Thesis (Ph. D.)--University of Chicago, 1910. / Text in German, t.p. in English. Originally published as: Die Schicksalsfrage in Schillers Dramen und dramatischen Entwürfen ... Includes bibliographical references.

Dissertação--Faculdade Pontificia de Filosofia de Braga, 1967. / Bibliography: p. [313]-350.

Thesis (Ph. D.)--University of Pennsylvania, 1932. / On cover: University of Pennsylvania. Bibliography: p. 109-136.

Drugs that alter microtubule dynamics are often used in chemotherapy regimes in combination with other agents in order to treat various cancers. Despite the success over many years, there remain problems in toxicity, resistance and predictability to the drugs. In order to overcome these problems, there is a need to gain an understanding of how these drugs kill cancer cells in cell culture. As microtubule function is particularly important for chromosome movement in mitosis, cells treated with these agents cause a mitotic arrest through activation of the spindle assembly checkpoint. Following induction of a mitotic arrest, cells can escape this arrest (mitotic slippage) or undergo mitotic death, determined in part by the response of the apoptotic network. Levels of an anti-apoptotic protein, Mcl-1, are often lost over time in mitosis. Using time-lapse analysis on a cell line unable to escape the mitotic arrest, this thesis shows that Mcl-1 protein contributes to cell death both in mitosis and the subsequent interphase in response to microtubule toxin, taxol. This suggests that inhibiting Mcl-1 may increase the efficacy of anti-mitotic agents. In addition, mitotic cell lines prone to mitotic slippage were found to have higher levels anti-apoptotic protein, Bcl-xL, in comparison to Mcl-1, indicating one way in which these cells can cope with loss of Mcl-1 during mitosis. Secondly, an evaluation of the contribution of the previously identified interaction between Mcl-1 and mitotic E3 ligase complex, the APC/C-Cdc20, to the rate of mitotic death and mitotic slippage was assessed. Inhibition of APC/C-Cdc20 activity or mutation of a Mcl-1 motif (RxxL) thought to engage with the APC/C-Cdc20 complex did not have a substantial effect on Mcl-1 degradation or mitotic death, thereby questioning the functional significance of this interaction. However, it appears that Mcl-1 protein levels can influence the rate of mitotic slippage and this influence was affected via Mcl-1’s RxxL motif within Mcl-1. This suggests that Mcl-1 protein may delay mitotic slippage via substrate competition for the APC/C-Cdc20 complex with Cyclin B1, whose degradation is required for mitotic exit. Further analysis of this effect showed that this interaction may not be a universal effect. This together with the specific functional effect on mitotic slippage rather than mitotic death, suggests that this is an indirect effect caused by network interference between the components of the death and slippage pathways.

Philosophers who work on time often ignore the implications their doctrines have for the common sense intuition that the past is fixed and the future not. Similarly, those who work on fatalism, and whose arguments often imply an assertion or denial of the common sense intuition, rarely take into account the implicit dependence their arguments have upon specific theories of time. I take the intuition, and its relation to the nature of time, seriously. In Part I of my thesis, I investigate the relations between the dynamic and static theories of time, on the one hand, and the intuition, on the other. I argue that the so called 'pure' forms of these theories, inasmuch as they both posit an ontological temporal symmetry, cannot do justice to the intuition. The 'pure' B-Theory, with its denial of objective temporal becoming, cannot allow for a robust sense in which the future is non-fixed. The 'pure' A-Theory, according to which only the present exists, acknowledges the robustness of the asymmetry, but cannot provide a ground for it. I conclude Part I of my thesis with the claim that only a conception of time according to which the past exists and the future does not, can account for the intuition. In Part II, I discuss those fatalistic arguments which rely upon the determinateness of future truth as their key premise, and argue that these fail either because they rely on an illegitimate modal concept, or because they rely on a key undefended assumption. Finally, in the Epilogue, I provide a more detailed sketch of the account of time posited at the end of Part I, and suggest that it can also provide a more thoroughgoing rejection of the logical fatalistic argument.

No description available.

As conventional oil reserves deplete and more efficient refining technologies emerge, the use and transportation of heavy fuel oils such as dilbit is rising. Despite the risk of accidental dilbit spills, the fate and behaviour in aquatic systems is largely unknown. The objective of this thesis was to develop new approaches and insights to directly address knowledge gaps surrounding the fate and behaviour of diluted bitumen (dilbit) in freshwater systems. During the summers of 2017 and 2018, a large-scale collaborative field study was conducted at the International Institute for sustainable Development’s – Experimental Lakes Area (IISD-ELA), a world-renowned freshwater research station located in Northwestern Ontario, Canada. First, two tank-based dilbit spill simulations were carried out at oil:water ratios of 1:8000 and 1:800 v/v (Chapter 2). Here I examined the physical fate and behaviour of dilbit spilled onto the water’s surface for 11 days. In this chapter I provide, for the first time, experimental evidence of dilbit physically sinking after 8 days of environmental weathering in land-based tanks containing natural lake water. Building on the findings of chapter 2, the remaining four chapters focus on a series of 70-d long experimental dilbit spills carried out in limnocorrals (10 m diameter x 1.5 m depth) installed directly in a freshwater lake. Chapter 3 provides, to our knowledge, the most detailed temporal account to date of dilbit submergence in freshwater at multiple oil:water ratios. In Chapter 4 I provide the rates at which over 100 individual hydrocarbons are depleted over time from the dilbit slicks and apply diagnostic ratios to postulate which weathering processes are responsible for the observed depletions. As predicted, evaporation, dissolution, and photooxidation are prominent weathering processes whereas biodegradation is not. I then describe both the short- and long-term behaviour of these compounds as they partition from the dilbit slick to the air, water, and sediments of the limnocorrals in Chapter 5. While the concentrations of polycyclic aromatic hydrocarbons (PAHs) were elevated in the water columns of each treatment, they were orders of magnitude lower than concentrations that pose a toxicological risk. The same was true for all sediment samples except those that were in direct contact with sunken dilbit. This suggests that the major threat of dilbit spills from an ecotoxicological point of view is the dilbit-laden sediments produced by submergence. Finally, I demonstrated the successful application of a mass transfer model to predict the dissolution trends of the highly toxic benzene, toluene, ethylbenzene, and o,m,p-xylene (BTEX) compounds following the dilbit spills. In Chapter 7 I detail the implications and conclusions for each chapter and the thesis as a whole. I also describe areas where future research is needed. In the end, the conclusions of this thesis were: 1) dilbit has the propensity to sink following spills in freshwater, 2) prominent weathering processes include evaporation, dissolution, and photooxidation, 3) our regression design allowed for important relationships between contamination and spill size to be realized, 4) sunken dilbit poses a toxicological threat to aquatic biota, and 5) mass transfer models can accurately predict BTEX dynamics in the water column following a dilbit spill.

