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Efficient α-Selective Chlorination of Meta- and Ortho-Substituted Phenylacetic Acids
No full textTreatment with trichloroisocyanuric acid (TCCA) in the presence of catalytic PCl3 under solvent-free conditions is a preparative method, simple and efficient, to selectively α-chlorinate not only phenylacetic acid and its para-substituted analogues, but also meta- and more arduous ortho-substituted phenylacetic acids. With electron-withdrawing or weakly electron-donating substituents, such as NO2, CF3, COOMe, halogen, and methyl, the potentially competing electrophilic aromatic chlorination did not occur and the substrates were univocally chlorinated at the benzylic position. Within our selection of 13 o- and m-substituted phenylacetic acids, the only 2 outliers were m-methylphenylacetic acid, which, unlike the ortho and para regioisomers, gave complex mixtures of products, and o-nitrophenylacetic acid, which was refractory to any chlorination. α-Chlorophenylacetic acids are synthons with a great potential, here exemplified by the preparation of clopidogrel, a very important active pharmaceutical ingredient, from α-chloro-o-chlorophenylacetic acid
DEFINING THE ROLE OF DNA POLYMERASE η IN TOLERATING REPLICATION STRESS
No full textTranscription–replication conflicts (TRCs) and RNA:DNA hybrids (R-loops) are major sources of replication stress and genome instability, particularly under hydroxyurea (HU)-induced nucleotide depletion. Here we describe a translesion synthesis (TLS)-independent function of DNA polymerase η (pol η) in Saccharomyces cerevisiae during HU stress. Pol η localizes to a subset of replication origins and to regions adjacent to highly transcribed genes, accumulating at TRC sites independently of collision orientation, consistent with a general role in limiting transcription–replication interference. Genetic and biochemical evidence indicates that pol η promotes TRC bypass by incorporating RNA into DNA and elongating nascent RNA transcripts. These RNA:DNA tracts require RNase H for resolution; otherwise, they elicit DNA damage checkpoint activation, persistent stress, and lethality. The toxic effect of pol η is suppressed by overexpression of Sen1 or RNase H1, or by inhibition of transcriptional elongation, supporting its direct role in RNA-mediated replication stress. We propose that pol η facilitates TRC bypass by stabilizing or remodelling RNA:DNA hybrids at stalled forks. This work identifies an unexpected genome maintenance role for pol η, dependent on its RNA-extension activity
SCIENCE ON TRIAL: BRIDGING SCIENTIFIC AND LEGAL EPISTEMOLOGIES IN STRATEGIC CLIMATE LITIGATION
No full textCome possono i tribunali confrontarsi con la complessità della scienza climatica di
fronte all’urgenza della crisi climatica? È questa la domanda che guida questa tesi,
dedicata a indagare l’incontro, spesso difficile ma imprescindibile, tra diritto e scienza
nelle aule di giustizia. Negli ultimi anni il contenzioso climatico è cresciuto in maniera
esponenziale, assumendo forme strategiche che mirano non solo a risolvere singoli
casi, ma anche a influenzare politiche pubbliche, ridefinire responsabilità e ampliare il
contenuto dei diritti fondamentali. Al centro di questi processi vi è la scienza del clima
– probabilistica, interdisciplinare e in continua evoluzione – che mette alla prova
l’attitudine del diritto a fornire risposte binarie e definitive.
La ricerca si sviluppa in tre passaggi. Nel primo capitolo vengono ricostruite le basi
concettuali e i quadri normativi che consentono alla scienza climatica di entrare nel
diritto, incluso il principio della “riserva di scienza.” Il secondo capitolo si concentra
sulla prassi giudiziaria, confrontando il modo in cui la Corte internazionale di giustizia,
la Corte europea dei diritti dell’uomo e i tribunali italiani accolgono, valutano o
talvolta resistono all’evidenza scientifica. Il terzo capitolo affronta direttamente le
tensioni epistemologiche, analizzando due nodi cruciali: il ruolo e l’imparzialità degli
esperti e le difficoltà di dimostrare il nesso di causalità in un fenomeno globale e
cumulativo come il cambiamento climatico.
