Development of process control strategies exploiting knowledge from systems biology: application to MDCK suspension cells

Madine Darby Canine Kidney (MDCK) cell lines have been extensively evaluated for their potential as host cells for influenza vaccine production. Recent studies allowed the cultivation of these cells in a fully defined medium and in suspension. However, reaching high cell densities in animal cell cultures still remains a challenge. To address this shortcoming, a combined methodology allied with knowledge from systems biology was reported to study the impact of the cell environment on the flux distribution. An optimization of the medium composition was proposed for both a batch and a continuous system in order to reach higher cell densities. To obtain insight into the metabolic activity of these cells, a detailed metabolic model previously developed by Wahl A. et. al was used. The experimental data of four cultivations of MDCK suspension cells, grown under different conditions and used in this work came from the Max Planck Institute, Magdeburg, Germany. Classical metabolic flux analysis (MFA) was used to estimate the intracellular flux distribution of each cultivation and then combined with partial least squares (PLS) method to establish a link between the estimated metabolic state and the cell environment. The validation of the MFA model was made and its consistency checked. The resulted PLS model explained almost 70% of the variance present in the flux distribution. The medium optimization for the continuous system and for the batch system resulted in higher biomass growth rates than the ones obtained experimentally, 0.034 h-1 and 0.030 h-1, respectively, thus reducing in almost 10 hours the duplication time. Additionally, the optimal medium obtained for the continuous system almost did not consider pyruvate. Overall the proposed methodology seems to be effective and both proposed medium optimizations seem to be promising to reach high cell densities.

A historical overview of leprosy epidemiology and control activities in Amazonas, Brazil

Leprosy is an ancient infectious disease caused by Mycobacterium leprae. According to comparative genomics studies, this disease originated in Eastern Africa or the Near East and spread with successive human migrations. The Europeans and North Africans introduced leprosy into West Africa and the Americas within the past 500 years. In Brazil, this disease arrived with the colonizers who disembarked at the first colonies, Rio de Janeiro, Salvador and Recife, at the end of the sixteenth century, after which it was spread to the other states. In 1854, the first leprosy cases were identified in State of Amazonas in the north of Brazil. The increasing number of leprosy cases and the need for treatment and disease control led to the creation of places to isolate patients, known as leprosaria. One of them, Colonia Antônio Aleixo was built in Amazonas in 1956 according to the most advanced recommendations for isolation at that time and was deactivated in 1979. The history of the Alfredo da Matta Center (AMC), which was the first leprosy dispensary created in 1955, parallels the history of leprosy in the state. Over the years, the AMC has become one of the best training centers for leprosy, general dermatology and sexually transmitted diseases in Brazil. In addition to being responsible for leprosy control programs in the state, the AMC has carried out training programs on leprosy diagnosis and treatment for health professionals in Manaus and other municipalities of the state, aiming to increase the coverage of leprosy control activities. This paper provides a historical overview of leprosy in State of Amazonas, which is an endemic state in Brazil.

