Archivio istituzionale della ricerca - Università dell'Insubria
Not a member yet
60118 research outputs found
Sort by
Expected multi-utility representations of preferences over lotteries
No full textLet ≿ be a binary relation on the set of simple lotteries over a countable outcome set Z. We provide necessary and sufficient conditions on ≿ to guarantee the existence of a set U of von Neumann–Morgenstern utilities u:Z→R such that p≿q⟺Ep[u]≥Eq[u]for allu∈Ufor all simple lotteries p,q. In this case, the set U is essentially unique. Then, we show that the analogous characterization does not hold if Z is uncountable. This provides an answer to an open question posed by Dubra, Maccheroni, and Ok in [J. Econom. Theory 115 (2004), no. 1, 118–133]. Lastly, we show that different continuity requirements on ≿ allow for certain restrictions on the possible choices of the set U of utility functions (e.g., all u are bounded), providing a wide family of expected multi-utility representations. Some implications are proved in a much wider setting
Metformin protects retinal ganglion cells in a preclinical model of retinal ischemia/reperfusion injury and stabilizes visual field in diabetic patients with glaucoma
Get PDFMetformin, a first-line treatment for type 2 diabetes, has gained attention as a promising neuroprotective agent due to its pleiotropic effects - including anti-inflammatory, anti-apoptotic, and autophagy-enhancing properties. Here we provide both preclinical and clinical evidence demonstrating the neuroprotective effects of metformin in the context of retinal ganglion cell (RGC) degeneration, a hallmark of glaucoma, a leading cause of irreversible blindness for which no direct RGC-neuroprotective therapies are currently available. In a mouse model of retinal ischemia/reperfusion injury systemic administration of metformin significantly prevented RGC loss and preserved retinal structure. Enhanced phosphorylation of AMP-activated protein kinase (AMPK) was observed, along with increased autophagosome formation and upregulation of key mitophagy markers - including LC3II, optineurin, and Parkin - indicating improved mitochondrial quality control mechanisms. Proteomic analysis revealed that metformin modulated several proteins implicated in mitochondrial respiratory function, ubiquitination, and intracellular trafficking, suggesting broader effects on retinal cellular homeostasis. Complementing our preclinical observations, a retrospective clinical study in diabetic patients with glaucoma showed that individuals treated with metformin maintained stable visual field (VF) parameters over a six-month period, whereas those treated with insulin exhibited significant VF deterioration. These findings position metformin as a promising intraocular pressure (IOP)-independent neurotherapeutic for slowing or preventing glaucomatous neurodegeneration
‘The Importance of being Earnest?’ The Fight Against Fraud within the Institutions of the Union
No full textEsplorando la biosintesi di metaboliti specializzati antimicrobici in attinomiceti rari
No full textAntimicrobial resistance (AMR) is reducing antibiotic efficacy faster than new drugs can be developed. This thesis integrates genome-guided discovery of antibiotics with genetic engineering in actinomycetes, moving from scaffold identification to biosynthesis elucidation and strain improvement. Two research lines are presented: (i) discovery of kineomicins, a novel glycopeptide antibiotic (GPA) complex from Actinokineospora auranticolor DSM 44650; and (ii) biosynthesis and production improvement of GE23077, a selective RNA polymerase inhibitor from Actinomadura lepetitiana DSM 109019. Genome mining revealed an atypical GPA biosynthetic gene cluster (BGC) in A. auranticolor, and structural analysis confirmed kineomicins as a new GPA subclass with an unprecedented aglycone. Process optimisation delivered titres above 1 g/L, identifying A. auranticolor as a natural overproducer. For GE23077, a high-quality genome assembly uncovered the gec BGC, encoding a non-canonical NRPS system, tailoring enzymes, transporters, and the regulator gecA. Comparative genomics revealed gec-like clusters in four additional Actinomadura species, which produced GE23077 and new congeners, including a phenyl-substituted analogue. Morphotype selection doubled GE23077 titres, while strain engineering with gecA overexpression or ribosome recycling factor insertion yielded 2- and 4-fold improvements. Overall, this workflow provides novel scaffolds, genetic insights, and enhanced production, advancing antibiotic discovery against AMR.La resistenza agli antibiotici (AMR) riduce l’efficacia degli antibiotici più velocemente di quanto si riesca a sviluppare nuovi farmaci. Questa tesi integra la scoperta genome-guided di antibiotici con l’ingegneria genetica negli attinomiceti, passando dall’identificazione di nuovi scaffold alla chiarificazione della biosintesi e al miglioramento delle produzioni. Il lavoro si concentra su due linee: (i) la