Synthesis of Modified Amino Acids and Insertion in Peptides and Mimetics. Structural Aspects and Impact on Biological Activity.

I studied the effects exerted by the modifications on structures and biological activities of the compounds so obtained. I prepared peptide analogues containing unusual amino acids such as halogenated, alkylated (S)- or (R)-tryptophans, useful for the synthesis of mimetics of the endogenous opioid peptide endomorphin-1, or 2-oxo-1,3-oxazolidine-4-carboxylic acids, utilized as pseudo-prolines having a clear all-trans configuration of the preceding peptide bond. The latter gave access to a series of constrained peptidomimetics with potential interest in medicinal chemistry and in the field of the foldamers. In particular, I have dedicated much efforts to the preparation of cyclopentapeptides containing D-configured, alfa-, or beta-aminoacids, and also of cyclotetrapeptides including the retro-inverso modification. The conformational analyses confirmed that these cyclic compounds can be utilized as rigid scaffolds mimicking gamma- or beta-turns, allowing to generate new molecular and 3D diversity. Much work has been dedicated to the structural analysis in solution and in the receptor-bound state, fundamental for giving a rationale to the experimentally determined bioactivity, as well as for predicting the activity of virtual compounds (in silico pre-screen). The conformational analyses in solution has been done mostly by NMR (2D gCosy, Roesy, VT, molecular dynamics, etc.). A special section is dedicated to the prediction of plausible poses of the ligands when bound to the receptors by Molecular Docking. This computational method proved to be a powerful tool for the investigation of ligand-receptor interactions, and for the design of selective agonists and antagonists. Another practical use of cyclic peptidomimetics was the synthesis and biological evaluation of cyclic analogues of endomorphin-1 lacking in a protonable amino group. The studies revealed that a inverse type II beta-turn on D-Trp-Phe constituted the bioactive conformation.

Homological and Hodge-theoretic aspects of matroids and polymatroids

In the first part of this thesis, we study the action of the automorphism group of a matroid on the homology space of the co-independent complex. This representation turns out to be isomorphic, up to tensoring with the sign representation, with that on the homology space associated with the lattice of flats. In the case of the cographic matroid of the complete graph, this result has application in algebraic geometry: indeed De Cataldo, Heinloth and Migliorini use this outcome to study the Hitchin fibration. In the second part, on the other hand, we use ideas from algebraic geometry to prove a purely combinatorial result. We construct a Leray model for a discrete polymatroid with arbitrary building set and we prove a generalized Goresky-MacPherson formula. The first row of the model is the Chow ring of the polymatroid; we prove Poincaré duality, Hard-Lefschetz theorem and Hodge-Riemann relations for the Chow ring.

Internet of healthcare (law): privacy and data protection aspects in an internet of everything

The purpose of this research study is to discuss privacy and data protection-related regulatory and compliance challenges posed by digital transformation in healthcare in the wake of the COVID-19 pandemic. The public health crisis accelerated the development of patient-centred remote/hybrid healthcare delivery models that make increased use of telehealth services and related digital solutions. The large-scale uptake of IoT-enabled medical devices and wellness applications, and the offering of healthcare services via healthcare platforms (online doctor marketplaces) have catalysed these developments. However, the use of new enabling technologies (IoT, AI) and the platformisation of healthcare pose complex challenges to the protection of patient’s privacy and personal data. This happens at a time when the EU is drawing up a new regulatory landscape for the use of data and digital technologies. Against this background, the study presents an interdisciplinary (normative and technology-oriented) critical assessment on how the new regulatory framework may affect privacy and data protection requirements regarding the deployment and use of Internet of Health Things (hardware) devices and interconnected software (AI systems). The study also assesses key privacy and data protection challenges that affect healthcare platforms (online doctor marketplaces) in their offering of video API-enabled teleconsultation services and their (anticipated) integration into the European Health Data Space. The overall conclusion of the study is that regulatory deficiencies may create integrity risks for the protection of privacy and personal data in telehealth due to uncertainties about the proper interplay, legal effects and effectiveness of (existing and proposed) EU legislation. The proliferation of normative measures may increase compliance costs, hinder innovation and ultimately, deprive European patients from state-of-the-art digital health technologies, which is paradoxically, the opposite of what the EU plans to achieve.

Equine and human mutual welfare: a whole subject? Critical aspects and possible strategies in equine-assisted activities and therapies

General aim of the study is equine welfare, particularly concerning different husbandry methodic and inter-specific relational factors. Specific aim is the evaluation of possible mutual (to humans and to equines) benefits and the analysis of critical factors/strength points, of human-horse relationship within Therapeutic Riding context (TR). The peculiarities of human-horse relationship (compared to the bond with “Pet”) are analyzed, concerning their socio-anthropological, psychological, psycho-dynamic distinctive characteristics. 8 European representative therapeutic riding centers (TRC) were therefore selected (on the basis of their different animals’ husbandry criteria, and of the different rehabilitative methodologies adopted). TRC were investigated through 2 different questionnaires, specifically settled to access objective/subjective animal welfare parameters; the quality of human-horse relationship; technicians’ emotional experienced. 3 Centers were further selected, and behavioral (145 hours of behavioral recording) and physiological parameters (heart rate and heart rate variability) were evaluated, aimed to access equine welfare and horses’ adaptive responses/coping (towards general environment and towards TR job). Moreover a specific “handling-task” was ideated and experimented, aimed to measure the quality of TR technicians-horses relationship. We did therefore evaluate both the individual horses’ responses and the possible differences among Centers. Data collected highlight the lack of univocal standardized methodic, concerning the general animals’ management and the specific methodologies (aimed to improve animal welfare and to empower TR efficacy). Some positive and some critical aspects were detected concerning TR personnel-horse relationship. Another experimental approach did evaluate the efficacy (concerning the mutual benefits’ empowerment) of an “ethologically-fitted” TR intervention, aimed to educate children to and through the relationship with horses. Our data evidenced that the improvement of human horse relationship, through structured educational programs for TR personnel might have important consequences both to human and equine welfare.