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Overview of protein misfolding amplification methods and their use in prion disease diagnosis and in investigations of within- and inter-species prion transmission
No full textThe presentation provides an overview of in vitro protein misfolding amplification assays used in prion research, with particular emphasis on Protein Misfolding Cyclic Amplification (PMCA). After summarizing the principles of prion replication and the limitations of conventional CWD diagnostics, the talk illustrates how RT‐QuIC and PMCA reproduce misfolded prion‐driven conversion mechanisms with high analytical sensitivity. The presentation details the optimization of PMCA conditions using reindeer PRNP variants as substrates and CWD isolates as seeds, highlighting genotype‐dependent differences in amplification efficiency. These experimental insights demonstrate how PMCA can be used not only for sensitive prion detection but also to investigate strain properties, host–substrate compatibility, and the potential impact of PRNP genetic variation on CWD susceptibility
Intersectional (in)visibility and forms of (de)professionalization: the case of migrant domestic platform workers in Italy
No full textThis paper adopts a feminist and intersectional perspective to investigate platform-mediated domestic work in Italy. While existing scholarship has extensively analysed classed, gendered and racialized hierarchies in traditional domestic labour, the growing role of digital platforms in mediating these work arrangements deserves further theoretical and empirical attention. Focusing on the experiences of migrant cleaning workers in Milan, this study contributes to the debate on domestic platform work by interrogating the relationship between (de)professionalization and (in)visibility. First, we show how digital labour platforms, while claiming to enhance visibility and professionalization, often reproduce existing intersectional inequalities through mechanisms of legal stratified access to platform work, gendered, racialized and classed division of labour, as well as social invisibility. Second, we challenge the victimization narrative of workers, highlighting not only the lived forms of oppression but also the individual and collective agency actively exercised by platform domestic workers. By adopting an intersectional approach, we then critically challenge the dominant narratives of professionalization and increased visibility related to platform work, illuminating the complex entanglements of oppression and agency in contemporary digital economies
Hepatic GPR110 contributes to sex disparity in the development of MASH through oestrogen receptor α-dependent signalling
No full textMetabolic dysfunction-associated steatohepatitis (MASH) is an important phase in the progression of metabolic dysfunction-associated steatotic liver disease to end-stage liver diseases, posing an increasing threat to public health worldwide with limited treatment options. Here we show that GPR110 is a liver-selective G-protein-coupled receptor closely associated with MASH in a sex-specific manner. Hepatocyte-specific Gpr110 knockout protects against MASH in female, but not male mice. The GPR110 variant rs937057 T > C is associated with a higher prevalence of metabolic dysfunction-associated steatotic liver disease in women. The improved liver phenotypes in female mice are abrogated by knocking down the expression of hepatic oestrogen receptor alpha (Esr1). Mechanistically, GPR110 couples to Gαs and activates protein kinase A, thereby inducing phosphorylation of NFAT2, which inhibits its nuclear translocation and transcriptional activity, leading to suppressed Esr1 transcription in hepatocytes. Taken together, these results demonstrate a sex-specific role of GPR110 in MASH by regulating hepatic oestrogen sensitivity, suggesting inhibition of GPR110 as a potential sex-specific therapy for MASH
Insights into the catalytic mechanism of formate dehydrogenases from different microbial sources
No full textFour formate dehydrogenases (FDHs) from Pseudomonas sp. 101, Myceliophthora thermophila, Chaetomium thermophilum, and Ogataea parapolymorpha were recombinantly produced, purified, and characterized to investigate their catalytic properties and reaction mechanisms. The enzymes were studied for their ability to oxidize formate to carbon dioxide (CO2) coupled with NAD+ reduction. In contrast, their CO2 reduction activity was undetectable under the tested conditions. Oxidative reactions revealed significant differences in catalytic efficiency and substrate specificity, prompting further investigation through molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) ONIOM calculations. Structural models were derived from high-resolution structural data available for enzymes from Pseudomonas sp. 101 (pseFDH) and Chaetomium thermophilum (ctFDH) and extended to all four variants. Comparative analyses of the transition states revealed distinct interaction patterns within the active sites, allowing us to discriminate between high- and low-performing catalysts, in full agreement with the experimental kcat values. These findings provide a mechanistic rationale for the observed disparities in catalytic performance and offer structural insights into the determinants of FDH activity. Notably, ctFDH emerged as a potential candidate for the development of CO2-reducing reactions, with QM/MM data guiding the rational design of transition-state stabilizing mutations
Effects of activated sludge processes on bacterial communities and antibiotic resistance assessed by intra- and extracellular DNA analysis
