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High-brightness beams for advancing light sources
No full textThis thesis investigates the generation and preservation of high‐brightness electron beams for advanced radiation sources, with applications ranging from compact inverse Compton facilities to large‐scale free‐electron lasers (FEL) and plasma‐based accelerators. The work aims to identify and mitigate the main physical mechanisms that limit beam quality during acceleration and compression, combining analytical modeling, numerical simulations, and machine design studies. The first part focuses on the BoCXS inverse Compton source, a proposal for a compact dual‐interaction‐point facility driven by a high‐gradient C‐band linac. Start‐to‐end simulations demonstrate the production of stable, low‐emittance, and low‐energy‐spread beams, and introduce optics strategies to preserve brightness through the switchyard and into the interaction region, ensuring tunable X‐ray emission in the 0.1–1 MeV range. The second part addresses the microbunching instability in the context of FEL facilities, such as FERMI and EuPRAXIA@SPARC_LAB. Using a semi‐analytical approach based on the Huang–Kim formalism, we study instability growth under different machine configurations and compression schemes, aiming at maximizing the beam quality required for FEL operation. In the end, we also present a theoretical outline of a laser heater, designed to ensure full compatibility with all EuPRAXIA@SPARC_LAB operation modes. The results highlight the importance of a model‐driven approach to accelerator design, while the methods and tools developed here provide a framework for optimizing brightness preservation across future light sources
Inference on the attractor space via functional approximation
No full textThis paper discusses semiparametric inference on hypotheses on the cointegration and
the attractor spaces for I(1) linear processes with moderately large cross-sectional dimension. The
approach is based on empirical canonical correlations and functional approximation of Brownian
motions, and it can be applied both to the whole system and or to any set of linear combinations
of it. The hypotheses of interest are cast in terms of the number of stochastic trends in specified
subsystems, and inference is based either on selection criteria or on sequences of tests. This pa-
per derives the limit distribution of these tests in the special one-dimensional case, and discusses
asymptotic properties of the derived inference criteria for hypotheses on the attractor space for
sequentially diverging sample size and number of basis elements in the functional approximation.
Finite sample properties are analyzed via a Monte Carlo study and an empirical illustration on
exchange rates is provided
Interplay between the RBP SYNCRIP and RNA methylation in determining EV miRNA-cargo and functional role in cell-to-cell communication
No full textThe RNA-binding protein SYNCRIP is a central mediator of the loading into Extracellular Vesicles (EVs) of specific miRNAs that bear the hEXO consensus core sequence (DDDVWS; D=not C, V=not U, W=A/U, S=C/G). This work identifies a previously uncharacterized dependence of SYNCRIP miRNA binding activity on m6A modification. This has been uncovered in an in vitro model of hepatocellular carcinoma (HCC).
Our previous findings reported that SYNCRIP and METTL3 control the composition of the EV cargo. Specifically, METTL3 methylates target miRNAs thus allowing the binding of a second RNA-binding protein (RBP) working as miRNA EV-loader, A2B1.
The present work focuses on: i) the impact of SYNCRIP in the specific miRNA loading into HCC-derived small EVs (sEVs); ii) the impact of SYNCRIP on the sEVs ability to induce EMT in non-tumorigenic liver cells; iii) the impact of m6A epitranscriptomic modification on miRNA loading into HCC-derived sEVs and in turn the ability to trigger EMT on recipient cells; iv) the interplay between SYNCRIP and m6A modification in determining SYNCRIP binding to
microRNAs.
Specifically, we demonstrate that METTL3-dependent methylation allows the recognition of a subset of miRNAs by SYNCRIP, thus promoting their selective export into sEVs.
Beyond unraveling this molecular interplay, we also investigated its biological impact on tumor
cell ability to influence epithelial target cells. Functionally, sEVs released by HCC cells silenced for SYNCRIP showed an impaired ability to induce EMT in healthy hepatocytes with respect to control HCC-derived sEVs; this reveals the direct EV involvement in the tumor microenvironment and in the establishment of pro-tumorigenic niches. More interestingly, sEVs released by METTL3-silenced HCC cells are unable to induce the expression of mesenchymal markers in target cells, while the epithelial ones remain mostly
unaffected. This indicates that epitranscriptomic modifications profoundly impact miRNA EV-loading and, in turn, EV function.
