No description available.

Thesis (Ph. D.)--Ohio University, June, 2001. / Title from PDF t.p.

Thesis (Ph.D.) - University of Queensland, 2007. / Includes bibliography.

Thesis (MSc)--University of Stellenbosch, 2006. / Bibliography. Also available via the Internet.

Neurofibromatosis type 2 (NF2) is an autosomal dominant inherited condition that predisposes individuals to develop multiple nervous system tumours, primarily schwannoma, meningioma and ependymoma. NF2 is characterised by loss of the tumour suppressor protein Merlin, caused by bi-allelic mutations of the encoding gene NF2 or by loss of heterozygosity. These tumours can occur either sporadically or as part of the NF2 condition. The majority are slow growing and display benign features, but this benignancy renders them largely unresponsive to classic chemotherapeutic agents leaving surgery and radiosurgery as the only remaining treatment options. Depending on their location, NF2-related tumours can cause a number of side effects, including nausea, balance problems, and in some cases hearing and/or vision loss. Phosphorylation is a key regulatory mechanism leading to changes in cell signalling. By identifying phosphoproteins that are significantly activated in tumour cells, novel therapies can be developed aiming to specifically target the phosphorylated status of these proteins thus ‘switching off’ the signalling cascade. The objective of this study is to identify and validate common targets in both Merlin-deficient meningioma and schwannoma to eventually exploit in novel therapeutic approaches. Using phosphoprotein purification followed by mass spectrometry analysis, we identified Signal Transducer and Activator of Transcription 1 (STAT1), phosphorylated at Serine (S) 727 and Tyrosine (Y) 701, PDZ and LIM domain protein 2 (PDLIM2), Heat Shock 70kDa Protein 1A (HSPA1A) and Filamin B (FLNB) as potential common, novel therapeutic targets. We validated these candidates in human primary meningioma and schwannoma tumour cells using a variety of techniques. We also showed that specific 7 knockdown of STAT1 and PDLIM2 was related to a significant decrease in cellular proliferation. Additionally, we performed co-immunoprecipitation using PDLIM2 as the bait protein and identified STAT1, HSPA1A and FLNB as binding partners, suggesting a novel interaction network involving all of the potential targets identified in this study. We also identified activation of several pathways and/ or biological processes in both tumour types that warrant further investigation i.e. endocytosis in schwannoma and the proteasome in meningioma. In conclusion, with our approach we substantially increased the overall body of knowledge regarding the proteome and phosphoproteome of meningioma and schwannoma. We generated a comprehensive set of data that highlighted several potential therapeutic targets and dysregulated pathways which will be further investigated.

O objetivo desta dissertação, primeiramente, é analisar empiricamente se a adoção do regime de metas de inflação (RMI) tem se mostrado eficaz ao longo dos anos no controle e manutenção dos índices de preços. Posteriormente é analisado o grau de impacto da condução da política monetária, imposta pelo RMI, sobre a taxa de desemprego e crescimento real do produto. Para alcançar estes objetivos, é feita uma análise comparativa dos períodos que compreendem o antes e o depois da adoção (até o ano de 2014) deste regime monetário, em especial o caso brasileiro. Outros objetivos incluem, com o intuito de melhor compreender a operacionalização do RMI, discutir as principais teorias de inflação e de regimes monetários, enfatizando o RMI por ser objeto central deste estudo. Desta forma, são discutidos os fundamentos teóricos, seus formatos estruturais, bem como as vantagens e desvantagens apontadas pelos críticos deste regime. Por fim, é apresentada a conclusão acerca da eficácia, ou não, deste regime na manutenção de baixos índices de inflação, e se o mesmo sacrificou em algum grau os níveis de emprego e produto, em especial no Brasil. / The first aim of this dissertation is to examine empirically whether the adoption of inflation targeting regime (IT) has proven effective over the years for the control and maintenance of low and stable inflation rates. Next, it is analyzed the impact of monetary policy based on the IT on the unemployment rate and real GDP growth. To achieve these goals, a comparative analysis is carried out, following the “before and after” methodology (until the year 2014), focusing especially on the Brazilian case. Other objectives include achieving a better understanding about the operation of the IT, discussing the main theories of inflation and monetary regimes, emphasizing the IT. Thus, the theoretical foundations of the IT are presented, its many structural formats, as well as the advantages and disadvantages cited by critics of this regime. Finally, the work presents the conclusion about the effectiveness, or lack thereof, of this regime in maintaining low inflation rates, and if it has sacrificed employment levels and product, especially in Brazil.

