Establishing a high titer transient gene expression process in conditioned media for CHO-DG44 cells

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Enterococcus and biocides: mechanisms of tolerance and selection for vancomycin resistance

Dissertation presented to obtain a Doctoral degree in Biology, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa.

An approach for automated service selection and ranking using services choreography

In today’s highly competitive market, it is critical to provide customers services with a high level of configuration to answer their business needs. Knowing in advance the performance associated with a specific choreography of services (e.g., by taking into account the expected results of each component service) represents an important asset that allows businesses to provide a global service tailored to customers’ specific requests. This research work aims at advancing the state-of-the-art in this area by proposing an approach for service selection and ranking using services choreography, predicting the behavior of the services considering customers’ requirements and preferences, business process constraints and characteristics of the execution environment.

Criteria for the selection of foster families and monitoring of placements.: Comparative study of the application of the Casey Foster Applicant Inventory-Applicant Version (CFAI-A)

Based on a literature review, this article frames different stages of the foster care process, identifying a set of standardized measures in the American and Portuguese contexts which, if implemented, could contribute towards higher levels of foster success. The article continues with the presentation of a comparative study, based on the application of the Casey Foster Applicant Inventory-Applicant Version (CFAI-A) questionnaire, in the aforementioned contexts. Taking a comparative analyses of CFAI-A's psychometric characteristics in four different samples as a starting point, one discovered that despite the fact that the questionnaire was adapted to Portuguese reality, it kept the quality values presented on the American samples. It specifically shows significant values regarding reliability and validity. This questionnaire, which aims to assess the potential of foster families, also supports the technical staff's decision making process regarding the monitoring and support of foster families, while it also promotes a better decision in the placement process towards the child's integration and development.

Calcificações vasculares nos doentes em diálise : elo de ligação entre doença óssea e doença vascular

