University of Udine
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FALCON-qPCR: a new method for the quantification of oxidative lesions in mitochondrial DNA
No full textAccurate quantification of oxidative mitochondrial DNA (mtDNA) lesions remains technically challengingdue to the limitations of existing assays, which often require large sample inputs, multi-day workflows,and offer limited sensitivity. Here we introduce FALCON-qPCR (Fpg-assisted Long-PCR), a streamlined,high-sensitivity method for quantifying oxidative damage in mtDNA. FALCON-qPCR couples digestionwith formamidopyrimidine [fapy]-DNA glycosylase (Fpg) to long-range PCR and qPCR-based normal-ization, enabling precise lesion quantification from as few as 10,000 cells (~300 ng total DNA) withina single day. The assay provides a robust dynamic range and reproducibility across diverse biologicalsystems, including human cell lines, hepatocellular carcinoma biopsies, and Caenorhabditis elegans.Compared with established methods, FALCON-qPCR exhibits markedly higher sensitivity in detectingmtDNA damage induced by hydrogen peroxide, antimycin A, and rotenone. Its performance was furtherdemonstrated in assessing mitochondrial toxicity of ruthenium-based compounds, highlighting its poten-tial for pharmacological screening. By integrating enzymatic lesion recognition with quantitative ampli-fication in a unified workflow, FALCON-qPCR eliminates the need for mitochondrial isolation. Thismethodological advance provides a rapid, accurate, and scalable platform for studying oxidative DNAdamage, with broad applicability in mitochondrial research and translational toxicology
Seismic Retrofitting of a Reinforced Concrete Building with Unidirectional Frames and Low Strength Concrete
No full textThe displacement capacity of an existing Reinforced Concrete (RC) school building, representative of medium-high vulnerability structures, does not meet the requirements of the current Italian Building Code. The building structure is made by unidirectional frames and shear walls. The modal analysis reveals that the building has low torsional stiffness, with translation in the direction of the frames coupled with torsional motion. For seismic retrofitting, a minimally invasive solution involving external steel braced frames, placed adjacent to the building façades, is proposed. These frames aim to enhance the building’s torsional stiffness and reduce the ductility demands on the RC structural elements. The proposed intervention is deemed adequate, with its effectiveness evaluated through nonlinear dynamic analysis. To comply with the Code requirements, local strengthening interventions are also proposed
Energy Flexibility: a Hotel and Supermarket case study
No full textIn the context of smart grid development, energy flexibility is a critical factor for optimizing the integration of renewable energy sources and improving overall energy efficiency. This study focuses on the energy flexibility analysis of a simulated hotel and a supermarket refrigeration system. The main objective is to evaluate the potential for energy flexibility within the hotel building, that would en-able it to dynamically interact with the smart grid by adjusting its energy consump-tion based on supply conditions and demand response strategies.
The hotel building was modelled with Type 56, which provides comprehensive ca-pabilities for simulating thermal zones, including heat gains, losses, and thermal storage effects. The building model was then coupled with a PV system, designed to meet part of the hotel’s electricity demand. Additionally, the model included a su-permarket equipped with a CO2 refrigeration system with heat recovery capabilities, here implemented to produce domestic hot water for the hotel.
