Sistema de reposição e de gestão de inventários na rede de lojas de uma empresa de retalho de moda

Dissertação de mestrado integrado em Engenharia e Gestão Industrial

Efeito da dissipação térmica nas juntas de soldagem de componentes through hole

Dissertação de mestrado integrado em Engenharia de Materiais

Synthesis of iminosugars through diastereo/enantioselective diels-alder cycloaddition

Tese de Doutoramento em Ciências (Especialidade em Química)

A network approach to brain aging through multimodal neuroimaging

Tese de Doutoramento em Ciências da Saúde.

Cathepsin D protects colorectal cancer cells from acetate-induced apoptosis through autophagy-independent degradation of damaged mitochondria

Acetate is a short-chain fatty acid secreted by Propionibacteria from the human intestine, known to induce mitochondrial apoptotic death in colorectal cancer (CRC) cells. We previously established that acetate also induces lysosome membrane permeabilization in CRC cells, associated with release of the lysosomal protease cathepsin D (CatD), which has a well-established role in the mitochondrial apoptotic cascade. Unexpectedly, we showed that CatD has an antiapoptotic role in this process, as pepstatin A (a CatD inhibitor) increased acetate-induced apoptosis. These results mimicked our previous data in the yeast system showing that acetic acid activates a mitochondria-dependent apoptosis process associated with vacuolar membrane permeabilization and release of the vacuolar protease Pep4p, ortholog of mammalian CatD. Indeed, this protease was required for cell survival in a manner dependent on its catalytic activity and for efficient mitochondrial degradation independently of autophagy. In this study, we therefore assessed the role of CatD in acetate-induced mitochondrial alterations. We found that, similar to acetic acid in yeast, acetate-induced apoptosis is not associated with autophagy induction in CRC cells. Moreover, inhibition of CatD with small interfering RNA or pepstatin A enhanced apoptosis associated with higher mitochondrial dysfunction and increased mitochondrial mass. This effect seems to be specific, as inhibition of CatB and CatL with E-64d had no effect, nor were these proteases significantly released to the cytosol during acetate-induced apoptosis. Using yeast cells, we further show that the role of Pep4p in mitochondrial degradation depends on its protease activity and is complemented by CatD, indicating that this mechanism is conserved. In summary, the clues provided by the yeast model unveiled a novel CatD function in the degradation of damaged mitochondria when autophagy is impaired, which protects CRC cells from acetate-induced apoptosis. CatD inhibitors could therefore enhance acetate-mediated cancer cell death, presenting a novel strategy for prevention or therapy of CRC.

SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3

Prostate cancer (PCa) is one of the most incident cancers worldwide but clinical and pathological parameters have limited ability to discriminate between clinically significant and indolent PCa. Altered expression of histone methyltransferases and histone methylation patterns are involved in prostate carcinogenesis. SMYD3 transcript levels have prognostic value and discriminate among PCa with different clinical aggressiveness, so we decided to investigate its putative oncogenic role on PCa.We silenced SMYD3 and assess its impact through in vitro (cell viability, cell cycle, apoptosis, migration, invasion assays) and in vivo (tumor formation, angiogenesis). We evaluated SET domain's impact in PCa cells' phenotype. Histone marks deposition on SMYD3 putative target genes was assessed by ChIP analysis.Knockdown of SMYD3 attenuated malignant phenotype of LNCaP and PC3 cell lines. Deletions affecting the SET domain showed phenotypic impact similar to SMYD3 silencing, suggesting that tumorigenic effect is mediated through its histone methyltransferase activity. Moreover, CCND2 was identified as a putative target gene for SMYD3 transcriptional regulation, through trimethylation of H4K20.Our results support a proto-oncogenic role for SMYD3 in prostate carcinogenesis, mainly due to its methyltransferase enzymatic activity. Thus, SMYD3 overexpression is a potential biomarker for clinically aggressive disease and an attractive therapeutic target in PCa.

Dynamic wet etching of silicon through isopropanol alcohol evaporation

In this paper, Isopropanol (IPA) availability during the anisotropic etching of silicon in Potassium Hydroxide (KOH) solutions was investigated. Squares of 8 to 40 m were patterned to (100) oriented silicon wafers through DWL (Direct Writing Laser) photolithography. The wet etching process was performed inside an open HDPE (High Density Polyethylene) flask with ultrasonic agitation. IPA volume and evaporation was studied in a dynamic etching process, and subsequent influence on the silicon etching was inspected. For the tested conditions, evaporation rates for water vapor and IPA were determined as approximately 0.0417 mL/min and 0.175 mL/min, respectively. Results demonstrate that IPA availability, and not concentration, plays an important role in the definition of the final structure. Transversal SEM (Scanning Electron Microscopy) analysis demonstrates a correlation between microloading effects (as a consequence of structure spacing) and the angle formed towards the (100) plane.

