All over the place localization system

The MAP-i Doctoral Programme in Informatics, of the Universities of Minho, Aveiro and Porto

Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-d pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.

Development of polymeric nanoparticles containing neuroprotective compounds of Hypericum perforatum

Tese de Doutoramento em Biologia das Plantas - MAP BIOPLANT

The role of the mammalian DNA end-processing enzyme polynucleotide kinase 3'-phosphatase in spinocerebellar ataxia Type 3 pathogenesis

DNA strand-breaks (SBs) with non-ligatable ends are generated by ionizing radiation, oxidative stress, various chemotherapeutic agents, and also as base excision repair (BER) intermediates. Several neurological diseases have already been identified as being due to a deficiency in DNA end-processing activities. Two common dirty ends, 3'-P and 5'-OH, are processed by mammalian polynucleotide kinase 3'-phosphatase (PNKP), a bifunctional enzyme with 3'-phosphatase and 5'-kinase activities. We have made the unexpected observation that PNKP stably associates with Ataxin-3 (ATXN3), a polyglutamine repeat-containing protein mutated in spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD). This disease is one of the most common dominantly inherited ataxias worldwide; the defect in SCA3 is due to CAG repeat expansion (from the normal 14-41 to 55-82 repeats) in the ATXN3 coding region. However, how the expanded form gains its toxic function is still not clearly understood. Here we report that purified wild-type (WT) ATXN3 stimulates, and by contrast the mutant form specifically inhibits, PNKP's 3' phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity. Furthermore, transgenic mice conditionally expressing the pathological form of human ATXN3 also showed decreased 3'-phosphatase activity of PNKP, mostly in the deep cerebellar nuclei, one of the most affected regions in MJD patients' brain. Finally, long amplicon quantitative PCR analysis of human MJD patients' brain samples showed a significant accumulation of DNA strand breaks. Our results thus indicate that the accumulation of DNA strand breaks due to functional deficiency of PNKP is etiologically linked to the pathogenesis of SCA3/MJD.

Fluência no betão desde as primeiras idades: um estudo experimental

Dissertação de mestrado integrado em Engenharia Civil

Reforço à flexão de lajes de betão armado com laminados de CFRP pré-esforçados

Dissertação de mestrado integrado em Engenharia Civil (área de especialização em Estruturas e Geotecnia)

Videovigilância nos espaços públicos e criminalidade contra o Património: Santuário de Fátima

Dissertação de mestrado em Crime, Diferença e Desigualdade

A utilização de materiais didáticos diversificados como estratégia de motivação

Relatório de estágio de mestrado em Ensino da Filosofia no Ensino Secundário

Development of a poly(L-Lactic acid) based drug release system

Dissertação de mestrado em Biofísica e Bionanossistemas

A prática da Filosofia na sala de aula

Relatório de estágio de mestrado em Ensino de Filosofia no Ensino Secundário

Impact of wind power generation on the electricity supply industry

The objective of this dissertation is to investigate the effect wind energy has on the Electricity Supply Industry in Ireland. Wind power generation is a source of renewable energy that is in abundant supply in Ireland and is fast becoming a resource that Ireland is depending on as a diverse and secure of supply of energy. However, wind is an intermittent resource and coupled with a variable demand, there are integration issues with balancing demand and supply effectively. To maintain a secure supply of electricity to customers, it is necessary that wind power has an operational reserve to ensure appropriate backup for situations where there is low wind but high demand. This dissertation examines the affect of this integration by comparing wind generation to that of conventional generation in the national grid. This is done to ascertain the cost benefits of wind power generation against a scenario with no wind generation. Then, the analysis examines to see if wind power can meet the pillars of sustainability. This entails looking at wind in a practical scenario to observe how it meets these pillars under the criteria of environmental responsibility, displacement of conventional fuel, cost competitiveness and security of supply.

A comparison of environmental licensing systems in operation in the wood panel manufacturing industry in the Northern Hemisphere

The objective of this thesis is to compare and contrast environmental licensing systems, for the wood panel industry, in a number of countries in order to determine which system is the best from an environmental and economic point of view. The thesis also examines the impact which government can have on industry and the type of licensing system in operation in a country. Initially, the thesis investigates the origins of the various environmental licensing systems which are in operation in Ireland, Scotland, Wales, France, USA and Canada. It then examines the Environmental Agencies which control and supervise industry in these countries. The impact which the type of government (i.e. unitary or federal) in charge in any particular country has on industry and the Regulatory Agency in that country is then described. Most of the mills in the thesis make a product called OSB (Oriented Strand Board) and the manufacturing process is briefly described in order to understand where the various emissions are generated. The main body of the thesis examines a number of environmental parameters which have emission limit values in the licenses examined, although not all of these parameters have emission limit values in all of the licenses. All of these parameters are used as indicators of the potential impact which the mill can have on the environment. They have been set at specific levels by the Environmental Agencies in the individual countries to control the impact of the mill. Following on from this, the two main types of air pollution control equipment (WESPs and RTOs) are described in regard to their function and capabilities. The mill licenses are then presented in the form of results tables which compare air results and water results separately. This is due to the fact that the most significant emission from this type of industry is to air. A matrix system is used to compare the licenses so that the comparison can be as objective as possible. The discussion examines all of the elements previously described and from this it was concluded that the IPC licensing system is the best from an environmental and economic point of view. It is a much more expensive system to operate than the other systems examined, but it is much more comprehensive and looks at the mill as a whole rather than fragmenting it. It was also seen that the type of environmental licensing system which is in place in a country can play a role in the locating of an industry as certain systems were seen to have more stringent standards attached to them. The type of standard in place in a country is in turn influenced by the type of government which is in place in that country.

