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- Estrogens and the G protein-coupled estrogen receptor in prostate cancer: angels or demons?Publication . Figueira, Marília Isabel Neto; Socorro, Sílvia Cristina da Cruz MarquesProstate cancer (PCa) is the second most frequent type of cancer among men, with an increasing incidence worldwide. PCa is highly regulated by hormones, with androgens playing a crucial role in its development and progression. However, also estrogens are accepted to influence PCa. In fact, estrogens were used in PCa treatment for decades, after the pioneer work of Huggins and Hodges demonstrating that PCa is a hormone-sensitive cancer, stimulated by androgenic activity and inhibited by suppression of androgens levels or estrogens administration. Nevertheless, despite the effectiveness of estrogens administration in delaying the progression of metastatic PCa, this therapy was discontinued because of the adverse side effects. Over the years, a vast number of studies were performed with the aim of deciphering the role of estrogens in PCa and find new estrogen-based alternatives for PCa treatment without the adverse effects. However, a contradiction in the estrogens actions remains evident in the literature until now. Many studies have pointed out estrogens as causative agents of PCa, contributing to its development and progression. Though, also a panoply of reports defended estrogens as protective against PCa, suppressing tumor growth, inducing apoptosis and inhibiting metastization, in line with their efficacy as therapeutic agents. This dual activity was associated with the diversity of receptors activated by estrogens, with the pro-carcinogenic actions associated with the activation of the estrogen receptor α (ERα), whereas anti-carcinogenic effects are linked to ERβ activation. Moreover, the discovery of G protein-coupled estrogen receptor (GPER) increased the complexity of mechanisms orchestrating estrogens actions. GPER is a membrane-bound ER that mediates the rapid, non-genomic effects of estrogens by mobilizing intracellular calcium and activating several signaling pathways. A substantial amount of evidence in different cancer types has been describing the anti-tumorigenic effects of GPER suppressing tumor growth and progression. A research area with increasing interest is the determination of the anti-carcinogenic actions of phytoestrogens, strengthened by the evidence of the lower incidence of PCa in Eastern countries, which typically have high consumption of these compounds in a consequence of plant-enriched diets. Furthermore, the mechanism of action of some of these compounds in PCa cells has been shown to require GPER activation. The present thesis aimed to answer some of the existent questions on the estrogens and GPER actions in PCa cells, which would lay the foundations for the development of new and safe estrogen-based therapies. First, it was investigated the action of estrogens as regulators of apoptosis and proliferation in prostate cells in the interplay with the SCF/c-KIT system, a set of ligand and receptor highly involved in carcinogenesis and a target of steroid hormones. Herein, it was demonstrated that E2 down-regulated the expression of the SCF/c-KIT system both in human PCa cell lines and rat prostate in vivo, which was accompanied by the effects of E2 suppressing proliferation and inducing apoptosis in rat prostates. These results supported the protective role of estrogens against PCa. Considering the promising results in other types of cancer, it was determined the effect of GPER activation in PCa cells covering several cancer hallmarks, from cell fate to metabolic reprogramming. It was found that GPER is highly expressed in PCa compared to benign prostatic hyperplasia (BPH) cases. Furthermore, GPER immunoreactivity was inversely correlated with PSA levels. GPER protein levels also were higher in neoplastic LNCaP cells than in the non-neoplastic PNT1A cells. Nevertheless, castrate-resistant PCa (CRPC) cells displayed reduced expression of GPER compared to the androgen-responsive cell line, supporting that GPER protein levels could be modulated by androgens. GPER was found to be localized at the cell membrane, endoplasmic reticulum and, residually, in the nucleus of prostate cells and this subcellular localization was altered by the GPER-specific agonist G1. G1-treatment showed a multiplicity of beneficial effects in PCa, targeting a panoply of cancer hallmarks. It reduced PCa cells viability and proliferation, arresting cell cycle and increasing apoptosis. It was also able to reduced migration and invasion, concomitantly with epithelial-mesenchymal transition (EMT) attenuation, depending on the cell line. Moreover, GPER activation by G1 increased energy metabolism and oxidative stress in PCa cells. Finally, it was evaluated how natural compounds, such as diosgenin, can influence the behavior of PCa in the interplay with GPER. Diosgenin diminished the viability of androgen-responsive and CRPC cells, without affecting the viability of non-neoplastic PNT1A cells. Moreover, the compound induced apoptosis and modulated glycolytic metabolism of PCa cells. The effects of diosgenin were enhanced when combined with G1, supported by the ability of diosgenin to augment the expression levels of GPER. Furthermore, GPER knockdown by a siRNA approach abrogated diosgenin effects inducing apoptosis of PCa cells, which implicates this receptor in the diosgenin mechanism of action. Globally, the findings of this thesis support the protective role of estrogens in PCa, disclosing new molecular targets and cellular processes. Moreover, it provides valuable information to find new therapeutic options, namely, estrogen-like, to deaccelerate the progression of disease and improve the survival of PCa patients.
