ARUd’A (Università “G. d’Annunzio CHIETI -PESCARA)
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    Use of in situ tests to measure and predict shear wave velocity: the peculiarity of silty-sandy deposits in Emilia (Italy)

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    The results of Medusa SDMT (Seismic Dilatometer) and SCPTu (Seismic Piezocone) that were performed in 2023 at two different sites in the Emilia (Italy) plain are described in this paper. The focus is on the measurement of the shear wave velocity (Vs) and the predictive capability of existing (cone penetration test – CPT and flat dilatometer – DMT based) empirical correlations. Both the pseudo-interval and true interval approaches were applied when interpreting the in situ measurements. The comparison between measured Vs (SDMT – true interval) and predicted Vs from four different CPT and one DMT empirical correlations shows that not all of them have good performance. In this respect, we propose an updated DMT correlation to improve the accuracy of the predicted Vs in silty-sandy deposits, which are predominant in the sites investigated in this paper. The studies connected to these peculiar intermediate soils are still ongoing and their behavior needs further research sites to test and validate this preliminary correlation

    CD19.CAR-T cell-derived extracellular vesicles express CAR and kill leukemic cells, contributing to antineoplastic therapy

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    : Chimeric Antigen Receptor (CAR) T cell-derived Extracellular Vesicles (EVs) might represent a new therapeutic tool for boosting CAR-T cell antileukemic effects. Here, a cohort of 22 patients infused with CD19.CAR-T cells was monitored for the presence of circulating CD19.CAR+-T cell-derived EVs (CD19.CAR+EVs), which were then separated and functionally characterized for their killing abilities. A GMP-compliant separation method was also developed. Results demonstrated that CD19.CAR+EVs were detectable in peripheral blood up to 2 years after infusion indicating long-lasting persistence of their parental cells. Notably, early decreases of circulating CD19.CAR+EVs concentrations correlated with failure of CAR-T therapy. Circulating CD19.CAR+EVs displayed a median size (SD) of 133.1±65.5 nm and carried a pro-apoptotic protein cargo. These EVs expressed higher CAR levels than their parental cells. Furthermore, CD19.CAR+EVs did not activate heterologous T cells and produced significant, specific and dose-dependent cytotoxic effects on CD19+ cell lines and on primary cells. The new GMP-compliant EV isolation method allowed a recovery of 63±5.7 % of CD19.CAR+EVs. A deeper analysis of the different protein cargoes carried by EVs derived from different CAR-T cell subpopulations identified a pro-apoptotic functional pathway linked to CD8+LAG-3+ EVs. Overall, our data indicate that CD19.CAR+EVs may be proposed as promising dynamic new biomarkers of CAR-T cell activity and, contributing to the direct killing of the leukemic target, represent a new product with a strong therapeutic potential that could be infused independently from CAR-T cells

    L'espace public politique, internet et les réseaux sociaux. Sur la derniere actualisation de Jürgen Habermas

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    L’essai examine les réflexions récentes de Jürgen Habermas sur la transfor-mation structurelle de l’espace public politique générée par l’Internet et les réseaux sociaux. Après avoir juste introduit la centralité du modèle habermassien dans le domaine des sciences de l’information-communication (SIC) et, inver-sement, avoir souligné le fait que Habermas a constamment mis à jour ses propres élaborations théoriques en s’appropriant les perspectives et les résul-tats empiriques produits dans ce champ scientifique, neuf aspects relatifs à la structure des relations interpersonnelles et à la qualité de l’information et de la communication dans la nouvelle ère numérique et connective sont considérés. Il s’agit de nouvelles opportunités, mais surtout d’aspects critiques qui risquent de compromettre les fonctions que le système médiatique a assurées – malgré ses imperfections – pour la formation d’opinions publiques « réflexives » dans les régimes démocratiques

    A Geranylated Natural Product Simamycin Disrupts the Allosteric Catalysis of tRNA-2-selenouridine Synthase SelU

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    tRNA-2-selenouridine synthase (SelU) is a tRNA-modifying enzyme that is instrumental to bacterial translation by exploiting certain chalcogens. Specifically, this enzyme catalyzes the geranylation of 2-thiouridine at the wobble position of three bacterial tRNAs to enhance the recognition of codons ending in guanosine over adenosine using geranyl pyrophosphate as the cofactor. In addition, SelU is also the working enzyme for a selenation process at the same tRNA position in the presence of selenophosphate. How this enzyme conducts two mechanistically different reactions is a fundamentally interesting question. In order to gain more details about the substrate recognition of SelU, in this work, we identified a small natural compound simamycin (5′-O-geranyluridine) with strong interactions with this enzyme. Further, through biophysical affinity assays and NMR structural studies, we postulated an allosteric mechanism of SelU catalysis involving cooperativity among each domain and a conformational rearrangement around the active site of its N-terminal domain. This conclusion is supported by the bimolecular quenching constants, number of binding sites, and thermodynamic parameters calculated for this compound complexed with the N-terminal domain of SelU

