Fondamento e limiti costituzionali del potere punitivo nel sistema di legalità integrata

La ricerca affronta la questione della punizione nella prospettiva del diritto costituzionale nazionale integrata con quella del diritto europeo dei diritti dell’uomo. Nella Parte I è sostenuta la tesi secondo cui la trasformazione della Costituzione penale avviata sotto l’influsso della giurisprudenza CEDU rappresenta complessivamente un avanzamento nel processo di costituzionalizzazione del potere punitivo. Questa conclusione è supportata attraverso un confronto della filosofia costituzionale classica sulla punizione con i diversi approcci interpretativi alla Costituzione penale sviluppati durante il XX secolo (approcci tradizionale, costituzionalistico ed EDU). Nella Parte II è invece sostenuta la tesi secondo cui, nonostante gli effetti positivi dell’armonizzazione sovranazionale, lo statuto costituzionale della punizione dovrebbe comunque rimanere formalmente autonomo dal diritto EDU. Non solo, infatti, nessun paradigma dei rapporti interordinamentali finora sviluppato può giustificarne un’integrazione totale, ma essa rischierebbe anche di diminuire la normatività dell’aspetto sociale della Costituzione penale, già ipocostituzionalizzato rispetto a quello liberale. Nella Conclusione sono quindi sviluppati gli elementi fondamentali di un approccio interpretativo alternativo alla Costituzione penale che risponda meglio di quelli esistenti alle esigenze sia di garantire la massima costituzionalizzazione della punizione sia di facilitare l’integrazione sovranazionale. In base a un simile approccio costituzionalmente fondato, sostanzialista, rights-based e inclusivo di tutte le ideologie costituenti, la Costituzione potrebbe essere letta nel senso di prevedere un modello di disciplina unitario per tutte le forme di esercizio del potere punitivo (salvo quello disciplinare, distinguibile sotto l’aspetto istituzionale) caratterizzato da: una riserva di legge a intensità variabile; uno scrutinio stretto della Corte sulla giustificabilità costituzionale della pena; l’estensione dell’ambito di applicazione dei principi di colpevolezza e rieducazione; un pieno sviluppo degli aspetti di garanzia collettiva dei classici principi costituzionalpenalistici (obblighi di tutela penale e garanzia dell’effettiva collocazione della pena in capo al soggetto colpevole), nonché derivabili dall’art. 3 Cost. (proporzionalità della pena alle condizioni materiali del soggetto punito).

Cross-sensors analysis of multispectral Earth observation data for environmental monitoring

Time Series Analysis of multispectral satellite data offers an innovative way to extract valuable information of our changing planet. This is now a real option for scientists thanks to data availability as well as innovative cloud-computing platforms, such as Google Earth Engine. The integration of different missions would mitigate known issues in multispectral time series construction, such as gaps due to clouds or other atmospheric effects. With this purpose, harmonization among Landsat-like missions is possible through statistical analysis. This research offers an overview of the different instruments from Landsat and Sentinel missions (TM, ETM, OLI, OLI-2 and MSI sensors) and products levels (Collection-2 Level-1 and Surface Reflectance for Landsat and Level-1C and Level-2A for Sentinel-2). Moreover, a cross-sensors comparison was performed to assess the interoperability of the sensors on-board Landsat and Sentinel-2 constellations, having in mind a possible combined use for time series analysis. Firstly, more than 20,000 pairs of images almost simultaneously acquired all over Europe were selected over a period of several years. The study performed a cross-comparison analysis on these data, and provided an assessment of the calibration coefficients that can be used to minimize differences in the combined use. Four of the most popular vegetation indexes were selected for the study: NDVI, EVI, SAVI and NDMI. As a result, it is possible to reconstruct a longer and denser harmonized time series since 1984, useful for vegetation monitoring purposes. Secondly, the spectral characteristics of the recent Landsat-9 mission were assessed for a combined use with Landsat-8 and Sentinel-2. A cross-sensor analysis of common bands of more than 3,000 almost simultaneous acquisitions verified a high consistency between datasets. The most relevant discrepancy has been observed in the blue and SWIRS bands, often used in vegetation and water related studies. This analysis was supported with spectroradiometer ground measurements.

