To date there is no accepted clinical diagnostic test for Parkinson's disease (PD) based on biochemical analyses of blood or cerebrospinal uid. Currently, diagnosis, measurement of disease progression and response to therapeutic intervention are based on clinical observation, but the rst neuronal dysfunction precede the earliest recognition of symptom by at least 5 - 10 years. A potential diagnostic biomarker is oligomeric alpha-synuclein which in recent papers have reported a signicant quantitative dierence between PD and controls. In this master thesis, a method for measuring oligomeric levels of alpha-synuclein is presented together with a monomeric measuring commercial kit used to measure alpha-synuclein in a preclinical model of PD. A signicant dierence of monomeric levels could be detected between two weeks and four weeks post injection of a vector containing the gene for human alpha-synuclein, no signicant dierence between four and eight weeks was found.

No description available.

No description available.

Thesis (Ph. D.)--University of Missouri--Columbia, 2002. / "May 2002." Typescript. Vita. Includes bibliographical references (leaves 237-245).

In this thesis we analyze the financial performance of Football clubs following an initial public offering (IPO). We conduct several analyses using time series stock data with a focus on finding evidence of long-run underperformance and IPO over/underpricing. To this end, we estimate cumulative abnormal returns (CAR) and Jensen’s Alpha. We also analyze coefficients such as beta to describe the volatility and the link football clubs’ stocks have to the general market. We look at historical events that may have affected the movement of stock prices and confirm this by benchmarking an index (STOXX index) compiled of a number of European football teams. Our results show that football clubs do in fact follow the clear pattern of other entities and sectors and previous research with regard to underperformance in the long run. We find that football clubs’ stocks are less volatile than the general market and have a low beta. With regards to over/underpricing, we only obtain data for a few football clubs. We find small signs of underpricing but are not able to confirm that this is statistical significant due to the size of our sample.

Gloveboxes, where special nuclear material is handled and such as those present at Los Alamos National Labs, LANL, provide an experimental area confined within a protective shell and with strict environmental controls. These gloveboxes allow workers to indirectly interact with hazardous material. Unfortunately, these gloveboxes are not fail proof and are subject to occasional accidental failures resulting in possible breaches of containment and release of nuclear material. In particular, fires within the gloveboxes are of major concern with regard to the potential for breaches and damage to not only the glovebox but also to surrounding areas as well. Another, potentially even catastrophic, result of glovebox fires is the potential for the spread of radioactive contamination. There is some historical precedent of contaminant release resulting from glovebox fires, such as those at the Rocky Flats Plant (Buffer, 2012). Gloveboxes at LANL are currently equipped with manually activated fire suppression systems. In the event of an incident, a worker would hit a nearby emergency button and the system would be activated. However, this method relies on the worker to have the presence of mind in the face of danger to activate the system, and as such there is no true guarantee that the systems will be triggered. Since the level of consequence is dire, then the ideal situation requires that other fire suppression systems be present which do not rely on human interaction to function. The Fire Foe™ system has been chosen as a secondary failsafe measure in order to meet this need. Analysis of how the casing of the Fire Foe™ system, composed of nylon 6,6 polymer, weathers under irradiation in gloveboxes is paramount in determining the effectiveness and potential lifetimes of the systems within the gloveboxes. Samples of nylon 6,6 were exposed to a 5 Ci PuBe neutron source located at the University of Texas as well as a high dose rate beam of 4.5 MeV alpha particles located at Los Alamos to determine the effect of neutron and alpha particle damage on the polymer material. Subsequent mechanical testing was conducted to determine alteration to the tensile properties of the nylon 6,6 material for both irradiated and non-irradiated samples. / text

No description available.

No description available.

Cancer metastasis is a multi-stage process initiated by the cancer cell acquiring the ability to migrate. The protein profile of such a cell undergoes dramatic changes including changes in integrin expression. Integrins play a major role in cell adhesion, motility, differentiation, blood clotting, tissue organization and cell growth as well as cancer cell migration, invasion and metastasis. Integrin a6, which can pair with integrin b4 or b1 is a laminin receptor and is detected in epithelial cells. Earlier studies have reported uPA mediated integrin a6 cleavage in prostate cancer resulting in loss of the ligand binding domain. Site-directed mutagenesis studies have identified the cleavage site to be at R594R595 located in the "stalk" region of the integrin a6. Prostate cancer cells PC3N-a6-RR cells, bearing a R594R595 to A594A595 mutation, engineered to express the uncleavable form of integrin a6 were found to migrate 6.4 folds lesser on Laminin-1 as compared to the PC3N-a6-WT cells which expressed the wild-type integrin a6. This result suggests that integrin a6 cleavage enhances migration. Prostate cancer is known to metastasize to the bone. Injection of the PC3N-a6-WT cells in mouse femurs resulted in increased bone destruction and pain behavior when compared to the femurs injected with PC3N-a6-RR cells indicating that the integrin a6 cleavage could affect and modify the bone microenvironment. An observation that complete conversion of integrin a6 to a6p was not observed in cell lines even in presence of excess uPA suggested a regulatory mechanism. Integrins are known to associate with many proteins including tetraspanins, which are transmembrane proteins, that function as protein adapters. Integrin a6 was found to be refractory to uPA mediated cleavage when complexed with tetraspanin CD151. The amount of integrin a6 available for cleavage increased when CD151 levels were decreased by CD151 siRNA treatment. These results suggest that the integrin a6 available and unavailable for cleavage can be modulated by interaction with CD151 and hence affect the migratory potential of the cell. Collectively these data suggest that integrin a6 cleavage can enhance cell migration, initiate signals to modify the tumor microenvironment and can be regulated by interaction with tetraspanin CD151.

The search for anticancer drugs that are tumor specific and cause minimal side effects and the development of effective cancer vaccines are focal points of cancer therapy today. Dendritic cells (DC) are considered potential candidates for cancer immunotherapy due to their ability to process and present antigens to T cells and stimulate immune responses. However, DC-based vaccines have exhibited minimal effectiveness in abrogating established tumors in mice and human cancer patients. The use of appropriate adjuvants can enhance the efficacy of DC-based cancer vaccines in treating established tumors.The studies in this dissertation describe a chemo-immunotherapeutic strategy, which combines a Vitamin E analog, a-tocopheryl succinate (a-TOS) that is selectively toxic to tumor cells with non-antigen pulsed, non-matured dendritic cells (nmDC) to treat established murine lung and breast tumors. The results demonstrate that a-TOS synergizes with nmDC to inhibit the growth of established tumors and significantly reduce residual lung metastasis when therapy is initiated after surgical removal of primary tumors. This outcome was correlated with increased IFN-g and IL-4 production by splenic and draining lymph node lymphocytes. In trying to understand the mechanism of action of the combination treatment we observed that a-TOS treated tumor cells factors cause DC maturation in vitro. This effect is mediated in part by heat shock proteins 60, 70 and 90 induced during a-TOS-mediated killing of tumor cells. This study demonstrates the potential usefulness of a-tocopheryl succinate, an agent non-toxic to normal cell types, as an adjuvant to augment the effectiveness of DC-based vaccines in treating cancer.