RESUMO: A presente dissertação para tese de doutoramento apresenta o desenvolvimento e a validação de um método simples e original para o diagnóstico de calcificações vasculares em doentes em diálise, utilizando um score semiquantitativo criado por nós e obtido em RX simples da bacia e das mãos, denominado score de calcifi cação vascular simples. Demonstramos que este score vascular simples é preditor de risco cardiovascular nos doentes em diálise. O score de calcificação vascular simples associou-se ainda à baixa densidade mineral óssea avaliada por dual energy X -ray absortiometry (DXA) no colo do fémur. Verifi camos igualmente que, em doentes em diálise, as calcifi cações coronárias quantifi cadas pelo score de Agatston e o score de calcifi cação vascular simples se associaram a um menor volume ósseo avaliado em biopsias ósseas. Estes trabalhos corroboram a hipótese da existência de um elo de ligação entre a doença óssea e a doença vascular nos doentes em diálise, e um dos elementos que contribuem para este elo de ligação podem ser as calcificações vasculares. Este score de calcificação vascular simples avalia calcifi cações em artérias de grande, médio e pequeno calibre, e inclui os dois padrões radiológicos de calcificação: calcificação linear, associada à calcifi cação da camada média da parede arterial, e calcificação irregular, associada à calcifi cação da camada íntima arterial1. Nos diferentes trabalhos por nós publicados demonstramos que as calcificações vasculares avaliadas por este método simples e barato permitem a identificação de indivíduos com elevado risco cardiovascular. Este score vascular associa -se a maior risco de mortalidade cardiovascular2, de mortalidade de causa global3, de internamentos cardiovasculares2, de doença ardiovascular2, de doença arterial periférica2,4,de calcifi cações valvulares5 e de rigidez arterial3. As guidelines KDIGO (Kidney disease: improving global outcomes), publicadas em 2009,sugerem que os doentes renais crónicos nos estadios 3 a 5, com calcificações vasculares e valvulares, devem ser considerados como apresentando o mais elevado risco cardiovascular6. A elevada mortalidade dos doentes renais crónicos não é totalmente explicada pelos fatores de risco tradicionais7. A organização KDIGO defende, desde 2006, a hipótese da existência de um elo de ligação entre a doença óssea e a doença vascular8. Esta ligação pode ser explicada pelas alterações do metabolismo mineral e ósseo e pela sua interação com as calcificações vasculares. Verificamos, nos nossos trabalhos, uma associação entre calcifi cações vasculares e doença óssea. O baixo volume ósseo diagnosticado por análise histomorfométrica de biopsias ósseas foi preditor de maior risco de calcificações vasculares avaliadas pelo score de calcifi cação vascular simples (dados apresentados nesta dissertação, no capítulo 6) e pelo score coronário de Agatston num grupo de doentes em diálise9. A contribuição original deste artigo9 foi considerada merecedora de um editorial feito pelo Dr. Gérard London10, investigador líder na área da calcificação vascular dos doentes renais crónicos e actual Presidente da EDTA (European Dialysis and Transplantation Association). Fomos também os primeiros a descrever uma associação independente e inversa entre a densidade mineral avaliada no colo do fémur por DXA (dual energy X -ray absortiometry) com calcificações vasculares avaliadas pelo score de calcificação vascular simples, com rigidez arterial avaliada por velocidade de onda de pulsocarotidofemoral e com doença arterial periférica diagnosticada por critérios clínicos11. Fomos igualmente os primeiros a mostrar uma correlação signifi cativa entre a densidade mineral óssea avaliada por DXA no colo do fémur, mas não na coluna lombar, com a espessura cortical avaliada por análise histomorfométrica em biopsia óssea12. O nosso estudo atribui pela primeira vez à DXA um papel no diagnóstico de porosidade cortical nos doentes em diálise. A utilidade da avaliação diferencial da densidade mineral óssea cortical e trabecular necessita ainda de ser confirmada em estudos prospectivos. Este achado inovador do nosso estudo foi mencionado pela ERBP (European Renal Best Practice) no comentário feito à posição da KDIGO que considera ser reduzida a utilidade da densidade mineral óssea nos doentes em diálise13. Dois dos trabalhos incluídos nesta dissertação foram referenciados nas guidelines KDIGO 2009 para avaliar a prevalência das calcificações vasculares (KDIGO 2009: Tabela suplementar 10, Fig. 3.6) e para validar a associação entre calcificações vasculares e mortalidade cardiovascular (KDIGO 2009: Tabela suplementar 12, Fig. 3.7)6. A inclusão destes nossos dois estudos nas referências destas guidelines, que utilizaram o exigente sistema GRADE (Grades of recommendation, assessment, development, and evaluation) na classificação e selecção dos estudos, valida o interesse científico dos nossos trabalhos. O diagnóstico de calcificações vasculares tem um interesse prático para os doentes renais crónicos. A presença de calcifi cações vasculares é um sinal de alerta para a existência de um elevado risco cardiovascular, e esta informação pode ser utilizada para modificar a terapêutica nestes doentes6. Diferentes métodos podem ser usados para diagnosticar calcificações vasculares nos doentes em diálise14,15. O score de calcificação vascular simples tem a vantagem da simplicidade e de poder ser facilmente interpretado pelo nefrologista, sem necessidade de um radiologista. A reprodutibilidade deste score já foi demonstrada por diferentes grupos em estudos nacionais e internacionais16-24. Nestes estudos foi demonstrado que as calcifi cações vasculares avaliadas pelo método criado por nós são preditoras de maior risco de eventos cardiovasculares16, de amputações dos membros inferiores17, de velocidade de onda de pulso18,19, de calcificações corneanas e conjuntivais20 e de calcifi cações coronárias21. Também foi demonstrada uma associação inversa entre o score de calcificação vascular simples com os níveis séricos de PTH21, com os níveis de 25(OH)vitamina D 22,23 e com os níveis de fetuína A19,24. Todos estes estudos, realizados por diferentes grupos, que utilizaram o score de calcificação vascular simples na sua metodologia, comprovam a facilidade de utilização deste score e a concordância de resultados atestam a sua reprodutibilidade e a utilidade na avaliação dos doentes renais crónicos. ---------------------------ABSTRACT: This