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Building Limits to the Over-criminalisation of Facilitating Irregular Migration : The Kinsa case
No full textThis Chapter critically addresses the offense of facilitating irregular migration, as provided by EU law and implemented by Italian criminal law, from the perspective of the principle of proportionality, regarded as an effective limit to overcriminalisation. Arguments are built around a case of a Congolese woman charged with facilitating the illegal entry of her daughter and her niece, both minors at the relevant time. The case has triggered the intervention of both the Italian Constitutional Court, which ruled on the disproportionality of the penalty, and the European Court of Justice (C-460/23, Kinsa), which ruled on the disproportionality of the criminalisation itself. These rulings look crucial for the European debate on the limits to legislative discretion in the fight against smuggling of migrants, a particularly topical debate as the Facilitators Package is currently under revision
Le decisioni cautelari monocratiche pronunciate dal TAR Lombardia, sede di Milano (anno di riferimento 2024) : Introduzione
No full textLo scritto introduce alla ricerca sulle decisioni cautelari monocratiche adottate nel corso dell’anno 2024 dal Tar Lombardia, sede di Milano, che aspira a coniugare teoria e pratica del diritto, indagine empirica e analisi speculativa,
secondo una tradizione non frequente nei nostri studi giuridici, ma utilizzata ampiamente altrove
Le gestione dei rischi fiscali nel contesto Environment, Social and Governance (ESG) quale nuovo approccio culturale nei rapporti tra fisco e contribuente
No full textTracing anatexis and bottom-up crustal homogenisation with in situ Sm-Nd isotopes
No full textWhole rock Nd isotopes are commonly used to assess mantle-crust contributions in magma sources and to constrain the timing of magmatic and metamorphic events. However, such measurements provide limited insights into deep crustal roots, where complex processes (e.g., open system melting, magma hybridisation) may occur. Here, we combine whole rock and in situ Sm-Nd isotopic analyses across a 25–30 km thick crustal section in Calabria (Italy). This section exposes lower crustal granulites and migmatites overlain by mid-crustal post-collisional granitoids, forming a 13 km thick batholith. The lower crust is strongly heterogeneous (whole rock ɛNd(i) = −10.5 to +1.7) with isotopic variability evident from outcrop to grain scale. By contrast, the mid-crustal igneous rocks display remarkable homogeneity with consistent crustal signatures (ɛNd(i) ≈ −7). Our results indicate efficient isotopic homogenisation from a 1–2 km thick transition zone at the lower-middle crust boundary, where hybridisation between mafic and felsic magmas is evidenced at the grain scale using Sm-Nd isotopic analyses. A minor mantle contribution was likely involved in the batholith genesis but largely obscured by processes like crustal assimilation and cannot be resolved in the granitoids using the Sm-Nd system
Co-production and nudging in the digital era: enhancement of public services?
No full textThis chapter explores the synergies between co-production and nudging, aiming to better
understand their combined potential in enhancing public services. The qualitative study starts
by comparing these approaches and then examines the rise of blended engagement practices,
integrating both analogue and digital elements alongside policy interventions rooted in
deliberative and behavioural principles. A novel conceptual model is then introduced, capturing
the essential elements of co-production and nudging. The model systematises the variety of
objectives, strategies, and policies that can be pursued through an integrated approach.
Furthermore, detailing the diverse moments of interaction (or public service encounters)
between citizens and professionals throughout the service cycle helps public administrators
easily identify the conditions essential for well-designed collaborative initiatives. Overall, the
chapter provides valuable perspectives on integrating co-production and nudging, offering a
fresh viewpoint on their application in public service enhancement
DISSECTING THE ROLE OF THE TETRASPANIN MS4A4A IN MODULATING MACROPHAGE PLASTICITY AND FUNCTION
No full textMS4A4A belongs to the membrane-spanning 4A (MS4A) family, whose proteins show preferential expression in distinct cell types and structural similarities to tetraspanins, including the ability to interact with and modulate the activity of various immunoreceptors, such as pattern recognition receptors (PRRs) and Ig receptors. MS4A4A is selectively expressed by macrophages, and its expression is upregulated upon treatment with Interleukin-4 (IL-4) and glucocorticoids (Dexamethasone, Dex). However, the molecular mechanisms by which MS4A4A exerts its biological function in macrophages remains largely uncharacterised.
