HSP70. Northern blot analysis revealed that exposure of cells to 5 μM WA induced hsp30 and hsp70 mRNA accumulation in a time-dependent manner up to 12 h. The activation of heat shock factor 1 (HSF1) DNA-binding may be involved in WA-induced hsp gene expression in A6 cells, since pretreatment with the HSF1 inhibitor, KNK437, reduced the accumulation of HSP30 and HSP70. Also, WA acted synergistically with mild heat shock to enhance HSP accumulation to a greater extent than the sum of both stressors individually. In cells recovering from WA, the relative levels of HSP30 and HSP70 accumulation remained elevated from 6 to 12 h after removal of WA. Immuocytochemical analysis and laser scanning confocal microscopy revealed that WA-induced HSP30 accumulation occurred primarily in the cytoplasm with some staining in the nucleus in a granular or punctate pattern. Prolonged exposure to WA resulted in some disorganization of the actin cytoskeleton as well as large cytoplasmic HSP30 staining structures in some cells. Prior exposure of cells to WA treatment conferred thermotolerance since it protected them against a subsequent thermal challenge at 37 °C. In conclusion, this study has shown that WA can induce an inhibition of proteasome activity and an increase hsp gene expression. Activating the heat shock response is a potential avenue for novel drug therapies, which can confer cytoprotection in disease states involving cytotoxic protein aggregation.