thesis presents the development and validation of a simple and original method to identify vascular calcifications in dialysis patients, using a semi -quantitative score that we have created and that is obtained in plain X -ray of pelvis and hands. This score was named in different publications as “simple vascular calcifi cation score”. We have demonstrated that this score is a predictor of higher cardiovascular risk in dialysis patients. The simple vascular calcification score was also associated with lower mineral bone density evaluated by DXA in femoral neck. In hemodialysis patients coronary calcifications evaluated by the coronary Agatston score and by the simple vascular calcification score were associated with lower bone volume analysed in bone biopsies. These studies corroborate the hypothesis of the existence of a link between bone disease and vascular disease in dialysis patients and one of the elements of this link may be vascular calcifications. This simple vascular calcification score identifi es calcifications in large, medium and small calibre arteries and includes the two radiological patterns of arterial calcifi cation: linear calcification which has been associated with the calcifi cation of the media layer of the arterial wall and irregular and patchy calcification which has been associated with the calcifi cation of the intima layer of the arterial wall1. In the several studies that we have published we have demonstrated that vascular calcifications evaluated by this simple and inexpensive method allow the identification of patients with high cardiovascular risk. This simple vascular calcification score is an independent predictor of cardiovascular mortality2, all -cause mortality3, cardiovascular hospitalizations2, cardiovascular disease2, peripheral artery disease2,4, valvular calcifi cations5 and arterial stiffness3.KDIGO (Kidney Disease: Improving Global Outcomes) guidelines published in 2009 suggest that chronic kidney disease patients in stages 3 to 5, with vascular and valvular calcifications should be considered to be at the highest cardiovascular risk6. The high mortality of chronic kidney disease patients is not completely explained by the traditional risk factors7 and KDIGO group supports, since 2006, the hypothesis of the existence of a link between bone disease and vascular disease8.This link may be explained by the alterations of the bone and mineral metabolism and their interaction with development and progression of vascular calcifications. We have also verifi ed in our studies the existence of an association between vascular calcifications and bone disease. Low bone volume diagnosed by histomorphometric analysis of bone biopsies, in a group of dialysis patients, was independently associated with the simple vascular calcification score (data presented in this thesis,chapter 6) and with coronary calcifications evaluated by the Agatston score9. The original contribution of this article published in CJASN9 deserved a commentary in an Editorial written by Prof. Gérard London10 leader investigator in this area and current EDTA (European Dialysis and Transplantation Association) President. We were also the fi rst group to describe an independent and inverse association between bone mineral density evaluated in the femoral neck by DXA (dual energy X -ray absortiometry) with vascular calcifications evaluated by the simple vascular calcification score, with arterial stiffness evaluated by carotid-femoral pulse wave velocity and with peripheral artery disease diagnosed by clinical criteria11. We were also the first group to demonstrate a significant correlation between bone mineral density evaluated by DXA in femoral neck but not in lumbar spine, with cortical thickness evaluated by histomorphometric analysis of bone biopsy12. Our study has attributed to DXA, for the first time, a role in the diagnosis of cortical porosity in dialysis patients. The clinical utility of the differential evaluation of bone mineral density in cortical or trabecular bone needs, however, to be confi rmed in prospective studies. This original fi nding of our study was mentioned by ERBP (European Renal Best Practice) commenting the KDIGO position in relation with the reduced utility of bone mineral density evaluation in dialysis patients13. Two of the studies included in this thesis have been integrated in a group of studies selected as references by the KDIGO guidelines published in 2009 to evaluate the prevalence of vascular calcifications in CKD patients (KDIGO 2009: Supplementary Table 10, Fig. 3.6) and to corroborate the association between vascular calcifications and cardiovascular mortality (KDIGO 2009: Supplementary Table 12, Fig. 3.7)6. The inclusion of both studies as references in the KDIGO guidelines that have used the exigent GRADE system (Grades of Recommendation, Assessment, Development, and Evaluation) in the classifi cation and selection of studies, validates the scientifi c value of our studies. The diagnosis of vascular calcifi cations has a practical interest for chronic kidney disease patients. The presence of vascular calcifications is an alert sign to the existence of a high cardiovascular risk and this information may be used to modify the treatment of these patients6. Different methods may be used to detect the presence of vascular calcifications in dialysis patients14,15. The simple vascular calcifi cation score has the advantage of being simple, inexpensive and easily evaluated by the Nephrologist without the need for a Radiologist interpretation. The reproducibility of this method has already been demonstrated by other groups in national and international studies16 -24. It was demonstrated in those studies that vascular calcifi cations evaluated by the method created by us, predict higher risk of cardiovascular events16, higher risk of lower limbs amputations17, higher pulse wave velocity18,19, corneal and conjuntival calcifi cations 20 and coronary calcifi cations21. A negative association between the simple vascular calcification score and PTH levels21, 25(OH) vitamin D levels22,23 and Fetuin A levels19,24 has also been demonstrated. All these studies performed by different groups that have used the simple vascular calcifi cation score in their methods demonstrate that this score is simple, useful and reproducible in the evaluation of chronic kidney disease patients simple, useful and reproducible in the evaluation of chronic kidney disease patients.