No full textWastewater treatment plants are widely recognized as hotspots for antibiotic resistance. Although activated sludge processes are not designed to lower the abundance of pathogens or antibiotic resistance genes (ARGs), their effects on the pathobiome and antibiotic resistome require in-depth investigation. To this end, we collected wastewater samples before and after activated sludge process from five municipal wastewater treatment plants, each characterized by different inlet composition and treatment capacity. We extracted both intracellular and extracellular DNA and performed shotgun sequencing to characterize the bacterial community, pathobiome, and antibiotic resistome. Our aim was to assess the effects of activated sludge processes on bacterial community composition, the abundance of potentially pathogenic bacteria and high-risk ARGs, and the potential horizontal mobility of detected ARGs. Our results showed that activated sludge processes significantly reduced the abundance of potentially pathogenic bacteria and several high-risk ARGs. Notably, while the prevalence of plasmid-associated ARGs decreased following treatment, ARG-carrying contigs assigned to bacteriophages increased, particularly in extracellular DNA samples. Overall, activated sludge processes demonstrated a beneficial microbiological effect by lowering potentially pathogenic bacteria. However, the enrichment of viral particles carrying ARGs highlights a potential risk for ARG spreading during the following processes. These findings underscore the importance of analyzing both intracellular and extracellular DNA to fully understand the role of activated sludge in mitigating antibiotic resistance and pathogens in wastewater
Artificial Intelligence, VR, and the Virtual
No full textDrawing on theology, Andrea Pinotti’s contribution explores the concept of virtuality and its manifold implications in the age of artificial intelligence and virtual reality. Beginning with the etymological roots of “virtual” in virtus, the author traces a lineage through Scholastic philosophy, Aristotelian metaphysics, and modern thinkers like Deleuze and Lévy. The notion of virtual containment (continentia virtu-alis) is central, positing that the virtual is not unreal but a realm of latent potentialities awaiting actualisation. This metaphysical framework is then applied to AI, especially in relation to latent space in image generative models, where virtualities (e.g. styles) are harboured and actualised in particular pictures through prompts. Through exper-iments with text-to-image model DALL·E and referring to Neural Style Transfer, the essay highlights how generative AI seems to presuppose a clean separation between form and content: this leads to a problematic extrapolation of the style as a universal from a given corpus of images, which ends up reviving the ancient Scholastic debate on universals. In the last section, the essay considers the adjective “virtual” as it appears in the strictly technical sense of the term “Virtual Reality” and highlights analogies and differences in AI and VR as technologies of actualising virtualities
Giurisdizione extraterritoriale e coercizione economica negli orders di Trump contro i programmi di diversità, equità e inclusione
No full textReal-time error mitigation for variational optimization on quantum hardware
No full textIn this work, we put forward the inclusion of error mitigation routines in the process of training variational quantum circuit (VQC) models. In detail, we define a real-time quantum error mitigation (RTQEM) algorithm to assist in fitting functions on quantum chips with VQCs. While state-of-the-art QEM methods cannot address the exponential loss concentration induced by noise in current devices, we demonstrate that our RTQEM routine can enhance VQCs’ trainability by reducing the corruption of the loss function. We tested the algorithm by simulating and deploying the fit of a monodimensional u-quark parton distribution function on a superconducting single-qubit device, and we further analyzed the scalability of the proposed technique by simulating a multidimensional fit with up to eight qubits
Identifying delegation and constraints in legislative texts: A computational method applied to the European Union
No full textWe introduce a computational method for identifying delegating and constraining provisions in European Union (EU) laws. Leveraging the syntactic structures employed by legislators, we developed a set of extraction rules applied through a custom-built computational linguistics pipeline. We run through the pipeline more than 600,000 legal sentences that we extracted from 9319 laws adopted between 1958 and 2019. The application performs very well vis-á-vis human annotation and outperforms transformer models. The produced patterns of authority delegation and constraint resonate with our knowledge of the policymaking and history of the EU. Our approach provides valuable insights for designing transparent and adaptable rule-based computational linguistic methods of legal text analysis. We also release the comprehensively annotated dataset and the fine-tuned transformer models developed for this task
IL PRINCIPIO DI SUSSIDIARIETÀ. TRA LIMITI TEORICI E DEGENERAZIONI PRATICHE DELLA LEGISLAZIONE IN MATERIA PENALE
No full textIl presente lavoro di tesi si propone di analizzare, in una prospettiva teorica ed applicativa, il principio di sussidiarietà, fondamento e limite dello ius puniendi.
Muovendo dall’assunto di matrice liberale in virtù del quale la pena dovrebbe costituire l’extrema ratio dell’ordinamento, l’indagine si è orientata a verificare se il citato principio conservi ancora oggi una effettiva ed efficace capacità di orientamento e di contenimento
dell’espansione legislativa in materia penale.
L’elaborato si articola in tre momenti principali. Nel primo capitolo si ricostruiscono le origini teoriche e la portata sistematica del principio di sussidiarietà, individuandone la funzione di metaprincipio ordinante del sistema e le connessioni con i principi di offensività, di proporzionalità, di necessità e di frammentarietà. In questa prospettiva, la sussidiarietà si configura come criterio di razionalità e di legittimazione del diritto penale, volto a garantire l’equilibrio tra difesa sociale e tutela della libertà individuale, come tale suscettibile di un utilizzo non solo in sede di progettazione della politica criminale, ma anche in ipotesi di vaglio della legittimità costituzionale delle scelte legislative.