scoperta della kineomicina, un nuovo complesso di antibiotici glicopeptidici (GPA) da Actinokineospora auranticolor DSM 44650T; e (ii) la biosintesi e l’aumento della produzione di GE23077, un inibitore selettivo dell’RNA polimerasi da Actinomadura lepetitiana DSM 109019T. Il genome mining ha rivelato un cluster genico biosintetico (BGC) atipico in A. auranticolor, e le analisi strutturali hanno confermato come la kineomicina sia una nuova sottoclasse di GPA, con un aglicone inedito. L’ottimizzazione dei processi ha portato a titoli superiori a 1 g/L, rendendo A. auranticolor un naturale overproduttore. Per lo studio di GE23077, il genoma completo ha permesso di identificare il cluster gec, contenente un sistema NRPS non canonico, enzimi per la sintesi dei precursori, trasportatori e il regolatore gecA. Analisi comparative hanno individuato cluster simili in altre quattro specie di Actinomadura, produttrici di GE23077 e nuovi congeneri, incluso un analogo fenil-sostituito. La selezione morfotipica ha raddoppiato le rese di GE23077, mentre l’ingegneria razionale con la sovraespressione di gecA o l’inserimento del fattore di riciclo ribosomiale ha portato a incrementi rispettivamente di 2 e 4 volte. Nel complesso, questo approccio fornisce nuovi scaffold, conoscenze genetiche e maggiore disponibilità, passi chiave verso nuovi antibiotici contro l’AMR
The AGORA High-Resolution Galaxy Simulations Comparison Project VII. Satellite quenching in zoom-in simulation of a Milky Way-mass halo
No full textContext. Satellite galaxies experience multiple physical processes when interacting with their host halos, often leading to the quenching of star formation. In the Local Group, satellite quenching has been shown to be highly efficient, affecting nearly all satellites except the most massive ones. While recent surveys study Milky Way-analogs to assess how representative our Local Group is, the dominant physical mechanisms behind satellite quenching in Milky Way-mass halos remain under debate. Aims. We analyze satellite quenching within the same Milky Way-mass halo simulated using various widely used astrophysical codes, each using different hydrodynamic methods and implementing different supernovae feedback recipes. The goal is to determine whether quenched fractions, quenching timescales, and the dominant quenching mechanisms are consistent across codes or if they show sensitivity to the specific hydrodynamic method and supernovae feedback physics employed. Methods. We used a subset of high-resolution cosmological zoom-in simulations of a Milky Way-mass halo from the multiple-code AGORA CosmoRun suite. Our analysis focuses on comparing satellite quenching across the different models and against observational data. We also analyzed the dominant mechanisms driving satellite quenching in each model. Results. We find that the quenched fraction is consistent with the latest SAGA Survey results within its 1 sigma host-to-host scatter across all the models. Regarding quenching timescales, all the models reproduce the trend observed in the ELVES survey, Local Group observations, and previous simulations: The less massive the satellite, the shorter its quenching timescale. All of our models converge on the dominant quenching mechanisms: Strangulation halts cold gas accretion in all satellites, while ram pressure stripping is the predominant mechanism for gas removal, and it is particularly effective in satellites with M-*<10(8) M-circle dot. Nevertheless, the efficiency of the stripping mechanisms differs among the codes, showing a strong sensitivity to the different supernovae feedback implementations and/or hydrodynamic methods employed
The Caprera Canyon (north–eastern Sardinia): A hotspot of cetacean diversity in the western Mediterranean Sea
No full textThe Caprera Canyon, a submarine canyon system off Sardinia in the western Mediterranean, was thought to be an important cetacean habitat, though studies on the area remained limited. To address this knowledge gap, 216 boat-based surveys were conducted between 2011 and 2019, covering 8443 km, using both research and whale-watching vessels. The distribution, diversity, relative abundance (Encounter Rate - ER), and habitat use of cetaceans were described, along with relevant behavioural and ecological observations. A total of 8 species were reported across 810 sightings, encompassing 7 out of the 8 cetaceans regularly found in the western Mediterranean Sea. These species, in order of relative abundance, include the striped dolphin (Stenella coeruleoalba), fin whale (Balaenoptera physalus), Cuvier's beaked whale (Ziphius cavirostris), sperm whale (Physeter macrocephalus), Risso's dolphin (Grampus griseus), common dolphin (Delphinus delphis), bottlenose dolphin (Tursiops truncatus), and a single observation of Sowerby's beaked whale Mesoplodon bidens. This results in an overall ER of 10.6 sightings/100 km. ERs indicate that some species are particularly abundant in the study area, with Cuvier's beaked whale