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A significant number of individuals begin drinking alcohol early in life during adolescence, a period in which their brain is developing. Drinking alcohol at an early age is linked to a greater likelihood that a person will become an alcoholic later in life. Levels of Glutamate (GLU), a major neurotransmitter, in the medial prefrontal cortex (mPFC) has been directly linked to the expression of alcohol-use disorders. Thus, a better understanding of how childhood drinking produces alterations in the brain, thereby contributing to alcoholism, is needed. The current research utilized an animal model of alcoholism to examine the long range consequences of alcohol consumption during adolescence on GLU functioning within the mPFC in adulthood. It was hypothesized, adolescent drinking would lead to a higher levels of GLU in the mPFC in adulthood. Two groups of alcohol-preferring (P) rats received either free-access to alcohol (15% v/v) and water or water alone in their home cage (24 hrs a day; 7 days a week) during their adolescent period. At the end of the adolescent period, alcohol was removed and all animals were provided only water to drink for approximately 21 days. Next, animals were implanted with guide cannula aimed at infralimbic and prelimbic regions of the mPFC and provided one-week to recover before undergoing quantitative microdialysis, a method that allows for the direct sampling of GLU from brain tissue. During testing, samples were collected every 10 minutes and animals were first exposed to artificial cerebral spinal fluid (aCSF) followed by aCSF containing three GLU concentrations (1 µM, 5 µM , and 10 µM; presented in randomized order across rats). By exposing the animals to different levels of GLU, the average brain level of GLU can be established as well as how fast the brain is removing/clearing GLU. Samples were analyzed using high-pressure liquid chromatography a method that quantifies GLU levels in each sample. Analyses revealed a significantly lower level of GLU removal/clearance in the prelimbic region of the mPFC of the alcohol-drinking group compared to the water group. Analyses also revealed a significantly higher average level of GLU in the alcohol-drinking group compared to the water drinking control group. There were no differences between groups in average GLU levels or GLU clearance in the infralimbic region of the mPFC. Overall, the data from the current study suggest that the consumption of alcohol during adolescence may produce a long-lasting reduction of GLU removal/clearance thereby resulting in increased GLU levels within the prelimbic region of the mPFC. The current findings may represent a long-lasting change that happens in the brain when an individual consumes alcohol during adolescence which could then contribute to the development of an alcohol-use disorder later in life.

The thesis explores current debates ,around postfeminism and neoliberalism, and young women's articulations of femininity within the context of young women's excessive drinking practices. Alcohol plays a key ro le in UK culture today, and for young people, getting drunk is an accepted, expected and indeed normalised part of a night out in the current 'culture of intoxication'. It is also a space for enacting highly visible displays of gender, femininities and class, and one that represents an important 'space of attention' for exploring contemporary subjectivity. As such this space provides a productive source for carrying out in-depth analysis of how young women negotiate and manage 21st century femininities in the UK. Data is provided in the form of white working-class women's accounts of excessive drinking in various drinking venues within the county of Hampshire, England. Thirty-three women, aged between 18 and 24 years, took part in several phases of data collection, and these include individual interviews, friendship group discussions, and ethnographic methods. I employed a version of Foucauldian discourse analysis to identify key themes and discourses in the young women's talk, and note how young women use excessive alcohol for confidence within what has become a drinking culture of hyper-sexuality, where the emphasis is on the traditional male gaze, but also and possibly even more powerfully, the postfeminist female gaze. The young women draw on a number of discourses to construct drunkenness as a routine part of going out, and how the female gaze plays an important role in 'mirroring' and/or 'othering' women in terms of their feminine recognition. Furthermore, the women draw on postfeminist discourses to emphasise how painful and hard it is becoming a young female subject today.

Motivated by the need to design minimally-invasive treatments for wide-necked cerebral aneurysms, we used computational modeling to assess aneurysm hemodynamics, examined in vitro cellular responses arising from mechanical and chemical stresses, and designed novel materials that cooperatively adhere to the endothelium. We first hypothesized that because aneurysm geometry plays an important role in hemodynamics, changes in flow patterns may affect the shear stress experienced on the aneurysm wall. We defined flow regimes based on aneurysm hemodynamic and geometric parameters, which may correlate with aneurysm rupture. Because of the direct contact between endothelial cells (ECs) and blood flow, we then evaluated how changes in hemodynamics and inflammatory cytokines affect the expression of cell adhesion molecules (CAMs) and matrix remodeling factors on ECs. We subsequently designed biomaterials that complement the dynamic EC surface and have the ability to conform to any geometry through in situ crosslinking. Antibody-conjugated hydrogels facilitated synergistic EC adhesion using cooperativity as an adhesion strategy. We optimized the presentation of antibodies to inflammatory CAMs on polyvinyl alcohol (PVA) and alginate hydrogels to achieve strong adhesion to inflamed ECs. We synthesized photocrosslinkable, aminated PVA hydrogels and determined the effect of substrate stiffness on cell adhesion. We also evaluated the effects of antibody presentation on cell adhesion strength and dynamics using alginate hydrogels. Taken together, the results of this work may be used to design hydrogels for vascular remodeling applications under shear stress, including embolic agents for cerebral aneurysms. / Engineering and Applied Sciences