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Intra-farm dynamic of environmental conditions in commercial rabbitries with respiratory disorders using an innovative IoT device
No full textThe microclimate inside rabbitries is a well-established predisposing factor for respiratory diseases, influencing animal growth and health. This study investigated the fluctuations of key environmental parameters in fattening rabbitries with and without respiratory disorders. To this purpose, six multifunctional IoT (Internet of Things) devices were placed at animal level in different locations within each barn. These devices can measure continuously various parameters, including temperature, relative humidity, light intensity, sound pressure, gas concentrations (ammonia, sulphuric acid, carbon dioxide) and particulate levels. Measurements were collected for 7 to 10 days in each farm, with external conditions simultaneously recorded from local meteorological stations. Considering the optimal welfare values, the continuous monitoring system provided valuable information regarding significant deviations of some parameters, irrespective of the external conditions.
The results highlighted that temperatures were consistently above 20 °C for 51%, 89%, and 100% of the time in three out of four problematic farms, whereas relative humidity was below the suggested value of 60% in all of them for 30% to 89% of the time. Moreover, multi-site measurements within the same building revealed a heterogeneous distribution of the parameters investigated. Differences in ammonia concentrations up to 11 ppm have been found in the same barn, indicating a low uniformity of air quality. Dustiness, sound pressure, and sulphuric acid concentrations never reached levels of concern.
The findings demonstrate the utility of this real-time evaluation method as a valuable tool for farmers' decision-making, specifically in efforts to mitigate the adverse impact of environmental conditions on animal health
SYNTHESIS, CHARACTERIZATION AND EVALUATION OF BIOACTIVE MOLECULES LINKED TO PHOTOREMOVABLE PROTECTING GROUPS FOR SPATIO-TEMPORAL CONTROL OF THEIR ACTIVITY THROUGH PHOTOACTIVATION
No full textBiological processes are highly complex phenomena governed by a series of precise spatio-temporal events. Among the most innovative approaches developed over the last decade to investigate such processes, photopharmacology has emerged as a powerful tool, as it exploits light to control biological functions. In particular, optopharmacology enables the regulation of pathophysiological processes through the use of molecules that become bioactive upon light stimulation. Initially applied mainly to biological investigations, optopharmacology is now increasingly recognized for its great potential in the clinical and medical fields.
Among the various photosensitive systems, molecular switches, molecular motors, photodynamic therapy (PDT), and photoremovable protecting groups (PPGs) play important roles in pharmaceutical research. The focus of this doctoral research lies on PPGs: these are chromophores covalently linked to approved drugs or bioactive molecules at functional groups essential for their activity. The resulting species, generally referred to as photo-prodrugs or caged compounds, are able to release the native drug upon light irradiation at a specific wavelength, which cleaves the bond between the PPG and the bioactive molecule. In the literature, several classes of PPGs have been described, including o-nitrobenzyl, coumarin, and BODIPY derivatives, all of which can cage and release a variety of functional groups. However, when focusing on alcohols, phenols, and primary or secondary amines, these are typically linked through carbonate or carbamate linkers, which are intrinsically unstable under physiological conditions due to the presence of esterases. Moreover, the photorelease of tertiary amines has been only rarely reported for such PPGs.
A notable exception is represented by derivatives of 8-cyano-7-hydroxyquinolin-2-ylmethyl (8CyHQ), which have been specifically developed and optimized for the release of tertiary aliphatic amines and tertiary anilines upon both one-photon excitation (1PE, 365–405 nm) and two-photon excitation (2PE, 740 nm). The interest of this thesis is focused on the photorelease of tertiary amines through 1PE. Consequently, the first objective of this work was the optimization study of the quinoline core to achieve both absorption maxima shifted toward safer irradiation wavelengths (>420 nm) and higher chemical yield of payload release. Starting from 8-bromo-7-hydroxyquinolin-2-ylmethyl (8BHQ), the first quinoline based PPG described, we first demonstrated the ability of it in releasing tertiary amines, exploiting a residual absorption tail at 440 nm. From this starting point, we synthesized novel quinoline-based PPGs bearing various electron-withdrawing substituents at position 8 with the aim of improving 8BHQ properties. Unfortunately, among all the newly synthesized derivatives, only 8BHQ proved to be the most efficient quinoline-based PPG for tertiary amine release at 440 nm, even outperforming the well-established 8CyHQ. However, upon 365 nm light irradiation all new derivatives showcase excellent photoreactivity, in particular the compound containing a CF3 which demonstrated to have a significant superior quantum yield (Qu) value. We subsequently explored substitution at position 3, introducing different substituents of diverse electronic and steric nature while keeping the 8BHQ substitution pattern otherwise constant. Although this study is still ongoing, several derivatives have already shown improved performance compared to the 8BHQ reference, in particular the derivative bearing a cyano group in C3 significantly improved 8BHQ performance dramatically increasing photoreactivity and the yield of released leaving amine upon blue light irradiation.