Control in distribution networks with demand side management

The way in which electricity networks operate is going through a period of significant change. Renewable generation technologies are having a growing presence and increasing penetrations of generation that are being connected at distribution level. Unfortunately, a renewable energy source is most of the time intermittent and needs to be forecasted. Current trends in Smart grids foresee the accommodation of a variety of distributed generation sources including intermittent renewable sources. It is also expected that smart grids will include demand management resources, widespread communications and control technologies required to use demand response are needed to help the maintenance in supply-demand balance in electricity systems. Consequently, smart household appliances with controllable loads will be likely a common presence in our homes. Thus, new control techniques are requested to manage the loads and achieve all the potential energy present in intermittent energy sources. This thesis is focused on the development of a demand side management control method in a distributed network, aiming the creation of greater flexibility in demand and better ease the integration of renewable technologies. In particular, this work presents a novel multi-agent model-based predictive control method to manage distributed energy systems from the demand side, in presence of limited energy sources with fluctuating output and with energy storage in house-hold or car batteries. Specifically, here is presented a solution for thermal comfort which manages a limited shared energy resource via a demand side management perspective, using an integrated approach which also involves a power price auction and an appliance loads allocation scheme. The control is applied individually to a set of Thermal Control Areas, demand units, where the objective is to minimize the energy usage and not exceed the limited and shared energy resource, while simultaneously indoor temperatures are maintained within a comfort frame. Thermal Control Areas are overall thermodynamically connected in the distributed environment and also coupled by energy related constraints. The energy split is performed based on a fixed sequential order established from a previous completed auction wherein the bids are made by each Thermal Control Area, acting as demand side management agents, based on the daily energy price. The developed solutions are explained with algorithms and are applied to different scenarios, being the results explanatory of the benefits of the proposed approaches.

Medium access control design for distributed opportunistic radio networks

Existing wireless networks are characterized by a fixed spectrum assignment policy. However, the scarcity of available spectrum and its inefficient usage demands for a new communication paradigm to exploit the existing spectrum opportunistically. Future Cognitive Radio (CR) devices should be able to sense unoccupied spectrum and will allow the deployment of real opportunistic networks. Still, traditional Physical (PHY) and Medium Access Control (MAC) protocols are not suitable for this new type of networks because they are optimized to operate over fixed assigned frequency bands. Therefore, novel PHY-MAC cross-layer protocols should be developed to cope with the specific features of opportunistic networks. This thesis is mainly focused on the design and evaluation of MAC protocols for Decentralized Cognitive Radio Networks (DCRNs). It starts with a characterization of the spectrum sensing framework based on the Energy-Based Sensing (EBS) technique considering multiple scenarios. Then, guided by the sensing results obtained by the aforementioned technique, we present two novel decentralized CR MAC schemes: the first one designed to operate in single-channel scenarios and the second one to be used in multichannel scenarios. Analytical models for the network goodput, packet service time and individual transmission probability are derived and used to compute the performance of both protocols. Simulation results assess the accuracy of the analytical models as well as the benefits of the proposed CR MAC schemes.

Determinant factors to merger control decisions in Portugal

The present paper aims to investigate the determinant factors of Portuguese merger control. Our sample comprises 652 M&A cases occurred between January of 2003 and September of 2015. Through a probit model we have tested the relevance of product and geographic market, entry barriers, type of concentration, merger effects, year of decision and the President of the Competition Authority at the time. The results suggests that the conglomerate and vertical effects, the existence of barriers to entry as well as the number of regulatory agencies listened are the main explanatory variables to determine a need for an in-depth investigation and to make a final decision. According to the evidence, cases cleared at Phase 1 are increasing over time. The number of prohibited mergers is close to zero.

A doença pulmonar obstrutiva crónica e o exercício: impacto da doença no declínio funcional e importância do treino de exercício nos benefícios para a saúde

