Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). PD affects ~1% of the population over 65, as demonstrated by characteristic symptoms such as tremor, rigidity, and bradykinesia. While the majority of PD cases are idiopathic, some cases are familial, including those caused by homozygous loss-of-function mutations in DJ-1 (PARK7), which lead to early onset PD. Although the physiological role of DJ-1 is not fully understood, DJ-1’s neuroprotective role against oxidative stress is well documented. DJ-1 is required for AKT-mediated neuroprotective effects, however the mechanism by which DJ-1 affects membrane localization/activation of AKT is unknown and is likely a critical aspect of DJ-1 function. In this thesis we explore the mechanism through which DJ-1 confers neuroprotection through AKT membrane recruitment, particularly in the case of oxidative stress insult. We demonstrate here that DJ-1 interacts with PHLDA3, a negative regulator of AKT, and loss of DJ-1 leads to hypersensitivity of neurons to PHLDA3-mediated death. Additionally, we demonstrate that in the absence of DJ-1, PHLDA3 localization at the membrane is increased, and overexpression of PHLDA3 causes reduced AKT phosphorylation in DJ-1 KO MEFs in response to oxidative stress. Taken together, these studies provide a potential novel mechanism by which DJ-1 regulates the activity of AKT, a critical neuronal survival pathway. Elucidation of these mechanisms may provide insight into the design of neuroprotective therapies for PD.

Indiana University-Purdue University Indianapolis (IUPUI) / Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of motor function resulting from dopaminergic neuronal death in the substantia nigra pars compacta leading to subsequent decreased striatal dopamine levels. The majority of PD cases are diagnosed as sporadic in nature, however 10% - 15% of patients show a positive family history of the disease. While many genes have been found to be implicated in the familial form of PD, early-onset autosomal recessive PD has been associated with mutations in PARK7, a gene which codes for the protein DJ-1. While there are many proposed roles of DJ-1 across numerous systems, the function of DJ-1 in relation to the development and progression of PD remains largely unclear. A first step towards determining this function is the creation of biologically relevant cell models of PD. The goal of this work was to design a representative cell model of DJ-1-associated PD in order to further study DJ-1 with the intention of elucidating its relevant function in relation of PD pathogenesis.

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This dissertation focuses on the intercultural relations between the French-speaking and Dutch-speaking world in Holland in the first half of the fifteenth century. After a turbulent war of succession between the claimants Jacqueline of Bavaria and her uncle John the Pitiless, the counties of Holland, Zeeland and Hainault were incorporated into the largely francophone Burgundian empire. It has been suggested that this event marked the end of a flourishing period of cultural production in the Dutch vernacular at the court of Holland. However, as it seems, throughout the fifteenth century translations of French texts were produced for regional and local administrators. Possibly, the Burgundian regional government of Holland, which consisted of foreign as well as indigenous noblemen, may have played an important role in the dissemination of these texts. In this thesis, the subject is addressed by means of the contextualisation of the Middle Dutch version of Jean Froissart’s Chroniques. An analysis of documentary sources suggests that the comital residence at the Hague is best characterised as a multicultural environment inhabited by both bilingual and monolingual individuals. The results of an analysis of the variant readings in the French manuscripts of the Chroniques as compared to its Dutch counterpart show that the French manuscript which served as a model for the translation was probably produced between 1410 and 1418 by the Parisian libraire Pierre de Liffol. A comparison of the translated and original text shows that the translator wants to provide his readership with a text that is optimally intelligible and relevant to their context. Gerijt Potter’s modifications show that his intended audience was familiar with the habits of European courts and had a considerable geographical horizon. Because of the presence of doublets, repetitions and French loans, Potter’s style of writing resembles the official style of the comital chancery. However, a similar style is also found in other late fourteenth and early fifteenth-century translations. In The Hague the translation was probably dispersed (be it on a small scale) among members of the council and their contacts among the high nobility of Holland. Through the intensive contact between the regional councillors and members of local administration, the translation of the Chroniques became available to an audience in the cities.

