Archivio Istituzionale della Ricerca - Università degli Studi di Pavia
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The Years of Transition. English Translations of the Commedia, 1900-1950
No full textThis chapter examines English translations of Dante’s Commedia produced between 1900 and 1950 as a transitional phase shaped by modernism, the World Wars, and the institutional consolidation of Dante studies. It traces the shift from Victorian models toward a plural landscape of translation strategies—ranging from prose and blank verse to experimental linguistic registers—driven by competing priorities of fidelity, readability, pedagogy, and literary innovation. By situating key translators and editions within broader cultural and scholarly developments, the chapter argues that this period established new audiences, critical tools, and aesthetic paradigms that decisively reshaped the Anglophone reception of Dante
A differentiable and uncertainty-aware mutual information regularizer for bias mitigation
No full textEnsuring algorithmic fairness is a central challenge in high-stakes machine learning applications, where biased predictions can have harmful societal consequences. Discrimination may persist even when sensitive features are excluded from model inputs, due to statistical dependencies between protected and ostensibly non-sensitive attributes that allow bias to be indirectly learned. Mutual information is a principled measure of such dependence, yet its non-differentiability under hard-threshold classification rules precludes direct use in gradient-based training. This paper proposes a fairness-aware learning strategy that embeds a differentiable surrogate of mutual information directly into the objective of nonlinear classifiers. The surrogate replaces hard label assignment with a Bernoulli relaxation of predicted probabilities, stabilizes empirical distributions via kernel smoothing, and accounts for epistemic uncertainty through Monte Carlo dropout, yielding an uncertainty-aware regularizer compatible with stochastic gradient optimization. Experiments on synthetic and real-world datasets show that the method achieves favorable fairness–accuracy trade-offs, with substantial bias reduction and minimal impact on predictive performance. Additional evaluations confirm robustness under counterfactual perturbations and reveal sublinear runtime growth with dataset size, contrasting favorably with the superlinear scaling of a genetic algorithm baseline. Overall, the framework offers a general, theoretically grounded, and practically viable approach to fairness-aware learning in complex, high-dimensional settings, supporting responsible algorithmic decision-making alongside expressive modeling
LIPID NANOPARTICLES PRODUCTION AND CHARACTERIZATION FOR NUCLEIC ACID DELIVERY
No full textLipid nanoparticles (LNPs) were produced using a microfluidic MicroMixer chip. Formulations are composed of either an ionizable lipid (ALC-0315, 50%) or a cationic lipid (DDA, 43.5%), along with cholesterol, DSPC, and DMG-PEG2000. A fluorescent probe (25-NBD cholesterol) was added, and a model mRNA (mCherry) was encapsulated.
Optimization by Design of Experiment identified optimal production parameters: 5 mg/mL lipid concentration, a flow rate ratio of 1:3, and total flow rates of 960 μL/min for ALC-LNPs and 1400 μL/min for DDA-LNPs.
Characterization by DLS, NTA, and TRPS analysis for size, concentration, and surface charge confirmed low polydispersity (PDI < 0.3) and a stable particle size of 200 nm. TEM confirmed particle morphology, and fluorescence spectroscopy allowed tracking and quantification. With the Quant-iT RiboGreen assay the encapsulation efficiency of mRNA was assessed (EE ≈ 80%). In vitro studies on HMC-3 and HEK cells confirmed LNPs uptake and mRNA expression. ALC-LNPs exhibit lower toxicity compared to DDA-LNPs. Finally, protein corona formation was examined using LC-MS, highlighting a different protein composition based on LNP components and brain organoids were developed for further internalization studies.Lipid nanoparticles (LNPs) were produced using a microfluidic MicroMixer chip. Formulations are composed of either an ionizable lipid (ALC-0315, 50%) or a cationic lipid (DDA, 43.5%), along with cholesterol, DSPC, and DMG-PEG2000. A fluorescent probe (25-NBD cholesterol) was added, and a model mRNA (mCherry) was encapsulated.