RESUMO: A reabilitação respiratória (RR) é uma intervenção abrangente e interdisciplinar dirigida aos doentes respiratórios crónicos e inclui o treino de exercício, programas de educação e de modificação comportamental, entre outros, desenhados individualmente para melhorar o desempenho físico e psicossocial e promover a adesão a longo prazo a comportamentos promotores de saúde. A doença pulmonar obstrutiva crónica (DPOC) é uma doença comum, afetando cerca de 210 milhões de pessoas em todo o mundo, com elevada mortalidade e com custos económicos significativos decorrentes do agravamento progressivo da doença, das hospitalizações e de reinternamentos frequentes. Apesar do crescente conhecimento da DPOC e do papel da RR nos benefícios para a saúde, existem aspetos ainda não esclarecidos que têm impacto na prática clínica e de investigação e nas decisões das autoridades de saúde. A primeira parte desta tese focou a DPOC e o seu impacto negativo e incluiu: o estudo da prevalência da DPOC em Portugal; os fatores clínicos e funcionais que se associam à mortalidade em doentes com DPOC avançada; a morbilidade, impacto funcional e risco dos doentes se tornarem dependentes para as atividades diárias e a influência da inflamação sistémica. A prevalência estimada da DPOC de 14,2% indica que esta é uma doença comum em Portugal e alerta para a necessidade de uma maior sensibilização da população, dos profissionais de saúde e autoridades de saúde com vista a um diagnóstico precoce e à alocação dos recursos terapêuticos adequados. A elevada taxa de mortalidade em doentes com DPOC avançada - 36,6% em 3 anos - associou-se a insuficiência respiratória, a elevado número de exacerbações, ao cancro do pulmão e a reduzida capacidade funcional para a marcha, salientando a importância da referenciação precoce para RR, a identificação e o tratamento das comorbilidades e a prevenção das exacerbações. A aplicação de um questionário que avaliou as atividades da vida diária básicas e instrumentais, permitiu identificar um marcador clínico do risco de dependência, complementando as avaliações funcionais e associando-se a outros marcadores de mau prognóstico, como as exacerbações. Em doentes com DPOC, com FEV1 médio de 46,76% (desvio padrão: 20,90%), 67% da categoria D do GOLD, verificou-se uma associação positiva entre a expressão de genes inflamatórios avaliada pela reação em cadeia da polimerase (ARN mensageiro de IFNg, IL1b, IL6, IL8, TNFa, TGFb1, iNOS) e o índice de massa corporal em repouso, acentuando-se após o exercício. Este estudo aponta a inflamação como o potencial elo de ligação entre a obesidade e a inflamação sistémica em doentes com DPOC. A segunda parte da tese focou a RR, nomeadamente os seus efeitos em doentes das categorias GOLD A, B, C e D; o impacto das comorbilidades nos resultados da RR e os resultados de diferentes intensidades de treino aeróbio. Após o programa de RR, verificaram-se melhorias significativas na capacidade de exercício funcional e de endurance e no estado geral de saúde dos doentes de todas as categorias GOLD. Esta classificação não distingue os doentes que melhor poderão beneficiar desta intervenção, indicando que devem ser referenciados para RR, os doentes sintomáticos ou com repercussão na qualidade de vida, independentemente da categoria da DPOC a que pertençam. A prevalência das comorbilidades no grupo de doentes com DPOC que é referenciado para RR, é elevada, sendo as mais frequentes, as cardiovasculares, as respiratórias e as psicológicas. Apesar de poderem diminuir o impacto da RR, os resultados desta foram semelhantes independentemente do número de comorbilidades. A identificação e o tratamento sistemáticos das comorbilidades conferem maior segurança clínica a esta intervenção terapêutica a qual, por apresentar bons resultados, não deve limitar a referenciação dos doentes. Com o programa de RR, verificou-se melhoria significativa em todos os resultados centrados no doente para ambas as intensidades de treino aeróbio, a 60% e a 80% da potência aeróbica máxima (Wmax), com melhoria do estado geral de saúde, nos sintomas e na capacidade para o exercício, o que questiona a indicação sistemática de elevadas intensidades de treino em doentes com DPOC para a obtenção de benefícios a curto prazo. Na terceira e última parte da tese foi estudado o papel da atividade física na DPOC, focando os fatores que influenciam a atividade física diária; a evolução da capacidade funcional e o estado de saúde 2 anos após um programa de RR e o papel da telemonitorização na quantificação e monitorização da atividade física. Confirmámos que os doentes com DPOC são marcadamente sedentários e os fatores que se associaram ao sedentarismo nestes doentes foram a dispneia e a distância percorrida na prova de marcha de seis minutos. Este estudo sublinha a importância do controlo sintomático, nomeadamente da dispneia, bem como, mais uma vez, o potencial papel da reabilitação respiratória no aumento da capacidade funcional para o exercício e na aquisição de hábitos de vida fisicamente ativa. Verificámos que, apesar de os doentes com DPOC apresentarem benefícios clinicamente significativos na capacidade funcional para o exercício e no estado geral de saúde com o programa de RR, apenas os que se mantêm ativos, podem, no final dos dois anos de seguimento, manter os efeitos benéficos desse programa. O sistema de telemonitorização que combina a oximetria e a quantificação da atividade física provou ser clinicamente útil na avaliação da necessidade de oxigenoterapia de longa duração (OLD) e na aferição do débito de oxigénio em repouso, no esforço e no sono, podendo contribuir para uma melhor adequação da prescrição da OLD. A monitorização dos níveis de atividade física regular é um importante instrumento de avaliação dos programas de RR e o seu uso potencial na telereabilitação permitirá prolongar a eficácia dos programas e reduzir os custos associados aos cuidados de saúde.