Therapeutics bioconjugates: evaluation of iminoboronates as payload delivery system for cancer

The advent of bioconjugation impacted deeply the world of sciences and technology. New biomolecules were found, biological processes were understood, and novel methodologies were formed due to the fast expansion of this area. The possibility of creating new effective therapies for diseases like cancer is one of big applications of this now big area of study. Off target toxicity was always the problem of potent small molecules with high activity towards specific tumour targets. However, chemotherapy is now selective due to powerful linkers that connect targeting molecules with affinity to interesting biological receptors and cytotoxic drugs. This linkers must have very specific properties, such as high stability in plasma, no toxicity, no interference with ligand affinity nor drug potency, and at the same time, be able to lyse once inside the target molecule to release the therapeutic warhead. Bipolar environments between tumour intracellular and extracellular medias are usually exploited by this linkers in order to complete this goal. The work done in this thesis explores a new model for that same task, specific cancer drug delivery. Iminoboronates were studied due to its remarkable selective stability towards a wide pH range and endogenous molecules. A fluorescence probe was design to validate this model by creating an Off/On system and determine the payload release location in situ. A process was optimized to synthetize the probe 8-(1-aminoethyl)-7-hydroxy-coumarin (1) through a reductive amination reaction in a microwave reactor with 61 % yield. A method to conjugate this probe to ABBA was also optimized, obtaining the iminoboronate in good yields in mild conditions. The iminoboronate model was studied regarding its stability in several simulated biological environments and each half-life time was determined, showing the conjugate is stable most of the cases except in tumour intracellular systems. The construction of folate-ABBA-coumarin bioconjugate have been made to complete this evaluation. The ability to be uptaken by a cancer cell through endocytosis process and the conjugation delivery of coumarin fluorescence payload are two features to hope for in this construct.

O estatuto disciplinar da literatura angolana : contributo para uma epistemologia dos estudos literários africanos

A presente investigação procura inscrever-se no domínio da epistemologia dos estudos literários, fazendo apelo a uma abordagem interdisciplinar que aponta para a necessidade de um comparatismo literário africano e, ao mesmo tempo, mundial. O conceito-chave com que operamos neste trabalho é o de disciplinarização, tendo em conta o seu potencial explicativo para entender o processo que nos irá conduzir à integração dos Estudos Literários Africanos no sistema disciplinar actual. Por disciplinarização entendemos o processo de definição que consiste na demarcação de uma determinada disciplina, por força de dinâmicas endógenas e exógenas, durante o qual se transita de uma fase pré-disciplinar para outra disciplinar, admitindo-se a existência de uma compatibilidade entre os fundamentos epistemológicos e metodológicos da produção e transmissão de conhecimentos e, por outro lado, a consagração da institucionalidade da disciplina como objecto de estudo. A profissionalização disciplinar será uma consequência desse processo e da formação de comunidades de agentes epistémicos que, conhecendo profundamente a história e os universos de referência da disciplina, sejam capazes de aplicar as metodologias mais adequadas no domínio da investigação e do ensino. Para compreender os fundamentos epistemológicos dos Estudos Literários Africanos, importa refletir sobre o momento a partir do qual se constituem como campo disciplinar na história da produção do conhecimento sobre o continente africano. Por outro lado, com o presente trabalho pretende-se avaliar o estatuto disciplinar da Literatura Angolana, num exercício que procura justificar as determinações da epistemologia disciplinar, operacionalizando os sentidos em que se pode analisar o conceito de disciplina. Deste modo, a atribuição do referido estatuto pressupõe o domínio de um instrumental teórico que implica a descrição dos tipos de conhecimento veiculados através dos processos de transmissão que caracterizam as disciplinas escolares e as disciplinas académicas.

Good vibrations

The work reported in this thesis addresses the research question of when and how positive psychological states impact positive behavior and positive organizational development. We present two theoretical essays and three empirical studies to find possible answers to this question and we use a multitude of methodologies with different epistemological assumptions, including quantitative correlation analysis, social network analysis and qualitative grounded theory analysis. In the whole, our work shows that positive psychological states are fundamental to promote individual and organizational higher-levels of performance and well-being. It also points that the capability to induce positive psychological states in others (an “alter-positive” approach) is a powerful way to develop outstanding individuals and organizations. In a broader sense, it stresses the need to promote good vibrations as a fundamental route to create a better world.

‘Wooden Man’? : Masculinities in the Work of J. M. Coetzee (Boyhood, Youth and Summertime)

In seeking to advance the possibility of justice, gender and postcolonial studies have argued for the importance of the study of masculinities, through the acknowledgment that a richer understanding of such gendered formations may provide the basis for recognition of the Other and that, left uncriticised, such formations may be continuously delineated by the reproduction of systems of domination. The current study finds as its object the representations of masculinities in J. M. Coetzee’s Boyhood (1997), Youth (2002) and Summertime (2009). As works of transition in terms of Coetzee’s oeuvre - post-apartheid and post-Disgrace - the trilogy provides an account of the development of a man through several stages of life. While portraying the tensions of different geographical and cultural locations, such as apartheid South Africa and the London of the Sixties, the trilogy articulates the various norms that impact in the formation of gender, particularly of masculinities, through a complex system of power relations. The adherence to such norms is never linear, as the trilogy provides imaginative accounts of the contradictions that assist in the formulation of gender, depicting both the allure and the terror that constitute hegemonic masculinity. Located in the intersection of gender and postcolonial studies, the present study is based on the works by Raewyn Connell on masculinities. Animated by such a critical framework, the main research question of the present study is whether the trilogy advances a notion of masculinity that differs from the traditional rigid model, that is, whether there is resistance to hegemonic masculinity and what the spaces inhabited by the subaltern are. It is suggested that the trilogy presents the reader with instances of resistance to normative formulations of masculinity, by contrasting domination with the possibility of justice, and advancing an understanding of the often fatal consequences of gender norms to one’s sense of being in the world.