Thesis advisor: Judith Schwartz / Increased access to media and production tools has given the civilized masses the means not only to consume an increasingly comprehensive wealth of content, but also the means to interact with that content in ways never before imagined. This has allowed the digital generation to grow ever more comfortable creating and editing content outside of the professional environment. Much of the creative output of our day comes in the form of the “remix,” a piece of content which is constructed, in full or in part, from bits (most often in the form of bytes) of other media artifacts. However, because of American law and international copyright agreements that prohibit the copying (reproduction or derivation) of creative works, a generation of amateur producers has been criminalized. Despite the message sent by recent prosecutions in light of the letter of copyright law, the original spirit of copyright law was to encourage creative production, not restrict it. Within the music industry, the international electronic dance music community demonstrates how new forms of content and copyright management within a hybrid economy could benefit artists, fans, and industry alike. / Thesis (BA) — Boston College, 2009. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: College Honors Program. / Discipline: Communication.

This thesis assesses the extent of social isolation experienced by Dutch and British ‘children of the red flag', i.e. people who grew up in communist families during the Cold War. This study is a comparative research and focuses on the political and non-political aspects of the communist movement. By collating the existing body of biographical research and prosopographical literature with oral testimonies this thesis sets out to build a balanced picture of the British and Dutch communist movement. The study is divided into two parts. Part I discusses the political life of communists within the wider context of the history of British and Dutch communist organizations (i.e. both communist parties and their youth organizations) from 1901-1970. Part II discusses the private and public life of British and Dutch communists in the period 1940-1970. The latter draws upon oral testimonies and questions if non-political aspects of communist life were based on a Soviet model. The experiences of communist children are explored into detail within the context of the following topics; political and cultural upbringing, prescription and aspirations, neighbourhood, school & education, work & employment, money & poverty and friendships & relationships. The interviews are being used as a means of testing the accuracy of two authors in particular; Jolande Withuis and Raphael Samuel, who both published pioneering works on communist mentality. The originality of this project rests in its approach; it is a comparative research inspired by both oral history and memory studies. Instead of emphasizing the idea of a unified and centralized (international) communist movement, this thesis argues that cultural, social and political differences between Britain and the Netherlands fundamentally influenced the nature and form of their respective communist movement and explain the discrepancy between the Dutch and British respondents' experiences. Applying the comparative approach this study challenges the existing definitions of communist identity and as such it contributes to recent comparative studies of the communist movement as well as studies of communist mentality.

Digital collections have been amassed by institutions and individuals for over two decades. Large collections are becoming increasingly available as resources for research, learning, creativity, and pleasure. However, the value of these collections can remain elusive. Systems and methods are needed to unlock the potential held within collections, to access the knowledge and to make new discoveries with the available information. The aim of this research is to identify and describe a system for interacting with large volumes of digital material that supports both learning and creative development. This is done by investigating the Disc Jockey (DJ) who works with electronic media files. DJs have worked with large digital collections since the birth of file sharing in the 1990s. Their activities necessitate a library system that supports retrieval, creative play, and public presentation of material. The investigation will develop a model of information interaction from their activities. To examine the practice, the research employs an autoethnographic diary study, video interviews, and a practice-led method that combines Grounded Theory with digital interface development. Findings indicate a model of interaction which facilitates learning through the development of a personal collection, and allows creative innovation through key information behaviours of selecting and mixing. The research distinguishes fundamental interface requirements that support the process, and demonstrates transferability of the model to other data representations.

This thesis looks to techno music, and subsequently to the DJ, as models for a way of understanding urban spatial ecology. In its compositional use of rhythm to create a sense of musical space punctuated by time, the DJ’s act of mixing audio in performance is akin to the design process: architects similarly do well to observe and acknowledge the rhythm of city life, history, climate, geology, and to mould their dynamic into an appropriate spatial interface. By aligning aspects of documentation and process with DJ methods, the thesis translates the city’s various rhythms to produce responsive, intuitive architecture. A proposal for a built intervention on a former rail yard in central Halifax, Canada, the architectural response seeks to mix aspects of the city into the site, creating a multivalent graft between military facilities and civilian neighborhoods.