    Inhibition of Human Coronavirus 229E by Lactoferrin-Derived Peptidomimetics

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    Background/Objectives: Viral respiratory infections have a significant impact on global health and the economy. While vaccines are effective in preventing infection, they might not be available or sufficient when used alone and must be complemented by specific therapeutic strategies. The development of new antiviral agents is increasingly important due to the continual emergence of novel respiratory pathogens. Previously we identified bovine lactoferrin (bLf)-derived tetrapeptides and peptidomimetics that showed potent in vitro activity against the influenza A virus in the picomolar range. Methods: Inspired by these results, in this study, we evaluated the antiviral potential of these compounds against HCoV-229E, a human coronavirus that can cause severe disease in immunocompromised individuals, using a compound repositioning approach. Results: Functional studies revealed that SK(N-Me)HS (3) interferes with viral entry and replication, while compound SNKHS (5) primarily blocks infection in the early stages. Biophysical analyses confirmed the occurrence of high-affinity binding to the viral spike protein, and computational studies suggested that the compounds target a region involved in conformational changes necessary for membrane fusion. Conclusions: These findings highlight these compounds as promising candidates for coronavirus entry inhibition and underscore the value of compound repurposing in antiviral development

    Toward a Multi-Trait Genetic Panel Targeting Training, Rehabilitation, and Chronic Disease Prevention: A Narrative Review

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    Athletic performance results from complex interactions between genetic and environmental factors. This review compiles and synthesizes available literature on polymorphic genes associated with endurance, power, and strength performance, as well as their links to injury susceptibility and chronic metabolic diseases. Endurance performance is modulated by ACE, PPARGC1A, HFE, UCP2, UCP3, CDKN1A, and PPARA, regulating mitochondrial biogenesis, oxygen utilization, and muscle fiber composition. Power performance involves ACTN3, MCT1, IGF1, AMPD1, AGT, and AGTR2, affecting anaerobic metabolism, lactate clearance, and fast-twitch fiber recruitment. Strength performance is influenced by AR, PPARG, ARK2N, MMS22L, LRPPRC, PHACTR1, and MTHFR, related to androgen signaling, muscle hypertrophy, and recovery. Injury-related genes (COL1A1, COL5A1, IL6, VEGFA, NOG) and metabolic risk genes (FTO, PPARG, ADRB3) further highlight the clinical relevance of genomics. Collectively, these insights support the application of genetic information to personalize training, enhance performance, prevent injuries, and guide exercise interventions to mitigate metabolic disease risk

    Research and analysis of teaching contents on Design and EDI in the Italian system of Design Education

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    The paper presents the current picture of the introduction of EDI (Equality, Diversity, Inclusion) into design education curricula in Poland. We focused on design programs taught at eight public art universities. Desk research confirmed EDI-related topics in 51 modules taught on undergraduate first-cycle, postgraduate second-cycle, and unified master’s long-cycle programs. Further interviews with educators allowed us to identify best practices, activities, and challenges in EDI education across various design disciplines. The findings reveal the specifics and outcomes of EDI in the Polish context. We outline a comprehensive overview of educational practices developed by teachers, revealing diverse, multi-level, and often innovative approaches to EDI-related education. It provides rich data and a detailed picture of the characteristics of Polish design education, which could serve as a foundation for developing more systematic national regulations. These regulations could promote the EDI approach more broadly within society and among institutions, enabling more effective collaboration with Academies

    Do reshoring and nearshoring drive reindustrialization? The case of Germany

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    This study investigates the evolution of the German manufacturing sector in response to recent global disruptions, such as COVID-19. Using a new multi-country input-output framework, we analyze whether reshoring (bringing production back to Germany) and nearshoring (relocating it to neighboring European countries) have contributed to a process of reindustrialization. Our results indicate a clear shift in manufacturing value chains, particularly in medium-high-tech sectors, toward domestic and regional production. These sectors have increased employment within Germany and the EU while reducing dependence on distant (non-EU) production, suggesting a growing preference for resilient and regionally integrated supply chains. Concomitantly, the integration of services, particularly knowledge-intensive business services, has reinforced this transformation by supporting innovation and operational efficiency, reflecting the ongoing transformation to a knowledge-based economy. This study provides new insights into the changing geography of manufacturing and highlights the importance of reshoring and nearshoring as strategic responses to global uncertainty

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