Green approach to Palladium Cross-Coupling reactions and development of new methodologies based on highly abundant metals

Transition metal catalyzed cross-coupling reactions represent among the most versatile and useful tools in organic synthesis for the carbon-carbon (C-C) bond formation and have a prominent role in both the academic and pharmaceutical segments. Among them, palladium catalyzed cross-coupling reactions are currently the most versatile. In this thesis, the applications, impact and development of green palladium cross-coupling reactions are discussed. Specifically, we discuss the translation of the Twelve Principles of Green Chemistry and their applications in pharmaceutical organometallic chemistry to stimulate the development of cost-effective and sustainable catalytic processes for the synthesis of active pharmaceutical ingredients (API). The Heck-Cassar-Sonogashira (HCS) and the Suzuki-Miyaura (SM) protocols, using HEP/H2O as green mixture and sulfonated phosphine ligands, allowed to recycle and recover the catalyst, always guaranteeing high yields and fast conversion under mild conditions, with aryl iodides, bromides, triflates and chlorides. No catalyst leakage or metal contamination of the final product were observed during the HCS and SM reactions, respecting the very low limits for metal impurities in medicines established by the International Conference of Harmonization Guidelines Q3D (ICH Q3D). In addition, a deep understanding of the reaction mechanism is very important if the final target is to develop efficient protocols that can be applied at industrial level. Experimental and theoretical studies pointed out the presence of two catalytic cycles depending on the counterion, shedding light on the role of base in catalyst reduction and acetylene coordination in the HCS coupling. Finally, the development of a cross-coupling reaction to form aryldifluoronitriles in the presence of copper is discussed, highlighting the importance of inserting fluorine atoms within biological structures and the use of readily available metals such as copper as an alternative to palladium.

TiMMing: developing an innovative suite of bioinformatic tools to harmonize and track the origin of copy number alterations in the evolutive history of multiple myeloma

Multiple Myeloma (MM) is a hematologic cancer with heterogeneous and complex genomic landscape, where Copy Number Alterations (CNAs) play a key role in the disease's pathogenesis and prognosis. It is of biological and clinical interest to study the temporal occurrence of early alterations, as they play a disease "driver" function by deregulating key tumor pathways. This study presents an innovative bioinformatic tools suite created for harmonizing and tracing the origin of CNAs throughout the evolutionary history of MM. To this aim, large cohorts of newly-diagnosed MM (NDMM, N=1582) and Smoldering-MM (SMM, N=282) were aggregated. The tools developed in this study enable the harmonization of CNAs as obtained from different genomic platforms in such a way that a high statistical power can be obtained. By doing so, the high numerosity of those cohorts was harnessed for the identification of novel genes characterized as "driver" (NFKB2, NOTCH2, MAX, EVI5 and MYC-ME2-enhancer), and the generation of an innovative timing model, implemented with a statistical method to introduce confidence intervals in the CNAs-calls. By applying this model on both NDMM and SMM cohorts, it was possible to identify specific CNAs (1q(CKS1B)amp, 13q(RB1)del, 11q(CCND1)amp and 14q(MAX)del) and categorize them as "early"/ "driver" events. A high level of precision was guaranteed by the narrow confidence intervals in the timing estimates. These CNAs were proposed as critical MM alterations, which play a foundational role in the evolutionary history of both SMM and NDMM. Finally, a multivariate survival model was able to identify the independent genomic alterations with the greatest effect on patients’ survival, including RB1-del, CKS1B-amp, MYC-amp, NOTCH2-amp and TRAF3-del/mut. In conclusion, the alterations that were identified as both "early-drivers” and correlated with patients’ survival were proposed as biomarkers that, if included in wider survival models, could provide a better disease stratification and an improved prognosis definition.

Transatlantic regulatory divergence in pharmaceuticals: exploring economic and cultural explanations

The analysis delves into the regulatory divergence between the EU and the US in the pharmaceutical sector. Through law and economics, political science, and cultural theory perspectives, the study explores how collective preferences within each jurisdiction shape regulations. By identifying cultural orientations such as individualism in the US and hierarchy in the EU, the research suggests that underlying cultural factors play a significant role in regulatory decisions. Despite calls for regulatory harmonization, the recognition of legitimate differences in preferences due to cultural diversity emphasizes that uniformity may not always be the best solution, showcasing the importance of understanding cultural influences in shaping regulatory landscapes.