Optimization by Design of Experiment identified optimal production parameters: 5 mg/mL lipid concentration, a flow rate ratio of 1:3, and total flow rates of 960 μL/min for ALC-LNPs and 1400 μL/min for DDA-LNPs.
Characterization by DLS, NTA, and TRPS analysis for size, concentration, and surface charge confirmed low polydispersity (PDI < 0.3) and a stable particle size of 200 nm. TEM confirmed particle morphology, and fluorescence spectroscopy allowed tracking and quantification. With the Quant-iT RiboGreen assay the encapsulation efficiency of mRNA was assessed (EE ≈ 80%). In vitro studies on HMC-3 and HEK cells confirmed LNPs uptake and mRNA expression. ALC-LNPs exhibit lower toxicity compared to DDA-LNPs. Finally, protein corona formation was examined using LC-MS, highlighting a different protein composition based on LNP components and brain organoids were developed for further internalization studies
COMPUTATIONAL ANALYSIS OF ENGINEERED NETWORK MOTIFS AT DIFFERENT SCALES
No full textLa biologia sintetica mira a progettare e implementare circuiti genetici con un comportamento che sia prevedibile e robusto. Tuttavia, raggiungere una stabilità nell'espressione genica rimane una sfida importante a causa delle molteplici fonti di variabilità, tra cui le fluttuazioni stocastiche nelle interazioni molecolari, il contesto genetico e fisiologico dell'ospite e il carico metabolico imposto dai costrutti sintetici. Questi fattori possono portare a discrepanze significative tra le previsioni teoriche e i risultati sperimentali, evidenziando la necessità di strategie integrative che combinino la modellizzazione matematica con l'analisi dei dati sperimentali per migliorare la comprensione e il controllo dei circuiti sintetici.
Date queste premesse, questo progetto di dottorato affronta il problema sviluppando e applicando modelli matematici deterministici e stocastici per studiare la variabilità dei circuiti genici sintetici. Questi modelli sono integrati dall'analisi dei dati sperimentali ottenuti sia da test a livello di popolazione che da tecniche su singole cellule, come la citometria a flusso e la microfluidica. Questo approccio integrato consente di analizzare in dettaglio come il rumore biologico, il contesto dell’ospite e la competizione per le risorse influenzano le prestazioni dei circuiti, fornendo informazioni che non possono essere acquisite solo con metodi teorici o sperimentali.Synthetic biology seeks to design and implement genetic circuits with predictable and robust behavior. However, achieving stability in gene expression remains a central challenge due to multiple sources of variability, including stochastic fluctuations in molecular interactions, the genetic and physiological context of the host, and the metabolic burden imposed by synthetic constructs. These factors can lead to significant discrepancies between theoretical predictions and experimental outcomes, highlighting the need for integrative strategies that combine mathematical modeling with experimental data analysis to improve the understanding and control of synthetic circuits.
Given these premises, this PhD project addresses the challenge by developing and applying both deterministic and stochastic mathematical models to study the contex-dependent and between-cell variability of synthetic gene circuits. These models are complemented with the analysis of experimental data obtained from both population-level assays and single-cell techniques, such as flow cytometry and microfluidics. This integrated approach enables the dissection of how noise, host context, and resource competition influence circuit performance, providing insights that cannot be captured by theoretical or experimental methods alone
Radiation‐Induced Luminescence of a Medium‐OH Pure Silica Core Multimode Optical Fiber in Steady State and Pulsed X‐Ray Irradiations: Potential and Limitations for Dosimetry
No full textA pure silica-core (PSC) optical fiber (OF) with medium hydroxyl (M–OH) content, optimized for visible signal transmission in harsh radiation environments, is studied as a candidate for radiation-induced luminescence (RIL) based dosimetry. The objective of this article is twofold: i) to evaluate whether this fiber can serve as a transport fiber for radioluminescence measurements when coupled to scintillating doped fiber probes and ii) to investigate its potential for standalone RIL-based dosimetry, particularly for high dose rates and pulsed radiation applications. A dedicated experimental setup, developed to simulate X-ray pulses, enables time-resolved RIL measurements to investigate memory effects and the exploitability under high dose rates, close to the ones of FLASH radiotherapy treatments (>40 Gy/s). The M–OH PSC OF exhibits promising response for RIL-based dosimetry, with a linear sensitivity increase with fiber length and significantly lower parasitic effects compared to the reference Ce3+ ion doped fiber. Its use as transport fiber seems promising as well, thanks to its overall negligible RIL contribution supporting its use in high-performance dosimetry systems
Esplorando i molteplici ruoli di RACK1: dall'integrità della barriera intestinale alla disfunzione immunitaria-endocrina e alla terapia antitumorale
No full textIl recettore per la Chinasi C 1 attivata (RACK1) è una proteina da 36 kDa con una struttura a sette β- foglietti che facilita il legame proteico. Di conseguenza, RACK1 è in grado di integrare gli input provenienti da diversi percorsi di segnalazione interagendo con vari complessi multiproteici, contribuendo così al mantenimento delle attività cellulari essenziali. L'espressione anomala di RACK1 è stata implicata in numerosi processi fisiologici e patologici, tra cui il cancro.