Nel secondo capitolo l’analisi si sposta sul piano sistemico, approfondendo la distinzione tra fenomeni di espansione fisiologica e manifestazioni patologiche dell’intervento penale. Laddove le prime istanze rispondono ad un’esigenza di ragionevole adattamento del diritto ai mutamenti sociali e tecnologici, le seconde si manifestano, invece, quali forme di populismo penale e di diritto simbolico, in cui la pena assume una funzione
prevalentemente comunicativa e di rassicurazione collettiva.
Il terzo capitolo affronta, infine, una verifica empirica della produzione legislativa italiana dalla XVI alla XIX legislatura, al fine di accertare se l’ordinamento nazionale versi effettivamente in una condizione di ipertrofia penale, come sostenuto dalla maggiore
porzione della dottrina. L’analisi quantitativa e qualitativa dei provvedimenti normativi mostra, tuttavia, che l’espansione del penale non assume i tratti di una patologia endemica ed irreversibile, bensì quelli di una deviazione episodica e contingente, riferibile a specifici
interventi di natura politica o emergenziale; a questi si affianca, invero, un incremento della penalità fisiologico, risposta naturale all’evoluzione della società ed all’emersione di nuovi beni giuridici, nuove esigenze di tutela e nuove fattispecie criminose.
Le conclusioni delineano un quadro nel quale il sistema penale italiano, pur segnato da fasi di espansione disordinata, non può dirsi irrimediabilmente degenerato. L’ipertrofia penale non rappresenta una malattia cronica, bensì un fenomeno episodico e contenibile. In questa prospettiva, il principio di sussidiarietà si rivela non soltanto un canone teorico, ma un possibile rimedio operativo e giuridico: da un lato quale criterio di orientamento per le scelte del legislatore, volto a ricondurre la pena nella sua sede naturale di extrema ratio; dall’altro, quale parametro di legittimità costituzionale, suscettibile di guidare una verifica di dette scelte in sede giudiziale.
La ricerca giunge così ad affermare che il diritto penale contemporaneo, se opportunamente governato dal principio di sussidiarietà, può ancora mantenere la propria coerenza con i valori dello Stato di diritto e con la funzione garantista che ne costituisce la ragion d’essere.This doctoral dissertation aims to analyse, from both a theoretical and practical perspective, the principle of subsidiarity as the foundation and limitation of the ius puniendi.
Starting from the liberal assumption that punishment should represent the extrema ratio of the legal system, the research seeks to determine whether this principle still retains an effective capacity to guide and constrain legislative expansion in criminal matters.
The work is divided into three main sections. The first chapter reconstructs the theoretical origins and systematic scope of the principle of subsidiarity, identifying its role as an overarching metaprinciple of the criminal law system and its connections with the principles of harm, proportionality, necessity and fragmentation. From this perspective, subsidiarity emerge sas a criterion of rationality and legitimacy of criminal law, intended to ensure balance between social defence and the protection of individual freedom. As such, it may serve not only as a guiding principle in the design of criminal policy, but also as a potential parameter in assessing the constitutional legitimacy of legislative choices.
The second chapter shifts the focus to the systemic level, deepening the distinction between physiological expansions and pathological manifestations of criminal intervention. While the former correspond to a reasonable adaptation of law to social and technological change, the latter take the form of penal populism and symbolic legislation, in which punishment assumes a primarily communicative and reassuring function within the social body.
The third chapter provides an empirical assessment of Italian legislative production from the XVI to the XIX legislature, with the aim of verifying whether the national legal system can truly be said to suffer from a condition of penal hypertrophy, as argued by much of the legal scholarship. The quantitative and qualitative analysis of the legislative measures reveals, however, that the expansion of criminal law does not display the features of an endemic or irreversible pathology, but rather those of an episodic and contingent deviation,
linked to specific political or emergency-driven interventions. Alongside these, the research identifies a physiological increase in criminal regulation, representing a natural response to the evolution of society, the emergence of new legally protected interests and the appearance of novel forms of criminal conduct.
The conclusions depict a framework in which the Italian criminal system, although marked by phases of disordered expansion, cannot be deemed irreversibly degenerated. Pena hypertrophy appears not as a chronic disease, but as an episodic and manageable phenomenon. In this light, the principle of subsidiarity emerges not only as a theoretical canon but as a potentially operative and legal remedy: on the one hand, as a guiding criterion for legislative choices, aiming to restore punishment to its proper function as extrema ratio; and on the other, as a constitutional standard, capable of guiding judicial review of such choices.
The research ultimately concludes that contemporary criminal law, if properly governed by the principle of subsidiarity, can still preserve it coherence with the fundamental values of the rule of law and with the guarantee-based function that defines its very raison d’être