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Le decisioni cautelari monocratiche pronunciate dal TAR Lombardia, sede di Milano (anno di riferimento 2024) : Report analitico statistico finale
No full textCharcot-Marie-Tooth disease type 1E: clinical natural history and molecular impact of PMP22 variants
No full textCharcot-Marie-Tooth disease type 1E (CMT1E) is a rare, autosomal dominant peripheral neuropathy caused by missense variants, deletions, and truncations within the peripheral myelin protein-22 (PMP22) gene. CMT1E phenotypes vary depending on the specific variant, ranging from mild to severe, and there is little natural history and phenotypic progression data on individuals with CMT1E. Patients with CMT1E were evaluated during initial and follow-up visits at sites within the Inherited Neuropathy Consortium. Clinical characteristics were obtained from history, neurological exams, and nerve conduction studies. Clinical outcome measures were used to quantify baseline and longitudinal changes, including the Rasch-modified CMT Examination Score version 2 (CMTESv2-R) and the CMT Pediatric Scale (CMTPedS). The trafficking of PMP22 variants in transfected cells was correlated to disease severity. Twenty-four presumed disease-causing PMP22 variants were identified in 50 individuals from 35 families, including 19 missense variants, three in-frame deletions, and two truncations. Twenty-nine patients presented with delayed walking during childhood. At their baseline evaluation, the mean CMTESv2-R in 46 patients was 16 ± 7.72 (out of 32), and the mean CMTPedS from 17 patients was 28 ± 6.35 (out of 44). Six individuals presented with hearing loss, eleven with scoliosis, three with hip dysplasia, and one with both scoliosis and hip dysplasia. Twenty variants were localized within in transmembrane domains; 31 of 35 individuals with these variants had moderate to severe phenotypes. Three variants were found in the extracellular domain and were associated with milder phenotypes. Reduced expression of PMP22 at the cell surface, and the location of missense variants within in the transmembrane domain correlated with disease severity. Pathogenic PMP22 variants located within the transmembrane regions usually cause a moderate to severe clinical phenotype, beginning in early childhood, and have impaired trafficking to the plasma membrane
High Field Cos-Theta FalconD-C Dipole Magnet Development at CERN
No full textThe FalconD (Future Accelerator post-LHC Cosθ Optimized Nb3Sn Dipole magnet is part of the High Field Magnet (HFM) CERN programme. In collaboration with the Italian Institute for Nuclear Physics (INFN Genova and LASA Milano), CERN is developing a cos θ dipole magnet beyond 12 T based on proven Nb3Sn technology in the MQXF quadrupole used in the high-luminosity upgrade of the LHC. The magnet, with design aperture diameter of 50 mm, provides a bore field of 12 T for a 73 TeV center-of-mass energy scenario for the Future FCC-hh Circular Collider. The project has specific objectives to investigate cos-θ short magnet model design based on a two-layers coil with a wide high current cable. Moreover, the study of mechanical dipole structures based on aluminum shell with bladders and key (B&K) developed for the HL-LHC MQXF quadrupole will be presented as a baseline. The structure pre-loading system assembly baseline shall be tested on sub-scale mechanical mock ups at 77 K prior to building two single aperture 1.5 m long Nb3Sn magnet models followed by a 2-in-1 dipole magnet assembly. In this paper, we provide an overview of the magnetic and structural design carried out at CERN on an increased aperture diameter variant supported by first preliminary winding trials and give insights of the project timeline. Some preliminary protection scheme assessment is presented as baseline to be tested. Following the cable winding outcomes and the mechanical properties measured, some alternative coil optimized magnetic cross-section is reported
Intellectual Capital for sustainability: evidence from green patents and Geographical Indications in European regional agricultural systems
No full textPurpose
This paper investigates how Geographical Indications (GIs) operate as territorial ecosystems of Intellectual Capital (IC) that mobilize human, structural, and relational resources to foster green innovation in the European agricultural systems. It also examines how this relationship varies with regions' technological proximity to the frontier.
Design/methodology/approach
We compile a panel dataset for 251 regions in the EU-27 (1996–2022), combining eAmbrosia, OECD RegPat and ARDECO data. Green patents in agriculture are used as proxies for technological environmental innovation. A two-way fixed-effects Poisson Pseudo Maximum Likelihood estimation and additional robustness checks assess the effect of GIs on regional green innovation conditional on the distance to the technological frontier.
