Computational design with flexible backbone sampling for protein remodeling and scaffolding of complex binding sites

Dissertation presented to obtain the Doutoramento (Ph.D.) degree in Biochemistry at the Instituto de Tecnologia Qu mica e Biol ogica da Universidade Nova de Lisboa

From the Lisbon strategy to EU2020: illusion or progress for european economies?

To be published at Krings, Bettina-J. ed. (2011), Brain Drain or Brain Gain? Changes of Work in Knowledge-based Societies, Berlin, Ed. Sigma. The author wants to thanks the comments and suggestions from Bettina Krings and Sylke Wintzer. They are not, however, responsible for the final result.

A go-to-market strategy for vertebral metrics

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

Real-Time Application Mapping for Many-Cores Using a Limited Migrative Model

Many-core platforms are an emerging technology in the real-time embedded domain. These devices offer various options for power savings, cost reductions and contribute to the overall system flexibility, however, issues such as unpredictability, scalability and analysis pessimism are serious challenges to their integration into the aforementioned area. The focus of this work is on many-core platforms using a limited migrative model (LMM). LMM is an approach based on the fundamental concepts of the multi-kernel paradigm, which is a promising step towards scalable and predictable many-cores. In this work, we formulate the problem of real-time application mapping on a many-core platform using LMM, and propose a three-stage method to solve it. An extended version of the existing analysis is used to assure that derived mappings (i) guarantee the fulfilment of timing constraints posed on worst-case communication delays of individual applications, and (ii) provide an environment to perform load balancing for e.g. energy/thermal management, fault tolerance and/or performance reasons.

Backside-surface imprinting as a new strategy to generate specific plastic antibody materials

A backside protein-surface imprinting process is presented herein as a novel way to generate specific synthetic antibody materials. The template is covalently bonded to a carboxylated-PVC supporting film previously cast on gold, let to interact with charged monomers and surrounded next by another thick polymer. This polymer is then covalently attached to a transducing element and the backside of this structure (supporting film plus template) is removed as a regular “tape”. The new sensing layer is exposed after the full template removal, showing a high density of re-binding positions, as evidenced by SEM. To ensure that the templates have been efficiently removed, this re-binding layer was cleaned further with a proteolytic enzyme and solution washout. The final material was named MAPS, as in the back-side reading of SPAM, because it acts as a back-side imprinting of this recent approach. It was able to generate, for the first time, a specific response to a complex biomolecule from a synthetic material. Non-imprinted materials (NIMs) were also produced as blank and were used as a control of the imprinting process. All chemical modifications were followed by electrochemical techniques. This was done on a supporting film and transducing element of both MAPS and NIM. Only the MAPS-based device responded to oxLDL and the sensing layer was insensitive to other serum proteins, such as myoglobin and haemoglobin. Linear behaviour between log(C, μg mL−1) versus charged tranfer resistance (RCT, Ω) was observed by electrochemical impedance spectroscopy (EIS). Calibrations made in Fetal Calf Serum (FCS) were linear from 2.5 to 12.5 μg mL−1 (RCT = 946.12 × log C + 1590.7) with an R-squared of 0.9966. Overall, these were promising results towards the design of materials acting close to the natural antibodies and applied to practical use of clinical interest.

Echinococcosis in southern Brazil: efforts toward implementation of a control program in Santana do Livramento, Rio Grande do Sul

This investigation aimed to design a strategy for echinococcosis control in Santana do Livramento county, an endemic area in state of Rio Grande do Sul (Brazil). Fecal samples from 65 dogs were obtained from urban, suburban and rural areas. Purging with Arecoline Bromhidrate (AB) was done to visualize Echinococcus granulosus, and Enzyme Linked Immunosorbent Assay (ELISA) was performed to detect parasite coproantigen. Samples were obtained at the beginning and at the end of treatment with Praziquantel. A third fecal sampling was also done in rural areas four months after the end of treatment. Each dog was treated immediately after the first purging and every 30 days for eight months. In urban and suburban areas no infected dogs were found. In rural areas, first evaluation showed 11.36% and 27.69% of infected dogs by AB and ELISA, respectively. No infected dogs were diagnosed in the second evaluation and in the third evaluation 36.84% and 47.37% infected dogs were identified by AB and ELISA, respectively. Medication program to combat dog infection resulted in successful interruption of parasite transmission, but the project failed to create awareness of the need for dog prophylaxis among rural populations as well as to establish a permanent control program in this municipality.