---------------------------------------------------------------------------------------------------ABSTRACT: Pulmonary rehabilitation (PR) is a comprehensive interdisciplinary intervention that includes, but is not limited to, exercise training, education, and behavior change, individually designed to improve physical and psychological conditions of people with chronic respiratory disease and to promote long-term adherence to health-enhancing behaviors. Chronic obstructive pulmonary disease (COPD) is a common disease, affecting about 210 million people worldwide, with high mortality and significant health-related costs due to disease progression, hospitalizations and frequent hospital readmissions. Although the increasing knowledge about COPD and benefitial outcomes of PR, some aspects with impact in clinical practice, research and health authorities’ decisions, remain to be clarified. The first part of this thesis focused on COPD and its negative impact, including the study of COPD prevalence in Portugal; clinical and functional factors associated with mortality in advanced COPD patients; morbidity, functional impact and risk of others’ dependance to perform activities of daily living; and the role of systemic inflammation. The evidence of 14.2% estimated COPD prevalence as a common disease in Portugal raises the need of an increasing awareness of population, health care professionals and health authorities towards an earlier diagnosis and apropriate treatment resources allocation. High mortality in patients with advanced COPD – 36.6% in 3 years - was associated with respiratory failure, high frequency of exacerbations, lung cancer and a low functional capacity in walking. This highlightens the importance of an earlier referral to PR, comorbidity identification and treatment, and prevention of exacerbations. A questionnaire evaluated basic and instrumental activities of daily living, and identified a clinical marker of the risk of becoming dependent. This clinical marker complemented other functional evaluations and was associated with prognosis markers such as the number of exacerbations. In COPD patients with a mean FEV1 46.76% (SD 20.90%), 67% belonging to GOLD grade D, we found a positive association between inflammatory gene expression evaluated by polymerase chain reaction (IFNg, IL1b, IL6, IL8, TNFa, TGFb1, iNOS RNA messenger) and body mass index at rest, and a further increase with exercise. This study evidenced obesity as one potential link between COPD and systemic inflammation. The second part of this thesis focused PR, namely its outcomes in patients of GOLD categories A, B, C and D; comorbidities impact in PR outcomes, and the impact of different exercise training intensities in patient related outcomes. xviii With PR intervention, we found significant improvement in functional exercise capacity, endurance exercise capacity and health status in patients of all GOLD categories. This classification did not differentiate which patients would benefit more from PR, hence all symptomatic patients with a negative impact in health status should be referred to PR, regardless of the GOLD category they belong to. There is a high prevalence of comorbidities in COPD patients referred to PR, being cardiovascular, respiratory and psychological, the most prevalent. Although some comorbidities might reduce PR impact, the results were similar regardless of the number of comorbidities. Systematic comorbidities identification and treatment provides safety to PR intervention, and its good results should not preclude patients referral. With PR intervention we found a significant improvement in all patient reported outcomes for exercise training intensities at 60% and 80% maximum work rate (Wmax), namely in health status, symptoms and exercise capacity. These findings challenge the current systematic indication of high exercise training intensities to achieve PR short-term benefits. In the third and last part of the thesis, the role of physical activity in COPD was studied, focusing factors that may influence daily physical activity; the evolution of functional capacity and health status two years after a PR program, and the role of a telemonitoring system in physical activity quantification and monitoring. We confirmed that COPD patients are markedly inactive and factors associated with a sedentary lifestyle are dyspnea and 6 minute walking distance. This study emphasized the importance of symptom control, namely of dyspnea, as well as, once again, the potential role of PR in functional exercise improvement and in integrating physically active habits in daily life. We verified that, although COPD patients improve functional exercise capacity and health status after a PR program, only those who kept physical activity habits were able to maintain those effects after 2 years of follow-up. A telemonitoring system that combines oximetry and physical activity quantification proved to be clinically useful in the evaluation of long-term oxygen therapy (LTOT) indication, as well as in the titration of oxygen levels at rest, exertion, and sleeping, which might contribute to a more adequate LTOT prescription. Monitoring of daily physical activity levels is an important PR evaluation instrument and its potential use in telerehabilitation might allow lengthening programs efficacy, while reducing health-care costs.

