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Navigando la governance attraverso i confini: il ruolo delle vie di pellegrinaggio transnazionali nei processi di governance territoriale
No full textThis PhD research examines the territorial governance processes enabled by transnational pilgrimage routes. These ancient paths, now revitalised with contemporary objectives such as cultural tourism, health and wellbeing, and slow mobility, offer significant potential to stimulate local development, particularly in rural areas facing economic and demographic challenges. The primary aim of the study is to explore how pilgrimage routes contribute to the implementation of territorial governance across various geographical scales. This is achieved by employing multiple dimensions of territorial governance as interpretative devices, including multi-stakeholder coordination, policy sector integration, and transcalar cooperation dynamics,
to address territorial challenges and opportunities. Conducted within the framework of the EU-funded project rurAllure (a coordination and support action funded under the call H2020-SC6-TRANSFORMATIONS-2020) the research involves six historic pilgrimage routes: The St. James Ways, Via Francigena, Via Romea Germanica, Romea Strata, St. Olav Ways, and Mary’s Way. Organised as a collection of papers, including a policy brief and six academic articles, this thesis employs a multi-method, qualitative case study approach. Each article illustrates how the study of pilgrimage routes intersects with the various dimensions of
territorial governance at interconnected geographical scales: European, national, regional, local, and organisational levels. Findings from these studies underscore the importance of effective coordination and alignment across policy sectors, governance levels, and diverse stakeholders for pilgrimage routes to serve as catalysts for rural development. Addressing these
challenges requires a transcalar governance approach that transcends administrative boundaries to enable cross-scale collaboration. This research contributes to a deeper understanding of transnational pilgrimage routes as tools of territorial governance, advancing scholarship on their role in rural development and cross-border cooperation, while expanding the application of territorial governance within the discipline of geography.Questa ricerca di dottorato esamina i processi di governance territoriale attivati dalle vie di pellegrinaggio transnazionali. Questi antichi percorsi, ora rivitalizzati con obiettivi contemporanei come il turismo culturale, la salute e il benessere, e la mobilità lenta, offrono un potenziale significativo per stimolare lo sviluppo locale, in particolare nelle aree rurali che affrontano sfide economiche e demografiche. L'obiettivo principale dello studio è esplorare come le vie di pellegrinaggio contribuiscano alla governance territoriale su diverse scale geografiche, utilizzando dimensioni come la coordinazione tra attori, l'integrazione dei settori politici e la cooperazione transcalare per affrontare le sfide territoriali. La ricerca è condotta nell'ambito del progetto finanziato dall'UE rurAllure (un'azione di coordinamento e supporto finanziata dal bando H2020-SC6-TRANSFORMATIONS-2020), e coinvolge sei rotte storiche: il Cammino di Santiago, la Via Francigena, la Via Romea Germanica, la Romea Strata, i Cammini di San Olav e il Cammino di Maria. La ricerca è organizzata in una serie di articoli, tra cui un policy brief e sei articoli accademici, e adotta un approccio qualitativo e multimetodo per lo studio di casi. Ogni articolo esplora come le vie di pellegrinaggio interagiscano con le diverse dimensioni della governance territoriale su scale interconnesse: europea, nazionale, regionale, locale e organizzativa. I risultati evidenziano l'importanza di una coordinazione efficace tra settori, livelli di governance e attori, affinché le vie di pellegrinaggio possano fungere da catalizzatori per lo sviluppo rurale. La ricerca sottolinea la necessità di un approccio transcalare per favorire la collaborazione tra diverse scale amministrative e contribuisce a una comprensione più approfondita delle vie di pellegrinaggio come strumenti di governance territoriale, ampliando al contempo l'applicazione della governance territoriale all'interno della disciplina geografica
Detection of circulating tumour cells, spread through air space and lymph-nodal micrometastasis in patients with lung cancer undergoing surgical resection
No full textIntroduction
Lung cancer is one of the most lethal malignancies worldwide. In early-stage cases, surgery is considered the cornerstone of therapy; however, despite radical resection, recurrence rates remain as high as 20% for stage I.
