Identificação de compostos que modulam a patogénese da doença de Machado-Joseph em C.elegans: autofagia como alvo terapêutico: identification of small compounds that modulate pathogenesis of Machado-Joseph disease in a C.elegans model: targeting autophagy

A doença de Machado-Joseph (DMJ) ou ataxia espinocerebelosa do tipo 3 (SCA3), conhecida por ser a mais comum das ataxias hereditárias dominantes em todo o mundo, é uma doença neurodegenerativa autossómica dominante que leva a uma grande incapacidade motora, embora sem alterar o intelecto, culminando com a morte do doente. Atualmente não existe nenhum tratamento eficaz para esta doença. A DMJ é resultado de uma alteração genética causada pela expansão de uma sequência poliglutamínica (poliQ), na região C-terminal do gene que codifica a proteína ataxina-3 (ATXN3). Os mecanismos celulares das doenças de poliglutaminas que provocam toxicidade, bem como a função da ATXN3, não são ainda totalmente conhecidos. Neste trabalho, usamos, pela sua simplicidade e potencial genético, um pequeno animal invertebrado, o nemátode C. elegans, com o objetivo de identificar fármacos eficazes para o combate contra a patogénese da DMJ, analisando simultaneamente o seu efeito na agregação da ATXN3 mutante nas células neuronais in vivo e o seu impacto no comportamento motor dos animais. Este pequeno invertebrado proporciona grandes vantagens no estudo dos efeitos tóxicos de proteínas poliQ nos neurónios, uma vez que a transparência das suas 959 células (das quais 302 são neurónios) facilita a deteção de proteínas fluorescentes in vivo. Para além disso, esta espécie tem um ciclo de vida curto, é económica e de fácil manutenção. Neste trabalho testámos no nosso modelo transgénico da DMJ com 130Qs em C.elegans dois compostos potencialmente moduladores da agregação da ATXN3 mutante e da resultante disfunção neurológica, atuando pela via da autofagia. De modo a validar a possível importância terapêutica da ativação da autofagia os compostos candidatos escolhidos foram o Litío e o análogo da Rapamicina CCI-779, testados independentemente e em combinação. A neuroproteção conferida pelo Litío e pelo CCI-779 independentemente sugere que o uso destes fármacos possa ser considerado uma boa estratégia como terapia para a DMJ, a testar em organismos evolutivamente mais próximos do humano. A manipulação da autofagia, segundo vários autores, parece ser benéfica e pode ser a chave para o desenvolvimento de novos tratamentos para várias doenças relacionadas com a agregação proteica e o envelhecimento.

Day-ahead resource scheduling in smart grids considering Vehicle-to-Grid and network constraints

Energy resource scheduling becomes increasingly important, as the use of distributed resources is intensified and massive gridable vehicle use is envisaged. The present paper proposes a methodology for dayahead energy resource scheduling for smart grids considering the intensive use of distributed generation and of gridable vehicles, usually referred as Vehicle- o-Grid (V2G). This method considers that the energy resources are managed by a Virtual Power Player (VPP) which established contracts with V2G owners. It takes into account these contracts, the user´s requirements subjected to the VPP, and several discharge price steps. Full AC power flow calculation included in the model allows taking into account network constraints. The influence of the successive day requirements on the day-ahead optimal solution is discussed and considered in the proposed model. A case study with a 33 bus distribution network and V2G is used to illustrate the good performance of the proposed method.

Fuzzy Monte Carlo mathematical model for load curtailment minimization in transmission power systems

This paper presents a methodology which is based on statistical failure and repair data of the transmission power system components and uses fuzzyprobabilistic modeling for system component outage parameters. Using statistical records allows developing the fuzzy membership functions of system component outage parameters. The proposed hybrid method of fuzzy set and Monte Carlo simulation based on the fuzzy-probabilistic models allows catching both randomness and fuzziness of component outage parameters. A network contingency analysis to identify any overloading or voltage violation in the network is performed once obtained the system states by Monte Carlo simulation. This is followed by a remedial action algorithm, based on optimal power flow, to reschedule generations and alleviate constraint violations and, at the same time, to avoid any load curtailment, if possible, or, otherwise, to minimize the total load curtailment, for the states identified by the contingency analysis. In order to illustrate the application of the proposed methodology to a practical case, the paper will include a case study for the Reliability Test System (RTS) 1996 IEEE 24 BUS.