I risultati mettono in luce tanto le potenzialità quanto i rischi dell’ingresso della scienza
nel diritto: se da un lato le evidenze scientifiche sono ormai indispensabili per
rafforzare la responsabilità climatica, dall’altro rischiano di mettere in crisi principi
cardine del processo. Per affrontare questa tensione, la tesi propone alcune soluzioni –
dal rafforzamento delle procedure peritali al ripensamento degli standard di causalità
– che possano aiutare i tribunali a emettere decisioni al tempo stesso scientificamente
fondate e giuridicamente solide. Oltre al tema specifico del contenzioso climatico, il
lavoro parla di una sfida più ampia: come mantenere la legittimità dei sistemi giuridici
democratici, garantendo al contempo un dialogo autentico con le scienze che plasmano
il nostro futuro collettivo.How do courts grapple with the complexity of climate science when faced with the
urgency of the climate crisis? This question lies at the heart of this dissertation, which
explores the uneasy but essential encounter between law and science in the courtroom.
Climate litigation has grown exponentially in recent years, often driven by strategic
objectives that go beyond individual disputes and aim to reshape policies,
responsibilities, and even the meaning of rights. At the center of these cases stands
climate science – probabilistic, interdisciplinary, and constantly evolving – which
challenges the law’s preference for binary answers and definitive judgments.
The thesis unfolds in three steps. The first chapter sets the conceptual and normative
stage, tracing how climate science has entered legal frameworks and testing the
boundaries of concepts such as the “scientific reserve.” The second chapter turns to
judicial practice, comparing how the International Court of Justice, the European Court
of Human Rights, and Italian courts receive, assess, and sometimes resist scientific
evidence in climate disputes. The third chapter engages directly with the
epistemological tensions that arise, focusing on two pivotal issues: the credibility and
role of experts, and the difficulties of proving causation in a world of cumulative and
diffuse emissions.
The findings highlight both the promise and the pitfalls of letting science into the law:
while scientific evidence has become indispensable for advancing climate
accountability, it also risks unsettling fundamental principles of adjudication. To
navigate this tension, the thesis advances reform proposals – from strengthening expert
procedures to rethinking causation standards – that could help courts deliver judgments
that are both scientifically informed and legally sound. Beyond climate litigation, this
study speaks to a broader challenge of our time: how to ensure that democratic legal
systems can remain legitimate while engaging meaningfully with the sciences that
define our collective future
Effects of transcranial photobiomodulation on performance and cardiovascular responses in trained cyclists
No full textBackground: Transcranial photobiomodulation (PBM) has been proposed to enhance prefrontal cortex (PFC) oxygenation and modulate central mechanisms of fatigue, potentially improving endurance performance. This study investigated the acute effects of PBM on cycling time-trial (TT) performance in well-trained cyclists.Methods: In a randomized, double-blind, crossover design, 18 trained cyclists completed two experimental conditions (PBM and SHAM) prior to a constant-load (CL) test at 5% above the first lactate threshold (LT1) and a 25-min self-paced TT on their own bicycles mounted on an ergometer.Results: No significant condition × time interactions were found for heart rate, blood lactate, ratings of perceived exertion (RPE), or power-related ratios during either the constant-load or TT trials (p > 0.05).Conclusion: Acute transcranial PBM did not influence cycling performance or perceptual and physiological responses in trained athletes. These findings suggest that the applied PBM parameters may have been insufficient to elicit measurable cortical or performance effects. Future research should explore optimized stimulation parameters and chronic application protocols to clarify the potential ergogenic role of PBM in endurance exercise
IDENTIFICATION OF MICROBIAL FUNCTIONS INTERFERING WITH HOST-CELL PHYSIOLOGY: A QUICK VIEW INTO STREPTOCOCCUS THERMOPHILUS METABOLIC POTENTIAL
No full textStreptococcus thermophilus, long typecast as a dairy workhorse, is ready for a role upgrade. Despite decades of safe use in fermentation in large volume consumer products, this species has been largely sidelined in probiotic research, overshadowed by genera like bifidobacteria and strains belonging to the group formerly classified within lactobacilli, such as Lactiplantibacillus, Lacticaseibacillus, and Limosilactobacillus. This thesis redefines S. thermophilus as a metabolically dynamic, functionally relevant, and therapeutically promising candidate in the probiotic field.
