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Unraveling the molecular mechanisms driving brain tumorigenesis to unlock innovative therapies
No full textBrain tumors remain among the most challenging malignancies to treat due to high heterogeneity, aggressive growth, immunosuppressive microenvironment, and resistance to therapy. Despite advances in clinical care, long-term survival remains poor, underscoring the need for innovative therapeutic strategies. Recent progress in elucidating the genetic basis of central nervous system tumors has shifted classification toward molecular features, accompanied by an increasing number of clinical trials targeting genetic and epigenetic alterations as well as immune modulation.
Within this context, my PhD research focused on two of the most lethal brain tumors, glioblastoma (GB) and medulloblastoma (MB), with the goal of identifying novel molecular targets that could be exploited therapeutically.
In GB, we identified MEX3A, an RNA-binding protein and E3 ubiquitin ligase, as a key regulator of tumor growth. MEX3A is highly upregulated in GB and inversely correlates with RIG-I, a cytosolic RNA sensor activating type I interferon (IFN) signaling and apoptosis. We revealed that MEX3A promotes RIG-I ubiquitin-dependent degradation, whereas its silencing restores RIG-I levels, suppresses GB proliferation, and prolongs survival in orthotopic xenograft models. Given the role of RIG-I in immune activation and tumor suppression, we explored whether the stimulation of RIG-I could provide therapeutic benefit. We tested RNA agonists of RIG-I and found that M8 (5′pppRNA) potently activates IFN signaling, apoptosis, and tumor suppression. Notably, the combination of MEX3A silencing with M8 achieved stronger anti-tumor effects in GB cells than either intervention alone. Together, these results establish the MEX3A/RIG-I axis as a promising therapeutic target in GB supporting the development of RNA-based interventions to potentiate anti- tumor responses.
In parallel, we investigated the molecular mechanisms underlying MB tumorigenesis, focusing on the Sonic Hedgehog (SHH) subgroup, the most prevalent and genetically defined. In this context, we uncovered a novel role for formins, main regulators of cytoskeletal dynamics, with INF2 acting as a negative regulator of SHH signaling by counteracting mDia2-mediated activation of Gli1 transcription. Notably, INF2 expression increases during late cerebellar development, coinciding with SHH pathway being switched off, whereas its genetic inhibition enhances Gli1 expression and proliferation of granule neuron progenitors (GNPs), the cells of origin of SHH-MB. Consistently, INF2 was downregulated in SHH-MB samples, and its overexpression reduced proliferation and invasion of primary tumor cells. These findings highlight formins as novel regulators of SHH-MB biology and relevant therapeutic candidates.
Collectively, our studies underscore novel molecular vulnerabilities in GB and MB, providing a strong rationale for innovative therapeutic strategies that could ultimately transform the treatment landscape of these devastating brain tumors
Long-term impact of vitamin k antagonist treatment on left ventricular thrombus: Insights from an ambispective study
No full textIntroduction: The optimal duration of anticoagulant therapy for patients presenting with left ventricular thrombosis (LVT) remains a matter of debate. This study was designed to evaluate both the efficacy and safety of treatment with vitamin K antagonists (VKAs), administered either until complete thrombus resolution or for a maximum treatment period of 12 months.
Materials and Methods: This ambispective observational study enrolled patients diagnosed with LVT who were assessed at the Atherothrombosis Center of Policlinico Umberto I Hospital in Rome. Participants received VKA therapy until full thrombus resolution was achieved or for no longer than one year. The primary outcome measure was the rate of LVT resolution during therapy. Secondary outcomes included the occurrence of acute ischemic stroke, acute myocardial infarction, acute peripheral embolism, and both major and clinically relevant non-major bleeding events during a 12-month follow-up period.
Results: Thirty-six patients were analyzed, with a median age of 65 years, and 91.7% were male. The average time in the therapeutic range was 55% (±19%). VKA monotherapy was prescribed in 41.9% of cases, whereas the remainder received combination therapy with antiplatelet agents. The cumulative proportions of patients achieving LVT resolution at 3, 6, and 12 months were 11% (95% confidence interval [CI], 3–24), 39% (95% CI, 23–55), and 71% (95% CI, 52–84), respectively. Multivariable Cox regression analysis identified reduced left ventricular ejection fraction (hazard ratio [HR], 0.36; 95% CI, 0.12–1.09) and the presence of a left ventricular aneurysm (HR, 0.42; 95% CI, 0.16–1.11) as predictors of lower likelihood of thrombus resolution. Throughout the observation period, no arterial thromboembolic events occurred; one patient experienced a major bleeding episode and another a clinically relevant non-major bleeding event.