ANN based day-ahead ancillary services forecast for electricity market simulation

Adequate decision support tools are required by electricity market players operating in a liberalized environment, allowing them to consider all the business opportunities and take strategic decisions. Ancillary services (AS) represent a good negotiation opportunity that must be considered by market players. Based on the ancillary services forecasting, market participants can use strategic bidding for day-ahead ancillary services markets. For this reason, ancillary services market simulation is being included in MASCEM, a multi-agent based electricity market simulator that can be used by market players to test and enhance their bidding strategies. The paper presents the methodology used to undertake ancillary services forecasting, based on an Artificial Neural Network (ANN) approach. ANNs are used to day-ahead prediction of non-spinning reserve (NS), regulation-up (RU), and regulation down (RD). Spinning reserve (SR) is mentioned as past work for comparative analysis. A case study based on California ISO (CAISO) data is included; the forecasted results are presented and compared with CAISO published forecast.

Factors associated with infant feeding practices after hospital discharge

OBJECTIVE: To assess factors associated with infant feeding practices on the first day at home after hospital discharge. METHODS: A total of 209 women, who had a child aged four months or less and were living in Itapira, Brazil, were interviewed during the National Immunization Campaign Day in 1999. Statistical analysis was performed using the Chi-square test and a logistic regression model was used for verifying an association between dependent and independent variables. RESULTS: Women aged 25.5 years on average and 18.2% were teenagers. Fifty-three percent of the women delivered vaginally and most vaginal deliveries (78.5%) took place in the public hospital. The prevalence of exclusive breastfeeding on the first day at home was 78.1% and 11.6% of the infants were receiving formula at this time. The only factor associated with EBF on the first day at home was being a teenaged-primiparous mother (OR=9.40; 95% CI: 1.24-71.27). This association remained statistically significant even after controlling for type of delivery and hospital where the birth took place. Feeding formula on the first day at home was only significantly associated with the hospital (i.e., birth at the city hospital was a protective factor (OR=0.33; 95% CI: 0.13-0.86), even after controlling for vaginal delivery. CONCLUSIONS: On the first day at home after hospital discharge, teenaged-primiparous mothers were more likely to exclusive breastfeeding as well as those infants born in the municipal public hospital. Further studies are needed from a multidisciplinary approach.

Context-aware emotion-based model for group decision making

Involving groups in important management processes such as decision making has several advantages. By discussing and combining ideas, counter ideas, critical opinions, identified constraints, and alternatives, a group of individuals can test potentially better solutions, sometimes in the form of new products, services, and plans. In the past few decades, operations research, AI, and computer science have had tremendous success creating software systems that can achieve optimal solutions, even for complex problems. The only drawback is that people don’t always agree with these solutions. Sometimes this dissatisfaction is due to an incorrect parameterization of the problem. Nevertheless, the reasons people don’t like a solution might not be quantifiable, because those reasons are often based on aspects such as emotion, mood, and personality. At the same time, monolithic individual decisionsupport systems centered on optimizing solutions are being replaced by collaborative systems and group decision-support systems (GDSSs) that focus more on establishing connections between people in organizations. These systems follow a kind of social paradigm. Combining both optimization- and socialcentered approaches is a topic of current research. However, even if such a hybrid approach can be developed, it will still miss an essential point: the emotional nature of group participants in decision-making tasks. We’ve developed a context-aware emotion based model to design intelligent agents for group decision-making processes. To evaluate this model, we’ve incorporated it in an agent-based simulator called ABS4GD (Agent-Based Simulation for Group Decision), which we developed. This multiagent simulator considers emotion- and argument based factors while supporting group decision-making processes. Experiments show that agents endowed with emotional awareness achieve agreements more quickly than those without such awareness. Hence, participant agents that integrate emotional factors in their judgments can be more successful because, in exchanging arguments with other agents, they consider the emotional nature of group decision making.