In parallel with this photochemical optimization, two photopharmacological projects were also pursued.
The first project involved the photocaging of ivabradine in order to achieve selective antagonism of different subtypes of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Ivabradine is a clinically used bradycardic agent indicated for the treatment of stable angina pectoris. Its mechanism of action involves antagonism of the HCN4 channel; however, the drug itself is unable to discriminate between the four HCN subtypes. Through a photocaging strategy, ivabradine was covalently linked to 8BHQ, and its effective photorelease was demonstrated in vitro, ex vivo on neuronal HCN channels, and in vivo on cardiac HCN channels in zebrafish. This study has been completed and published, and it opens the way to new perspectives for the use of caged ivabradine in diseases involving dysregulation of non-cardiac HCN channels, such as HCN2-related neuropathic pain.
The second project focused on the photocaging of the antitubercular drug bedaquiline, a highly potent agent against Mycobacterium tuberculosis due to its ability to deplete ATP resources by inhibiting the enzyme ATP synthase (ATPe). However, its clinical use is limited by severe cardiac and hepatic toxicities. The rationale behind designing 8BHQ-caged bedaquiline was therefore to reduce the systemic side effects of the native drug. Unlike the ivabradine project, however, we observed residual anti-mycobacterial activity of caged bedaquiline in the dark, particularly against M. tuberculosis in macrophages. To address this issue, a series of novel quinoline-based PPGs was synthesized, introducing polyethylene glycol (PEG) chains of variable length at position C4 of the quinoline chromophore. This modification was hypothesized to hinder enzymatic cleavage of the drug–PPG linkage by activated macrophage enzymes. Among the synthesized derivatives, the compound bearing a triethylene glycol chain proved the most promising, as it displayed complete inactivity in the dark. This project is currently nearing completion, with ongoing experiments to evaluate the light-induced uncaging and anti-mycobacterial activity of these derivatives in infected macrophages
LA TUTELA DELL¿ONESTÀ FEMMINILE NELLA DISCIPLINA DEI REATI SESSUALI IN BRASILE TRA MODERNIZZAZIONE E CONSERVAZIONE DELL¿ORDINE PATRIARCALE (1890-1930)
No full textLa presente ricerca indaga, sul piano legislativo, dottrinale e giurisprudenziale, la riproduzione delle discriminazioni di genere nei reati di stupro (estupro), ratto (rapto) e deflorazione (defloramento) in Brasile, attraverso la tutela dell’onestà femminile nella Prima Repubblica (1890-1930). È stato adottato un orientamento metodologico volto a verificare la (ri)produzione delle discriminazioni di genere nei reati sessuali in Brasile, mettendo in luce le apparenti contraddizioni del contesto storico in cui esse si collocavano e le convergenze con le esperienze giuridico-penali italiane, considerando la storia comparata del diritto come parte di una storia di intrecci (entanglements) giuridico-contestuali. Muovendo dalle teorizzazioni di Mario Sbriccoli sul duplice livello di legalità che caratterizza il “penale”, si è analizzata l’esistenza di differenti livelli di trattamento soggettivo nell’ambito dei reati sessuali, a partire dalla produzione normativa di discriminazioni intergenere e intragenere. Sono stati inoltre messi in evidenza i conflitti tra riformismo e continuità, tra l’intenzione di “civilizzare” il diritto penale e la conservazione di istituti, concetti e stereotipi appartenenti a una tradizione secolare e discriminante. Come caso di studio, sono state esaminate le decisioni del Tribunale Superiore di Giustizia dello Stato di Santa Catarina, con sede nella città di Florianópolis, al fine di comprendere l’estensione degli intrecci tra le discriminazioni di genere promosse dalla dottrina, dalla legge e dalla giurisprudenza, ponendole in relazione con il più ampio panorama nazionale. Il Código Penal del 1890, pur cercando di emanciparsi dalle figure giuridiche del passato, mantenne vive tradizioni morali, introducendo, sul piano normativo, categorie giuridiche discriminatorie quali ‘donna vergine’, ‘donna onesta’ e ‘prostituta’. La dottrina elaborava ulteriori livelli di discriminazione, fondati su ruoli specifici di genere e, a loro volta, radicati in concezioni ristrette di onestà femminile. Anche la penalistica italiana categorizzava le donne in base all’onestà, pur in assenza di una disciplina legislativa specifica, e tali teorizzazioni venivano riprese e discusse dai giuristi brasiliani. Le differenziazioni di genere presenti nel Código Penal, riprodotte e sviluppate dalla