L'obiettivo della mia tesi di dottorato era quello di studiare le funzioni molecolari di RACK1 in diversi contesti biologici, con particolare attenzione a: (1) la funzione di RACK1 nel mantenimento dell'omeostasi della barriera epiteliale intestinale e i meccanismi molecolari coinvolti nel contesto delle malattie infiammatorie intestinali (IBD); (2) il ruolo di RACK1 nel sistema immunitario e la sua applicazione come strumento di screening per gli interferenti endocrini (EDC); (3) il ruolo di RACK1 nel cancro, compreso il suo coinvolgimento nella migrazione, proliferazione e sopravvivenza cellulare nel carcinoma mammario triplo negativo (TNBC), e la valutazione in vitro di nuove strategie terapeutiche - basate su miscele naturali complesse e agenti chemioterapici - mirate alla sopravvivenza cellulare e alle vie di segnalazione associate a RACK1.
Una comprensione più approfondita dei ruoli multifunzionali di RACK1 in diversi contesti biologici potrebbe fornire una solida base per future ricerche sulle sue funzioni fisiologiche e sul suo significato patologico. Nel complesso, questi risultati offrono nuove informazioni sulle attività di RACK1 dipendenti dal contesto cellulare.The receptor for activated C kinase 1 (RACK1) is a 36-kDa protein with seven-bladed β-propeller structure which facilitates protein binding. Consequently, RACK1 can integrate inputs from different signaling pathways by interacting with various multiprotein complexes, thereby contributing to the maintenance of essential cellular activities. Aberrant RACK1 expression has been implicated in numerous physiological and pathological processes, including cancer.
The aim of my PhD thesis was to investigate the molecular functions of RACK1 across different biological contexts, with a particular focus on: (1) RACK1 function in maintaining intestinal epithelial barrier homeostasis and the molecular mechanisms involved in the context of inflammatory bowel diseases (IBD); (2) RACK1 role in the immune system, and its application as a screening tool for endocrine-disrupting chemicals (EDCs); (3) RACK1 role in cancer, including its involvement in cell migration, proliferation, and survival in triple-negative breast cancer (TNBC), and the in vitro evaluation of novel therapeutic strategies - based on complex natural mixtures and chemotherapeutic agents-targeting cell survival and RACK1-associated signaling pathways.