An application of structural equation modeling of test dispositional optimism as mediator or moderator in quality of life in patients with chronic disease

The aim of the present study was to test a hypothetical model to examine if dispositional optimism exerts a moderating or a mediating effect between personality traits and quality of life, in Portuguese patients with chronic diseases. A sample of 540 patients was recruited from central hospitals in various districts of Portugal. All patients completed self-reported questionnaires assessing socio-demographic and clinical variables, personality, dispositional optimism, and quality of life. Structural equation modeling (SEM) was used to analyze the moderating and mediating effects. Results suggest that dispositional optimism exerts a mediator rather than a moderator role between personality traits and quality of life, suggesting that “the expectation that good things will happen” contributes to a better general well-being and better mental functioning.

The gambin model provides a superior fit to species abundance distributions with a single free parameter : evidence, implementation and interpretation

The species abundance distribution (SAD) has been a central focus of community ecology for over fifty years, and is currently the subject of widespread renewed interest. The gambin model has recently been proposed as a model that provides a superior fit to commonly preferred SAD models. It has also been argued that the model's single parameter (α) presents a potentially informative ecological diversity metric, because it summarises the shape of the SAD in a single number. Despite this potential, few empirical tests of the model have been undertaken, perhaps because the necessary methods and software for fitting the model have not existed. Here, we derive a maximum likelihood method to fit the model, and use it to undertake a comprehensive comparative analysis of the fit of the gambin model. The functions and computational code to fit the model are incorporated in a newly developed free-to-download R package (gambin). We test the gambin model using a variety of datasets and compare the fit of the gambin model to fits obtained using the Poisson lognormal, logseries and zero-sum multinomial distributions. We found that gambin almost universally provided a better fit to the data and that the fit was consistent for a variety of sample grain sizes. We demonstrate how α can be used to differentiate intelligibly between community structures of Azorean arthropods sampled in different land use types. We conclude that gambin presents a flexible model capable of fitting a wide variety of observed SAD data, while providing a useful index of SAD form in its single fitted parameter. As such, gambin has wide potential applicability in the study of SADs, and ecology more generally.

Aplicação dos princípios da manutenção Lean na indústria farmacêutica

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Performance of a Brazilian population on the test of functional health literacy in adults

OBJECTIVE: To analyze the scoring obtained by an instrument, which evaluates the ability to read and understand items in the health care setting, according to education and age. METHODS: The short version of the Test of Functional Health Literacy in Adults was administered to 312 healthy participants of different ages and years of schooling. The study was conducted between 2006 and 2007, in the city of São Paulo, Southeastern Brazil. The test includes actual materials such as pill bottles and appointment slips and measures reading comprehension, assessing the ability to read and correctly pronounce a list of words and understand both prose passages and numerical information. Pearson partial correlations and a multiple regression model were used to verify the association between its scores and education and age. RESULTS: The mean age of the sample was 47.3 years(sd=16.8) and the mean education was 9.7 years(sd=5; range: 1 - 17). A total of 32.4% of the sample showed literacy/numeracy deficits, scoring in the inadequate and marginal functional health literacy ranges. Among the elderly (65 years or older) this rate increased to 51.6%. There was a positive correlation between schooling and scores (r=0.74; p<0.01) and a negative correlation between age and the scores (r=-0.259; p<0.01). The correlation between the scores and age was not significant when the effects of education were held constant (rp=-0.031, p=0.584). A significant association (B=3.877, Beta =0.733; p<0.001) was found between schooling and scores. Age was not a significant predictor in this model (B=-0.035, Beta=-0.22; p=0.584). CONCLUSIONS: The short version of the Test of Functional Health Literacy in Adults was a suitable tool to assess health literacy in the study population. The high number of individuals classified as functional illiterates in this test highlights the importance of special assistance to help them properly understand directions for healthcare.