Is mental practice an effective adjunct therapeutic strategy for upper limb motor restoration after stroke? A systematic review and meta- analysis

Stroke is one of the most common conditions requiring rehabilitation, and its motor impairments are a major cause of permanent disability. Hemiparesis is observed by 80% of the patients after acute stroke. Neuroimaging studies showed that real and imagined movements have similarities regarding brain activation, supplying evidence that those similarities are based on the same process. Within this context, the combination of mental practice (MP) with physical and occupational therapy appears to be a natural complement based on neurorehabilitation concepts. Our study seeks to investigate if MP for stroke rehabilitation of upper limbs is an effective adjunct therapy. PubMed (Medline), ISI knowledge (Institute for Scientific Information) and SciELO (Scientific Electronic Library) were terminated on 20 February 2015. Data were collected on variables as follows: sample size, type of supervision, configuration of mental practice, setting the physical practice (intensity, number of sets and repetitions, duration of contractions, rest interval between sets, weekly and total duration), measures of sensorimotor deficits used in the main studies and significant results. Random effects models were used that take into account the variance within and between studies. Seven articles were selected. As there was no statistically significant difference between the two groups (MP vs control), showed a - 0.6 (95% CI: -1.27 to 0.04), for upper limb motor restoration after stroke. The present meta-analysis concluded that MP is not effective as adjunct therapeutic strategy for upper limb motor restoration after stroke.

Waste collection routing-limited multiple landfills and heterogeneous fleet

This article deals with a real-life waste collection routing problem. To efficiently plan waste collection, large municipalities may be partitioned into convenient sectors and only then can routing problems be solved in each sector. Three diverse situations are described, resulting in three different new models. In the first situation, there is a single point of waste disposal from where the vehicles depart and to where they return. The vehicle fleet comprises three types of collection vehicles. In the second, the garage does not match any of the points of disposal. The vehicle is unique and the points of disposal (landfills or transfer stations) may have limitations in terms of the number of visits per day. In the third situation, disposal points are multiple (they do not coincide with the garage), they are limited in the number of visits, and the fleet is composed of two types of vehicles. Computational results based not only on instances adapted from the literature but also on real cases are presented and analyzed. In particular, the results also show the effectiveness of combining sectorization and routing to solve waste collection problems.

PIASA: A power and interference aware resource management strategy for heterogeneous workloads in cloud data centers

Cloud data centers have been progressively adopted in different scenarios, as reflected in the execution of heterogeneous applications with diverse workloads and diverse quality of service (QoS) requirements. Virtual machine (VM) technology eases resource management in physical servers and helps cloud providers achieve goals such as optimization of energy consumption. However, the performance of an application running inside a VM is not guaranteed due to the interference among co-hosted workloads sharing the same physical resources. Moreover, the different types of co-hosted applications with diverse QoS requirements as well as the dynamic behavior of the cloud makes efficient provisioning of resources even more difficult and a challenging problem in cloud data centers. In this paper, we address the problem of resource allocation within a data center that runs different types of application workloads, particularly CPU- and network-intensive applications. To address these challenges, we propose an interference- and power-aware management mechanism that combines a performance deviation estimator and a scheduling algorithm to guide the resource allocation in virtualized environments. We conduct simulations by injecting synthetic workloads whose characteristics follow the last version of the Google Cloud tracelogs. The results indicate that our performance-enforcing strategy is able to fulfill contracted SLAs of real-world environments while reducing energy costs by as much as 21%.

Confined Placental Mosaicism in Chorionic Vilus Sampling - Case Report

Objectives: Chorionic Vilus Sampling (CVS) has several advantages over amniocentesis: it may be performed at an earlier gestational age, the results are quicker to obtain and there’s a lower miscarriage risk – 1%. However, the higher prevalence of discrepant fetal and vilus sampling material’s karyotype findings is a disadvantage of this technique – 0.5%. This is caused, amongst other causes, by placental mosaicism which consists of two genetically different cell lines. There are three types of placental mosaicism according to the abnormal cell line location: Type I – in the cytotrophoblast; Type II – in the vilus’ stroma; Type III – in both the above locations. Material and Methods: We present a case report about a 36-year-old pregnant woman going through our Department’s 1st trimester combined screening program; a CVS was performed, which showed Confined Placental Mosaicism (CPM). Results and Conclusion: Although the pregnant woman was in the low-risk group for aneuploidy, the patient wanted the cytogenetic study to be performed in order to reduce maternal anxiety. CVS was performed at the gestational age of 12 weeks + 5 days and the karyotype was 47XY+2/46XY. For the correct interpretation of this data an amniocentesis was performed at the gestational age of 15 weeks + 6 days, which showed a 46XY karyotype. We therefore conclude that the cytogenetic analysis of the CVS was the result of a CPM. A careful follow-up including fetal echocardiogram and seriated ultrasonographic monitoring was used to safely exclude malformations and fetal growth restriction. We verified no occurences throughout pregnancy, delivery and perinatal period. CVS practice was recently implemented in our country and has many advantages over amniocentesis. Besides the fact that an earlier gestational age usually means less affective bonding to the fetus and therefore makes medical termination of pregnancy somewhat less difficult, one should consider specific situations like the one reported in which CPM may be diagnosed. This condition is associated with increased risk of fetal growth restriction, so the clinician should be aware of the need for a more careful follow-up, since perinatal complications, which should be anticipated and treated, can be expected in 16-21% of these cases.