Made available in DSpace on 2014-10-09T12:38:54Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:02:00Z (GMT). No. of bitstreams: 1 02814.pdf: 7065257 bytes, checksum: 9cc7b6eb072600e69bbfbb2de41c251e (MD5) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

O objetivo desta dissertação, primeiramente, é analisar empiricamente se a adoção do regime de metas de inflação (RMI) tem se mostrado eficaz ao longo dos anos no controle e manutenção dos índices de preços. Posteriormente é analisado o grau de impacto da condução da política monetária, imposta pelo RMI, sobre a taxa de desemprego e crescimento real do produto. Para alcançar estes objetivos, é feita uma análise comparativa dos períodos que compreendem o antes e o depois da adoção (até o ano de 2014) deste regime monetário, em especial o caso brasileiro. Outros objetivos incluem, com o intuito de melhor compreender a operacionalização do RMI, discutir as principais teorias de inflação e de regimes monetários, enfatizando o RMI por ser objeto central deste estudo. Desta forma, são discutidos os fundamentos teóricos, seus formatos estruturais, bem como as vantagens e desvantagens apontadas pelos críticos deste regime. Por fim, é apresentada a conclusão acerca da eficácia, ou não, deste regime na manutenção de baixos índices de inflação, e se o mesmo sacrificou em algum grau os níveis de emprego e produto, em especial no Brasil. / The first aim of this dissertation is to examine empirically whether the adoption of inflation targeting regime (IT) has proven effective over the years for the control and maintenance of low and stable inflation rates. Next, it is analyzed the impact of monetary policy based on the IT on the unemployment rate and real GDP growth. To achieve these goals, a comparative analysis is carried out, following the “before and after” methodology (until the year 2014), focusing especially on the Brazilian case. Other objectives include achieving a better understanding about the operation of the IT, discussing the main theories of inflation and monetary regimes, emphasizing the IT. Thus, the theoretical foundations of the IT are presented, its many structural formats, as well as the advantages and disadvantages cited by critics of this regime. Finally, the work presents the conclusion about the effectiveness, or lack thereof, of this regime in maintaining low inflation rates, and if it has sacrificed employment levels and product, especially in Brazil.

No description available.

O objetivo desta dissertação, primeiramente, é analisar empiricamente se a adoção do regime de metas de inflação (RMI) tem se mostrado eficaz ao longo dos anos no controle e manutenção dos índices de preços. Posteriormente é analisado o grau de impacto da condução da política monetária, imposta pelo RMI, sobre a taxa de desemprego e crescimento real do produto. Para alcançar estes objetivos, é feita uma análise comparativa dos períodos que compreendem o antes e o depois da adoção (até o ano de 2014) deste regime monetário, em especial o caso brasileiro. Outros objetivos incluem, com o intuito de melhor compreender a operacionalização do RMI, discutir as principais teorias de inflação e de regimes monetários, enfatizando o RMI por ser objeto central deste estudo. Desta forma, são discutidos os fundamentos teóricos, seus formatos estruturais, bem como as vantagens e desvantagens apontadas pelos críticos deste regime. Por fim, é apresentada a conclusão acerca da eficácia, ou não, deste regime na manutenção de baixos índices de inflação, e se o mesmo sacrificou em algum grau os níveis de emprego e produto, em especial no Brasil. / The first aim of this dissertation is to examine empirically whether the adoption of inflation targeting regime (IT) has proven effective over the years for the control and maintenance of low and stable inflation rates. Next, it is analyzed the impact of monetary policy based on the IT on the unemployment rate and real GDP growth. To achieve these goals, a comparative analysis is carried out, following the “before and after” methodology (until the year 2014), focusing especially on the Brazilian case. Other objectives include achieving a better understanding about the operation of the IT, discussing the main theories of inflation and monetary regimes, emphasizing the IT. Thus, the theoretical foundations of the IT are presented, its many structural formats, as well as the advantages and disadvantages cited by critics of this regime. Finally, the work presents the conclusion about the effectiveness, or lack thereof, of this regime in maintaining low inflation rates, and if it has sacrificed employment levels and product, especially in Brazil.