The study analyzed several scenarios to assess the hotel’s energy flexibility poten-tial. These scenarios included varying levels of PV generation, different DHW stor-age sizes, and the implementation of demand response measures
Chitosan as a corrosion inhibitor for gray cast iron and its role in mitigating the stiction phenomenon in automotive braking systems
No full textObservation of W+W−γ production in pp collisions at s = 13 TeV with the ATLAS detector and constraints on anomalous quartic gauge-boson couplings
No full textThis Letter reports the observation of W+W−γ triboson production in 140 fb−1 of data collected by the ATLAS detector from proton–proton collisions at a centre-of-mass energy of s = 13 TeV at the LHC. Events with an opposite-charge eμ pair, a high transverse-momentum photon, and significant missing transverse momentum are considered. The observed (expected) significance of the signal is 5.9 (6.0) standard deviations. The measured fiducial cross-section, defined for the W+W−γ→e±μ∓νν ̄γ final state is 6.2 ± 0.8 (stat.) ± 0.6 (sys.) fb, in good agreement with the Standard Model prediction of 6.1−0.7+1.0 fb. Constraints on the Wilson coefficients of 13 dimension-8 operators describing physics beyond the Standard Model through anomalous quartic gauge-boson couplings are derived using the effective field theory framework
Iatrogenic NORSE: Immune checkpoint inhibitor-related anti-GFAP autoimmune astrocytopathy
No full textImmune checkpoint inhibitors (ICIs) have radically improved cancer therapy but are associated with a spectrum of immune-related adverse events (irAEs), including infrequent (1–3 %) neurological complications. Pembrolizumab, an anti-PD-1 monoclonal antibody, enhances antitumor immunity but may disrupt self-tolerance, leading to autoimmune phenomena. This case report describes a patient with triple metachronous malignancies (cerebral hemangioblastoma, clear cell renal carcinoma, and non-small cell lung cancer, NSCLC), who developed glial fibrillary acidic protein (GFAP)-antibody-associated autoimmune encephalitis following pembrolizumab therapy initiated as NSCLC treatment. The clinical course was marked by subacute neurocognitive decline followed by new-onset refractory status epilepticus (NORSE). Diagnostic workup revealed GFAP antibodies in cerebrospinal fluid as well as serum, with no evidence of tumor progression or infectious causes. Although GFAP astrocytopathy has been rarely linked to ICIs, this appears to be the first report manifesting with NORSE. The temporal association with cancer immunotherapy, the presence of GFAP autoantibodies, and a positive steroid response collectively suggest that ICI-induced immune dysregulation is the primary disease mechanism. This report, in conjunction with other isolated descriptions form the literature with other antibody specificities, paves the way to a new spectrum of etiologies for NORSE, namely iatrogenic causes related to cancer immunotherapy
Early antiproteinuric effect of voclosporin in patients with LN in a real-life setting: preliminary results from the VoRLiSS (Voclosporin in Real Life Setting Study) experience
No full textObjective To assess efficacy of voclosporin (VCL) from a retrospective, observational, clinical-practice-based, nationwide multicentre study of patients with LN. Methods Patients with biopsy-proven LN were enrolled from November 2023 to April 2025 from tertiary Rheumatology and Nephrology Italian Centres. Those with uncontrolled arterial hypertension and eGFR<30ml/min/1.73m2 were excluded. Patients received oral 23.7mg VCL BID and MMF 1g BID. Glucocorticoid schedule followed existing recommendations for LN management. Clinical and serological data were collected at SLE diagnosis, VCL initiation and after 6, 12, 24 and 48weeks. Complete renal response (CRR) was defined as eGFR≥60ml/min/1.73m2, <20% eGFR decrease from baseline, 24-h proteinuria <0.5g/day, no rescue therapy, prednisone ≤5mg/day and partial renal response (PRR) as a 50% decrease of 24h proteinuria and <20% eGFR decrease. Results Forty-two patients from 14 centres were enrolled, 26 females (61.9%), mean age 43.1±11.9years, follow-up 6.6±5.1months. A total of 31.5% of patients achieved CRR or PRR at 6weeks, 68.9% at 12weeks, 83.3% at 24weeks and 91.6% at 48weeks of follow-up. A significant decrease in 24-h proteinuria was observed at 6weeks (P=0.006) and at all subsequent time points. A mild eGFR decrease was observed at 6 (P=0.008) and 24weeks (P=0.01), but not at 48weeks. Significant decrease was also observed in anti-dsDNA positivity at 6 (P=0.0016) and 12weeks (P=0.0009), and in SLEDAI-2K after 24 (P=0.008) and 48weeks (P=0.05). Conclusions VCL may provide a valuable therapeutic option in LN management, achieving early 24h-proteinuria response consistent with clinical trial data