MS4A4A has been increasingly studied in relation to several diseases with inflammatory components. Specifically, it has been implicated in Alzheimer’s disease, potentially affecting microglial activation. In the context of cancer, we have previously reported that MS4A4A is required for the macrophage-dependent activation of NK cell anti-metastatic functions. Recently, we have shown that MS4A4A+ macrophages are detected in the synovial tissue of rheumatoid arthritis (RA) patients. Although less extensively studied, MS4A4A expression was associated with inflammatory diseases such as sepsis, atherosclerosis, and inflammatory bowel disease. Macrophages are key players in the pathogenesis of these diseases due to their ability to shift between pro-inflammatory and anti-inflammatory phenotypes, allowing them to drive tissue damage or promote repair.
In this context, the present study aimed to characterize the biological function of MS4A4A in macrophages and its involvement in macrophage activation and function.
Firstly, the structure of MS4A4A was investigated and characterised via artificial intelligence analysis and molecular dynamics simulation, to clarify its role in cellular signaling and potentially linking its structure to specific biological outcomes. Then, having observed only minimal differences in the transcriptional profiles between WT and KO macrophages, further investigation focused on the role of MS4A4A in macrophage activation. This led to the identification of two potential partners: the γ-chain of Fc gamma receptors (FcγRs) and Toll-like receptor 2 (TLR2), suggesting a possible involvement of MS4A4A in their inflammatory signaling. In the context of RA, where macrophages show altered FcγRIII expression, MS4A4A expression was found to be upregulated and positively correlated with disease pathogenesis, as well as with FcγRIII and the FcγR γ-chain expression in RA patients. Notably, both MS4A4A and FcγRIII are induced by Dex. MS4A4A was shown to limit the anti-inflammatory effects of Dex during FcγR-mediated inflammation by affecting the release of TNF-α and CXCL2. This modulatory role of MS4A4A appears to be independent on direct influence on FcγR signaling, and the precise mechanism remains to be defined.
To dissect the role of MS4A4A in macrophage activation mediated by TLR-2, we found that MS4A4A regulates the surface expression of TLR2 and affects the release of the anti-inflammatory cytokine IL-10. This impairment in IL-10 release is not limited to TLR2 stimulation but is also observed with other TLR agonists. Notably, during LPS stimulation, the reduced IL-10 release persists over time, starting as early as 2 hours post-stimulation. Further analysis showed that LPS induces MS4A4A expression and led to the identification of an IL-10 storage pool in resting macrophages. The defect in IL-10 release may result from a role of MS4A4A in regulating IL-10 de novo synthesis and/or the mobilization of this intracellular IL-10 pool. This study provides a valuable contribution to the field, expanding the current knowledge of MS4A4A’s role in macrophage activation and its impact on inflammatory response
PALLADIUM-BASED SYSTEMS IN HOMOGENEOUS CATALYSIS: EXPLORING NITROGEN LIGANDS FOR CO-MEDIATED REACTIONS
No full textThis work explores palladium‐based systems in homogeneous catalysis, focusing on CO‐mediated transformations and the role of nitrogen ligands. Building on the efficiency of palladium-phenanthroline catalytic system in reductive cyclization of nitroarenes, the study investigates CO and its surrogates as reductant for the synthesis of different nitrogen-containing heterocycles. Furthemore, the use of guanidines as ligands in carbonylation and alkoxycarbonylation of olefins has been attempted
Conceptual Design of a 3 T HTS Solenoid for Future Circular Collider Particle Detectors
No full textThe design activity described in this paper concerns the development of a new superconducting solenoid for particle collider detector magnets based on high-temperature superconductor technology. Developed by the Istituto Nazionale di Fisica Nucleare (INFN) Laboratorio di Acceleratori e Superconduttività Applicata (LASA), in the framework of the Innovative Detector for e-e+ Accelerator (IDEA) proposal for the Future Circular Collider project in the electron positron configuration (FCC-ee), the new superconducting solenoid design aims to reach a nominal field up to 3 T. By considering to use aluminum stabilized High-Temperature Superconductor (HTS) REBCO cables, this innovative design features an increased bore radius to accommodate enhanced dual-readout crystal calorimeters with the possibility to work at an operating temperature of 20 K. The proposed configuration has the potential to significantly reduce cryogenic power consumption, thereby improving overall accelerator sustainability while increasing the operating margin of the superconducting winding. In this paper, the electromagnetic performances and a preliminary mechanical analysis of the proposed HTS design are discussed. Details of the protection feasibility are provided together with transparency calculations of the coil volume showing the advantages of the proposed HTS configuration as an important step towards increased performances and enhanced energy efficiency of future particle detector magnets for lepton collider experiments