Conclusions: Incidence of LVT resolution increased progressively over the 12-month follow-up, with no arterial thromboembolic events and a low incidence of bleeding complications observed during anticoagulant therapy. Impaired left ventricular ejection fraction and the presence of ventricular aneurysm were associated with a decreased probability of thrombus resolution
Radiation risk mitigation in human space exploration: a primer, a vision, and the state of the art
No full textHuman exploration beyond low Earth orbit poses unique health and operational challenges, with space radiation recognizedas one of the most significant hazards. This comprehensive review examines the complex nature of the space radiation environment,its biological effects on humans and life support systems, and current strategies for risk assessment and mitigation. It details thecomposition and properties of galactic cosmic rays (GCRs) and solar particle events (SPEs), their interactions with spacecraftshielding, and the resulting biological impacts ranging from DNA damage to systemic effects including cancer, cardiovasculardisease, and central nervous system impairments. Special emphasis is given to the combined effects of radiation and microgravity,which together alter cellular function and influence health outcomes. The paper also explores the effects of radiation on plants andmicroorganisms as biological components of bioregenerative life support systems (BLSS). The issue of radiation-induced degradationof food and pharmaceuticals is also considered. Existing and emerging countermeasures, encompassing passive and active shielding,pharmacological agents, nutrition, physiological adaptations like synthetic hibernation, and personalized risk assessment throughtargeted crew selection are critically reviewed. Additionally, the work highlights the importance of high-fidelity analog studies,space-based experiments, and advanced risk models integrating physical, biological, and operational data to inform future missionplanning. Finally, the paper reviews existing infrastructures, experimental platforms, and European research programs, emphasizingthe critical role of ground-based accelerators, space analog environments, and in-flight studies in advancing our understanding ofradiation risks. By identifying key knowledge gaps and proposing a structured mitigation framework, this study presents a strategicroadmap for protecting human health and sustaining life during long-duration missions to the Moon, Mars, and beyond. (The reviewwork described in the paper stems from the discussions within the working group on Radiation sponsored by the Italian SpaceAgency.
SWOT Reimagined: Unraveling the Human-Technology Nexus in Agrivoltaic Transitions
No full textAgrivoltaics is increasingly discussed as a strategy to improve land-use efficiency, mitigate
environmental impacts, and strengthen agricultural resilience. By combining renewable
energy generation with food production, agrivoltaics reflects circular economy principles
and offers multifunctional land management. Yet its adoption depends on socio-cultural
perceptions, regulatory frameworks, and economic feasibility, requiring careful analysis
of how stakeholders assess its opportunities and constraints. This paper introduces “Hi-
erarchical SWOT Analysis”, a methodology that integrates hierarchical evocations with
semantic network analysis to examine stakeholder perceptions of emerging technologies.
Applied to the case of agrivoltaics diffusion in Jaén, Spain -a region where olive farm-
ing holds strong cultural and economic relevance- the method highlights both perceived
benefits and contested issues. While agrivoltaics is associated with energy independence
and economic stability, concerns emerge over landscape change, productivity trade-offs,
investment risks, technical incompatibilities, and regulatory uncertainty. By mapping the
relational structure of farmers’ social representations, the study connects technological
feasibility with social acceptability and offers insights for policy design. Findings point
to the importance of targeted incentives, cooperative models, and institutional support to
foster adoption while respecting local agricultural practices and land-use priorities. More
broadly, the proposed SWOT approach provides a scalable framework for analysing socio-
technical transitions and supporting the sustainable deployment of agrivoltaics and other
renewable energy technologies
Essays in environmental economics and climate justice
No full textThe global climate crisis has prompted governments to implement ambitious policies to mitigate environmental damage, reduce greenhouse gas emissions, and promote renewable energy. While essential, these policies impose significant socio-economic costs, that more likely disproportionately affecting vulnerable groups. This paper explores the dual distributional impacts of green policies: source-side income effects, such as job losses in carbon-intensive sectors, and use-side income effects, such as increased energy costs for households. The analysis highlights energy poverty as a severe consequence of use-side income effects, as it disproportionately burdens low-income households in their access to baskets of energy goods. Public perception plays a critical role in the success of climate policies. Resistance, such as the Yellow Vest protests in