In the first part of this work, we present a safe metabolic activation strategy that enhances lactose catabolism in S. thermophilus, starting from the biomass production phase, without compromising cell viability. Within just 30 minutes, activated cells exhibited up to a 30% increase in lactose conversion, compared to not-activated cells. Interestingly, in the presence of both urea and a carbon source, lactic acid release was significantly enhanced, alongside a marked improvement in glycolytic activity, without altering the optimized lactose uptake. This distinctive metabolic behavior of activated cells appears to modulate glycolysis and enhance acidification, positioning S. thermophilus as a promising tool not only for more efficiently supporting lactose digestion but also for additional applications requiring optimized biomass performance, rapid lactose consumption, and controlled glycolytic and lactate output. Importantly, these activated cells are currently being evaluated in a forthcoming in vivo study, where their enhanced metabolic profile is expected to translate into measurable reduced symptoms and improved subject well-being in individuals with lactose intolerance. This therapeutic potential, directed toward specific targets (e.g., lactose maldigestion), reinforces the concept of precision probiotics: microbial products designed not just for general health promotion, but for targeted interventions, tailored to specific conditions and consumer needs. The reproducibility of these effects across different substrates and at production scale underscores both the physiological relevance and industrial feasibility of this strategy, offering a compelling alternative to generalized probiotic strategies in favor of a novel approach in probiotic development.
The second study focuses on urease activity, an often overlooked yet highly relevant functional trait in S. thermophilus, closely associated with nitrogen and energy metabolism. Recent findings have linked urease activity in S. thermophilus to a specific beneficial effect on the host: administration of adequate amounts of viable biomass resulted in decreased fecal urease activity, suggesting that this effect may be mediated by the modulation of urea metabolism and a reduction in urease-positive pathogenic bacteria. Building on this and considering that targeting urease in conditions such as Irritable Bowel Syndrome (IBS) could be key to alleviate symptoms, we sought to determine whether this reduction is solely due to S. thermophilus urease contribution or whether additional microbial or host-related factors play a role. To this end, we controlled urease activity levels of S. thermophilus biomass through process-condition control. By fine-tuning fermentation parameters, we successfully modulated urease expression at both laboratory and industrial scales, generating distinct biomasses with tailored metabolic phenotypes. These engineered biomasses are currently being prepared for a forthcoming in vivo study in IBS patients to assess their effects on host symptoms and their influence on gut nitrogen metabolism, based on their urease activity levels. This is particularly relevant given that disruptions in the urea–ammonia balance, arising from the dysbiosis state that characterizes IBS, are known to exacerbate symptoms through altered microbial composition, increased intestinal permeability, and elevated luminal ammonia levels, which can aggravate mucosal inflammation and visceral hypersensitivity, leading to discomfort, abdominal pain, bloating, and other digestive disturbances typical of this syndrome. This work aims to open new avenues for developing targeted probiotic interventions and provides valuable insights into the complex and evolving interplay between urease activity and energy metabolism in S. thermophilus. Most importantly, it highlights a crucial yet often overlooked point: the fermentation process itself can be strategically optimized to predefine specific microbial functionalities. By establishing a direct link between upstream fermentation conditions and downstream functionality, this study reinforces the importance of precision at every stage of probiotic production, from fermentation to functional application, particularly when the effect is driven by the activity level of the administered biomass itself, rather than by downstream growth or adaptation in the host.
The final part of the thesis explores an innovative therapeutic application: leveraging S. thermophilus DSM 20617T/ATCC 19258T as a delivery vector of β-galactosidase in situ via prophage-mediated lysis, motivated by the recent evidence that intracellular β-galactosidase from S. thermophilus exerts protective effects against colorectal cancer by inhibiting cancer cell proliferation and tumor development. The strain’s ability to survive gastrointestinal transit, interact with the host microbiota, and potentially release therapeutic molecules in situ represents a novel intersection of microbiology, biotechnology, and therapeutic design. While challenges remain, particularly in controlling prophage induction and ensuring consistent release of bioactive enzymes, such as β-galactosidase, at the site of action in the intestine following administration and cell lysis, this work lays the foundation for using S. thermophilus as a microbial chassis in the design of live biotherapeutics.