Findings
GIs significantly enhance regional green innovation capability, particularly in technologically lagging regions, where they act as collective IC infrastructures that enable cooperation, knowledge diffusion and adaptation. In frontier regions, the effect weakens or reverses, suggesting that strong market protection may reduce incentives for innovation.
Research limitations/implications
Patent data capture only codified technological innovation; future research should explore non-technological innovations.
Practical implications
GIs can be leveraged as strategic IC architecture to strengthen regional innovation ecosystems and align local identity with green transition goals, especially in lagging regions.
Originality/value
The study advances IC research by conceptualizing GIs as territorial IC systems integrating human, relational and structural capital to support place-based sustainability transitions. It provides novel empirical evidence on how collective intangible assets foster green technological upgrading and regional resilience
Surface and Drip Irrigation Method in Maize Cultivation: Comparison of Environmental Performance
No full textMaize is a water-intensive crop widely cultivated in temperate regions, where irrigation practices strongly influence its environmental performance. This study applies Life Cycle Assessment (LCA) to compare the environmental impacts of surface and drip irrigation for maize green silage production in the Po Valley (Italy), following ISO 14040/44 standards and adopting a cradle-to-farm-gate perspective. Results show that, compared to drip irrigation, surface irrigation leads to lower impacts in 14 out of 15 categories, with reductions ranging from−0.2% (marine eutrophication) to−61% (human toxicity, non-cancer), particularly for human toxicity and resource use due to lower diesel and infrastructure
requirements. Conversely, drip irrigation achieves a 58% reduction in water use thanks to its higher irrigation efficiency. The single-score assessment highlights water use as the key differentiating factor, positioning drip irrigation as preferable under scenarios of water scarcity. Contribution and sensitivity analyses confirm that nitrogen fertiliser use and mechanisation are major hotspots, while yield variation (±30%) significantly affects the magnitude of results. These findings emphasise a clear trade-off: surface irrigation shows a lower environmental burden across most impact categories, whereas drip irrigation strongly reduces water scarcity impacts and provides robust, site-specific evidence to guide sustainable irrigation strategies in intensive maize systems
CONTINUOUS-FLOW STRATEGIES FOR THE PREPARATION OF ACTIVE PHARMACEUTICAL INGREDIENTS AND RELEVANT INTERMEDIATES
No full textThis PhD thesis explores the development and application of continuous-flow strategies for the synthesis of active pharmaceutical ingredients (APIs) and key intermediates, with the aim of improving reaction efficiency, safety, and scalability. The work focuses on the integration of modern synthetic methodologies with enabling technologies such as flow chemistry, photoredox catalysis, ultrasound, and electrochemistry. In the first part, palladium-catalyzed cross-coupling reactions involving highly reactive organolithium reagents are investigated under continuous-flow conditions, demonstrating how precise control of reaction parameters allows safer handling and improved selectivity compared to batch processes. The second part describes the use of metallaphotoredox catalysis for the synthesis of tryptamine derivatives, highlighting the potential of light-driven processes to access structurally complex motifs under mild conditions. The thesis further addresses one of the major limitations of flow chemistry, namely solid handling, through the development of ultrasound-assisted strategies that enable reliable processing of heterogeneous systems at an industrially relevant scale. Additionally, electrochemical methods are explored for the oxidative functionalization of quinoline and isoquinoline derivatives, providing sustainable and reagent-efficient alternatives to traditional oxidative protocols. Finally, the applicability of the developed methodologies to real-world pharmaceutical processes is demonstrated through a collaborative project with Suanfarma S.p.A. Overall, this work showcases continuous-flow chemistry as a powerful platform for the development of innovative, safe, and scalable synthetic processes relevant to the pharmaceutical industry
Copper biosorption by Serratia plymuthica: crucial role of tightly bound extracellular polymeric substances in planktonic and biofilm systems