dottrina, fungevano da guida per i giudici e conducevano alla produzione di ulteriori livelli di discriminazione. In combinazione con etichette di classe e di razza, esse si traducevano spesso in meccanismi di vittimizzazione secondaria, rendendo difficoltoso, se non impossibile, l’accertamento di tali reati. Nello Stato di Santa Catarina, i processi per reati sessuali si orientavano secondo una dialettica dell’onestà, e la verifica degli elementi costitutivi dei reati non seguiva un ragionamento uniforme, essendo condizionata dall’analisi dell’indole delle parti. Anche quando i magistrati cercavano di limitare le strategie difensive diffamatorie, lo facevano in modo paternalistico, muovendo da concezioni morali sulla vittima. La tutela dei reati sessuali, fondata sulla protezione dell’onestà femminile, si inseriva in una rete complessa, caratterizzata da molteplici livelli di discriminazione. L’intreccio dei diversi livelli del penale mostrava come tutto riconducesse al diritto comune, a una tradizione giuridica di matrice morale, precisa e ben definita. Produttrice di vittimizzazione secondaria e fondata su presupposti apparentemente contraddittori, tale cultura alimentava i “miti” dello stupro e si rivelava coerente con la protezione giuridico-patriarcale e paternalista rivolta alle vittime femminili, basata su uno specifico, secolare e persistente ideale di onestà sessuale.This research investigates, from legislative, doctrinal, and jurisprudential perspectives, the reproduction of gender discrimination in the crimes of rape (estupro), abduction (rapt), and defloration (defloramento) in Brazil, through the legal protection of female honesty or modesty during the First Republic (1890-1930). The adopted methodological approach sought to verify the (re)production of gender discrimination in sexual crimes in Brazil, highlighting the apparent contradictions of the historical context in which they emerged and the convergences with Italian criminal-legal experiences. This analysis conceives comparative legal history as part of a broader history of juridical and contextual entanglements. Drawing on Mario Sbriccoli’s theorization of the dual level of legality that characterizes the “penal”, the study examines the existence of differentiated subjective treatment within sexual crimes, starting from the normative production of inter-gender and intra-gender discrimination. It also exposes the tensions between reformism and continuity, between the intention to “civilize” criminal law and the persistence of institutions, concepts, and stereotypes rooted in a centuries-old discriminatory tradition. As a case study, the decisions of the Superior Court of Justice of the State of Santa Catarina, headquartered in Florianópolis, were analysed to understand the extent of the entanglements among gender discriminations promoted by doctrine, legislation, and case law, and to situate them within the broader national framework.The 1890 Código Penal, while seeking to emancipate itself from earlier legal formulations, preserved moral traditions by introducing discriminatory legal categories such as ‘virgin woman’, ‘honest woman’, and ‘prostitute’. Legal doctrine further developed layers of discrimination based on specific gender roles, themselves rooted in narrow conceptions of female honesty. Italian penal scholarship also categorized women according to honesty, even in the absence of explicit legislative provisions, and such theoretical formulations were adopted and debated by Brazilian jurists. The gender differentiations present in the Código Penal, reproduced and expanded by doctrine, guided judges and generated additional levels of discrimination. Combined with class and racial labeling, these distinctions often produced mechanisms of secondary victimization, making the ascertainment of such crimes difficult or even impossible. In the State of Santa Catarina, trials for sexual crimes were guided by a dialectic of honesty, and the verification of the constitutive elements of the offenses did not follow a uniform reasoning, being conditioned by the assessment of the moral character of the parties involved. Even when magistrates sought to limit defamatory defense strategies, they did so paternalistically, drawing upon moral assumptions regarding the victim. The protection of sexual crimes, grounded in the safeguarding of female honesty, thus operated within a complex network characterized by multiple layers of discrimination. The intertwining of the various levels of the penal sphere revealed how all paths ultimately led back to ius commune, a legal tradition of moral origin, precise and well-defined. Producer of secondary victimization and based on apparently contradictory premises, this culture fed the “myths” of rape and remained consistent with the patriarchal and paternalistic legal protection extended to female victims, founded on a specific, centuries-old, and enduring ideal of sexual honesty