Together, these studies reposition S. thermophilus as a precision-engineered tool for the future generation of microbiome-based health solutions.
In an industry still dominated by one-size-fits-all products and vague probiotic claims, this work challenges the standard narrative. It delivers measurable, mechanism-based evidence that S. thermophilus has been underestimated for too long. As the demand for personalized, effective, and evidence-based microbial therapies continues to rise, this thesis highlights the potential of S. thermophilus and advocates for its greater consideration. Moreover, by expanding the functional framework of S. thermophilus, this research paves the way for formulas designed with precision and purpose, moving probiotic science into a new era
Countering autocratization from the outside: evidence from Africa
No full textWith a focus on the autocratization episodes that occurred in Africa during the 2000–2023 period, this article examines how effectively external actors help constrain the unfolding of autocratization. While the recent literature has primarily highlighted how domestic actors can resist autocratization, the role of external actors should not be overlooked, especially in a region such as Africa characterized by a peculiarly high number and variety of external interventions
over time. Accordingly, we focus on two main strategies of external protection of democracy – namely, democracy sanctions and democracy aid – and discuss how their combined employment could trap autocratizing elites in between two opposite pressures. From above, as sanctions restrict elites’ access to revenue, and from below, as increased external democracy assistance empowers local democratic actors. To investigate empirically whether and how democracy sanctions and democracy aid interact with each other in countering autocratization, we apply regression methods and conduct a series of sensitivity analyses to confirm the validity of our results. Our findings show that such a combination of tools is an effective way in which external actors can help counter autocratization from abroad, provided that they are genuinely committed to accompany sanctions with substantial aid increases
Chi ha diritto a essere dimenticato? I diritti all’oblio e le sfide contemporanee
No full textIn un mondo che registra tutto e dimentica sempre meno, chi ha davvero diritto a essere dimenticato?
Tra archivi digitali, motori di ricerca e sistemi di intelligenza artificiale, il passato rischia di restare permanentemente accessibile, incidendo sulle biografie individuali e ridefinendo i confini tra memoria, identità e libertà personale.
Questo volume affronta il diritto all’oblio come una costellazione di tutele, più che come un diritto unitario: dalla protezione dei dati personali alla dignità della persona, dal diritto alla salute alle questioni identitarie e culturali, fino alle sfide poste dalla persistenza delle tracce digitali e dal funzionamento dei sistemi di apprendimento automatico. Attraverso un approccio interdisciplinare che intreccia diritto, semiotica e informatica, i contributi raccolti esplorano i molteplici volti dell’oblio nella società contemporanea.
Al centro del libro emerge il rapporto sempre più stretto - e problematico – tra tecnologia e diritto: da un lato, strumenti capaci di conservare, replicare e rielaborare informazioni su larga scala; dall’altro, regole giuridiche chiamate a ripensare categorie come tempo, responsabilità e cancellazione. In questo spazio di tensione, l’oblio diventa una questione di equilibrio tra interessi individuali ed interessi collettivi.
Ne risulta una lettura attuale e incisiva: nell’era delle memorie permanenti, l’oblio non coincide con la semplice cancellazione del passato, ma con la possibilità di governare la circolazione delle informazioni, tutelare l’identità personale e rendere effettive le seconde possibilità.
Un tema centrale per chi studia il diritto, per chi lavora con i dati e per chi vuole comprendere come tecnologia e diritti stiano ridefinendo il nostro rapporto con il tempo e con la memoria.In a world that records everything and increasingly forgets nothing, who truly holds the right to be forgotten? Between digital archives, search engines, and artificial intelligence systems, the past risks remaining permanently accessible, shaping individual biographies and redefining the boundaries between memory, identity, and personal freedom.
