Electron impact ionization cross sections and analysis of X-ray spectra

A thesis submitted for the degree of Ph. D. in Physic

Tunable CAR T Cell Responses Achieved by the Disruption of Protein-Protein Interactions via the Administration of a Small Molecule

Introduction: The adoptive transfer of T-cells engineered to express chimeric antigen receptors (CARs) has significantly widened the applicability of passive immunotherapy in cancer. Up until now, several studies of CAR therapy have emerged as a promising treatment for cancer, although there are serious concerns regarding potential risk of acute and chronic toxicity. Given the ability of CAR T-cells to engraft and proliferate in the patient, toxicity from excessive activity can be progressive and fulminant. This highlights the need for technologies to remotely control and tune the potency of the CAR T-cells after administration. Suicide gene approaches allow a level of control of CAR T-cell therapy. However, as suicide switches result in permanent loss of all engineered T-cells, a new strategy which can temporarily reduce or stop CAR T-cell activity without triggering CAR T-cell apoptosis is desirable. One way to achieve this is to use small molecules that present desired pharmacologic properties, such as tetracycline and analogues doxycycline and minocycline. Results: Therefore, we developed a Tet-Off signalling switch that enables tetracycline-dependent, titratable, and reversible control over CAR T-cells. The CAR was split into two: an antigen recognition component fused with TetR (Tet repressor) and a signalling component fused with TiP (TetR interacting peptide). Both TiP and tetracycline are known to bind to TetR with a high affinity. We predicted that although TiP bound to the same part of TetR as tetracycline, Tetracycline would bind with a much higher affinity than TiP and hence rapidly displace TiP. First with eGFP, we showed that in the absence of tetracycline such a system results in membrane localization of a TiP fusion protein, with the eGFP being displaced to the cytoplasm in the presence of tetracycline. Next as a CAR, we showed that in the absence of tetracycline, the two CAR components associate and the CAR signals in the presence of cognate antigens. On the addition of tetracycline, TiP was displaced and the receptor stopped signalling. Depending on the concentration of tetracycline present, tetCAR T-cells showed titratable activity, from as strong as that of conventional CAR T-cells to undetectable. Similar results were obtained when using the analogues doxycycline and minocycline. We tested the effectiveness of this tetCAR in murine and human T-cells. These results included IL-2 and IFN-γ production, the tetCAR T-cell ability to control target cell killing and also the killing of multiple types of target cells by the tetCAR T-cells. Regarding reversibility, we showed that the inhibition process is reversible. Once we wash off the tetracycline from the cultures, tetCAR T-cells regain activity. Conclusion: We successfully generated and controlled the activity of tetCAR T-cells by tetracycline administration

Stay away or stay together? Social contagion, common identity, and bystanders’ interventions in homophobic bullying episodes

Two studies explored the link between social contagion concerns and assertive bystanders’ behavioral intentions in homophobic bullying episodes. Study 1 (N = 216) examined if adolescents’ social contagion concerns (i.e., fear of being misclassified as gay/lesbian) relate to decreased behavioral intentions to help victims of bullying, by increasing negative attitudes towards lesbians and gay men. Study 2 (N = 230) further explored if inclusive identity representations (i.e., one-group or dual-identity) were related to decreased concerns of social contagion, thereby increasing adolescents’ assertive behavioral intentions. Results (partially) confirmed both expected mediations: social contagion concerns were associated with decreased assertive behavioral intentions via increased negative attitudes towards lesbians and gay men (Study 1); one-group representations, but not dual-identity representations, were associated with more assertive behavioral intentions via decreased social contagion concerns (Study 2). These findings extended previous studies illustrating the underlying mechanisms through which social contagion concerns and common identity affect assertive bystanders’ behavioral intentions.info:eu-repo/semantics/acceptedVersio

Having friends with gay friends? The role of extended contact, empathy and threat on assertive bystanders behavioral intentions

Peers are present in more than 80% of bullying episodes and research showed that bystanders have a very important role in stopping bullying episodes. However, little is known about the predictors of assertive interventions by bystanders. The current study explored if extended contact (i.e., having friends who have gay friends), is related to assertive behavioral intentions to help the victims of homophobic bullying, through increased empathy and decreased masculinity/femininity threat. An online survey was completed by 87 heterosexual adolescents (12 to 18 years old). Results revealed that, as expected, extended contact was associated with more assertive interventions, via increased affective empathy and decreased masculinity/femininity threat. These findings replicated and extended previous studies by illustrating the underlying mechanisms through which extended contact positively affects bystanders' interventions.info:eu-repo/semantics/publishedVersio

Cyberbullying during COVID-19 lockdowns: Prevalence, predictors, and outcomes for youth