Harvest control rule vs optimal harvesting of an age-structured population: The case of the Ibero-Atlantic Sardine Fishery

Research Masters

FPGA field oriented control of an axial flux motor-in-wheel

This paper presents the design and the prototype implementation of a three-phase power inverter developed to drive a motor-in-wheel. The control system is implemented in a FPGA (Field Programmable Gate Array) device. The paper describes the Field Oriented Control (FOC) algorithm and the Space Vector Modulation (SVM) technique that were implemented. The control platform uses a Spartan-3E FPGA board, programmed with Verilog language. Simulation and experimental results are presented to validate the developed system operation under different load conditions. Finally are presented conclusions based on the experimental results.

Field oriented control of an axial flux permanent magnet synchronous motor for traction solutions

Electric Vehicles (EVs) are increasingly used nowadays, and different powertrain solutions can be adopted. This paper describes the control system of an axial flux Permanent Magnet Synchronous Motor (PMSM) for EVs powertrain. It is described the implemented Field Oriented Control (FOC) algorithm and the Space Vector Modulation (SVM) technique. Also, the mathematical model of the PMSM is presented. Both, simulation and experimental, results with different types of mechanical load are presented. The experimental results were obtained using a laboratory test bench. The obtained results are discussed.

Predictive control of a current-source inverter for solar photovoltaic grid interface

Solar photovoltaic systems are an increasing option for electricity production, since they produce electrical energy from a clean renewable energy resource, and over the years, as a result of the research, their efficiency has been increasing. For the interface between the dc photovoltaic solar array and the ac electrical grid is necessary the use of an inverter (dc-ac converter), which should be optimized to extract the maximum power from the photovoltaic solar array. In this paper is presented a solution based on a current-source inverter (CSI) using continuous control set model predictive control (CCS-MPC). All the power circuits and respective control systems are described in detail along the paper and were tested and validated performing computer simulations. The paper shows the simulation results and are drawn several conclusions.

The residual effect of deltametrine in the control of Malaria as observed on fifferent types Of walls In the Brazilian Amazon 1

The residual power of deltametrine FW (25 mg 1 .a/m2) was evaluated and compared to that of DDT (2 g i.a./m2) by means of biological tests. The different kinds of material used in constructing houses in Amazonia, such as: masonry, wood, and wattle and daub, were used. Data from logistic regression showed that the drop in mortality, the inclination of the curve in relation to time, was similar for the two insecticides in the first samples. The negative coeficient for the variable, months after application, confirmed a reduction in the activity of both insecticides. Wooden and wattle walls showed positive and negative coeficiencies respectively from the beginning. The wooden walls retained a residual effect but the wattle walls were shown to be the least indicated for the application of insecticides The experiments demonstrated a more prolonged residual effect for deltametrine as compared to DDT, and that insecticides work better on brick and cement and wooden walls than they do on wattle and daub constructions. For these reasons, it would be necessary to spray brick and cement walls every 8 months, wooden ones every 9 months and wattle constructions every 7 months to control the vectors of malaria.

