Biomaterials for cartilage tissue engineering under mechanical stimulus

Tese de Doutoramento em Ciências (Especialidade de Física)

Development of a model for occupational risk acceptance criteria definition in industrial settings

Doctoral Dissertation for PhD degree in Industrial and Systems Engineering

O currículo da formação em engenharia no âmbito do processo de bolonha: desenvolvimento de competências e perfil profissional na perspetiva dos docentes, dos estudantes e dos profissionais

Tese de Doutoramento em Ciências da Educação (área de especilização em Desenvolvimento Curricular).

Pervasive business intelligence: a marketing intelligence framework proposal

Doctoral Thesis in Information Systems and Technologies Area of Information Systems and Technology

Sucesso escolar e percursos vocacionais na adolescência: variáveis pessoais e contextuais

Tese de Doutoramento Ciências da Educação (Especialidade em Psicologia da Educação)

On trust, knowledge, sharing and innovation

Organisations continuously innovate, create, and are competitive if they improve their performance through continuous intellectual capital development, a key resource for value creation and organisational performance driver. Apart from sustaining competitive advantage, intellectual capital is increasingly important due to its ability to increase shareholder value, especially in public organisations. Employee learning, talent development, and knowledge creation allow the organisation to generate innovative ideas due to the quickness of knowledge obsolescence. The organisation's dynamic capabilities create and re-ignite organisational competencies for business sustainability being co-ordinated by well-structured organisational strategic routines ensuring continuous value creation streams into the business. This chapter focuses on the relationship between notions of knowledge sharing and trust in organisations. Lack of trust can impact negatively organisational knowledge sharing, dependent on trust, openness, and communication. The research sample included graduates and postgraduate students from two universities in Portugal. The findings revealed different perceptions according to the age group.

Metabolic engineering with multi-objective optimization of kinetic models

Kinetic models have a great potential for metabolic engineering applications. They can be used for testing which genetic and regulatory modifications can increase the production of metabolites of interest, while simultaneously monitoring other key functions of the host organism. This work presents a methodology for increasing productivity in biotechnological processes exploiting dynamic models. It uses multi-objective dynamic optimization to identify the combination of targets (enzymatic modifications) and the degree of up- or down-regulation that must be performed in order to optimize a set of pre-defined performance metrics subject to process constraints. The capabilities of the approach are demonstrated on a realistic and computationally challenging application: a large-scale metabolic model of Chinese Hamster Ovary cells (CHO), which are used for antibody production in a fed-batch process. The proposed methodology manages to provide a sustained and robust growth in CHO cells, increasing productivity while simultaneously increasing biomass production, product titer, and keeping the concentrations of lactate and ammonia at low values. The approach presented here can be used for optimizing metabolic models by finding the best combination of targets and their optimal level of up/down-regulation. Furthermore, it can accommodate additional trade-offs and constraints with great flexibility.

Indicadores chave de sustentabilidade para edifícios residenciais em estrutura metálica

Dissertação de mestrado integrado em Engenharia Civil

Stress-triggered synaptic malfunction: a gate along the path from depressionto dementia

Tese de Doutoramento em Ciências da Saúde.

Concise server-wide causality management for eventually consistent data stores

Large scale distributed data stores rely on optimistic replication to scale and remain highly available in the face of net work partitions. Managing data without coordination results in eventually consistent data stores that allow for concurrent data updates. These systems often use anti-entropy mechanisms (like Merkle Trees) to detect and repair divergent data versions across nodes. However, in practice hash-based data structures are too expensive for large amounts of data and create too many false conflicts. Another aspect of eventual consistency is detecting write conflicts. Logical clocks are often used to track data causality, necessary to detect causally concurrent writes on the same key. However, there is a nonnegligible metadata overhead per key, which also keeps growing with time, proportional with the node churn rate. Another challenge is deleting keys while respecting causality: while the values can be deleted, perkey metadata cannot be permanently removed without coordination. Weintroduceanewcausalitymanagementframeworkforeventuallyconsistentdatastores,thatleveragesnodelogicalclocks(BitmappedVersion Vectors) and a new key logical clock (Dotted Causal Container) to provides advantages on multiple fronts: 1) a new efficient and lightweight anti-entropy mechanism; 2) greatly reduced per-key causality metadata size; 3) accurate key deletes without permanent metadata.

As universidades e a participação pública em ciência. Perceções e práticas de cientistas, profissionais de comunicação e cidadãos em Portugal e Espanha

Tese de doutoramento em Ciência da Comunicação.