The COVID-19 pandemic posed additional challenges to the safety and well-being of young people who were forced to engage in online learning, spending more time than ever online, and cyberbullying emerged as a notable concern for parents, educators, and students. Two studies conducted online examined the prevalence, predictors, and outcomes of cyberbullying episodes during the lockdowns due to the outbreak of COVID-19 in Portugal. Study 1 (N = 485) examined the prevalence of cyberbullying among youth during the first lockdown period in 2020, focusing on predictors, symptoms of psychological distress and possible buffers of the effects of cyberbullying. Study 2 (N = 952) examined the prevalence of cyberbullying, predictors, and symptoms of psychological distress during the second lockdown period in 2021. Results revealed that most participants experienced cyberbullying, symptoms of psychological distress (e.g., sadness and loneliness) during the lockdowns were higher for those who experienced than for those who did not experience cyberbullying, and those who experienced cyberbullying with higher levels of parental and social support showed lower levels of symptoms of psychological distress (i.e., suicidal ideation). These findings contribute to the existing knowledge on online bullying among youth, specifically during COVID-19 lockdowns.info:eu-repo/semantics/publishedVersio

Equity research - EDP Renováveis

Mestrado em FinançasA EDPR é uma empresa que opera no sector da energia renovável e é hoje uma das mais importantes a trabalhar nesta área. O seu principal objectivo consiste em ser uma referência na indústria, por desenvolver, construir e operar as melhores centrais eólicas e solares no mundo. Ao contrário de muitas outras empresas que estão a ter alguns problemas com a actual conjuntura económica, a EDPR, ao investir num moderno e atractivo sector, tem conseguido ultrapassar com sucesso as dificuldades e por isso, está a construir um crescimento significativo e sólido. A elaboração deste estudo tem o propósito de obter o valor intrínseco das acções da EDPR, assente numa análise do seu desempenho operacional e do seu ambiente exógeno. O método adoptado para determinar este valor consiste no Free Cash Flow to Firm, uma vez que, de acordo com a revisão da literatura, é o mais adequado a aplicar à EDPR. A avaliação realizada levou à conclusão de que em 31/12/2014, as acções da EDPR tinham um valor intrínseco de - 6.49, estando dessa forma subvalorizadas, uma vez que a sua cotação era - 5.40 na data referida. Deste modo, com uma potencial valorização de 20.2%, foi possível dar uma recomendação de compra aos investidores interessados.EDPR is a company that operates in the sector of the renewable energy and it is today one of the most important working in this area. Its main goal consists on being a reference in the industry for developing, building and operating the best wind farms and solar plants in the world. Unlike many other companies that are having some problems with the present economic framework, EDPR, by investing in a modern and most required sector, is successfully managing to overcome the difficulties and therefore it is building a significant and solid growth. The elaboration of this study has the aim to achieve the intrinsic value of EDPR stocks, by making a research of the operational performance and its exogenous environment. The method adopted in order to determine this value consists on the Free Cash Flow to Firm, since, according with the literature review, this is the most suitable one to apply to EDPR. The valuation performed led to the conclusion that on 31/12/2014, EDPR shares had an intrinsic value of - 6.49, being thus undervalued, since its quotation was - 5.40 at the time referred to. Therefore, with a potential appreciation of 20.2%, it was able to give a buy recommendation to the interested investors

Desenvolvimento de um esquema referencial de formação de professores de ciências para o uso de tecnologias

Procura-se fazer a apresentação de um esquema referencial para o desenvolvimento de programas de formação (PF) de professores de Ciências (inicial, contínua e pós-graduada), com vista ao desenvolvimento do seu Conhecimento Pedagógico Tecnológico de Conteúdo (CPTC). O CPTC representa o conhecimento de professores de ciências para integrar as tecnologias no processo de ensino e aprendizagem das Ciências. O esquema foi desenvolvido em duas fases: na primeira, assente num paradigma interpretativo, descreveram-se as estratégias para a promoção do desenvolvimento do CPTC de estudantes/professores; e na segunda, baseada num paradigma sócio-critico, desenvolveu-se um PF com esta orientação. Neste esquema descrevem-se alguns dos componentes curriculares a privilegiar na formação de professores, como por exemplo a avaliação formativa de portefólios digitais

Desenvolvimento de um esquema referencial de formação de professores de ciências para o uso de tecnologias

Procura-se fazer a apresentação de um esquema referencial para o desenvolvimento de programas de formação (PF) de professores de Ciências (inicial, contínua e pós-graduada), com vista ao desenvolvimento do seu Conhecimento Pedagógico Tecnológico de Conteúdo (CPTC). O CPTC representa o conhecimento de professores de ciências para integrar as tecnologias no processo de ensino e aprendizagem das Ciências. O esquema foi desenvolvido em duas fases: na primeira, assente num paradigma interpretativo, descreveram-se as estratégias para a promoção do desenvolvimento do CPTC de estudantes/professores; e na segunda, baseada num paradigma sócio-critico, desenvolveu-se um PF com esta orientação. Neste esquema descrevem-se alguns dos componentes curriculares a privilegiar na formação de professores, como por exemplo a avaliação formativa de portefólios digitais