Integral Implementation of Higher-Order Algebraic Petri Nets in Maude
No full textReisig’s Algebraic Petri nets are highly expressive but rarely based on a strict algebraic framework. We present an effective translation using the declarative language Maude, which employs rewriting semantics. By exploring two definitions, we tackle modeling challenges from Maude’s pattern-matching operational semantics. We demonstrate the advantages of using rewritable terms as active tokens, as supported by Maude, with examples including an adaptive Multilevel Feedback Queue scheduling
Cultivating hope: caring for a precarious emotion in the Ultima Generazione movement
No full textIn this article I explore how the Ultima Generazione (UG) movement in Italy cultivates different forms of hope in times of climate crisis and ecological breakdown. Based on ethnographic research, I argue that hope is not a stable emotion or a fixed starting point, but a fragile, shifting process requiring ongoing care. I identify two key practices: building a supportive, nonviolent grassroots community, and performing high-risk civil disobedience, such as road blockades or ‘coloring’ monuments and artworks. These practices generate multiple, sometimes conflicting hopes – some rooted in immediate communal survival, others directed toward long-term climate transformation. Rather than a unified feeling or motivational force, hope emerges as an uncertain sensibility shaped by collective action. ‘Cultivating hope’ thus entails a repertoire of practices that nurture, shape, and enact the ways in which hope is felt and sustained
Evaluation of large language models as decision support tools for head and neck cancer management: A blinded multidisciplinary simulation study
No full textBackground: The management of head and neck cancer relies on multidisciplinary expertise; however, access to tumor boards remains variable. Large language models (LLMs) may support guideline-based decision-making, although performance in complex oncologic scenarios is not well defined. Methods: Fourteen synthetic cases based on real tumor board encounters were evaluated. Five blinded comparator arms produced recommendations: a human expert, Non-RAG-GPT-4, Non-RAG-GPT-5, RAG-GPT-4, and RAG-GPT-5. Eight head and neck oncologic surgeons scored each recommendation for appropriateness, clarity, specificity, and feasibility using 5-point Likert scales. Paired permutation testing and inter-rater reliability were assessed. Results: LLM outputs showed close alignment with expert recommendations. RAG-based models achieved the highest mean scores across domains, with some statistically significant differences versus the expert comparator in appropriateness and clarity; however, absolute differences were modest. Inter-rater reliability was strong (ICC 0.73-0.87). Conclusions: Advanced LLMs can generate guideline-concordant management recommendations in simulated head and neck cancer cases, supporting potential utility for decision support and education; prospective validation and expert oversight remain essential
Stereodefined synthesis of 3-difluoromethyl-benzoxaboroles: novel antimicrobials with unlocked H-bonding
No full textBenzoxaboroles, prominent scaffolds in medicinal chemistry, are typically modified on the benzene ring. In contrast, functionalization of the oxaborol ring is less common and often challenging. Indeed, 3-hydroxy-benzoxaboroles are virtually impossible to isolate due to their tautomeric equilibrium with the carbonyl form. In this work, we introduce a novel class of stereodefined 3-difluoromethyl-benzoxaboroles. The replacement of the hydroxy group with -CHF2 preserves stability while promoting bioactivity, owing to the lipophilic H-bond donor properties of the latter
Dazi doganali: uno sguardo al regime giuridico internazionale e alle politiche recenti degli Stati Uniti
No full textRandom rotational invariance of integration by parts formulas within a Bismut-type approach
No full textThe stochastic rotational invariance of an integration by parts formula inspired by the Bismut approach to Malliavin calculus is proved in the framework of the Lie symmetry theory of stochastic differential equations. The non-trivial effect of the rotational invariance of the driving Brownian motion in the derivation of the integration by parts formula is discussed and the invariance property of the formula is shown via applications to some explicit two-dimensional Brownian motion-driven stochastic models