Resilience of concrete structures in the marine environment through microstructural innovation

Dissertação de mestrado integrado em Engenharia Civil

Design of bio-based supramolecular structures through self-assembly of α-lactalbumin and lysozyme

Bovine α-lactalbumin (α-La) and lysozyme (Lys), two globular proteins with highly homologous tertiary structures and opposite isoelectric points, were used to produce bio-based supramolecular structures under various pH values (3, 7 and 11), temperatures (25, 50 and 75 °C) and times (15, 25 and 35 min) of heating. Isothermal titration calorimetry experiments showed protein interactions and demonstrated that structures were obtained from the mixture of α-La/Lys in molar ratio of 0.546. Structures were characterized in terms of morphology by transmission electron microscopy (TEM) and dynamic light scattering (DLS), conformational structure by circular dichroism and intrinsic fluorescence spectroscopy and stability by DLS. Results have shown that protein conformational structure and intermolecular interactions are controlled by the physicochemical conditions applied. The increase of heating temperature led to a significant decrease in size and polydispersity (PDI) of α-La–Lys supramolecular structures, while the increase of heating time, particularly at temperatures above 50 °C, promoted a significant increase in size and PDI. At pH 7 supramolecular structures were obtained at microscale – confirmed by optical microscopy – displaying also a high PDI (i.e. > 0.4). The minimum size and PDI (61 ± 2.3 nm and 0.14 ± 0.03, respectively) were produced at pH 11 for a heating treatment of 75 °C for 15 min, thus suggesting that these conditions could be considered as critical for supramolecular structure formation. Its size and morphology were confirmed by TEM showing a well-defined spherical form. Structures at these conditions showed to be stable at least for 30 or 90 days, when stored at 25 or 4 °C, respectively. Hence, α-La–Lys supramolecular structures showed properties that indicate that they are a promising delivery system for food and pharmaceutical applications.

“Learning through Radio, Learning for Life!”: Notas sobre o desenvolvimento de uma rádio participativa online

(Excerto) Olhando para o percurso do RadioActive, há uma ideia que parece ser transversal a todo o projeto. Referimo-nos a um princípio que chamaríamos de “identificação” e que foi determinante – é determinante – nos processos de investigação participativa. Falamos da identificação dos investigadores com os princípios da investigação-ação, da identificação das intervenções com as particularidades de cada contexto. Da imprescindível e progressiva identificação dos participantes com o projeto. Na verdade, sem esta multifacetada identificação é impossível pensar em resultados sustentáveis e persistentes. Investigadores e demais participantes têm de sentir que o projeto é “seu”, que os objetivos são “seus”, embora o façam necessariamente a velocidades diferentes. A aprendizagem, neste âmbito, expande-se sempre de dentro para fora, emerge dos interesses do sujeito e não de uma estrutura pré-concebida e imposta pelos que chegam (Ravenscroft et al., 2011), neste caso, os investigadores. Uma das diferenças das pesquisas participativas em relação às tradicionais é, precisamente, a atuação coletiva e não solitária do investigador. Os pesquisadores fazem parte de um processo participatório em que estão envolvidos numa estrutura (Cammarota & Fine, 2008: 5). Paulo Freire é o autor primordial em todos os projetos e países onde a RA101 foi aplicada. As suas concepções em torno da investigação-ação participativa tentam apontar sempre para uma ação e também para uma reflexão sobre os processos.

O silêncio no contemporâneo: da técnica aos média

Dissertação de mestrado em Comunicação, Arte e Cultura

Contributo para o estudo da tutela do promitente - comprador

Dissertação de mestrado em Direito Judiciário

A modernidade para além da utopia tecnológica

Dissertação de mestrado em Ciências da Comunicação (área de especialização em Comunicação, Cidadania e Educação)

Microbial production of potent phenolic-antioxidants through solid state fermentation

The agroindustrial residues including plant tissues rich in polyphenols were explored for microbial production of potent phenolics under solid state fermentation processes. The fungal strains capable of hydrolyzing tannin-rich materials were isolated from Mexican semidesert zones. These microorganisms have been employed to release potent phenolic antioxidants during the solid state fermentation of different materials (pomegranate peels, pecan nut shells, creosote bush and tar bush). This chapter includes the critical parameters for antioxidants production from selective microbes. Technical aspects of the microbial fermentation of antioxidants have also been discussed.

Predicting pre-triage waiting time in a maternity emergency room through data mining

An unsuitable patient flow as well as prolonged waiting lists in the emergency room of a maternity unit, regarding gynecology and obstetrics care, can affect the mother and child’s health, leading to adverse events and consequences regarding their safety and satisfaction. Predicting the patients’ waiting time in the emergency room is a means to avoid this problem. This study aims to predict the pre-triage waiting time in the emergency care of gynecology and obstetrics of Centro Materno Infantil do Norte (CMIN), the maternal and perinatal care unit of Centro Hospitalar of Oporto, situated in the north of Portugal. Data mining techniques were induced using information collected from the information systems and technologies available in CMIN. The models developed presented good results reaching accuracy and specificity values of approximately 74% and 94%, respectively. Additionally, the number of patients and triage professionals working in the emergency room, as well as some temporal variables were identified as direct enhancers to the pre-triage waiting time. The imp lementation of the attained knowledge in the decision support system and business intelligence platform, deployed in CMIN, leads to the optimization of the patient flow through the emergency room and improving the quality of services.