No full textHeavy metals in aquatic environments pose significant environmental and human health risks, highlighting the urgent need for innovative remediation strategies. This study explores the role of bacterial extracellular polymeric substances as active binding surfaces for copper, in planktonic cells and biofilm-based adsorption systems. Serratia plymuthica strain As3-5a(5) achieved 92% Cu(II) biosorption (from an initial concentration of 3.14 mM) within 4 min in a non-proliferating planktonic cell system, and 98% biosorption in a biofilm-based system on sintered glass. Maximum metal biosorption was achieved by late stationary phase grown cells (72 h), likely due to an increased protein fraction in the tightly bound extracellular polymeric substances. When in the presence of real electroplating wastewater containing 40 mM Cu(II) at pH 1.9, planktonic cell system (10^11 cells mL−1) achieved 97% Cu(II) biosorption. These results highlight the strong potential of Serratia plymuthica strain As3-5a(5) for developing efficient biological systems for heavy metal removal from industrial wastewater. Furthermore, this work provides valuable insights into sustainable biotechnological approaches for copper remediation, with potential applications in catalytic processes and metal recovery within a circular economy framework. Future studies should involve synthetic biology approach to improve copper sequestration and to investigate the scalability of these systems to higher technology readiness levels under real industrial wastewater conditions
CHARACTERIZATION OF THE INTERACTION BETWEEN HEPARAN SULFATE AND THE SPIKE (S) PROTEIN OF THE LATEST SARS-COV-2 VARIANTS
No full textHeparan sulfate is a linear, highly sulfated polysaccharide that belongs to the glycosaminoglycan (GAG) family. The disaccharide repeating unit includes a uronic acid residue (either D-glucuronic or L-iduronic) 1→4 linked to a glucosamine (GlcN). The glucosamine residues can be mono- or polysulfated at the N-, 6-O, and rarely at the 3-O positions, while the uronic acids can be sulfated at the 2-O position. Furthermore, HS displays heterogeneity in chain length and block composition, in which acetyl- and sulfate-rich sequences alternate. HS is covalently attached to the membrane protein (via the O- or the N-glycosylation of a Ser or Asn residue, respectively), forming heparan sulfate proteoglycans (HSPGs). Due to the pronounced density of negative charge of HS, HSPGs play a key role in several biological processes, including cell hydration, intercellular communication, storage, protection, and exchange of biomolecules (e.g., cytokines, chemokines), and the regulation of receptors and proteolytic enzymes (e.g., tyrosine kinase-type growth factor). Moreover, HS is also involved in diverse physiological and pathological events, such as embryonic development, inflammatory response, blood coagulation, and bacterial and viral infection. In the latter context, several studies show that a wide range of pathogens can interact with HS during the early stage of the infection. This aspect has recently drawn significant attention following the outbreak of the SARS-CoV-2 pandemic. Indeed, the virus exploits HS in the extracellular matrix to tether viral particles to the host cell surface, thereby promoting the specific interaction between the cell surface human angiotensin-converting enzyme 2 receptor (hACE2) and the receptor binding domain (RBD) that decorates the capsid of SARS-CoV-2. In fact, this event triggers the fusion between the cell and virus membranes. The RBD region (and, more broadly, the S1 subunit) contains several positively charged amino acids that are solvent-exposed and form a positive channel in which HS chains can be hosted without overlapping the hACE2 binding site.
The primary goal of this study is to understand how the role of HS in these early molecular recognition events differs in the latest and most widespread variants of SARS-CoV-2, through the application of complementary computational and experimental approaches that combine NMR spectroscopy and different computational tools.
We have selected two hexasaccharides as HS mimetics to probe their interactions with different RBDs using docking calculations. We then focused our study on the Omicron variant and one of the hexasaccharide mimetics, performing molecular dynamic simulations and 1H-NMR Saturation Transfer Difference experiments. Structural insights into its binding modes were obtained using RedMat, an NMR-based analysis tool for the analysis of molecular dynamic simulation trajectories, and they were compared with the ligand interactions observed for the wild-type RBD. This knowledge will contribute to the structural biology knowledge of SARS-CoV-2 and to the development of new antiviral strategies and antiviral drugs
Evidence for the collective nature of radial flow in Pb+Pb collisions with the ATLAS detector
No full textEditorial: Informing Science Through Solidarity
No full textIn this editorial paper, I pose some questions about the role of informing sci-ence. I do so by considering the current global situation of polycrisis: war con-flicts, genocides, humanitarian crisis, the climate change and the exacerbation of social inequalities occurring in a polarized violent public opinion perpetuating racist and discriminatory ideology. What is the purpose of academic writing in a world in which there are lives that do not matter? I take into account the spirit of informing science and the idea of transdisciplinary research to launch ques-tions for prospective papers. The idea principle of solidarity is presented as a means for research-conducting, theory-building and informing science