Parkinson's disease (PD) is the most common neurodegenerative motor disorder, whose clinical features are rest tremor, bradykinesia, muscular rigidity and postural instability. Although most reported cases are sporadic, a handful of familial cases and their causative genes have been identified. Loss-of-function mutations in DJ-1, one of these genes, are responsible for 1% of familial PD cases. Our laboratory has previously reported that DJ-1- lacking neurons are sensitive to oxidative stress, induced by hydrogen peroxide or the neurotoxin MPTP. To investigate the possible mechanisms through which DJ-1 protects against oxidative stress, we performed a proteomic screen and identified Von Hippel Lindau (VHL) and Paraoxonase2 (PON2) as potential DJ-1 interacting partners. VHL is an E3 ubiquitin ligase which, in normal conditions, poly-ubiquitinates HIF-1 , a subunit of a master hypoxic/oxidative stress transcription factor, whose function is protective in oxidative and hypoxic stresses. In the present study, we provided further evidence of interaction of DJ-1 with VHL. We also demonstrated that HIF-1 protein level, as an indicator of VHL activity, is lower in cells lacking DJ-1, suggesting the inhibitory role of DJ-1 on VHL. Our in vitro studies also showed that DJ-1 inhibits ubiquitin ligase activity of VHL on HIF-1 by reducing the VHL-HIF-1 interaction. Importantly, accumulation of HIF-1 protects embryonic cortical neurons against MPP+ induced neuronal death. Finally, we confirmed the impairment of HIF-1 response to oxidative stress in human lymphoblastoids of DJ-1-linked PD cases. In the second part of this study, we demonstrated the interaction of DJ-1 and PON2. Interestingly, PON2 lactonase activity is reduced in DJ-1 deficient cells which could be rescued by re-introduction of DJ-1, suggesting a modulating role of DJ-1 on PON2 activity. In addition, PON2 deficiency, like DJ-1 deficiency, hypersensitizes neurons to MPP+, which could be rescued by over-expression of PON2 in both cases. Taken together, our data provide evidence that DJ-1 exerts its protective role by inhibiting VHL activity, enhancing HIF-1 stability, and increasing PON2 pro-survival function in PD models.

Submitted by Pós-Com Pós-Com (pos-com@ufba.br) on 2013-02-04T16:12:55Z No. of bitstreams: 1 Marcela Alexandre Moreira.pdf: 1981461 bytes, checksum: 967fd12b67520219dfc6566359e5ce2c (MD5) / Approved for entry into archive by Alda Lima da Silva(sivalda@ufba.br) on 2013-02-04T17:05:34Z (GMT) No. of bitstreams: 1 Marcela Alexandre Moreira.pdf: 1981461 bytes, checksum: 967fd12b67520219dfc6566359e5ce2c (MD5) / Made available in DSpace on 2013-02-04T17:05:34Z (GMT). No. of bitstreams: 1 Marcela Alexandre Moreira.pdf: 1981461 bytes, checksum: 967fd12b67520219dfc6566359e5ce2c (MD5) / Estudo sobre a música eletrônica e o drum’n bass enquanto gênero da música popular massiva a partir da análise da track Carolina Carol Bela LK. Fundamentam a análise as noções de gênero e cena, esta última materializada na música eletrônica através dos núcleos. Parte da história do DJ no rádio é recuperada com o objetivo de fornecer subsídios para a compreensão da popularização de gêneros como o drum'n bass no Reino Unido e no Brasil. Neste contexto, os discos de vinil se apresentavam como suporte decisivo enquanto estratégia de autenticidade do DJ. As tecnologias na produção musical exerceram importante papel na indústria fonográfica da música eletrônica e tensionaram a permanência e continuidade dos discos de vinil. Finalmente, a análise permitiu localizar o importante papel dos discos de vinil no gênero de música eletrônica drum’n bass à época do lançamento de LK. / Facom