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Many studies have shown that the effectiveness of radiations of varying LET is similar when yields of dsb have been measured, despite large differences in biological response. Recent evidence has suggested however, that current techniques underestimate the yields of dsb. By monitoring the fragmentation of DNA over a wide range of fragment sizes ( 6 Mbp) by pulsed field electrophoresis, RBE values greater than 1.0 for radiations of around 100 keV/mm have been determined. The data provide evidence for the production of correlated breaks produced within cells as particle tracks traverse the nucleus. The highly ordered structure of DNA within mammalian cells may lead to clustering of breaks over distances related to the repeating unit structures of the chromatin. As well as these regionally damaged sites, a major contributor to radiation effectiveness will be the localised clustering of damage in the 1-20 bp region. A major effort is required to elucidate the relative importance of these levels of clustering and their importance in biological response.

Many studies have shown that the effectiveness of radiations of varying LET is similar when yields of dsb have been measured, despite large differences in biological response. Recent evidence has suggested however, that current techniques underestimate the yields of dsb. By monitoring the fragmentation of DNA over a wide range of fragment sizes ( 6 Mbp) by pulsed field electrophoresis, RBE values greater than 1.0 for radiations of around 100 keV/mm have been determined. The data provide evidence for the production of correlated breaks produced within cells as particle tracks traverse the nucleus. The highly ordered structure of DNA within mammalian cells may lead to clustering of breaks over distances related to the repeating unit structures of the chromatin. As well as these regionally damaged sites, a major contributor to radiation effectiveness will be the localised clustering of damage in the 1-20 bp region. A major effort is required to elucidate the relative importance of these levels of clustering and their importance in biological response.

gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter of the central nervous system and it acts at the GABA(A) and GABA(B) receptors. A possible role for the GABA(A) receptors in alcohol action has been derived from in vitro cell models, animal studies and human research. GABA(A) subunit mRNA expression in cell models has suggested that the long form of the gamma2 subunit is essential for ethanol enhanced potentiation of GABA(A) receptors, by phosphorylation of a serine contained within the extra eight amino acids. Several animal studies have demonstrated that alterations in drug and alcohol responses may be caused by amino-acid differences at the GABA(A)alpha6 and GABA(A)gamma2 subunits. An Arg(100)/Glu(100) change at the GABA(A)alpha6 subunit conferring altered binding efficacy of the benzodiazepine inverse agonist Ro 15-4513, was found between the AT (alcohol tolerance) and ANT (alcohol non-tolerance) rats. Several loci related to alcohol withdrawal on mouse chromosome 11 which corresponds to the region containing four GABA(A) subunit (beta2, alpha6, alpha1 and gamma2) genes on human chromosome 5q33-34, were also identified. Gene knockout studies of the role of GABA(A)alpha6 and GABA(A)gamma2 subunit genes in mice have demonstrated an essential role in the modulation of other GABA(A) subunit expression and the efficacy of benzodiazepine binding. Absence of the GABA(A)gamma2 subunit gene has more severe effects with many of the mice dying shortly after birth. Disappointingly few studies have examined the effects of response to alcohol in these gene knockout mice. Human genetic association studies have suggested that the GABA(A)beta2, alpha6, alpha1 and gamma2 subunit genes have a role in the development of alcohol dependence, although their contributions may vary between ethnic group and phenotype. In summary, in vitro cell, animal and human genetic association studies have suggested that the GABA(A)beta2, alpha6, alpha1 and gamma2 subunit genes have an important role in alcohol related phenotypes (300 words).

gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter of the central nervous system and it acts at the GABA(A) and GABA(B) receptors. A possible role for the GABA(A) receptors in alcohol action has been derived from in vitro cell models, animal studies and human research. GABA(A) subunit mRNA expression in cell models has suggested that the long form of the gamma2 subunit is essential for ethanol enhanced potentiation of GABA(A) receptors, by phosphorylation of a serine contained within the extra eight amino acids. Several animal studies have demonstrated that alterations in drug and alcohol responses may be caused by amino-acid differences at the GABA(A)alpha6 and GABA(A)gamma2 subunits. An Arg(100)/Glu(100) change at the GABA(A)alpha6 subunit conferring altered binding efficacy of the benzodiazepine inverse agonist Ro 15-4513, was found between the AT (alcohol tolerance) and ANT (alcohol non-tolerance) rats. Several loci related to alcohol withdrawal on mouse chromosome 11 which corresponds to the region containing four GABA(A) subunit (beta2, alpha6, alpha1 and gamma2) genes on human chromosome 5q33-34, were also identified. Gene knockout studies of the role of GABA(A)alpha6 and GABA(A)gamma2 subunit genes in mice have demonstrated an essential role in the modulation of other GABA(A) subunit expression and the efficacy of benzodiazepine binding. Absence of the GABA(A)gamma2 subunit gene has more severe effects with many of the mice dying shortly after birth. Disappointingly few studies have examined the effects of response to alcohol in these gene knockout mice. Human genetic association studies have suggested that the GABA(A)beta2, alpha6, alpha1 and gamma2 subunit genes have a role in the development of alcohol dependence, although their contributions may vary between ethnic group and phenotype. In summary, in vitro cell, animal and human genetic association studies have suggested that the GABA(A)beta2, alpha6, alpha1 and gamma2 subunit genes have an important role in alcohol related phenotypes (300 words).

This thesis explores Germany’s *Energiewende* (‘energy transition’) and the role of citizen/community energy democracy initiatives at municipal and state levels in shaping developments that underpin this society-wide transformation - examining how grassroots agitation, in particular, has prompted meaningful action and policy change on the part of government at multiple levels. Using Berlin and Hamburg - Germany’s largest urban centers and leading city-states in the country’s federal system - as case studies, the research examines how citizens’ initiatives in both cities have campaigned for the remunicipalization of local energy networks to expedite, democratize, and incorporate social justice goals into each region’s Energiewende. Finally, this study pivots to consider the progress of the transition nationally in recent years, investigating how major events like the Covid-19 pandemic, watershed federal elections in 2021, war in Ukraine, and the resultant energy crisis have affected the evolution and direction of the Energiewende, and the important contributions of citizen/community energy initiatives to the national response here. The analytical framework draws on over 100 interviews conducted with relevant stakeholders and experts involved in the transition, representing different perspectives (e.g. on remunicipalization and the Energiewende itself) and diverse levels of government (e.g. from the district to federal level). This extensive body of original research is complemented by a wide array of other relevant source material that has likewise been consulted to inform this work and further evaluate the impacts of bottom-up energy democracy initiatives on the broader transition in Germany’s regions - and, by extension, nationally - as they continue to affect the pace and trajectory of the now-famous Energiewende. Ultimately, this study contributes an in-depth, ground-level analysis to the literature of key elements that have driven energy system change in Germany, shining a fresh light on the complex and interrelated nexus of sustained grassroots action, policy responses, and shifting sociopolitical realities that form the context in which the Energiewende has been (re)launched, reformed, and reimagined over the decades.

This thesis explores Germany’s *Energiewende* (‘energy transition’) and the role of citizen/community energy democracy initiatives at municipal and state levels in shaping developments that underpin this society-wide transformation - examining how grassroots agitation, in particular, has prompted meaningful action and policy change on the part of government at multiple levels. Using Berlin and Hamburg - Germany’s largest urban centers and leading city-states in the country’s federal system - as case studies, the research examines how citizens’ initiatives in both cities have campaigned for the remunicipalization of local energy networks to expedite, democratize, and incorporate social justice goals into each region’s Energiewende. Finally, this study pivots to consider the progress of the transition nationally in recent years, investigating how major events like the Covid-19 pandemic, watershed federal elections in 2021, war in Ukraine, and the resultant energy crisis have affected the evolution and direction of the Energiewende, and the important contributions of citizen/community energy initiatives to the national response here. The analytical framework draws on over 100 interviews conducted with relevant stakeholders and experts involved in the transition, representing different perspectives (e.g. on remunicipalization and the Energiewende itself) and diverse levels of government (e.g. from the district to federal level). This extensive body of original research is complemented by a wide array of other relevant source material that has likewise been consulted to inform this work and further evaluate the impacts of bottom-up energy democracy initiatives on the broader transition in Germany’s regions - and, by extension, nationally - as they continue to affect the pace and trajectory of the now-famous Energiewende. Ultimately, this study contributes an in-depth, ground-level analysis to the literature of key elements that have driven energy system change in Germany, shining a fresh light on the complex and interrelated nexus of sustained grassroots action, policy responses, and shifting sociopolitical realities that form the context in which the Energiewende has been (re)launched, reformed, and reimagined over the decades.