The aim of this project was to analyze the presence of Circulating Tumor Cells (CTCs), Spread Through Air Spaces (STAS), and lymph node micrometastasis in patients with clinical stage IA-IIA Non-Small Cell Lung Cancer (NSCLC) who received surgical treatment.
Materials and Methods
Clinical stage IA-IIA candidates for surgery were included. Patients who received neoadjuvant therapy were excluded.
CTCs were evaluated through peripheral blood samples collected the day before surgery and 30 days postoperatively.
The primary endpoints were: to verify whether the presence and/or levels of CTCs, STAS, and lymph node micrometastases are associated with long-term outcomes (DFI, OS) and to evaluate recurrence patterns in patients with CTCs, STAS, and lymph node micrometastases.
Results
Forty-six patients were enrolled in the study, with 42 meeting the inclusion criteria.
Half of the patients were female (21, 50%), and the mean age was 71.8 years (Standard Deviation, SD, ±8.0). Lymph node micrometastasis was found in only 2 cases (4.8%); conversely, STAS was confirmed in half of the patients (21, 50.0%). CTCs were detected in 20 patients (47.6%). Pre- and postoperative CTCs were present in 3 patients (7.1%), while in 11 patients CTCs were detectable only after surgery. The mean number of preoperative CTCs was 2.4 (±1.6), while the mean 30-day CTC count was 4.0 (±6.5). CTCs were more common in squamous cell carcinoma (p=0.047), and there was a trend towards a correlation between STAS presence and postoperative CTCs (p=0.085).
Conclusions
Our preliminary results confirm that CTCs are present even in early-stage lung cancer and suggest a possible correlation with other pathological features such as STAS
The role of PARP inhibitors in the cross-talk between DNA damage and activation of the cGAS/STING immune response in Ewing sarcoma cells
No full textInhibition of poly (ADP-ribose) polymerase (PARP)1 in cancer therapy is an adopted strategy to treat cancers where DNA repair is defective, particularly in those tumors in which mutations in BRCA1/2 genes or alterations mimicking BRCA1/2 loss occur. In Ewing sarcoma (EWS) the fusion product EWS::FLI1 impairs the correct functioning of the homologous recombination (HR) system by sequestering BRCA1, leading to a dysregulated transcription process and a consequent accumulation of R-loops. EWS sensitivity to PARP inhibitors (PARPi) has been demonstrated in several preclinical studies; yet, acquired resistance remains a major challenge that hinders the clinical success of PARPi treatment. Here, we demonstrated that PARP1 inhibition is relevant in promoting changes not only in tumor cells but also in the immune system. Indeed, PARP1 inhibition prompts double-stranded DNA (dsDNA) and micronuclei formation, triggers the cGAS/STING/IFNs pathway activation and enhances recruitment and polarization of macrophages. In addition, the PARPi-resistant model developed shows an impaired activation of the cGAS/STING/IFNs pathway which is related to a weak macrophages-mediated immune response. A further elucidation of pathways and mechanisms that contribute to or are affected by the PARPi resistance is urgently needed to improve the treatment response and provide novel therapeutic strategies for EWS patients
Dynamic modeling of heavy-tailed extreme events with applications to financial and environmental data
No full textExtreme events characterized by heavy-tailed distributions can cause significant damage, resulting in phenomena such as market crashes or flash floods.
The present thesis offers contributions on how to monitor the risk associated to such events through time, by adopting a dynamic modeling approach cast into the Extreme Value Theory (EVT) paradigm.
This strategy consists in modeling EVT distributions conditional upon past observed extreme values so that at each point in time an indication of risk is available.
The first contribution focuses on time-varying tail risk estimation where extreme events are defined as exceedances over a threshold. Since the threshold selection affects tail risk estimates, dynamic extended versions of Generalized Pareto distribution have been developed to lessen the impact of threshold selection. Simulation studies and real data analyses suggest that working with the extended version of the distribution helps capture departures from the Generalized Pareto approximation yielding robust estimates of tail risk.
The second contribution integrates the dynamic modeling approach into the environmental context, and aims at studying trends in hourly extreme precipitation. Despite the concern on increasing intensification of hourly precipitation, available statistical models borrow from a regression setting that is not designed to accommodate hourly precipitation characteristics. We propose a dynamic fixed-effects Generalized Pareto model that allows to capture trends in the extreme high quantiles without the need for strong arbitrary model assumptions.