Vision-based hand Wheel-chair control

Several studies have shown that people with disabilities benefit substantially from access to a means of independent mobility and assistive technology. Researchers are using technology originally developed for mobile robots to create easier to use wheelchairs. With this kind of technology people with disabilities can gain a degree of independence in performing daily life activities. In this work a computer vision system is presented, able to drive a wheelchair with a minimum number of finger commands. The user hand is detected and segmented with the use of a kinect camera, and fingertips are extracted from depth information, and used as wheelchair commands.

Geological control of Podocnemis expansa and Podocnemis unifilis nesting areas in Rio Javaés, Bananal Island, Brazil

The distribution of the nests of Podocnemis expansa (Amazon turtle) and Podocnemis unifilis (yellow-spotted side neck turtle) along the point bars of the Javaés River in Bananal Island, demonstrates a clear preference of these chelonians for differentiated geological environments, in respect to the morphology, grain size or height of the nests in relation to the level of the river. The topographical distribution and the differences in the grain size of the sediments that compose the point bars of the river, originated from the multiple sedimentary processes, and make possible the creation and separation of different nesting environments. Each turtle species takes advantage of the place that presents physiographic characteristics appropriate to the hatching success of their eggs. The superposition of the P. expansa and P. unifilis nest placement areas is rare. The P. expansa nests are concentrated on the central portion of the beaches where successive depositional sedimentary events produced sandy banks more than 3.3 m above the river water level. The P. unifilis nests are distributed preferentially in the upstream and downstream portions along the point bars where the sandy deposits rarely surpass 1.5 m at the moment of laying. P. expansa nests located on the beaches of fine to medium sized sand hatch in a mean of 68 days, while those incubated on beaches of medium to coarse sand size take a mean of 54 days to hatch.

Towards effective control of P2P traffic aggregates in network infrastructures

Nowadays, many P2P applications proliferate in the Internet. The attractiveness of many of these systems relies on the collaborative approach used to exchange large resources without the dependence and associated constraints of centralized approaches where a single server is responsible to handle all the requests from the clients. As consequence, some P2P systems are also interesting and cost-effective approaches to be adopted by content-providers and other Internet players. However, there are several coexistence problems between P2P applications and In- ternet Service Providers (ISPs) due to the unforeseeable behavior of P2P traffic aggregates in ISP infrastructures. In this context, this work proposes a collaborative P2P/ISP system able to underpin the development of novel Traffic Engi- neering (TE) mechanisms contributing for a better coexistence between P2P applications and ISPs. Using the devised system, two TE methods are described being able to estimate and control the impact of P2P traffic aggregates on the ISP network links. One of the TE methods allows that ISP administrators are able to foresee the expected impact that a given P2P swarm will have in the underlying network infrastructure. The other TE method enables the definition of ISP friendly P2P topologies, where specific network links are protected from P2P traffic. As result, the proposed system and associated mechanisms will contribute for improved ISP resource management tasks and to foster the deployment of innovative ISP-friendly systems.

Fuzzy maintenance costs of a wind turbine pitch control device

This paper deals with the problem of estimation maintenance costs for the case of the pitch controls system of wind farms turbines. Previous investigations have estimated these costs as (traditional) “crisp” values, simply ignoring the uncertainty nature of data and information available. This paper purposes an extended version of the estimation model by making use of the Fuzzy Set Theory. The results alert decision-makers to consequent uncertainty of the estimations along with their overall level, thus improving the information given to the mainte-nance support system.