A deeper understanding of the multifunctional roles of RACK1 across diverse biological contexts may provide a solid foundation for future investigations into its physiological functions and pathological significance. Collectively, these findings offer new insights into the context-dependent activities of RACK1
Structural characterization of chitosan/nanoclay nanocomposites as emergent engineered nanohybrid biomaterials
No full textChitosan-nanoclay nanocomposites (CNNCs) are attractive aqueous platforms for biorelevant manufacturing, yet the impact of clay morphology under identical preparation and testing conditions remains insufficiently resolved. In the present work, low-molecular-weight chitosan (CS) was combined with three nanoclays, bentonite (BEN, layered), halloysite (HAL, tubular) and sepiolite (SEP, fibrous), to prepare hybrid suspensions at pH 4.5 spanning defined CS/nanoclay ratios. BEN and SEP series were formulated from 15/85 to 75/25 (CS/nanoclay, w/w); HAL series ranged from 5/95 to 55/45. After 48 h aging and intermittent sonication, rheology was measured: all hybrids exhibited pronounced shear-thinning. For each clay type, the apparent viscosity increased steadily with higher chitosan content. This trend suggests that the flow behavior is mainly governed by the polymer, as protonated chitosan chains adsorb onto silicate surfaces and form bridges between particles, creating transient networks. Sepiolite-based hybrids showed the highest viscosities and the strongest shear-thinning, consistent with a network, fiber-driven architecture. Halloysite formulations displayed high viscosities with indications of a yield-like response, whereas bentonite afforded intermediate viscosities and smooth flow. The results indicate that nanoclay morphology plays a key role in determining network formation efficiency, enabling controlled modulation of rheological properties under fixed processing conditions. Complementary FTIR/XRPD and X-ray micro-computed tomography supported hybrid formation and uniform three-dimensional dispersion of the nanoclays. Collectively, these results provide clear design rules for programming CNNC rheology under mild, aqueous conditions, offering practical guidance for casting, molding and printing of bioactive formulations that require high shear injectability and structural integrity at rest. The materials palette provides a tunable basis for bioactive formulations and future device-oriented investigations
GLI ACCORDI DI SCELTA DEL FORO SPECIALIZZATO NEL CONTENZIOSO COMMERCIALE TRANSNAZIONALE
No full textNell’attuale contesto europeo e internazionale si sta assistendo al proliferare di corti specializzate per il contenzioso commerciale transnazionale e al relativo ampio dibattito sull’opportunità di introdurre nei vari ordinamenti interni dei fori ad hoc caratterizzati da una grande competenza e specializzazione, al fine di salvaguardare il carattere internazionalistico delle controversie in questione. La ratio sottesa all’istituzione di tali fori risponde alla necessità non solo di soddisfare esigenze pratico-giuridiche, legate all’elevata complessità di una materia così specialistica, ma anche di cogliere le notevoli opportunità sul piano economico-finanziario legate all’indotto che ruota attorno al contenzioso in generale. Dalla disamina dello stato dell’arte emerge un quadro molto articolato, ma è possibile individuare alcuni tratti comuni ricorrenti, tra cui, in particolare, l’utilizzo della lingua inglese come lingua procedurale, l’elevato livello di tecnologizzazione nello svolgimento dell’intero procedimento e la diffusione sui relativi siti internet di una clausola-modello di scelta del foro. La ricerca mira, pertanto, a indagare i temi di rilevanza internazionalprivatistica legati alla scelta e all’attività dei fori specializzati, sì da giungere, in conclusione, a delineare un modello razionale ed efficiente in grado di rispondere alle esigenze sottese all’istituzione di siffatti fori, al fine di salvaguardare l’effettività della scelta del foro specializzato operata dalle parti. D’altra parte, gli accordi di scelta del foro consentono l’attuazione di alcuni principi fondamentali del diritto internazionale privato, in particolare, la prevedibilità del giudice competente, la certezza del diritto e la tutela giurisdizionale effettiva, e, soprattutto, il principio autonomistico, rappresentato nel caso di specie dalla volontà delle parti di scegliere il foro specializzato competente per le future controversie transnazionali che dovessero insorgere tra loro. Entrando nel dettaglio, la ricerca è suddivisa in tre parti. La prima è volta a illustrare gli accordi di scelta del foro esaminando il fondamento del principio autonomistico, gli aspetti legati alla qualificazione e quelli di disciplina a livello internazionale, europeo e nazionale. In particolare, si è concentrata l’attenzione, anche alla luce delle recenti pronunce della Corte di Giustizia, sui requisiti legati alla validità formale e sostanziale di tali accordi, oltre che su aspetti specifici riguardanti, ad esempio, la collocazione in condizioni generali di contratto anche telematici, gli effetti sui terzi subentranti