The translational relevance of this study resides in the identification of the molecular events and players to be selectively targeted for therapeutic purposes to interfere with EV-mediated tumor progression and metastatization
Single-particle ICP-MS method for the determination of TiO2 nano- and submicrometric particles in biological tissues
No full textTitanium dioxide (TiO2) nano- and submicrometric particles’ widespread use in differ-
ent sectors raised concerns about human and environmental exposure. The validation
of analytical methods is essential to ensure reliability in risk assessment studies. In this
study, a single-particle inductively coupled plasma mass spectrometry (spICP-MS) method
was validated for the detection, quantification, and dimensional characterization of TiO2
particles in biological tissues. Tissue samples collected after exposure to TiO2 particles
underwent mild acidic digestion using a HNO3/H2O2 mixture to achieve complete matrix
decomposition while preserving particle integrity. The resulting digests were analyzed
by ICP-MS operated in single-particle mode to quantify and size TiO2 particles. Method
validation was conducted according to ISO/IEC 17025:2017 and included linearity, repeata-
bility, recovery, and detection limit assessments. The limit of detection for TiO2 particles
was 0.04 μg/g, and 55.7 nm was the size the detection limit. Repeatability was within
0.5–11.5% for both TiO2 mass concentrations and particle size determination. The validated
method was applied to tissues from inhalation-exposed subjects, showing TiO2 levels of
80 ±20 μg TiO2/g and particle number concentrations of 5.0 ×105 ±1.2 ×105 part.
TiO2/mg. Detected TiO2 particles’ mean diameter ranged from 230 to 330 nm. The devel-
oped and validated spICP-MS method provides robust and sensitive quantification of TiO2
particles in biological matrices, supporting its use in human biomonitoring and exposure
assessment studies
The mnemonic warriors of the European far right : memory politics, laws, narratives
No full textThe book is an interdisciplinary panorama of the European far-right populist instrumentalization of the authoritarian and totalitarian legacy of the 20th century in an attempt to boost political legitimacy. Consequently, the monograph equips scholars and students of political science, history, sociology, cultural and social anthropology, and the legal sciences with an analytical toolbox for the nexus of research in memory politics of the populist far-right. The broad range of empirical case study analyses examine the instrumentalization of this contested legacy in Western, Central, and Eastern Europe as promoted by AfD in Germany, FdI in Italy, Vox in Spain, Chega in Portugal, Fidesz in Hungary and PiS in Poland
Degradation-Aware Energy Management in Residential Microgrids: A Reinforcement Learning Framework
No full textThis paper presents a degradation-aware reinforcement learning (RL) framework for real-time energy management in residential microgrids, focusing on optimizing lithium-ion battery usage while balancing economic benefits and battery longevity. We employ the Soft ActorCritic (SAC) algorithm, implemented via Stable Baselines3, to learn non-linear dispatch policies for a 5.2 kWh LiCoO2 battery pack, with degradation modeled using a simplified energy-throughput approach calibrated with NASA dataset measurements. The framework is tested across diverse household profiles over 1-year and 10-year simulations. Results show that RL-SAC outperforms a Model Predictive Control (MPC) baseline, extending battery life and reducing energy purchases in both simulations. These findings highlight RL-SAC’s potential for practical deployment in microgrids, offering a scalable solution for sustainable energy management
Art. 33. Affiliate degli organismi e subappaltatori
No full textIl commento tratta delle affiliate e degli organismi subappaltatori nell'ambito di regolazione europea dell'intelligenza artificial
Calorie Restriction Suppresses Premature Ageing in Pro-Apoptotic Yeast Mutants Through an Autophagy-Independent Mechanism
No full textThe budding yeast Saccharomyces cerevisiae has long served as a valuable model for in-
vestigating the molecular mechanisms underlying aging. Calorie restriction (CR) is a
well-established intervention that extends lifespan across species, yet the underlying molec-
ular mechanisms remain incompletely understood. In this study, we examined the effects of
CR on the chronological lifespan, oxidative stress response, and autophagic activity of the
Saccharomyces cerevisiae mutant Sclsm4∆1, which exhibits premature aging and elevated reac-
tive oxygen species (ROS) levels due to defects in mRNA decapping and processing-bodies
(PB) dynamics. We found that both moderate (0.1% glucose) and extreme (water incubation)
CR significantly extended the lifespan of Sclsm4∆1 mutants and markedly reduced intra-
cellular ROS accumulation without activating autophagy. These findings indicate that the
beneficial effects of CR stem from improved redox homeostasis and metabolic adaptation,
rather than from canonical autophagic pathways. Similar protective effects were observed