France, arises from perceived inequities and mistrust in governmental management. Addressing these challenges requires targeted compensatory measures, including retraining programs, subsidies, and energy efficiency initiatives, to enable a just transition. By balancing environmental goals, cost- effectiveness, and equity, referred to as the "triple dividend", policymakers can foster societal support and mitigate the regressive effects of the green transition.Climate protection is a global public good. The related mitigation policies implemented by a single country could have little effect on climate change issue such that there could be no net gains for society. However, those measures might create winners and losers among individuals. We investigate the citizens’ support for different pro-climate policies in EU countries, by considering the degree of heterogeneity in their attitudes towards climate issues using a cluster analysis. We also exploit the extent to which carbon intensity and green skills requirement of jobs contribute to supporting climate policies. Our results suggest that individuals’ occupational exposure does matter: people in emission-intensive activities tend to be against stringent climate measures, whereas people in jobs that require high levels of green skills are in favour of them.This study examines the distributional consequences of rising energy prices, and the mitigation measures implemented by the Italian government from 2021 to 2022. Using the novel Energy Consumption and Poverty (ECOP) microsimulation model, we evaluate the effects of energy price fluctuations on income and energy-related expenditures across different income classes of Italian households. The analysis is conducted under three scenarios: pre-policy, post-policy, and a 2019 baseline. The primary objective is to assess the effectiveness of government interventions in alleviating the financial burden on households, particularly those most vulnerable to energy poverty. This research addresses a critical gap in the existing literature by providing the first estimation of the High Share of Energy Expenditure in Disposable Income Indicator for Italy, a key metric for understanding energy poverty in a broader European Union context. The findings reveal that mitigation policies, such as the "Bonus Sociale," VAT reductions, and excise rate adjustments, had a progressive impact, benefiting lower-income families the most
Marine health and human health: definition of chemical profiles of persistent contamination in the seas and oceans of the planet through validation of sampling methods, analysis and quality assurance for emerging chemical contaminants
No full textPer- and polyfluoroalkyl substances (PFAS) constitute a large and heterogeneous class of synthetic organofluorine compounds widely employed for their unique physicochemical properties, such as thermal stability, surfactant behavior, and resistance to degradation. These characteristics, while making PFAS technologically valuable in applications including textiles, food packaging, cosmetics, firefighting foams, construction materials, oil recovery, pesticides, and medical devices, also confer high environmental persistence, bioaccumulative potential, and mobility. Consequently, PFAS have been classified as contaminants of emerging concern.
Once discharged, they undergo long-range atmospheric and oceanic transport, resulting in global contamination of air, soil, water, sediments, and marine systems. Oceans represent major sinks for PFAS, but re-emission through sea spray aerosols contributes to their continuous cycling. Bioaccumulation and biomagnification, particularly of long-chain perfluoroalkyl acids (PFAAs) such as PFOS and PFOA, have been extensively documented. Human biomonitoring programs have consistently confirmed widespread exposure through food, drinking water, consumer products, and indoor environments. Epidemiological and toxicological evidence links PFAS exposure to immunotoxicity, endocrine disruption, hepatotoxicity, reproductive toxicity, developmental effects, and elevated cancer risk. These findings have driven international regulatory initiatives, including restrictions under the Stockholm Convention, binding European limits in drinking water and biota, and recent enforceable US EPA standards.
In this context, the present doctoral research, developed within the Sea Care project in collaboration with the Italian Navy and the National Institute of Health (ISS), focused on the development and validation of a sensitive multi-residual liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the trace-level determination of 30 PFAS in seawater. Sample preparation was performed via solid-phase extraction (SPE). Method validation yielded limits of detection and quantification in the ng/L range, with isotopically labeled internal standards ensuring accuracy and reproducibility. Specifically, LODs ranged from 0.003 to 0.05 ng/L, while LOQs were established between 0.006 and 0.15 ng/L. Quality control stability tests demonstrated robustness, with most analytes showing relative standard deviations below 20%. Particular attention was devoted to minimizing system- and solvent-derived contamination, including the replacement of fluoropolymer components with PEEK tubing, the use of polypropylene vials and PFAS-free solvents, and the introduction of a reversed-phase delay column.