The third contribution introduces the concept of financial tail contagion and aims at studying dynamic extreme cross-sectional dependence among risky assets observed for multiple units (e.g., countries).
We develop a dynamic Spatial Autoregressive model in the block maxima context, here the spatial dependence is summarized in just a time-varying parameter. Compared to existing EVT-based models, this approach allows to assess global dependence among units in a parsimonious way
Development of advanced adsorption and ion exchange technologies for nutrient recovery and contaminant removal from municipal and combined sewer overflow wastewaters
No full textThis study explores advanced adsorption and ion exchange technologies for the removal and recovery of nitrogen and phosphorus from municipal wastewater (MWW) and combined sewer overflow (CSO) wastewater. The growing demand for sustainable wastewater treatment highlights the need for innovative processes that minimize environmental impact while enabling resource recovery. Excessive nitrogen and phosphorus contribute to eutrophication, especially when wastewater is discharged without adequate treatment. CSO discharges, in particular, pose severe environmental risks due to high contaminant loads and untreated releases during heavy rainfall events. For MWW treatment, G13 geopolymer demonstrated superior ammonium adsorption, with a maximum capacity of 37 mgN g⁻¹ and the ability to treat 200 bed volumes (BVs) before reaching regulatory limits. Its high regeneration efficiency supports sustainable nitrogen recovery. Calcined pyroaurite emerged as the most effective phosphorus sorbent, achieving 12 mgP g⁻¹ capacity and treating 730 BVs before exceeding 1 mgP L⁻¹, complying with EU standards. Phosphate precipitation from the desorbed product confirmed its potential for fertilizer applications. CSO wastewater required different sorbents due to variable contaminant loads. MS13X zeolite effectively removed ammonium, with 18 mgN g⁻¹ of maximum adsorption capacity and sustained efficiency over 230 BVs before exceeding the 15 mgN L⁻¹ threshold. Calcined Sorbacid 911 showed the highest phosphate removal efficiency, achieving 37 mgP g⁻¹ adsorption and treating 400 BVs before reaching 2 mgP L⁻¹. A two-stage system integrating microfiltration and adsorption enhanced contaminant removal, targeting additional pollutants such as heavy metals, PFAS, and pesticides. Further investigations focus on long-term material stability, competitive ion exchange, and optimized regeneration strategies to enhance cost-effectiveness and operational efficiency. The study demonstrates the high potential of adsorption-based technologies for large-scale wastewater treatment, paving the way for improved sustainability and resource recovery. Future research will refine process parameters and explore advanced regeneration techniques to maximize material lifespan and system performance
Evaluation of agents targeting mechanisms involved in repair of drug-induced DNA damages in osteosarcoma
No full textOsteosarcoma (OS) is a highly aggressive bone tumor, which shows high prevalence among children and young adults and often displays drug resistance towards the most common neoadjuvant chemotherapy drugs. Provided that three out of the four drugs used induce DNA damage either directly (cisplatin and ifosfamide) or indirectly (doxorubicin), one of the resistance mechanisms observed in OS is represented by aberrantly activated DNA repair pathways, which allow tumor cells to survive and to cope with DNA damage. A thorough investigation of genetic status involved in such aberrant DNA repair activity, along with emergence of new inhibitors targeting these genes, could provide new treatment strategies to overcome drug resistance in OS. The present project aims to evaluate the efficacy of new inhibitor drugs targeting genes and pathways involved either directly or indirectly in DNA repair in human OS cell lines. Specific categories of inhibitors were examined in light of the important roles covered by targeted genes in OS and for their potential exploitation in treatment of this entity. Moreover, efficacy of PARP inhibitors was prioritized and Talazoparib peaked as most effective agent to be further investigated. Indeed, the selection of human OS cell lines resistant to prioritized DNA repair inhibitor Talazoparib was carried out to provide an experimental model for studying the underlying mechanisms of resistance which may be developed by OS cells. Moreover, potential use of Talazoparib as adjuvant to conventional chemotherapy was assessed in combined treatments with DX and CDDP. Lastly, such in vitro efficacy assessment was accompanied by NGS investigation provided by targeted multimodal sequencing of nucleic acids from human OS cell lines, which yielded preliminary results to be further explored. Such approach was attained in order to shed light on potential biomarkers to be considered for effective translation of new treatment approaches in OS clinical setting
"More than a place to sleep". Student housing in the age of financialization: a case study on Bologna