in a chromosomal lsm4∆1 mutant generated via CRISPR–Cas9, confirming that CR rescues
aging-related phenotypes in different genetic backgrounds. These insights reinforce the
roles of nutrient signaling, RNA metabolism, and redox balance in lifespan regulation,
offering new perspectives on the conserved anti-aging effects of calorie restriction
SIGNOR 4.0: the 2025 update with focus on phosphorylation data
No full textThe SIGnaling Network Open Resource (SIGNOR 4.0, https://signor.uniroma2.it) is a database of manually curated causal interactions between biological entities. These signaling events are annotated along with their effect—denoting the activation or inactivation of a target entity—and mechanism through which it is mediated, such as phosphorylation, binding, or transcriptional regulation. The data is freely accessible and can be explored as customizable signaling networks, allowing users to adapt them for different modeling purposes. In our latest update (version 4.0), we improved our curation interface to include additional data-validation tools, integrated text-mining-assisted curation, increased our curation content, and expanded the scope of our curation efforts, with a particular emphasis on phosphorylation data. Furthermore, we developed a subdomain of SIGNOR, PhosphoSIGNOR, a dedicated user interface designed to enable targeted access to phosphorylation-specific information and network visualization. This expanded dataset allows for a more comprehensive mapping of signaling alterations and their associations with dysregulated cellular processes. The platform enables users to dynamically query phosphosite-specific data, examine context-dependent modifications, and integrate findings with known regulatory mechanisms. The PhosphoSIGNOR section of SIGNOR serves as an essential resource for cancer systems biology, offering an intuitive interface for hypothesis generation and mechanistic insights
Valutazione degli outcomes oncologici e funzionali dei pazienti con carcinoma della laringe trattati chirurgicamente
No full textObiettivo: Questo studio ha lo scopo di mettere a confronto gli outcomes oncologici e funzionali dei pazienti affetti da carcinoma squamocellulare della laringe (SCCL) in base al trattamento chirurgico cui sono stati sottoposti. Sono stati messi a confronto i pazienti trattati tramite microchirurgia laser trans-orale (TOLMS) e quelli trattati tramite laringectomia parziale orizzontale con tecnica open (OPHL).
Mantenendo come obiettivo principale la radicalità oncologica, negli ultimi anni si è posta l’attenzione su approcci terapeutici più conservativi che potessero permettere di preservare quanto più possibile le funzioni laringee quali fonazione e deglutizione oltre alla respirazione.
Questo lavoro ha cercato di individuare quale fosse il miglior approccio chirurgico in termini funzionali, in base alle caratteristiche del tumore e alle caratteristiche cliniche del paziente.
Materiali e metodi: La popolazione presa in esame è composta da 130 pazienti con diagnosi di SCC della laringe (pT1 – pT3), trattati chirurgicamente presso il reparto di Otorinolaringoiatria del Policlinico Umberto I dal 2016 al 2025. Di questi 70 sono stati sottoposti a TOLMS e 60 a OPHL. L’outcome oncologico è stato valutato tramite follow-up clinico e radiologico. Gli outcomes funzionali sono stati valutati somministrando ai pazienti i seguenti questionari: Quality of Life Questionnaire (EORTC QLQ-H&N35), Voice Handicap Index-10 (VHI). La valutazione percettiva della voce è stata effettuata mediante la scala GRBAS e la valutazione oggettiva strumentale della deglutizione mediante la PAS (scala di aspirazione e di penetrazione) modificata per laringectomie parziali tramite endoscopia a fibre ottiche (FEES).
I valori sono stati considerati statisticamente significativi quando p<0,05 attraverso lo studio del T di Student e del metodo ANOVA. Lo studio statistico è stato effettuato mediante il programma informatico GraphPad Prism®.
Risultati: Tramite l’esame istologico definitivo è stato possibile suddividere i pazienti in base alla stadiazione: 50 pazienti sono stati classificati come pT1 (38%), di cui 42 trattati con TOLMS e 8 con OPHL, 59 pazienti (45%) sono stati classificati come pT2, di cui 28 trattati con TOLMS e 31 con OPHL, 21 pazienti (17%) sono stati stadiati come pT3, tutti trattati con OPHL. La sopravvivenza globale (OS) a cinque anni è stata dell'94,0%, 80,9%, 86,6% rispettivamente per T1, T2 e T3.
Per quanto concerne i risultati funzionali, in termini di deglutizione e fonazione, questi sono influenzati dall’estensione iniziale della patologia ma, a parità di stadiazione, risentono dell’entità della resezione chirurgica.
Conclusione: Lo studio mostra che sia per l'OPHL che per la TOLMS, l’outcome oncologico in termini di OS è in linea con la letteratura interanzionale. Gli outcomes funzionali confermano la diretta relazione con l’estensione della resezione chirurgica e la tecnica utilizzata. Questo studio conferma quanto la selezione accurata dell’approccio chirurgico in base alle caratteristiche del paziente e del tumore, sia fondamentale per ottimizzare i risultati oncologici e funzionali