Archivio Istituzionale della Ricerca - Università degli Studi di Pavia
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Materiali Innovativi per Scissione dell'Acqua
No full textQuesta tesi di dottorato esplora lo sviluppo di eterogiunzioni per la produzione fotocatalitica di H2 e NH3 verde, affrontando le sfide globali energetiche e ambientali. La ricerca dimostra che la progettazione delle interfacce dei materiali, dei meccanismi di trasferimento elettronico e della morfologia migliora le performance fotocatalitiche. Lo studio si concentra principalmente sul carbonitruro grafitico (g-C3N4) come fotocatalizzatore verde. I risultati principali includono l'ottimizzazione dei polimorfi di g-C3N4, dove diversi agenti sacrificali (NaCl,KCl,CaCl2) influenzano la morfologia, portando a un incremento della produzione di idrogeno. La ricerca esplora anche l'uso di eterogiunzioni a base di perovskite per la fissazione dell'azoto e la produzione di idrogeno, rivelando l'importanza delle composizioni specifiche dei materiali e dell'ingegneria dei difetti. Inoltre, vengono esplorati nuovi sistemi semiconduttori organici e ossidi di perovskite ad alta entropia per migliorare l'efficienza fotocatalitica di g-C3N4. La tesi sottolinea il ruolo cruciale della progettazione delle eterogiunzioni nel miglioramento dei fotocatalizzatori, offrendo soluzioni per la produzione sostenibile di H2 e NH3.This Ph.D. thesis explores the development of heterojunction systems for photocatalytic green H2 and NH3 production, addressing global energy and environmental challenges. The research demonstrates that engineering material interfaces, electron transfer mechanisms, and morphology enhances photocatalytic performance. The study primarily focuses on graphitic carbon nitride (g-C3N4) as an eco-friendly photocatalyst. Key findings include the optimization of g-C3N4 polymorphs, where various sacrificial templates (NaCl,KCl,CaCl2) influence morphology, leading to improved hydrogen production. The research also investigates the use of perovskite-based heterojunctions for nitrogen fixation and hydrogen generation, revealing the importance of specific material compositions and defect engineering. Additionally, novel organic semiconductor systems and high-entropy perovskite oxides are explored to enhance g-C3N4 photocatalytic efficiency. The thesis highlights the critical role of heterojunction design in improving photocatalysts, offering pathways for sustainable hydrogen and ammonia production
A Ge.F.I. Collaborative Study: Evaluating Reproducibility and Accuracy of a DNA‐Methylation‐Based Age‐Predictive Assay for Routine Implementation in Forensic Casework
No full textThe increasing interest in DNA methylation (DNAm) analysis within the forensic scientific community prompted a collaborative project by Ge.F.I. (Genetisti Forensi Italiani). The study evaluated a standardized bisulfite conversion–based Single Base Extension (SBE) protocol for the analysis of the methylation levels at five age-predictive loci (ELOVL2, FHL2, KLF14, C1orf132/MIR29B2C, and TRIM59). The study encompassed three phases: (1) setting up and validating the protocol to ensure consistency and reproducibility; (2) comparing fresh peripheral blood with blood spots; and (3) evaluating sources of intra- and inter-laboratory variability. Samples from 22 Italian volunteers were analyzed by 6 laboratories in replicates for a total of 528 records. From phase I emerged that the choice of genetic sequencer significantly contributed to inter-laboratory data variation, resulting in separate regression analyses performed for each laboratory. In phase II, blood spots were found to be a reliable source for DNAm analysis, despite exhibiting increased experimental variation compared to fresh peripheral blood. In phase III, a strong correlation between the individual's predicted and true ages was observed across different laboratories. Analysis of variance (ANOVA) of the residuals indicated that one-third of the total variance could be attributed to laboratory-specific factors, whereas two-thirds could be attributed to inter-individual biological differences. The leave-one-out cross-validation (LOO-CV) method yielded an overall mean absolute deviation (MAD) value of 4.41 years, with an average 95% confidence interval of 5.24 years. Stepwise regression analysis proved that a restricted model (ELOVL2, C1orf132/MIR29B2C, and TRIM59) produced results virtually indistinguishable from the five-loci model. Additionally, the analysis of samples in replicates greatly improved the fit of the regression model, balancing the slight effects of intra-laboratory variability. In conclusion, the bisulfite conversion–based SBE protocol, combined with replicate analysis and in-lab calibration of a regression-prediction model, proves to be a reliable and easily implementable method for age prediction in forensic laboratories
Silberstein, Dagmar: Modalpartikeln als Lerngegenstand. Partikelprofile für die Vermittlung von aber, ja, doch, mal, denn, eigentlich und etwa im DaF-Unterricht.