No full textUna nuova tipologia di studentati “di lusso” (PBSA) costruiti e gestiti da attori finanziari, sta ridefinendo lo student housing e i paesaggi urbani dell’Europa meridionale. Parallelamente, nuovi profili di studenti consumano questi spazi esclusivi, innescando trasformazioni urbane ancora poco studiate. Questa tesi analizza l’emergere e l’impatto dei luxury PBSA nella città di Bologna, adottando un approccio multi-scalare e sviluppando uno studio di caso che spazia dai PBSA e il quartiere in cui sono inseriti alle dinamiche delle convention immobiliari di questo mercato. L’obiettivo è indagare – connettendoli – tanto gli aspetti politico-economici che soggiaciono all’ingresso di questi capitali nella città, che l’esperienza vissuta degli studenti che li abitano e la loro relazione con il territorio. A livello teorico, la tesi mette in dialogo la letteratura sulla finanziarizzazione urbana con quella sulla studentification, fornendo una prospettiva integrata tra consumption e production side. Essa evidenzia come i PBSA siano il punto d’avvio di un processo di finanziarizzazione dell’abitare, mettendo in luce il ruolo degli intermediari, come developer e property manager, nel determinarne le configurazioni. Parimenti, emerge l’azione delle amministrazioni pubbliche nel sostenere i PBSA, integrandoli in strategie di sviluppo post-crisi. La natura dei PBSA appare influenzare le pratiche di vita e le geografie degli studenti, soprattutto internazionali, che li abitano. Accanto a dinamiche d’entre-soi e di polarizzazione socio-spaziale, l’analisi delle traiettorie di arrivo mostra anche dinamiche di segregazione “involontaria”, fomentate dalla crisi abitativa. Queste strutture rappresentano i vettori di una nuova fase del rapporto tra studenti e città e di un nuovo “abitare studentesco” plasmati dalle logiche della finanza. La stretta connessione tra questi processi e la trasformazione, in primis turistica, in atto a Bologna suggerisce l’importanza di considerarli come interconnessi, offrendo inoltre una critica alle letture anglocentriche della studentification e un resoconto della finanziarizzazione in una città “ordinaria”.A new type of “luxury” Purpose-Built Student Accommodation (PBSA), developed and managed by financial actors, is reshaping student housing and urban landscapes in Southern Europe. At the same time, new student actors are increasingly consuming these exclusive spaces, fostering urban transformations that remain largely underexplored. This thesis examines the rise and impact of luxury PBSA in the mid-sized Italian city of Bologna, adopting a multi-scalar approach that links PBSA, their surrounding neighbourhoods, and the real estate conventions shaping this market. It investigates both the political-economic forces driving financial investment in Bologna and students' lived experiences in these spaces, along with their relationship to the city. The study bridges urban financialization and studentification literature, integrating perspectives on both the consumption and production sides. It argues that PBSA are key sites of housing financialization, shaped by intermediaries such as developers and property managers. It also highlights the role of public administrations in supporting PBSA as part of post-crisis development strategies. PBSA influence students’ residential practices and spatial behaviours, particularly among international students. Alongside dynamics of entre-soi and socio-spatial polarization, the analysis of arrival trajectories reveals forms of “involuntary” segregation, exacerbated by the housing crisis. These accommodations are thus catalysts for a new phase in student-city relations, fostering an emerging form of “student dwelling” shaped by financial logic. The strong connection between these transformations and Bologna’s broader urban shifts—particularly tourism-led change—calls for an integrated perspective. This study also challenges Anglo-centric interpretations of studentification and contributes to the debate on financialization in an “ordinary” city
Memoria e nostalgia dell’Ottocento: Il Gattopardo e Bearn. La trasformazione della classe aristocratica italiana e spagnola e la sua rappresentazione nella letteratura del XX secolo
No full textEl presente trabajo examina la transformación de la aristocracia italiana y española del siglo XIX a través de su representación literaria en Il Gattopardo de Giuseppe Tomasi di Lampedusa y Bearn o la sala de las muñecas de Llorenç Villalonga. A partir de un enfoque interdisciplinario que integra historia, literatura e historia de las emociones, esta investigación analiza cómo la memoria y la nostalgia operan como mecanismos que humanizan la experiencia de la nobleza en declive y permiten una reinterpretación crítica de su legado en la Europa contemporánea. Ambientadas en los paisajes insulares de Sicilia y Mallorca, ambas novelas retratan a una élite atrapada entre la adaptación y la resistencia a la desaparición de su mundo, reflejando tanto las tensiones de sus protagonistas como las inquietudes de sus propios autores.