- Encryption and Authentication on a RISC-V ArchitecturePublication . Fernandes, João Cassiano Vicente; Santo, António Eduardo Vitória do EspiritoDeveloped in 2010 at the University of California, Berkley, the new ISA, called RISC-V, was created with the open-source extensibility ability in mind. The RISC-V ISA is designed to be modular, allowing for the implementation of custom instruction sets for specific applications. Its flexibility and ease of use gave the academic and commercial community an ideal choice for embedded systems development, it allows the creation of optimized processors for specific system requirements. Big companies, such as Google, NVIDIA, Western Digital, Samsung, and Qualcomm, are members of the RISC-V foundation, which is responsible for ensuring the RISC-V evolution as well as promoting its adoption and development of new ISAs. The support from the open-source community helped grow the RISC-V's popularity. The daily updates of different implementations, as well as adaptations and development of programming tools, gave any user, experienced or not, a fast and easy way to learn and implement a custom ISA tailored to his needs. Ensuring data security and user privacy is a big concern for all devices, especially those with limited computational resources. Building a system with good performance and security is a challenge. The computational effort required for encrypting and authenticating messages must be feasible with the available processing capacity. A hardware implementation of encryption and authentication algorithms can release some workload from the smaller microcontroller and, thus, allow for simpler and more efficient architectures to be diploid. This dissertation presents a survey around the RISC-V ISA and the ChaCha20 encryption and Poly1305 authentication algorithms to take advantage of the customization ability of the RISC-V ISA to implement a security module in the architecture, able to handle data encryption and authentication without the use of the SoC resources.
- Propriedades Químicas da Água e Soluções AquosasPublication . Simões, Maria Margarida Gaudêncio; Costa, Ana Paula Nunes de Almeida Alves daO presente relatório, realizado no âmbito do Mestrado em Ensino de Física e Química no 3º Ciclo do Ensino Básico e no Ensino Secundário da Universidade da Beira Interior, analisa e descreve, as atividades desenvolvidas pelo núcleo de estágio de físico-química durante o Estágio Pedagógico realizado, no ano letivo de 2022/2023, na Escola Secundária Quinta das Palmeiras, na cidade da Covilhã. No capítulo I, apresenta-se uma breve caracterização da escola, do grupo de estágio de físico-química e das turmas que foram lecionadas e supervisionadas. Descrevem-se também as atividades extracurriculares promovidas pelo núcleo de estágio e finalmente é apresentada a planificação das aulas assistidas, assim como, cinco planos de aula, três da componente de química e dois da componente de física. No capítulo II, é abordado teoricamente o tema “Ensino da química e as propriedades químicas da água e das soluções aquosas”, no qual são realçados temas, como a importância do ensino experimental das ciências e da utilização de simuladores. No capítulo III, apresenta-se uma breve síntese da investigação educacional que foi desenvolvida durante o estágio pedagógico, na componente de química, na turma do 11º ano do ensino secundário. No capítulo IV, apresentam-se as conclusões finais do estágio pedagógico, no qual são analisados vários aspetos inerentes à prática de ensino supervisionada. No final, indicam-se as referências bibliográficas e os anexos utilizados.