No full textChallenging the skin pigmentation bias in tissue oximetry via time domain near infrared spectroscopy
No full textCovalent adduct Grob fragmentation underlies LSD1 demethylase-specific inhibitor mechanism of action and resistance
No full textChromatin modifiers often work in concert with transcription factors (TFs) and other complex members, where they can serve both enzymatic and scaffolding functions. Due to this, active site inhibitors targeting chromatin modifiers may perturb both enzymatic and nonenzymatic functions. For instance, the antiproliferative effects of active-site inhibitors targeting lysine-specific histone demethylase 1A (LSD1) are driven by disruption of a protein-protein interaction with growth factor independence 1B (GFI1B) rather than inhibition of demethylase activity. Recently, next-generation precision LSD1 covalent inhibitors have been developed, which selectively block LSD1 enzyme activity by forming a compact N-formyl flavin adenine dinucleotide (FAD) adduct that spares the GFI1B interaction. However, the mechanism accounting for N-formyl-FAD formation remains unclear. Here we clarify the mechanism of these demethylase-specific inhibitors of LSD1, demonstrating that the covalent inhibitor-FAD adduct undergoes a Grob fragmentation. Using inhibitor analogs and structural biology, we identify structure-activity relationships that promote this transformation. Furthermore, we unveil an unusual drug resistance mechanism whereby distal active-site mutations can promote inhibitor-adduct Grob fragmentation even for previous generation compounds. Our study uncovers the unique Grob fragmentation underlying the mechanism of action of precision LSD1 enzyme inhibitors, offering insight into their reactivity with broader implications for drug resistance
“Energetics of the outer retina II: Calculation of a spatio-temporal energy budget in retinal pigment epithelium and photoreceptor cells based on quantification of cellular processes”
No full text: The outer retina (OR) is highly energy demanding. Impaired energy metabolism combined with high demands are expected to cause energy insufficiencies that make the OR susceptible to complex blinding diseases such as age-related macular degeneration (AMD). Here, anatomical, physiological and quantitative molecular data were used to calculate the ATP expenditure of the main energy-consuming processes in three cell types of the OR for the night and two different periods during the day. The predicted energy demands in a rod dominated (perifovea) area are 1.69 x 1013 ATP/s/mm2 tissue in the night and 6.53 x 1012 ATP/s/mm2 tissue during the day with indoor light conditions. For a cone-dominated foveal area the predicted energy demands are 6.41 x 1012 ATP/s/mm2 tissue in the night and 6.75 x 1012 ATP/s/mm2 tissue with indoor light conditions during daytime. We propose the likely need for diurnal/circadian shifts in energy demands to efficiently stagger all energy consuming processes. Our data provide insights into vulnerabilities in the aging OR and suggest that diurnal constraints may be important when considering therapeutic interventions to optimize metabolism
Impact of Triple Inhaler Therapy on COPD Patients with Non-Small Cell Lung Cancer After Radical Surgery: A Single-Centre Retrospective Analysis
No full textBackground: Chronic obstructive pulmonary disease (COPD) is among the most relevant comorbidity associated with lung cancer. The advent of innovative triple treatment approaches for COPD has significantly improved patients’ quality of life and outcomes. Few data are available regarding the impact of triple inhaler therapy on patients featuring COPD and lung cancer. Methods: We retrospectively evaluated the impact of triple inhale bronchodilators in a cohort of 56 patients with treated COPD who underwent lung surgery for primary cancer. Results: Triple bronchodilation can help to relieve the symptoms of the disease and improve lung function, allowing people with lung cancer to reduce the risk of serious exacerbations and improve their quality of life. Conclusions: Within the limits of the study, it should be underlined that bronchodilators can effectively affect the outcome and performance status after thoracic surgery
In-hospital bioimpedance-derived total body water predicts short-term cardiovascular mortality and re-hospitalizations in acute decompensated heart failure patients
No full textBackground: Hospital re-admissions in heart failure (HF) patients are mostly caused by an acute exacerbation of their chronic congestion. Bioimpedance analysis (BIA) has emerged as a promising non-invasive method to assess the volume status in HF. However, its correlation with clinically assessed volume status and its prognostic value in the acute intra-hospital setting remains uncertain.
Methods and results: In this single-center observational study, patients (n = 49) admitted to the cardiology ward for acute decompensated HF (ADHF) underwent a daily BIA-derived volume status assessment. Median hospital stay was 7 (4-10) days. Twenty patients (40%) reached the composite endpoint of cardiovascular mortality or re-hospitalization for HF over 6 months. Patients at discharge displayed improved NYHA class, lower body weight, plasma and blood volume, as well as lower NT-proBNP levels compared to the admission. Compared to patients with total body water (TBW) less than or equal to that predicted by body weight, those with higher relative TBW levels had elevated NT-proBNP and E/e ́ (both p < 0.05) at discharge. In the Cox multivariate regression analysis, the BIA-derived delta TBW between admission and discharge showed a 23% risk reduction for each unit increase (HR = 0.776; CI 0.67-0.89; p = 0.0006). In line with this finding, TBW at admission had the highest prediction importance of the combined endpoint for a subgroup of high-risk HF patients (n = 35) in a neural network analysis.
Conclusion: In ADHF patients, BIA-derived TBW is associated with the increased risk of HF hospitalization or cardiovascular death over 6 months. The role of BIA for prognostic stratification merits further investigation