Recommending media content based on machine learning methods

Dissertação para obtenção do Grau de Mestre em Engenharia Informática

Selection Constructive based Hyper-heuristic for Dynamic Scheduling

A função de escalonamento desempenha um papel importante nos sistemas de produção. Os sistemas de escalonamento têm como objetivo gerar um plano de escalonamento que permite gerir de uma forma eficiente um conjunto de tarefas que necessitam de ser executadas no mesmo período de tempo pelos mesmos recursos. Contudo, adaptação dinâmica e otimização é uma necessidade crítica em sistemas de escalonamento, uma vez que as organizações de produção têm uma natureza dinâmica. Nestas organizações ocorrem distúrbios nas condições requisitos de trabalho regularmente e de forma inesperada. Alguns exemplos destes distúrbios são: surgimento de uma nova tarefa, cancelamento de uma tarefa, alteração na data de entrega, entre outros. Estes eventos dinâmicos devem ser tidos em conta, uma vez que podem influenciar o plano criado, tornando-o ineficiente. Portanto, ambientes de produção necessitam de resposta imediata para estes eventos, usando um método de reescalonamento em tempo real, para minimizar o efeito destes eventos dinâmicos no sistema de produção. Deste modo, os sistemas de escalonamento devem de uma forma automática e inteligente, ser capazes de adaptar o plano de escalonamento que a organização está a seguir aos eventos inesperados em tempo real. Esta dissertação aborda o problema de incorporar novas tarefas num plano de escalonamento já existente. Deste modo, é proposta uma abordagem de otimização – Hiper-heurística baseada em Seleção Construtiva para Escalonamento Dinâmico- para lidar com eventos dinâmicos que podem ocorrer num ambiente de produção, a fim de manter o plano de escalonamento, o mais robusto possível. Esta abordagem é inspirada em computação evolutiva e hiper-heurísticas. Do estudo computacional realizado foi possível concluir que o uso da hiper-heurística de seleção construtiva pode ser vantajoso na resolução de problemas de otimização de adaptação dinâmica.

Social Media Integration in Video Games: A Social Overlay for Desktop Games

Simpósio de Informática (INForum 2015), Covilhã, Portugal. Notes: Best paper award nominee.