This volume approaches the right to be forgotten not as a single, unitary right, but as a constellation of safeguards: from personal data protection to human dignity, from the right to health to identity and cultural concerns, as well as the challenges posed by the persistence of digital traces and the functioning of machine-learning systems. Adopting an interdisciplinary framework that brings together law, semiotics, and computer science, the volume investigates the multiple dimensions of oblivion in contemporary society.
At its core lies the increasingly complex and problematic interplay between technology and law, whereby large-scale information-processing technologies challenge legal frameworks to reassess foundational concepts such as time, responsibility, and erasure. In this context, oblivion emerges as a normative issue requiring a careful balance between individual and collective interests.
The result is a timely and incisive contribution: in the era of permanent memory, oblivion does not merely entail the deletion of the past, but rather the capacity to govern the circulation of information, safeguard personal identity, and ensure the effective realization of second chances.
This volume addresses a central issue for legal scholars, data professionals, and all those seeking to understand how technology and fundamental rights are reshaping our relationship with time and memory
Artificial Intelligence for Automated Detection of Joint Bleeding via Ultrasound in Hemophilia: Advancing Standardization
No full textBackground: Musculoskeletal ultrasound (US) is a non-invasive tool for joint assessment in persons with hemophilia. Early detection of joint bleeding using a remote US system operated by patients or caregivers and reviewed by Comprehensive Care Centers could improve personalized management. A computer-aided diagnosis (CAD) system for automatic detection of joint effusion may support clinicians in prioritizing interventions. Objectives: This study aimed to validate a novel CAD system using a deep-learning algorithm to identify joint capsule distension in musculoskeletal US images. Methods: Longitudinal scans of the subquadricipital recess (SQR) of the knee were collected from people with hemophilia and varying degrees of arthropathy and labeled by an expert. The multi-task learning algorithm was trained to detect the recess and classify images as distended or not. Results: A total of 8,634 images (2,267 scans) were acquired from 158 adult persons with hemophilia (mean age 44.7 ± 18.6 years) and 66 age-matched healthy controls. After selecting longitudinal SQR images, 814 images were used, of which 711 for training and 103 for testing, ensuring a patient-based split. The model achieved a classification accuracy of 89.2% and a balanced accuracy of 93.9% compared to expert annotations. No significant differences were observed in classification performance between male and female healthy controls, supporting its broader applicability. Conclusions: The CAD system for automatic detection of joint capsule distension is feasible and reliable. It represents an important step toward telemedicine in hemophilia, enabling early recognition of joint bleeding and supporting personalized, timely therapeutic interventions to prevent further joint damage
Tuning Hydrogen versus Methane Production on Sustainable Biochar-Based Cathodes in Microbial Electrolysis Cells by Voltage Control
No full textDue to the intermittency of solar and wind energy generation, efficient energy storage solutions are essential to ensure a global transition to renewable energy sources. Bioelectrochemical Power-to-Hydrogen systems are a promising storage pathway, yet their development is limited by high costs and low productivity compared to conventional hydrogen production. Novel, sustainable, and cost-effective materials, such as carbon-based electrodes, can help to overcome these challenges. This study evaluates five cathodes for hydrogen and methane production in microbial electrolysis cells (MECs) operated at 600 and 800 mV: stainless steel mesh (SSM), two custom-made biochars derived from olive mill waste (OMW-1, OMW-2), and two commercial carbon-based materials (Carbon Black and Black Pearls). OMW-1 achieved a H2 yield of 257 ± 62 mL L–1 d–1 at 800 mV, showing the potential of noncommercial biochar. CB and SSM performed better, reaching 493 ± 57 and 496 ± 9 mL L–1 d–1 H2, respectively. Cyclic voltammetry and next-generation sequencing revealed that hydrogen-oxidizing bacteria colonization negatively impacted H2 yields. At 600 mV, increased CH4 production was observed for OMW-2, BP, and CB. Energetically, OMW-2 (3.0 ± 0.2 kWh L–1 d–1) performed comparably to CB and BP (both 3.3 kWh L–1 d–1), outperforming SSM at both voltages. These findings support the viability of carbon-based cathodes as sustainable alternatives to metal-based ones with the potential to reduce electrode costs while maintaining or improving energy productivity