Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-Aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors

The synthesis and biological evaluation of novel 1-aryl-3-[2-, 3- or 4-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 3, 4 and 5 as VEGFR-2 tyrosine kinase inhibitors, are reported. The 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 4a-4h, with the arylurea in the meta position to the thioether, showed the lowest IC50 values in enzymatic assays (10-206 nM), the most potent compounds 4d-4h (IC50 10-28 nM) bearing hydrophobic groups (Me, F, CF3 and Cl) in the terminal phenyl ring. A convincing rationalization was achieved for the highest potent compounds 4 as type II VEGFR-2 inhibitors, based on the simultaneous presence of: (1) the thioether linker and (2) the arylurea moiety in the meta position. For compounds 4, significant inhibition of Human Umbilical Vein Endothelial Cells (HUVECs) proliferation (BrdU assay), migration (wound-healing assay) and tube formation were observed at low concentrations. These compounds have also shown to increase apoptosis using the TUNEL assay. Immunostaining for total and phosphorylated (active) VEGFR-2 was performed by Western blotting. The phosphorylation of the receptor was significantly inhibited at 1.0 and 2.5 microM for the most promising compounds. Altogether, these findings point to an antiangiogenic effect in HUVECs.

Modelo de avaliação do impacto das TSI na produtividade das organizações

Dissertação de mestrado em Sistemas de Informação

Document-based databases: estudo comparativo no âmbito das bases de dados NoSql

Dissertação de mestrado integrado em Engenharia e Gestão de Sistemas de Informação

Facilitadores e obstáculos do empreendedorismo: o caso das muambeiras de Lubango

Dissertação de mestrado em Estudos de Gestão

Desenvolvendo a qualidade em parcerias: a voz de um grupo de educadoras

Tese de Doutoramento em Estudos da Criança (Especialidade de Metodologia e Supervisão em Educação de Infância)

Cognitive functioning and efficacy of cognitive intervention in Multiple Sclerosis

Tese de Doutoramento em Psicologia Clínica / Psicologia

O ajustamento psicossocial de jovens com consumos de substâncias psicoativas em escolas profissionais do grande Porto

Tese de Doutoramento em Estudos da Criança (Área de Especialidade Psicologia do Desenvolvimento e Educação)

Alfabetização de jovens e adultos no estado do Rio de Janeiro, Brasil: o significado de um desafio para a inclusão social

Tese de Doutoramento em Ciências da Educação

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.

Bioactive ceramics for tissue engineering and regenerative medicine derived from marine sponges

Publicado em "Journal of tissue engineering and regenerative medicine". Vol. 8, suppl. s1 (2014)

Adhesive bioactive coatings inspired by sea life

Inspired by nature, in particular by the marine mussels adhesive proteins (MAPs) and by the tough brick-and-mortar nacre-like structure, novel multilayered films are prepared in the present work. Organic-inorganic multilayered films, with an architecture similar to nacre based on bioactive glass nanoparticles (BG), chitosan and hyaluronic acid modified with catechol groups, which are the main responsible for the outstanding adhesion in MAPs, are developed for the first time. The biomimetic conjugate is prepared by carbodiimide chemistry and analyzed by ultraviolet-visible spectrophotometry. The build-up of the multilayered films is monitored with a quartz crystal microbalance with dissipation monitoring and their topography is characterized by atomic force microscopy. The mechanical properties reveal that the films containing catechol groups and BG present an enhanced adhesion. Moreover, the bioactivity of the films upon immersion in a simulated body fluid solution for 7 days is evaluated by scanning electron microscopy coupled with energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy and X-ray diffraction. It was found that the constructed films promote the formation of bone-like apatite in vitro. Such multifunctional mussel inspired LbL films, which combine enhanced adhesion and bioactivity, could be potentially used as coatings of a variety of implants for orthopedic applications.

Desafios de uma comunidade minoritária: os apoios sociais na comunidade cigana de Barcelos

Dissertação de mestrado em Crime Diferença e Desigualdade

Comparing heritage speakers and late L2-learners of European Portuguese: verb movement, VP ellipsis and adverb placement

This study compares the performance of Portuguese-German heritage children and adult L2 speakers of European Portuguese whose L1 is German with respect to two aspects of grammar, adverb placement and VP-ellipsis, which depend on a core syntactic property of the language, verb movement. The results show that both groups have acquired V-to-I and adverb placement, showing no influence of a V2 grammar. Performance in the VP-ellipsis task is more complex: heritage children produce VP-ellipsis at the level of controls, as opposed to L2 speakers; however, both L2 and heritage speakers show that crosslinguistic influence may produce a preference for pronoun substitution over VP-ellipsis in a task asking for redundancy resolution. Nevertheless, given that overall results show that heritage children perform at the level of L1 children, we take our results to support approaches to heritage bilingualism which suggest the development of an intact grammar in childhood.

Resiliência familiar e risco psicossocial: estudo das percepções das famílias e dos profissionais que as acompanham

Dissertação de mestrado em Estudos da Criança (área de especialização em Intervenção Psicossocial com Crianças, Jovens e Famílias)

Participação de fisioterapeutas em equipes multidisciplinares que atuam junto a alunos com necessidades educativas especiais: um estudo quantitativo em escolas de ensino fundamental da rede pública de Manaus

Dissertação de mestrado em Educação Especial (área de especialização em Dificuldades de Aprendizagem Específicas)