Fuzzy Monte Carlo model for transmission power systems reliability based decision making

This thesis presents the Fuzzy Monte Carlo Model for Transmission Power Systems Reliability based studies (FMC-TRel) methodology, which is based on statistical failure and repair data of the transmission power system components and uses fuzzyprobabilistic modeling for system component outage parameters. Using statistical records allows developing the fuzzy membership functions of system component outage parameters. The proposed hybrid method of fuzzy set and Monte Carlo simulation based on the fuzzy-probabilistic models allows catching both randomness and fuzziness of component outage parameters. A network contingency analysis to identify any overloading or voltage violation in the network is performed once obtained the system states. This is followed by a remedial action algorithm, based on Optimal Power Flow, to reschedule generations and alleviate constraint violations and, at the same time, to avoid any load curtailment, if possible, or, otherwise, to minimize the total load curtailment, for the states identified by the contingency analysis. For the system states that cause load curtailment, an optimization approach is applied to reduce the probability of occurrence of these states while minimizing the costs to achieve that reduction. This methodology is of most importance for supporting the transmission system operator decision making, namely in the identification of critical components and in the planning of future investments in the transmission power system. A case study based on Reliability Test System (RTS) 1996 IEEE 24 Bus is presented to illustrate with detail the application of the proposed methodology.

Hybrid adaptive control of a dragonfly model

Dragonflies show unique and superior flight performances than most of other insect species and birds. They are equipped with two pairs of independently controlled wings granting an unmatchable flying performance and robustness. In this paper, it is presented an adaptive scheme controlling a nonlinear model inspired in a dragonfly-like robot. It is proposed a hybrid adaptive (HA) law for adjusting the parameters analyzing the tracking error. At the current stage of the project it is considered essential the development of computational simulation models based in the dynamics to test whether strategies or algorithms of control, parts of the system (such as different wing configurations, tail) as well as the complete system. The performance analysis proves the superiority of the HA law over the direct adaptive (DA) method in terms of faster and improved tracking and parameter convergence.

Memória de longo prazo nos retornos acionistas dos índices de referência da euronext, implicações para a hipótese de mercados eficientes e contributo fractal para aperfeiçoamento do capital asset pricing model