A implementação de um programa de tutoria de pares na construção de textos narrativos em alunos do 4.º ano, com e sem Necessidades Adicionais de Suporte

O presente estudo teve como finalidade avaliar a implementação da estratégia de tutoria de pares (TP), em sala de aula, na construção de textos narrativos, em alunos com e sem Necessidades Adicionais de Suporte (NAS). Foi realizado com um grupo de 24 alunos do 4º ano de escolaridade, numa instituição do Porto, Portugal. Desenvolveram-se oito intervenções, sendo a primeira o pré-teste (texto escrito sem a estratégia de TP), a segunda a apresentação da TP e as restantes de implementação da estratégia (intervenção I e II e pós-teste). Os alunos foram agrupados em pares e ambos tiveram os papéis de tutor e de tutorado. As questões que orientaram o estudo foram: Em contexto de sala de aula, a estratégia de tutoria de pares melhora a escrita de textos narrativos?, A estratégia de tutoria de pares promove a inclusão? e A estratégia de tutoria de pares é um instrumento exequível em sala de aula? Os resultados demonstraram que a estratégia é motivadora para os alunos e promove interações positivas entre eles. O aluno Alvo (com NAS) obteve resultados positivos tanto na melhoria da escrita de textos como no aumento do sentido de pertença às atividades da turma. Para além disso, a estratégia mostrou-se exequível em contexto escolar. Compreendemos que as sessões foram escassas para aferir se a estratégia de TP foi eficaz na consistente melhoria da escrita de textos. Torna-se, por isso, importante que mais estudos se realizem neste domínio em Portugal, de modo a consolidar as conclusões desta estratégia.

Um sistema de informação – a solução?

Pequenas empresas reconhecem a necessidade de sistematizar os seus procedimentos, por forma, a alcançarem sucesso nas suas propostas de negócio. Esta padronização pressupõe uma avaliação do enquadramento social e de mercado existente e dos valores, missão e objetivos das próprias empresas. As constantes inovações na área tecnológica e as mudanças sociais, refletem-se no desenvolvimento e estratégia a seguir pelas organizações, que se desdobram num ambiente muito competitivo e dinâmico, o que lhes exige uma atenção constante e ponderada. Ao analisarmos uma micro empresa portuguesa, que desenvolve a sua atividade na área da gestão e promoção de imóveis para arrendamento de curta duração, verificamos a existência de lacunas ao nível do seu modelo de gestão operacional. A escassez de meios financeiros e humanos, e o fraco conhecimento das práticas de gestão organizacional e estratégica, são fatores limitadores para o bom desempenho da empresa, podendo colocar em causa a sua viabilidade a curto prazo. Esta constatação foi o ponto de partida para a realização deste projeto que, após as diversas leituras efetuadas, o levantamento dos processos existentes, a análise e ponderação das diversas soluções possíveis a aplicar, terminou na proposta de um Sistema de Informação - opção que nos pareceu ser a mais adequada. Esta proposta foi aprovada pela gestão da empresa e o Sistema de Informação irá ser implementado. O presente trabalho teve como objetivo ajudar esta organização a melhorar o seu desempenho. Para atingir estes objetivos foi necessário elencar os pontos fortes e fracos desta empresa, de forma a ser possível agregar num documento, as necessidades que a mesma demonstrava, para colmatar as falhas existentes e que poderiam ser, num futuro próximo, motivo de desagregação da mesma. A metodologia adotada seguiu uma estratégia de investigação descritiva, utilizando o método de investigação-ação. A recolha de dados baseou-se em entrevistas à equipa de gestão e colaboradores da empresa, em documentação levantada na mesma relativa aos processos de gestão e informação institucional, cujos conteúdos foram analisados numa perspetiva qualitativa.

Designing a vaccination strategy against dengue

In this work we propose a mathematical approach to estimate the dengue force of infection, the average age of dengue first infection, the optimum age to vaccinate children against dengue in a routine fashion and the optimum age interval to introduce the dengue vaccine in a mass vaccination campaign. The model is based on previously published models for vaccination against other childhood infections, which resulted in actual vaccination programmes in Brazil. The model was applied for three areas of distinct levels of endemicity of the city of Recife in Northeastern State of Pernambuco, Brazil. Our results point to an optimal age to introduce the dengue vaccine in the routine immunization programme at two years of age and an age interval to introduce a mass vaccination between three and 14 years of age.

A go-to-market strategy for green extration and impregnation

Dissertação para obtenção do Grau de Mestre em Biotecnologia