nella posizione dei firmatari, la questione dell’elemento di internazionalità derivante dalla mera scelta delle parti in una fattispecie totalmente interna, la scelta del foro di uno Stato terzo, con anche alcuni cenni sul peculiare regime della litispendenza. La seconda parte esamina, in un’ottica anche comparatistica, la disciplina delle corti commerciali transnazionali già operative in Europa e nel mondo, evidenziandone i tratti di assonanza e di dissonanza con particolare riguardo alla collocazione nell’ordinamento, alla modalità di instaurazione della giurisdizione, ai meccanismi procedurali legati al rito, alla lingua, alla composizione degli organi giudicanti, ai costi e alla rappresentanza legale. L’ultima parte ha l’obiettivo di coniugare gli aspetti teorici e pratici sopra esaminati e, in particolare, quale parte innovativa, vaglia l’opportunità, e le relative modalità de iure condendo, con cui potrebbe essere istituito un foro specializzato in Italia. Sulla scorta di tale disamina, si sono quindi delineati i tratti di un possibile modello generale di foro specializzato dedicato al contenzioso commerciale transnazionale valorizzando quelli dimostratisi più efficienti ed efficaci nei fori già operativi.In the current European and international context, we are witnessing a proliferation of specialized courts for transnational commercial litigation, accompanied by a wide-ranging debate among legal practitioners regarding the advisability of introducing specialized courts characterized by extensive expertise and specialization into various domestic legal systems, in order to safeguard the international nature of the disputes in question.
The rationale behind the establishment of these courts responds not only to practical legal needs related to the high complexity of such a specialized subject, but also to the significant economic and financial opportunities associated with the industry surrounding litigation in general.
In recent years, diverse models of specialized courts have emerged across Europe and worldwide.
Nonetheless, some recurring features are consistently observed. These include the use of English as the procedural language, the adoption of advanced technologies throughout the litigation proceedings, and the dissemination on relevant websites of a model clause for choosing the forum.
This research seeks to explore the private international law issues related to the selection and functioning of specialized courts, with the goal of outlining a coherent and efficient model capable of responding to the needs underlying the establishment of such forums, with a view to safeguarding the effectiveness of the choice of specialized court made by the parties.
Choice-of-court agreements play a key role in this context, enabling the implementation of several fundamental principles of private international law: predictability of jurisdiction, legal certainty, effective judicial protection, and above all, party autonomy. The latter is expressed in the parties’ deliberate decision to designate a specialized court as competent to resolve any future transnational disputes that may arise between them.
The study is structured into three parts.
The first part provides a general overview of choice-of-court agreements, focusing on the principle of party autonomy, the qualification of such agreements, and their regulation at international, European and national levels. Special attention is given, particularly in light of recent rulings by the Court of Justice, to the formal and substantive validity requirements for these agreements, as well as on specific aspects regarding incorporation into standard contractual terms (including electronic formats), the effects on third parties taking over the signatories’ positions, the issue of the international element arising from the mere choice of the parties in a wholly domestic case, the choice of a third-country forum, and specific issues relating to lis pendens.
The second part examines, from a comparative perspective, the regulation of existing transnational commercial courts in Europe and around the world. It highlights similarities and differences with respect to their role within the legal system, the mechanisms for establishing jurisdiction, procedural rules, use of language, composition of adjudicating bodies, litigation costs and legal representation.
The final part aims to combine the theoretical and practical findings of the previous sections. As an innovative element, it assesses the feasibility and the potential legislative avenues for establishing a specialized court in Italy. This discussion draws in part on the pilot project currently being conducted by Section XIV of the Court of Milan which, on a voluntary basis, has been implementing English-language proceedings in the oral phase of trials for approximately two years.
Building on the accumulated European and international experience, the study proposes a general model for a specialized court dedicated to transnational commercial litigation. This model incorporates best practices from successful existing courts, such as the use and dissemination of a model choice-of-court clause drafted by the forum itself