No description available.

Isoxaben is a preemergence (PRE) broadleaf herbicide used in turf and ornamentals. Field, greenhouse, and laboratory research evaluated this herbicide for PRE control of selected broadleaves in turf, suspected postemergence (POST) herbicidal effects, and the influence of application timings and rates on soil residual. During seed germination in moist filter paper, isoxaben concentrations required for 50% inhibition of radicle growth (GR50) were 0.013, 0.010, 0.008, 0.008, and 0.007 ppm for dandelion, buckhorn plantain, white clover, black medic, and common lespedeza, respectively. In greenhouse experiments, isoxaben applied POST at 2.24 kg ai/ha suppressed the growth of Florida betony, black medic and white clover by 45, 65, and 66%, respectively, and reduced regrowth of Florida betony by 71%. In soil bioassays, yellow rocket control from isoxaben applied in fall was approximately 20 and 30% greater than spring-applied isoxaben at 3 and 6 MAT, respectively. Buckhorn plantain control from fall treatments at 3 MAT was approximately 15% higher than spring-applied isoxaben at 3 MAT. Application timings did not influence control of spotted spurge, a less sensitive weed. Isoxaben applied to turf in spring at 1.12 kg/ha provided > 90% control of buckhorn plantain, dandelion, and corn speedwell at 4 MAT. Fall applied isoxaben at the same rate provided total control of common chickweed, corn speedwell and henbit at 3 MAT and 80 to 90% control of white sweet clover and buckhorn plantain that germinated the following spring. Double (spring followed by fall) application of isoxaben to turf appeared to enhance broadleaf weed control in some instances. Dissipation of isoxaben in the top 3.8 cm of a Ross silt-loam soil as affected by spring, fall, and spring followed by fall applications was determined using high performance liquid chromatography (HPLC) analysis. Isoxaben residues in soil decreased by 55 and 92% by 3 and 6 MAT, respectively, for spring teatments, and decreased 29 and 52% by 3 and 6 MAT for fall treatments, respectively. A soil-bioassay study correlated well with chemical analysis of isoxaben residues, as the correlation coefficients were 0.85 and 0.89 for yellow rocket and buckhorn plantain, respectively. / Ph. D.

The emergence of antibiotic resistance in riverine systems has become a growing issue worldwide. The use of watershed-scale models is popular with many other water quality issues but not in the case of antibiotic resistance. In this study, we introduce a watershed-scale bacteria fate and transport model to simulate antibiotic resistance in E. coli. This model was developed through amendments to an existing watershed-scale physically based hydrological model (SWAT), and the newly modified model was called SWAT-ARB. The SWAT-ARB model was employed in the receiving environment of a WWTP in the Adyar River basin, India. The SWAT-ARB model simulations of resistant fractions (resistant E. coli concentration/E. coli concentration) in stream water were analyzed by the flow levels with the application of a range of parameter values. It is concluded that the model can be used to test prevailing hypotheses and evaluate the current state of knowledge. For instance, model simulations suggest that the influx of ARB can be a primary driver of antibiotic resistance in rivers compared to ambient antibiotic concentrations. We used the SWAT-ARB model to quantify the impact of climate change on antibiotic resistance. Six climate models were used to obtain the future climates in two distinct scenarios. The model was applied to three watersheds as Adyar basin- India, Crab Creek basin- USA, and upper Viskan basin- Sweden. It was concluded that temperature increase may greatly affect the colder climates (Crab Creek and Viskan) with higher simulated resistant fractions. In case of Adyar basin, resistant fractions are alleviated in high flow conditions, while aggravated in low flow conditions. / Doctor of Philosophy / The antibiotic resistance occurs when bacteria no longer responds to antibiotics. Hence, the diseases that caused by resistant bacteria are harder to treat. These antibiotic resistant bacteria end up in our rivers because of our heavy use of antibiotics in human and animal treatments. Thus, the spread of antibiotic resistance has become a water quality issue in the rivers worldwide. Scientists generally use computer models to understand water quality issues in rivers. These computer models are important because of high cost of monitoring and their use in finding how environment works. Up to the date of this publication, there is no sophisticated enough model to simulate antibiotic resistance in rivers. Hence, we created a river basin scale model to simulate antibiotic resistance. We found that the influx of ARB can be a primary driver of antibiotic resistance in rivers compared to ambient antibiotic concentrations. The model was applied to three watersheds as Adyar basin- India, Crab Creek basin- USA, and upper Viskan basin- Sweden. It was concluded that temperature increase may greatly affect the colder climates (Crab Creek and Viskan) with higher antibiotic resistant bacteria compared to susceptible bacteria.