El objetivo de este estudio es incorporar una perspectiva emocional e íntima al análisis histórico de la aristocracia europea, demostrando cómo la literatura no solo conserva mentalidades y tradiciones, sino que también enriquece la historiografía al ofrecer perspectivas subjetivas y simbólicas de los procesos de cambio social. Así, las novelas se configuran como espacios de diálogo entre historia y ficción, donde el pasado es reescrito a través de la imaginación literaria.
Esta investigación revaloriza Il Gattopardo y Bearn como fuentes esenciales para comprender la aristocracia mediterránea en el imaginario cultural del siglo XX, destacando cómo ambas obras exploran las dimensiones existenciales de una clase marcada por la melancolía y la pérdida. En última instancia, estos textos permiten reconsiderar la literatura como testimonio más de la historia y revelar su papel en la preservación y resignificación de la memoria colectiva, proyectando en el presente las tensiones y dilemas de un mundo en transformación.This dissertation examines the transformation of the Italian and Spanish aristocracy in the 19th century through its literary representation in Il Gattopardo by Giuseppe Tomasi di Lampedusa and Bearn o la sala de las muñecas by Llorenç Villalonga. Adopting an interdisciplinary approach that integrates history, literature, and the history of emotions, this research analyzes how memory and nostalgia function as mechanisms that humanize the experience of the declining nobility and enable a critical reinterpretation of its legacy in contemporary Europe. Set against the insular landscapes of Sicily and Mallorca, both novels depict an elite caught between adaptation and resistance to the disappearance of their world, reflecting not only the tensions of their protagonists but also the concerns of their own authors.
The aim of this study is to incorporate an emotional and intimate perspective into the historical analysis of the European aristocracy, demonstrating how literature not only preserves mentalities and traditions but also enriches historiography by offering subjective and symbolic perspectives on social change. Thus, these novels serve as spaces of dialogue between history and fiction, where the past is rewritten through literary imagination.
This research reassesses Il Gattopardo and Bearn as essential sources for understanding the Mediterranean aristocracy in the cultural imagination of the 20th century, highlighting how both works explore the existential dimensions of a class marked by melancholy and loss. Ultimately, these texts invite us to reconsider literature not only as a testimony to history but also as a vehicle for the preservation and reinterpretation of collective memory, projecting the tensions and dilemmas of a transforming world into the present.Il presente lavoro esamina la trasformazione dell’aristocrazia italiana e spagnola del XIX secolo attraverso la sua rappresentazione letteraria in Il Gattopardo di Giuseppe Tomasi di Lampedusa e Bearn o la sala de las muñecas di Llorenç Villalonga. Partendo da un approccio interdisciplinare che integra storia, letteratura e storia delle emozioni, questa ricerca analizza come la memoria e la nostalgia operino come meccanismi che umanizzano l’esperienza della nobiltà in declino e permettano una reinterpretazione critica della sua eredità nell’Europa contemporanea.
Ambientati nei paesaggi insulari della Sicilia e di Maiorca, entrambi i romanzi ritraggono un’élite intrappolata tra l’adattamento e la resistenza alla scomparsa del proprio mondo, riflettendo sia le tensioni dei loro protagonisti che le inquietudini dei loro autori.
L’obiettivo di questo studio è incorporare una prospettiva emozionale e intima nell’analisi storica dell’aristocrazia europea, dimostrando come la letteratura non solo conservi mentalità e tradizioni, ma arricchisca anche la storiografia offrendo prospettive soggettive e simboliche sui processi di cambiamento sociale. Così, i romanzi si configurano come spazi di dialogo tra storia e finzione, in cui il passato viene riscritto attraverso l’immaginazione letteraria.