registering one of the highest ER values ever documented in the Mediterranean Sea. Calves and behavioural observations suggest that the study area serves as both a breeding and feeding ground for most species. The high cetacean diversity and relative abundance, along with the regular occurrence of endangered and vulnerable species, identify the Caprera Canyon as an important hotspot for cetacean diversity. Habitat suitability models using the maximum entropy (MaxEnt) approach highlight that other smaller canyons surrounding the Caprera Canyon could provide suitable habitats for deep diving species. The results presented here serve as reference data for future studies on the ecology and long-term dynamics of cetaceans in the central-western Tyrrhenian Sea. We highlight that the Caprera Canyon and surrounding areas could benefit from being designated as an Important Marine Mammal Area (IMMA), potentially supporting conservation efforts, guiding marine spatial planning, and informing policy development to mitigate threats in the region
Shaping food and well-being discourse across genres, contexts and centuries
No full textThe work explores how discourses surrounding food, diet, and nutrition have contributed to shaping and redefining ideas of health and well-being across time. It combines diachronic investigations of earlier centuries with analyses of contemporary discourses, offering a multifaceted view of how notions of well-being are constructed through language and culture. By examining a wide range of genres - from medical treatises and recipe books to media and digital communication - the study reveals food discourse as a privileged site for observing how linguistic choices and cultural practices reflect and shape evolving conceptions of health, identity, and the good life
Cambiamenti climatici e turismo nel comasco: impatti e misure di adattamento
No full textIl saggio analizza gli effetti dei cambiamenti climatici sul turismo nel territorio comasco, con particolare attenzione al Lago di Como e alle aree montane. Eventi meteorologici estremi, abbassamento e riscaldamento delle acque del Lario, riduzione del pescato e chiusura delle stazioni sciistiche incidono profondamente sull’economia turistica locale. L’autore propone misure di adattamento che includono una gestione idrica più sostenibile, interventi di tutela ambientale, revisione delle pratiche agricole e riconversione del turismo verso modelli destagionalizzati e meno impattanti. In conclusione, invita a superare modelli di sviluppo obsoleti e a promuovere un turismo resiliente, integrato e rispettoso della fragilità del territorio comasco
Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (URRAH Project)
No full textPurpose: Recently, a novel index [the triglyceride-glucose (TyG) index]) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk. Methods: The analysis included 16 649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. Results: During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only 1 of the 2 factors. Conclusion: The results of this study indicate that these TyG (a low-cost and simple, noninvasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality
Unravelling Plasma Extracellular Vesicle Diversity With Optimised Spectral Flow Cytometry
No full textExtracellular vesicles (EVs) are crucial for intercellular communication and are found in various biological fluids. The identification and immunophenotyping of such small particles continue to pose significant challenges. Here, we have developed a workflow for the optimisation of a next-generation panel for in-depth immunophenotyping of circulating plasma EVs using spectral flow cytometry. Our data collection followed a multistep optimisation phase for both instrument setup and 21-colour panel design, thus maximising fluorescent signal recovery. This spectral approach enabled the identification of novel EV subpopulations. Indeed, besides common EVs released by erythrocytes, platelets, leukocytes and endothelial cells, we observed rare and poorly known EV subsets carrying antigens related to cell activation or exhaustion. Notably, the unsupervised data analysis of major EV subsets revealed subpopulations expressing up to five surface antigens simultaneously. However, the majority of EVs expressed only a single surface antigen, suggesting they may not fully represent the phenotype of their parent cells. This is likely due to the small surface area or the biogenesis of EVs rather than antibody steric hindrance. Finally, we tested our workflow by analysing the plasma EV landscape in a cohort of systemic lupus erythematosus (SLE) patients. Interestingly, we observed a significant increase in CD54+ EVs, supporting the notion of elevated circulating ICAM under SLE conditions. To our knowledge, these are the first data highlighting the importance of a spectral flow cytometry approach in deciphering the heterogeneity of plasma EVs paving the way for the routine use of a high-dimensional immunophenotyping in EV research