Currently the treatment of alcohol use disorder is very difficult and often requires the combination of therapy and medications, with many who undertake treatment experiencing relapse over time. There is also no treatment in use to prevent the development of alcohol use disorder. It is the aim of this work to provide information that may be useful for the development of a preventative treatment for developing alcohol use disorder by elucidating more of the acute effects of alcohol use. It is known that these effects originate in the brain. Within the brain are circuits made up of neurons that communicate with each other through chemical synapses. These chemical synapses involve the release of neurotransmitters from one neuron that are detected by another neuron, which initiates its own response. It is known that ethanol can change how much neurotransmitter is released from a neuron, depending on the specific neuron tested, and many researchers have implicated the "release machinery" as a target. It is also known that alcohol can affect lipid membrane properties that are important for the fusion of the vesicle membrane, encapsulating the neurotransmitter, with the cell membrane for release of the neurotransmitter outside of the neuron. It is not known if alcohol directly affects the SNARE proteins ("release machinery") or the lipid membranes to initiate the change in neurotransmitter release previously observed. Within this work you will find a discussion of the steps of neurotransmitter release and the known effects of anesthetics on components of this process, as an introduction to the topic (Chapters 1 and 2). In Chapters 3-5 you will find studies that successively dive deeper and deeper into the effects of alcohol on the SNARE proteins and lipid membranes. We show that ethanol is effective at a dose of 0.4% v/v or 64 mM at increasing fusion probability in a model of neurotransmitter release that uses the 3 SNARE proteins to drive fusion of a vesicle with a supported membrane. We also show that alcohol has little direct effect on the SNARE proteins themselves. In addition, we provide evidence that alcohol alters fusion oppositely, depending on which membrane leaflet it has most direct access to. In Chapter 5 we show that alcohol increases the probability of lipid tail protrusion in silico. Previously it has been shown that protrusion of one fatty acid tail of one lipid can initiate fusion of that membrane with an apposing membrane. These data provide further insight into the effects of alcohol on a neuron and we would argue are valuable to research pursuing treatment and prevention of alcohol use disorder.

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<p>Low angle grain boundary (LAGB) mobility is an essential parameter for developing the analytical models that describe the kinetics of recovery and predict the nucleation of recrystallized grains. The thesis is aimed at the molecular dynamics (MD) simulations study of LAGB mobility determination in pure Al and Al-Mg alloys. All the previous experimental studies reported that the presence of several defects, such as solutes and dislocations, retard the boundary motion and provide lower mobility. However, very few studies have been conducted in MD simulation to capture the interactions of those defects with the migrating grain boundary. This thesis is focused on providing complete understanding of LAGB determination along with a comprehensive explanation of solute and dislocation retarding effects on boundary motion.</p> <p>The LAGB mobility in pure Al was computed from two different MD techniques as a function of temperature and misorientation. Within numerical uncertainties, both techniques provide the same magnitude of mobility at 300K for 7.785^o boundary and at 700K for 23.07^o boundary. It was observed that ADF method is not applicable to determine LAGB mobility at high temperature due to failure of order parameter computation. The MD derived activation energy is found to be approximately ten times lower than the experimental observations.</p> <p>A strong solute pinning effect on boundary motion was observed at all misorientations and solute concentrations studied in Al-Mg alloys. An approximate linear relationship is found between the restraining force and the solute concentration in a distributed solute approach. In addition, the extrinsic dislocations are found to completely pin both 7.785^o and 23.07^o boundary motion at low driving forces in pure Al at 300K. The MD results do not reveal significant qualitative differences of the pinned boundary structure for the low and high angle boundaries and will be discussed in terms of the previous experimental observations.</p> / Doctor of Philosophy (PhD)