Spatially defined peptidomimetics for pain relief and for targeted cancer therapy and diagnostics

Cancer is a disease that has plagued scientists for decades, and how to treat cancer and its complications are inevitable topics in current scientific research. Cancer pain is a major factor that reduces the quality of life of patients. Therefore, the development of analgesic agents with minimal adverse side effects, especially with low addiction, has attracted more and more attention. Among them, opioid analgesics are widely used to alleviate cancer pain and improve the quality of life of patients with advanced cancer, such as in the palliative therapy. Although peptide drugs are efficient, selective and safe, they have several unignorable disadvantages such as poor biological stability, rapid excretion, difficulty in penetrate blood brain barrier. In order to solve these problems, peptidomimetics were developed by introducing unnatural/modified amino acids, decorated peptide backbone, conformational restrictions and secondary structure mimics in peptide sequence. Compared with peptides, peptidomimetics have improved biological stability, increased bioavailability, high affinity and selectivity for receptor binding, and decreased adverse side effects. As the second part of this thesis, I explored the opportunity to design peptide-functionalized responsive biomaterials for the detection of cancer cell and the selective delivery of cytotoxic drugs. The conjugation of peptides with biomaterials enhanced the stability of the loaded drugs, improved targeted delivery, decreased side effects, and increased bioavailability. The precise and controllable drug delivery platform has profound application prospects in cancer treatment. Grafting specific peptides sequence on the surface of biomaterials can satisfy different drug delivery demands according to the characteristics of both peptides and biomaterials. For example, the introduction of tumor-targeting peptides can guide biomaterials into tumor lesions, and blood-brain barrier (BBB) shuttle peptides can lead biomaterials to penetrate the BBB, etc.

Escaping the debt trap: peripheral countries in prolonged debt crises and how to exit

This thesis is an interdisciplinary piece of academic research, situated within Critical Theory but engaging with other disciplines, mainly Political Economy and Politics, to tackle the topic at hand; sovereign debt crises. The thesis deals with the Problem of Debt and, more specifically, the Problem of Prolonged Sovereign Debt Crises, which is described in this thesis as the phenomenon of the “Debt Trap”. The specific question that will occupy us in this thesis is why countries appear unable to exit these prolonged debt crises. By exiting a debt crisis, we mean here a state of affairs in which a country has managed to render its debt sustainable, regain its democratic sovereignty, achieve economic recovery and, what is more, mitigate adverse effects of the crisis, especially in what human development, social inequality and poverty rates are concerned. This question is tackled through the use of an interdisciplinary approach that combines critical theory perspectives -which are grouped in two paradigms, the Subjectivity paradigm and the genealogies of Capitalism paradigm- with financialisation literature. The purpose is to form an interdisciplinary intellectual framework that will allow us to analyse with a critical perspective the two case studies of the Greek crisis from 2009 to 2015 and the Argentinean crisis from 1983 to 2005. The aim of the thesis is to develop a theoretical framework that allows us to deconstruct the various ideological approaches to these two particular cases of Debt traps, including neoclassical and neoliberal approaches, Conservative and Keynesian approaches and uncover the political, economic and class relation that underpin the prolonged crises that the two countries have experienced.

Reconciling the Irreconcilable? Sovereign Debt Restructuring and the Principles of International Law. A Law and Economics Perspective

This Thesis focuses on the principles of international law relevant to the resolution of legal disputes arising from sovereign insolvency conflicts. It attempts to contribute to the “incremental” approach literature by identifying principles, justifying their application in litigation and assessing whether they may help to reconcile the trade-offs prevalent in that context. For that purpose, this Thesis distinguishes between two different types of principles. First, it investigates the “Principles of Public International Law” (henceforth, “PIL principles”). Said category refers to norms of the law of nations which can be considered functionally and structurally similar to domestic constitutional principles (i.e., that can be regarded as “optimization” or “prima facie” requirements). This Thesis underscores the PIL principles protecting the interests of the creditors and citizens as well as the “public interest”, arguing that decision makers face a trade-off between these principles in the context of restructurings. Secondly, this Thesis inquires into the “general principles of domestic law” (henceforth, “GPDs”) which can be applied in sovereign debt restructuring. Two GPDs are identified: a “stay” on litigation and a “cram down” on dissenting creditors’ claims. Although both principles have been identified by the prior literature, this work advances a small but significant “twist” in the methodology used for that purpose: it relies exclusively on functional and comparative analysis. Moreover, this work justifies the application of said GPDs for two jurisdictions: New York and Germany. Finally, it posits that those GPDs can help to mitigate the trade-offs between PIL principles, thus reconciling the interests at stake.