Development and characterization of lipid-based nanosystems for controlled release of bioactive compounds

Tese de Doutoramento em Engenharia Química e Biológica.

As políticas tecnológicas para a educação e a literacia digital: o caso do programa governamental ‘e.escolinha’

Em 2008, o Governo português anunciou a iniciativa ‘e.escolinha’ que contemplou a distribuição de computadores ‘Magalhães’ aos alunos do 1º ciclo do ensino básico, durante três anos letivos consecutivos. Atualmente suspenso, o programa foi bandeira do XVII Governo Constitucional, liderado por José Sócrates, mas alvo de controvérsias por parte da oposição política e da comunidade escolar, sobretudo pela aparente tónica no acesso à tecnologia em vez de uma maior preocupação com a formação e as práticas pedagógicas. Ao abrigo do Plano Tecnológico da Educação, o ‘e.escolinha’ inseria-se numa política mais ampla para o desenvolvimento de uma economia competitiva e dinâmica, através das metas estabelecidas pela União Europeia na Estratégia de Lisboa 2000. A iniciativa foi apresentada ao país com objetivos ambiciosos, no que diz respeito às esperadas mudanças ao nível das práticas pedagógicas dos professores, do processo de aprendizagem das crianças e do sucesso escolar em geral. Porém, a face mais visível da política, embora possa compreender outros matizes, poderá ter ficado reduzida à questão do acesso, apostando pouco nas outras dimensões da literacia digital. Com base em entrevistas realizadas a atores-chave envolvidos no processo de conceção e implementação do ‘e.escolinha’, e nos documentos oficiais que enquadram o programa, o presente artigo pretende dar a conhecer a forma como decisores políticos e empresas enunciam e avaliam os objetivos desta iniciativa. Pretende-se, em particular, conhecer se partilham a ideia de uma deriva tecnológica desta medida governamental ou se entreveem, na mesma, objetivos de literacia digital. Este trabalho decorre do projeto de investigação “Navegando com o Magalhães: Estudo sobre o Impacto dos Media Digitais nas Crianças”, em curso no Centro de Estudos de Comunicação e Sociedade da Universidade do Minho, financiado pela Fundação para a Ciência e Tecnologia ((PTDC/CCI-COM/101381/2008) ) e co-financiado pelo FEDER (COMPETE: FCOMP-01-0124-FEDER-009056).

Methylation at the CpG island shore region upregulates Nr3c1 promoter activity after early-life stress

Early-life stress (ELS) induces long-lasting changes in gene expression conferring an increased risk for the development of stress-related mental disorders. Glucocorticoid receptors (GR) mediate the negative feedback actions of glucocorticoids (GC) in the paraventricular nucleus (PVN) of the hypothalamus and anterior pituitary and therefore play a key role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the endocrine response to stress. We here show that ELS programs the expression of the GR gene (Nr3c1) by site-specific hypermethylation at the CpG island (CGI) shore in hypothalamic neurons that produce corticotropin-releasing hormone (Crh), thus preventing Crh upregulation under conditions of chronic stress. CpGs mapping to the Nr3c1 CGI shore region are dynamically regulated by ELS and underpin methylation-sensitive control of this region's insulation-like function via Ying Yang 1 (YY1) binding. Our results provide new insight into how a genomic element integrates experience-dependent epigenetic programming of the composite proximal Nr3c1 promoter, and assigns an insulating role to the CGI shore.

KIAA1549: BRAF gene fusion and FGFR1 hotspot mutations are prognostic factors in pilocytic astrocytomas

Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations and Fibroblast growth factor receptor 1 (FGFR1) point mutations are key molecular alterations in Pas, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by fluorescence in situ hybridization and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 expression was analyzed using immunohistochemistry, and this was compared with gene amplification and hotspot mutations (exons 12 and 14) assessed by fluorescence in situ hybridization and capillary sequencing. KIAA1549:BRAF fusion was identified in almost 60% of cases. Two tumors harbored mutated BRAF. Despite high FGFR1 expression overall, no cases had FGFR1 amplifications. Three cases harbored a FGFR1 p.K656E point mutation. No correlation was observed between BRAF and FGFR1 alterations. The cases were predominantly pediatric (87%), and no statistical differences were observed in molecular alterations-related patient ages. In summary, we confirmed the high frequency of KIAA1549:BRAF fusion in PAs and its association with a better outcome. Oncogenic mutations of FGFR1, although rare, occurred in a subset of patients with worse outcome. These molecular alterations may constitute alternative targets for novel clinical approaches, when radical surgical resection is unachievable.