Distributed Linear Precoding and User Selection in Coordinated Multicell Systems

In this manuscript we tackle the problem of semidistributed user selection with distributed linear precoding for sum rate maximization in multiuser multicell systems. A set of adjacent base stations (BS) form a cluster in order to perform coordinated transmission to cell-edge users, and coordination is carried out through a central processing unit (CU). However, the message exchange between BSs and the CU is limited to scheduling control signaling and no user data or channel state information (CSI) exchange is allowed. In the considered multicell coordinated approach, each BS has its own set of cell-edge users and transmits only to one intended user while interference to non-intended users at other BSs is suppressed by signal steering (precoding). We use two distributed linear precoding schemes, Distributed Zero Forcing (DZF) and Distributed Virtual Signalto-Interference-plus-Noise Ratio (DVSINR). Considering multiple users per cell and the backhaul limitations, the BSs rely on local CSI to solve the user selection problem. First we investigate how the signal-to-noise-ratio (SNR) regime and the number of antennas at the BSs impact the effective channel gain (the magnitude of the channels after precoding) and its relationship with multiuser diversity. Considering that user selection must be based on the type of implemented precoding, we develop metrics of compatibility (estimations of the effective channel gains) that can be computed from local CSI at each BS and reported to the CU for scheduling decisions. Based on such metrics, we design user selection algorithms that can find a set of users that potentially maximizes the sum rate. Numerical results show the effectiveness of the proposed metrics and algorithms for different configurations of users and antennas at the base stations.

L'"errore di erode" e la media in Giovanni da Parigi

pp. 169-184

Gait Selection for Quadruped Legged Robots

This paper studies periodic gaits of quadruped locomotion systems. The purpose is to determine the best set of gait and locomotion variables for different robot velocities based on the system dynamics during walking. In this perspective, several performance measures are formulated and a set of experiments reveals the influence of the gait and locomotion variables upon those proposed indices. The results show that the locomotion parameters (β, LS and HB) should be adapted to the walking velocity in order to optimize the robot performance. Furthermore, for the case of a quadruped robot, we concluded that the gait should be adapted to VF .

Ex-ante evaluation by the media of the Guimarães 2012 European Capital of Culture

The nomination of Guimarães to host the 2012 European Capital of Culture (ECC) has put on the agenda of the city the need of measuring the effects that the implementation of this mega event could have in it and in the municipality a whole. The balance of the benefits and costs and an extended community involvement tend to reduce negative impacts and enhance positive ones. This chapter analyzes the involvement of population and local associations in the planning and organization of the 2012 Guimarães European Capital of Culture, using the coverage made during 2011 by local and national press of the mega event. A content analysis of the news published covering the period between January and December 2011 and using three newspapers was conducted. From those, two were local and weekly newspapers and one was a national daily one. Looking to data results, it can be concluded that it was poor the community involvement and, also, the one of the cultural associations in the organizations of the 2012 ECC. A strong negative reaction to the model choose to plan the mega event conducted by official organizers was found, which has cast doubts on the desirable participation of the residents and, consequently, on the success of the mega event, especially in a perspective of a medium and long term effects.

Comparison among tomato juice agar with other three media for differentiation of Candida dubliniensis from Candida albicans

The purpose of the present study is to compare the tomato juice agar, a well known medium employed to observe ascospore formation, with niger seed agar, casein agar and sunflower seed agar, applied to a differentiation between C. dubliniensis and C. albicans. After 48 hours of incubation at 30 ºC all 26 (100%) C. dubliniensis isolates tested produced chlamydospores on tomato juice agar as well as in the other three media evaluated. However, when we inoculated all media with C. albicans, the absence of chlamydospores became resulting in the following percents: tomato juice agar (92.47%), niger seed agar (96.7%), casein agar (91.39%), and sunflower seed agar (96.7%). These results indicate that tomato juice agar is another medium which can also be used in the first phenotypic differentiation between C. dubliniensis and C. albicans.

The Media Online and the Climate Change

Dissertação apresentada para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Novos Media e Práticas Web

Complementaridade da publicidade nos media tradicionais e o marketing online

Trabalho de Projecto apresentado para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Novos Media e Práticas Web