Questa ricerca rivaluta Il Gattopardo e Bearn come fonti essenziali per comprendere l’aristocrazia mediterranea nell’immaginario culturale del XX secolo, mettendo in evidenza come entrambe le opere esplorino le dimensioni esistenziali di una classe segnata dalla malinconia e dalla perdita. In ultima analisi, questi testi permettono di ripensare la letteratura come testimonianza della storia e di rivelarne il ruolo nella conservazione e nella ridefinizione della memoria collettiva, proiettando nel presente le tensioni e i dilemmi di un mondo in trasformazione
Innovative doped V/P/O catalysts for the selective oxidation of n-butane to maleic anhydride
No full textMaleic anhydride is widely used in industry, primarily produced via the selective oxidation of n-butane using vanadium/phosphorous oxides (V/P/O) catalysts, with vanadyl pyrophosphate (VPP) as the active phase. Despite extensive research, optimizing catalyst performance remains a challenge. This study investigates the effect of new dopants on VPP-based catalysts in fluidized and fixed-bed reactors, aiming to develop superior catalysts. Supported by Polynt S.p.A., various dopant combinations were tested to enhance structure and surface properties, improving activity and selectivity. Fluidized and fixed-bed samples underwent 24-hour screening under standard reaction conditions (SOC). In fluidized reactors, dopants such as niobium (Nb), iron (Fe), cobalt (Co), molybdenum (Mo), and bismuth (Bi) were tested, but none outperformed the industrial standard (P21). While Co- and Mo-doped samples performed similarly to P21, Fe and Bi dopants resulted in poor activity due to unfavorable P/V ratios and phase composition. Fixed-bed reactors showed more promising results. Coprecipitated Fe, Co, and Bi dopants enriched catalysts with the selective δ-VOPO₄ phase. The MFC-21 catalyst (Fe+Co+Bi) surpassed the industrial standard (M-STD), achieving 71% selectivity and 82% conversion at 400°C, leading to a patent for this dopant mix. New fluidized bed catalysts incorporating Fe+Co+Bi were synthesized and compared to Nb-doped industrial precursors under newly introduced WRC conditions. Nb-doped catalysts showed high activity and selectivity, while P22 (Nb via impregnation) had lower activity but improved stability. The C22-A catalyst (Fe+Co+Bi via coprecipitation) achieved 50% yield, 66% conversion, and 77% selectivity under SOC but lost selectivity at higher temperatures. Nb impregnation (C22-I) negatively impacted surface Brønsted acidity. While fixed-bed catalysts performed best, P22 and C22-A are promising alternatives to P21, provided further improvements in activity and thermal stability
Deep learning-based framework for toxicological assessment in early-stage drug discovery
No full textDrug toxicity remains a major challenge in pharmaceutical development, contributing significantly to drug candidate failures and market withdrawals while raising growing concerns about pharmaceutical contamination of ecosystems. Following green chemistry principles, particularly the design of inherently safer chemicals and prevention of waste through early prediction of toxicity, this thesis investigates two critical aspects of drug safety: environmental Persistence, Bioaccumulation, and Toxicity (PBT), and Drug-Induced Liver Injury (DILI). In the first case study, we developed a message-passing neural network model for PBT prediction, that demonstrated robust performance even when tested on structurally diverse compounds. The model successfully identified potential PBT chemicals among pharmaceuticals and revealed specific structural features associated with PBT properties. These findings provide valuable guidance for designing environmentally safer drugs during early development stages, supporting the implementation of green chemistry principles in pharmaceutical research. The second case study advanced our understanding of DILI prediction through the development of an interpretable deep learning model. This work explored novel approaches in deep learning to understand and predict hepatotoxicity risk through analysis of molecular structures. Our research introduces computational approaches that can enhance the early assessment of drug toxicity, supporting the development of safer and more sustainable pharmaceuticals. These methodologies represent a significant step toward integrating green chemistry principles into drug discovery, potentially reducing both environmental impact and development costs through early identification of toxicity risks