The validated protocol was applied to 137 seawater samples collected from 86 sites during the SeaCare 2022–2025 international monitoring campaign, covering the Atlantic Ocean, Mediterranean Sea, Arctic Ocean, Red Sea, Persian Gulf, and Indian and Pacific Oceans, with both surface and deep-water layers investigated. Results revealed widespread PFAS occurrence, including detection in remote regions such as the Arctic Ocean, confirming their long-range transport capacity. The highest concentrations (>40 ng/L Σ30PFAS) were observed in industrialized or traffic-intensive areas such as Venice, Ravenna, Dubai, and Doha, where PFBA, PFHxA, PFOA, PFNA, PFOS, and emerging PFAS including ADONA and FBSA were most frequently detected.
Overall, this work demonstrates the reliability of the validated LC–MS/MS method for trace PFAS quantification in complex marine matrices and provides new insights into their global occurrence, transport mechanisms, and potential ecotoxicological implications, contributing to improved risk assessment strategies and regulatory frameworks for the protection of human health and ecosystems
ADRC Parameters Tuning using Traditional and AI-based Methods: A Survey
No full textActive Disturbance Rejection Control (ADRC) has emerged as a prominent strategy for mitigating uncertainties and disturbances in complex systems. However, the performance of ADRC heavily depends on how well its parameters are tuned, which can be quite challenging in dynamic and nonlinear environments. This paper reviews both traditional and AI-based methods for tuning ADRC parameters, covering developments from 1990 to 2024. Traditional methods like trial-and-error, mathematical optimization, and frequency domain analysis are appreciated for their simplicity and stability guarantees. However, they often struggle with complex, nonlinear, or time-varying systems. On the flip side, AI-based methods—including machine learning, evolutionary algorithms, and neural networks—offer greater adaptability and efficiency, effectively addressing many limitations of traditional techniques. However, they also introduce new challenges related to data quality, computational complexity, and how interpretable they are. We highlight the potential of hybrid approaches that blend the strengths of both traditional and AI-based methods. By providing a thorough analysis of various tuning techniques, we aim to help design and implement more effective ADRC systems. Our findings are particularly relevant for advancing control engineering and automation in applications where high performance and robustness are crucial. We also point out future research directions, such as developing hybrid methodologies, creating interpretable AI models, and designing real-time adaptive tuning algorithms to meet the evolving demands of sophisticated control systems
Sapienza per la valorizzazione del patrimonio museale internazionale. L'esperienza di Maputo
No full textL’articolo riflette sul ruolo contemporaneo del museo universitario come luogo di integrazione tra ricerca, didattica e comunicazione culturale, sottolineando come la qualità dell’allestimento e dello spazio architettonico sia elemento strutturale della trasmissione dei contenuti. A partire da un inquadramento storico del rapporto tra musei e università, viene presentato il caso del Museo di Storia Naturale dell’Università Eduardo Mondlane di Maputo, oggetto di un intervento di recupero e valorizzazione promosso dal Polo Museale della Sapienza nell’ambito del bando AICS 2021. Dopo aver ricostruito la complessa evoluzione storica dell’istituzione, dalla fondazione in epoca coloniale alla trasformazione in museo universitario, il contributo evidenzia le criticità funzionali, conservative e comunicative che mettevano a rischio le collezioni e l’efficacia della fruizione. Il progetto ha affrontato tali problemi proponendo una nuova idea di museo come esperienza culturale coerente, in cui contenitore e contenuto dialogano attraverso sequenze spaziali, soluzioni ambientali e dispositivi museografici capaci di rendere più chiara, accessibile e coinvolgente la narrazione scientifica. Particolare attenzione è dedicata alla riorganizzazione distributiva, alla creazione di spazi per l’educazione e la ricerca, al potenziamento della dimensione immersiva della sala della Savana e alla trasformazione del ballatoio in galleria dinamica per la restituzione pubblica delle ricerche universitarie. Il caso di Maputo è infine proposto come modello virtuoso di cooperazione internazionale e come esempio di come i musei universitari possano contribuire alla crescita culturale, alla consapevolezza ambientale e allo sviluppo sostenibile di contesti socio-economici complessi.The article reflects on the contemporary role of the university museum as a place of integration between research, teaching and cultural communication, highlighting how the quality of exhibition design and architectural space constitutes a structural component of content transmission. Starting from a historical overview of the relationship between museums and universities, the paper presents the case of the Natural History Museum of Eduardo Mondlane University in Maputo, which has been the subject of a restoration and enhancement project promoted by the Oilo Museale Sapienza within the framework of the 2021 AICS call.
