Multicomponent reactions, applications in medicinal chemistry & new modalities in drug discovery

The aim of this dissertation is to discuss new targets, to apply multicomponent reaction chemistry on scaffolds significant for medicinal chemistry applications and to implement new modalities in drug design and medicinal chemistry. In particular, the protein-protein interaction of PD-1/PD-L1 is discussed regarding its significance in the field of immuno-oncology. Moreover, multicomponent reaction methodologies are discussed, as a valuable tool to access natural product analogues and heterocycles of great significance in drug discovery. The last part of the thesis focuses on the new modality of proteolysis targeting chimeras (PROTACs) and their applications on cancer-related and Parkinson-related targets

Mnemophrenia: a science fiction film-essay on the future of cinema and artificial memories

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.“What is more real than the thoughts in your mind?”, “Re/structure your memories, re/construct your reality, re/define yourself”. The foundation of my research is about practising theory instead of theorising practice. My project begins with theory, which then leads to the science fiction film Mnemophrenia that constitutes the practical aspect of it. I attempt to demonstrate how theory and practice can be joined to create a fruitful union, each one feeding the other. In my research, I am inspired by Marshall McLuhan’s idea and use the medium as the message in order to depict and explore how cinema can affect human memory and more specifically create artificial memories and thus contribute to the dissolution of any boundaries between reality and fiction. The key research question that Mnemophrenia explores is: what would happen if in a future postmodern society the Bazinian myth of ‘total’ cinema becomes a reality? If ‘total cinema’ is pure realism and cinema can lead to artificial memories, then artificial memories and pure realism become one and films become artificial memories. Mnemophrenia depicts a different kind of human being or species, a schizophrenic ‘cyborg’ changed from within due to the advancement of virtual reality films which signals the end of cinema as we know it today. Mnemophrenia is about the future of cinema and maintains a horizon of hope that could lead to utopia; it does not discard technology as something evil as many previous science fiction films have done. I am interested in depicting through the film and examining in my thesis the possibility of a society where the dissolution of borders between fiction and reality does not lead to horrific consequences for humanity but instead promotes a potential for a new kind of identity that is an amalgam of real and artificial memories.Scholarship from Royal Holloway Universit

Interkulturelle Erziehung: eine Erziehung zur universalistischen Moral : die Berücksichtigung der moralischen Dimension von Integrations- und Migrationsfragen und deren Wirkung auf die Einstellungen gegenüber Migrantinnen und Migranten

This dissertation reflects the concept of immigrants’ integration from the angle of morality and justice. It discusses therefore Aristotle’s and Rawls’s theories of justice in a multicultural context and develops a fair model which understands integration as a two-way process of mutual accommodation (Mesotes) and a value system that neither discriminates immigrants nor disadvantages the host society (Maximin Strategy). Furthermore, this work illustrates the moral dimension of immigration and integration issues with semi-real stories and shows that a different framing of the issues (political, economic, moral, etc.) can lead to different attitudes and actions within a multicultural society, with people approaching immigration and integration under a moral point of view being more open and having more positive attitudes toward immigrants. This makes a moral approach within the intercultural education necessary, which finally aims at the intercultural moral person. The results of a quantitative study that took place in Switzerland with students of grade 8 confirm the assumption that moral framing of migration and integration issues explains openness and positive or negative attitudes towards immigrants and shows correlations between moral framing of migration and integration issues and other background information and skills like sex, type of visiting school, knowledge about reasons of immigration etc

Targeted Therapies for Pancreatic Cancer: Overview of Current Treatments and New Opportunities for Personalized Oncology.

Cytotoxic chemotherapy remains the only treatment option for most pancreatic ductal adenocarcinoma patients. Currently, the median overall survival of patients with advanced disease rarely exceeds 1 year. The complex network of pancreatic cancer composed of immune cells, endothelial cells, and cancer-associated fibroblasts confers intratumoral and intertumoral heterogeneity with distinct proliferative and metastatic propensity. This heterogeneity can explain why tumors do not behave uniformly and are able to escape therapy. The advance in technology of whole-genome sequencing has now provided the possibility of identifying every somatic mutation, copy-number change, and structural variant in a given cancer, giving rise to personalized targeted therapies. In this review, we provide an overview of the current and emerging treatment strategies in pancreatic cancer. By highlighting new paradigms in pancreatic ductal adenocarcinoma treatment, we hope to stimulate new thoughts for clinical trials aimed at improving patient outcomes

Editorial: Oncogenic RAS-Dependent Reprogramming of Cellular Plasticity.

No abstract availlable