Towards more effective Glioblastoma Multiforme therapies: HDAC6 and HDAC8 combined targeting
No full textGlioblastoma Multiforme (GBM) is the most common and lethal tumor of the central nervous system in adults, with recurrence and poor prognosis. To date, therapeutic intervention consists of surgical resection followed by radio and chemotherapy. Temozolomide (TMZ) is the standard treatment for GBM, but most patients do not respond or develop resistance. Among the aberrant pathways involved in GBM, several histone deacetylases (HDACs), such as HDAC6 and HDAC8, have been reported to be upregulated. Indeed, we previously demonstrated that the specific inhibition of HDAC6 reduces GBM progression. In this work, we explored whether the combined inhibition of HDAC6 and HDAC8 could be more effective than single inhibition, due to the different specificity of the two HDACs. To accomplish this, we performed in vivo analyses using the GBM zebrafish model zic:RAS, in which tumor development is induced by the specific oncogene expression in neural cells. In parallel, we employed the human GBM cell lines U87MG and T98G, which differ in their genetic profile and sensitivity to TMZ treatment, as in vitro models. Our results revealed that the combined inhibition of HDAC6 and HDAC8 induced a stronger reduction of the vitality of the GBM cell lines, as well as of tumor growth in the zic:RAS zebrafish larvae, compared to the single treatments. Additionally, the HDAC6/HDAC8 combined inhibition enhanced TMZ sensitivity both in vivo and in vitro. From a functional point of view, our in vitro findings suggest that only HDAC6 inhibition impairs the acidic compartments, leading to the disruption of lysosomal trafficking. In zebrafish, blocking HDAC8, but not HDAC6, results in an apoptotic response. To better characterize the cellular and molecular mechanisms involved, we will perform omics analyses of the acetylation status and the transcriptional profile of both our models when HDAC6 and HDAC8 are inhibited. This integrated approach provides a powerful platform to evaluate the effect of the selective and combined HDAC6/HDAC8 inhibition, and to dissect the biological mechanisms that could be relevant for GBM onset and resistance. Our results support the potential of the dual inhibition as a promising therapeutic approach for GBM and other HDAC6/HDAC8 overexpressing cancers
Electrochemical Benchmarking and Reproducibility of Commercial Screen-Printed Carbon Electrodes
No full textScreen-printed carbon electrodes (SPCEs) have become widely adopted in electroanalytical
applications due to their affordability, portability, and adaptable surface properties [1,2]. These features have enabled their extensive use in both environmental monitoring and biomedical sensing platforms [3,4]. Nevertheless, variations arising from manufacturing processes and production batches often lead to inconsistent electrochemical responses, raising concerns about data reliability and comparability [2,5]. This underscores the need for systematic evaluation strategies to assess the consistency and practical interchangeability of commercially available SPCEs.
In the present study, multiple commercial SPCEs were comparatively investigated using
cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The ferri/ferrocyanide redox system was selected as a standardized electrochemical probe [3,4] to examine key performance parameters, including electron transfer kinetics, electroactive surface area, and signal stability. The comparative analysis revealed marked differences in electrochemical behavior, reproducibility, and batch-to-batch variability, even among electrodes with similar nominal characteristics [1,5]. To complement the electrochemical measurements, morphological and compositional characterizations were performed to elucidate the origin of the observed discrepancies.
Overall, this work establishes practical criteria for the benchmarking and selection of SPCEs,
supporting informed decisions when balancing electrochemical performance against reproducibility requirements in applied sensing scenarios [5,6]. In addition, preliminary investigations into surface modification approaches, such as electropolymerization, were conducted to explore routes for performance enhancement and to probe the role of surface properties in governing selectivity.
[1] R.D. Crapnell, C.E. Banks, ChemElectroChem, 2024, 11.
[2] R. Andreeva, A. Tsanev, G. Avdeev, D. Stoychev, Metals, 2025, 15.
[3] Z. Taleat, A. Khoshroo, M. Mazloum-Ardakani, Microchimica Acta, 2014, 181, 865-891.
[4] J. Barton, M.B.G. García, D.H. Santos, Microchim Acta, 2016, 183, 503–517.
[5] Z. Lihua, H. Hongliang, M. Zhanfang, Biosensors and Bioelectronics, 2018, 101, 304-310.
[6] S.R. Subramaniam, Z.Z. Abidin, M.A. Issa, N.H. Harun, M.Y. Pudza, Water, Air, and Soil Pollution, 2025, 236(14)