Não existe uma definição única de processo de memória de longo prazo. Esse processo é geralmente definido como uma série que possui um correlograma decaindo lentamente ou um espectro infinito de frequência zero. Também se refere que uma série com tal propriedade é caracterizada pela dependência a longo prazo e por não periódicos ciclos longos, ou que essa característica descreve a estrutura de correlação de uma série de longos desfasamentos ou que é convencionalmente expressa em termos do declínio da lei-potência da função auto-covariância. O interesse crescente da investigação internacional no aprofundamento do tema é justificado pela procura de um melhor entendimento da natureza dinâmica das séries temporais dos preços dos ativos financeiros. Em primeiro lugar, a falta de consistência entre os resultados reclama novos estudos e a utilização de várias metodologias complementares. Em segundo lugar, a confirmação de processos de memória longa tem implicações relevantes ao nível da (1) modelação teórica e econométrica (i.e., dos modelos martingale de preços e das regras técnicas de negociação), (2) dos testes estatísticos aos modelos de equilíbrio e avaliação, (3) das decisões ótimas de consumo / poupança e de portefólio e (4) da medição de eficiência e racionalidade. Em terceiro lugar, ainda permanecem questões científicas empíricas sobre a identificação do modelo geral teórico de mercado mais adequado para modelar a difusão das séries. Em quarto lugar, aos reguladores e gestores de risco importa saber se existem mercados persistentes e, por isso, ineficientes, que, portanto, possam produzir retornos anormais. O objetivo do trabalho de investigação da dissertação é duplo. Por um lado, pretende proporcionar conhecimento adicional para o debate da memória de longo prazo, debruçando-se sobre o comportamento das séries diárias de retornos dos principais índices acionistas da EURONEXT. Por outro lado, pretende contribuir para o aperfeiçoamento do capital asset pricing model CAPM, considerando uma medida de risco alternativa capaz de ultrapassar os constrangimentos da hipótese de mercado eficiente EMH na presença de séries financeiras com processos sem incrementos independentes e identicamente distribuídos (i.i.d.). O estudo empírico indica a possibilidade de utilização alternativa das obrigações do tesouro (OT’s) com maturidade de longo prazo no cálculo dos retornos do mercado, dado que o seu comportamento nos mercados de dívida soberana reflete a confiança dos investidores nas condições financeiras dos Estados e mede a forma como avaliam as respetiva economias com base no desempenho da generalidade dos seus ativos. Embora o modelo de difusão de preços definido pelo movimento Browniano geométrico gBm alegue proporcionar um bom ajustamento das séries temporais financeiras, os seus pressupostos de normalidade, estacionariedade e independência das inovações residuais são adulterados pelos dados empíricos analisados. Por isso, na procura de evidências sobre a propriedade de memória longa nos mercados recorre-se à rescaled-range analysis R/S e à detrended fluctuation analysis DFA, sob abordagem do movimento Browniano fracionário fBm, para estimar o expoente Hurst H em relação às séries de dados completas e para calcular o expoente Hurst “local” H t em janelas móveis. Complementarmente, são realizados testes estatísticos de hipóteses através do rescaled-range tests R/S , do modified rescaled-range test M - R/S e do fractional differencing test GPH. Em termos de uma conclusão única a partir de todos os métodos sobre a natureza da dependência para o mercado acionista em geral, os resultados empíricos são inconclusivos. Isso quer dizer que o grau de memória de longo prazo e, assim, qualquer classificação, depende de cada mercado particular. No entanto, os resultados gerais maioritariamente positivos suportam a presença de memória longa, sob a forma de persistência, nos retornos acionistas da Bélgica, Holanda e Portugal. Isto sugere que estes mercados estão mais sujeitos a maior previsibilidade (“efeito José”), mas também a tendências que podem ser inesperadamente interrompidas por descontinuidades (“efeito Noé”), e, por isso, tendem a ser mais arriscados para negociar. Apesar da evidência de dinâmica fractal ter suporte estatístico fraco, em sintonia com a maior parte dos estudos internacionais, refuta a hipótese de passeio aleatório com incrementos i.i.d., que é a base da EMH na sua forma fraca. Atendendo a isso, propõem-se contributos para aperfeiçoamento do CAPM, através da proposta de uma nova fractal capital market line FCML e de uma nova fractal security market line FSML. A nova proposta sugere que o elemento de risco (para o mercado e para um ativo) seja dado pelo expoente H de Hurst para desfasamentos de longo prazo dos retornos acionistas. O expoente H mede o grau de memória de longo prazo nos índices acionistas, quer quando as séries de retornos seguem um processo i.i.d. não correlacionado, descrito pelo gBm(em que H = 0,5 , confirmando- se a EMH e adequando-se o CAPM), quer quando seguem um processo com dependência estatística, descrito pelo fBm(em que H é diferente de 0,5, rejeitando-se a EMH e desadequando-se o CAPM). A vantagem da FCML e da FSML é que a medida de memória de longo prazo, definida por H, é a referência adequada para traduzir o risco em modelos que possam ser aplicados a séries de dados que sigam processos i.i.d. e processos com dependência não linear. Então, estas formulações contemplam a EMH como um caso particular possível.

Model for the evaluation of drug-dispensing services in primary health care

OBJECTIVE To develop a model for evaluating the efficacy of drug-dispensing service in primary health care. METHODS An efficacy criterion was adopted to determine the level of achievement of the service objectives. The evaluation model was developed on the basis of a literature search and discussions with experts. The applicability test of the model was conducted in 15 primary health care units in the city of Florianópolis, state of Santa Catarina, in 2010, and data were recorded in structured and pretested questionnaires. RESULTS The model developed was evaluated using five dimensions of analysis for analysis. The model was suitable for evaluating service efficacy and helped to identify the critical points of each service dimension. CONCLUSIONS Adaptations to the data collection technique may be required to adjust for the reality and needs of each situation. The evaluation of the drug-dispensing service should promote adequate access to medications supplied through the public health system.

Oysters return to the Tagus estuary through an ecological model

Dissertation submitted to the Faculty of Sciences and Technology of New University of Lisbon for obtaining the degree of Master in Environmental Management Systems