After reconstructing the complex historical development of the institution, from its foundation in the colonial period to its transformation into a university museum, the contribution highlights the functional, conservation and communication-related critical issues that were putting both the collections and the effectiveness of public engagement at risk. The project addressed these problems by proposing a new idea of the museum as a coherent cultural experience, in which container and content engage in dialogue through spatial sequences, environmental solutions and museographic devices capable of making the scientific narrative clearer, more accessible and more engaging.
Particular attention is devoted to the reorganization of circulation and layout, the creation of spaces for education and research, the strengthening of the immersive dimension of the Savanna Hall, and the transformation of the gallery walkway into a dynamic gallery for the public presentation of university research. Finally, the Maputo case is proposed as a virtuous model of international cooperation and as an example of how university museums can contribute to cultural growth, environmental awareness and the sustainable development of complex socio-economic contexts
Decarbonization through electrification of large non-residential civil users: development of simulation models of aggregates of active and passive users for the access to the electricity market
No full textDecarbonization, nowadays, is maybe the main goal of the entire humanity since it is the key to arrest the Climate Change and its consequences on the environment and on human health and activities. This thesis describes the role and explores the potential contribution of non-residential civil buildings in this process. The research, conducted between 2022 and 2025, focuses on elaborating a consistent methodology to analyse large non-residential civil users, in order to assess their carbon footprint (energy related), energy needs, electricity consumption and, above all, to define a feasible and reliable “decarbonization through electrification” path that can habilitate these users to access to the electricity market.
Chapter 1 provides an overview of the current policies for the decarbonisation of the civil sector, led by the Fit-for-55 EU program. Chapter 2 focuses on electrification of large non-residential civil users, defining the boundaries of this research, demonstrating the feasibility of this solution, explaining the main efficiency (electric heat pumps, above all) and renewable energy production (especially photovoltaic) technologies. Chapter 3 gives an overview of the possibilities, for decarbonized and electrified buildings, to access to the electricity market both to sell demand response services and to buy/sell renewable energy in optimized modern configurations (“prosumers”). Chapter 4 shows the simulation methodologies used to analyse the case studies of the research. These models are based on current available standards, especially EN 16247 and UNI/TS 11300, and on literature review.
Chapters 5, 6, 7 and 8 provide details on the four case studies object of this study, selected according to their common characteristics (tertiary sector, public entities, Rome metropolitan area), in order to start the definition of a representative sample to be used in following researches. The first case study is an Italian museum in historic building, the National Gallery of Modern and Contemporary Art in Rome. This museum underwent a decarbonization through electrification process and real measured data were collected and analysed, to demonstrate the reliability and feasibility of the decarbonization through electrification. The second case study is a European research centre, ESA ESRIN in Rome; the third case study is an Italian research centre, whose identity cannot be published since this research contains sensitive data for a tender that will be announced in the next months; the fourth and last case study is the headquarter of an Italian public administration, hosted in an historic building, that has a very strong security policy and has not given the permission to report its sensitive data. These last three case studies are related to efficiency and decarbonization proposals that demonstrate the potential goals achievable through this process.
Chapter 9 collects the final conclusions of the research, with a focus on future developments. The last chapters report scientific publications and other research activities carried out by the candidate during the PhD
With Due Force: A Corpus‐Based Study of Boosters in Supreme Court Judgements
No full textThis study investigates the rhetorical function of adjectives and adverbs as boosters in dissenting opinions issued by judges of the Supreme Court of the United States. It focuses on the linguistic strategies through which dissenting judges assert their individual stance, engage critically with the majority’s reasoning and position themselves within the broader institutional discourse of the Court. Drawing on an ad hoc corpus comprising 934,370 tokens from dissenting opinions delivered between 2021 and 2025, the analysis employs corpus linguistic tools, including TagAnt and AntConc, to identify and categorise lexical items that intensify evaluative meaning. Boosters are examined in terms of their pragmatic function, with five primary categories emerging, namely, Criticising (C), Emphasising (E), Hedging (H), Stance (S) and Shared Values (SV). These categories reveal how lexical choices signal varying degrees of alignment, resistance and persuasion. Particular attention is paid to multi-word expressions or n-grams, specifically adverb-adjective and adverb-adverb combinations, through which judges construct nuanced evaluative meanings and reinforce rhetorical force. The study shows how these lexico-grammatical patterns contribute to the construction of judicial authority, the negotiation of institutional identity and the performative aspects of dissent. By foregrounding the role of linguistic intensification, the research contributes to a richer understanding of dissent as a site of rhetorical agency within legal discourse