Acoustic emission analysis of the effect of a 2D wedge shaped blade on the compact bone cutting process

Surgeons may use a number of cutting instruments such as osteotomes and chisels to cut bone during an operative procedure. The initial loading of cortical bone during the cutting process results in the formation of microcracks in the vicinity of the cutting zone with main crack propagation to failure occuring with continued loading. When a material cracks, energy is emitted in the form of Acoustic Emission (AE) signals that spread in all directions, therefore, AE transducers can be used to monitor the occurrence and development of microcracking and crack propagation in cortical bone. In this research, number of AE signals (hits) and related parameters including amplitude, duration and absolute energy (abs-energy) were recorded during the indentation cutting process by a wedge blade on cortical bone specimens. The cutting force was also measured to correlate between load-displacement curves and the output from the AE sensor. The results from experiments show AE signals increase substantially during the loading just prior to fracture between 90% and 100% of maximum fracture load. Furthermore, an amplitude threshold value of 64dB (with approximate abs-energy of 1500 aJ) was established to saparate AE signals associated with microcracking (41 – 64dB) from fracture related signals (65 – 98dB). The results also demonstrated that the complete fracture event which had the highest duration value can be distinguished from other growing macrocracks which did not lead to catastrophic fracture. It was observed that the main crack initiation may be detected by capturing a high amplitude signal at a mean load value of 87% of maximum load and unsteady crack propagation may occur just prior to final fracture event at a mean load value of 96% of maximum load. The author concludes that the AE method is useful in understanding the crack initiation and fracture during the indentation cutting process.

Optimising the design and manufacture of a customised, prescription fit, Maxillo-facial prosthesis

This thesis is a continuation of the Enterprise-Ireland Research Innovation Fund (RIF) Project entitled’ "Design and Manufacturing of Customised Maxillo-Facial Prostheses" The primary objective of this Internal Research Development Program (IRDP) project was to investigate two fundamental design changes 1 To incorporate the over-denture abutments directly into the implant. 2 To remove the restraining wings by the addition of screws, which affix the. implant to the dense material of the jawbone. The prosthetic was redesigned using the ANSYS Finite Element Analysis software program and analysed to* • Reduce the internal von Mises stress distribution The new prosthetic had a -63.63 % lower von Mises stress distribution when compared with the original prosthetic. • Examine the screw preload effects. A maximum relative displacement of 22 6 * lO^mm between the bone and screw was determined, which is well below the critical threshold of micromotion which prevents osseointegration • Investigate the prosthetic-bone contact interface. Three models of the screw, prosthesis, and bone, were studied. (Axisymmetnc, quarter volume, and full volume), a recommended preload torque of 0 32 Nm was applied to the prosthetic and a maximum von Mises stress of 1.988 MPa was predicted • Study the overdenture removal forces. This analysis could not be completed because the correct plastic multilinear properties of the denture material could not be established The redesigned prosthetic was successfully manufactured on a 3-axis milling machine with an indexing system The prosthetic was examined for dimensional quality and strength The research established the feasibility of the new design and associated manufacturing method.

Equações para a previsão da potência aeróbia (VO2) de jovens adultos brasileiros

FUNDAMENTO: O VO2 pode ser previsto, com base em parâmetros antropométricos e fisiológicos, para determinadas populações. OBJETIVO: Propor modelos preditivos do VO2 submáximo e máximo para jovens adultos brasileiros. MÉTODOS: Os 137 voluntários (92 homens) foram submetidos ao teste progressivo de esforço máximo (GXT) no ciclo ergômetro (Monark®, Br). Medidas de trocas gasosas e ventilatórias foram realizadas em circuito aberto (Aerosport® TEEM 100, EUA). Em outro grupo, 13 voluntários foram submetidos ao GXT e a um teste de onda quadrada (SWT), para avaliar a validade externa das fórmulas do ACSM, de Neder et al e do nomograma de Åstrand-Ryhming. Adotou-se o delineamento experimental de validação cruzada e o nível de significância de p < 0,05. RESULTADOS: Para homens durante esforços submáximos deduziu-se um modelo matemático, com base na carga de trabalho, massa corporal e idade, que explicou 89% da variação do VO2 com o EPE (erro padrão da estimativa) = 0,33 l.min-1. Para a carga máxima do grupo masculino outro modelo, com as mesmas variáveis, explicou 71% da variação VO2 com EPE = 0,40 l.min-1. Para as mulheres foi possível explicar 93% da variação VO2 com EPE = 0,17 l.min-1, no esforço submáximo e máximo, com apenas uma equação que empregava as mesmas variáveis independentes. CONCLUSÃO: Os modelos derivados no presente estudo demonstraram ser acurados para a previsão do VO2 submáximo e máximo em jovens adultos brasileiros.