published_or_final_version / Surgery / Master / Master of Philosophy

published_or_final_version / Microbiology / Master / Master of Philosophy

published_or_final_version / Medicine / Master / Master of Philosophy

This thesis describes a search for the rare radiative decay of a B meson to two photons. where the charged congugate mode is implied throughout. These decays are highly suppressed in the Standard Model where the branching fraction is expected to be of order 10^-8. In some new physics scenarios this could be enhanced by up to an order of magnitude to 10^-7. Therefore an observation of a significant signal above the Standard Model prediction could be a sign of new physics. The search for this rare decay was performed using the data collected with the BaBar detector at the SLAC National Accelerator Laboratory PEP-II storage ring operating at the Upsilon(4S) resonance. The analysis uses a dataset with an integrated luminosity of 425.7 fb-1 corresponding to 467 million BB pairs. A signal yield of 21.3 +12.8 -11.8 events with a significance of 1.88 sigma was measured using an unbinned extended maximum likelihood fit. An upper limit on the branching fraction is set at the 90% confidence level of less than 3.2 times 10^-7. This is about two times more stringent than the best upper limit of less than 6.2 times 10^-7 published by the Belle collaboration. / text

Liver transplantation (LT) is the most effective treatment for hepatitis B virus (HBV) related liver failure and hepatocellular carcinoma (HCC). Nevertheless, HBV and HCC recurrence rate remains high after LT. Previous studies have shown that HBV reactivation is associated with HCC recurrence and poor prognosis after LT. The main objectives of this study are to investigate the risk factors for HBV and HCC recurrence after LT, the efficacy of antiviral drugs to prevent HBV reactivation and the underlying mechanisms contributing to HBV reactivation. Firstly, we investigate the risk factor for HBV and HCC recurrence in 551 HBsAg seropositive LT patients, of whom374 had no tumor and 177 had HCC. All patients received indefinite antiviral treatment after LT. The study showed that pre-LT HBV DNA levels and HCC recurrence were significantly associated with HBV reactivation after LT. Younger age, lower Child-Pugh score, beyond UCSF criteria, higher AST level, salvage LT, older donor, HBsAg seropositive at the last follow-up and HBV reactivation after LT were independent risk factors for HCC recurrence. HCC recurrence alone accounts for poor overall survival. The sequence analysis identified drug-resistant mutants as the main contributors to HBV reactivation. In addition, wild-type (antiviral drug-sensitive) HBV reactivation was identified in patients with HCC recurrence. Secondly, we investigate the efficacy of antiviral drugs monotherapy (Lamivudine or Entecavir) in preventing HBV reactivation. This study showed that patients receiving lamivudine (LAM) experienced significantly greater HBV reactivation and HCC recurrence than those receiving entecavir (ETV). In patients with no tumors, HBV reactivation was found in the LAM groups but not in the ETV groups, due to the appearance of a LAM drug-resistant mutant. In patients with HCC recurrence, HBV reactivation was found in both treatment groups. Wild-type HBV reactivation was identified in 17% (5/29) and 100% (1/1) of HCC patients receiving LAM and ETV respectively. This suggests that, although ETV had higher genetic barriers to HBV drug resistance; it still cannot prevent wild-type HBV reactivation in HCC-recurrent patients. Thirdly, we investigate the expression of HBV markers in HCC and adjacent non-tumor tissues. Origin of circulating HBV was identified using genetic distance analysis of HBV isolated from different compartments (i.e. HCC and adjacent non-tumor tissues). The study showed that, in some HCC cases, the expressions of HBsAg and HBV replicative efficiency are higher in HCC tissues than in adjacent non-tumor tissues. Moreover, through genetic distance analysis, we demonstrated that HBV reactivation could originate from recurrent HCC. These data suggest that HCC supports HBV replication and that HBV is secreted from recurrent HCC. Finally, we demonstrate that the up-regulation of drug-specific ABC-transporters is significantly associated with patients with HCC recurrence. In vitro studies also showed that the up-regulation of ABCG2 contributes to antiviral drug-resistant. Finally, we demonstrate that the up-regulation of drug-specific ABC-transporters is significantly associated with patients with HCC recurrence. In vitro studies also showed that the up-regulation of ABCG2 contributes to antiviral drug-resistant. / published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

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This thesis examines Thomas Aquinas' concept of human freedom in the context of his treatment of God's knowledge of future contingents. Much has been written about Aquinas' attempt to solve the problem of how humans can act freely if God knows all future things, but little of that work comments on a major underlying assumption in his treatment of the problem - namely, the concept of human freedom presupposed. This thesis therefore seeks to establish the nature of the freedom that Aquinas was assuming in the important discussions of God's knowledge of future contingents. Chapter 1 sets out Aquinas' statement of the problem and his solution to it, that since God is outside time, he knows things not as future but as 'present'; and knowing x as 'present' imposes no necessity on x itself. Some criticism of Aquinas' solution is reviewed. It is noted that although Aquinas' approach seems to imply a concept of freedom which includes the possibility of doing otherwise than one does, other interpretations are possible. It is noted also that modern commentators hold differing views on what Aquinas' concept of freedom is. Chapter 2 examines the link between contingency and freedom and makes the point that, for Aquinas, contingency in human behaviour seems to arise from the peculiarly human way of bringing things about i.e. by voluntary action. As a preliminary to looking at his analysis of voluntary action, Aquinas' distinction between 'human acts' and 'acts of man' is noted and a further distinction drawn between 'simply' and 'fully' voluntary acts. It is concluded that the nature of freedom will be found in Aquinas' description of human, or fully voluntary, acts.

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