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SidF, a dual substrate N5-acetyl-N5-hydroxy-L-ornithine transacetylase involved in Aspergillus fumigatus siderophore biosynthesis
No full textSiderophore-mediated iron acquisition is essential for the virulence of Aspergillus fumigatus, a fungus causing life-threatening aspergillosis. Drugs targeting the siderophore biosynthetic pathway could help improve disease management. The transacetylases SidF and SidL generate intermediates for different siderophores in A. fumigatus. A. fumigatus has a yet unidentified transacetylase that complements SidL during iron deficiency in SidL-lacking mutants. We present the first X-ray structure of SidF, revealing a two-domain architecture with tetrameric assembly. The N-terminal domain contributes to protein solubility and oligomerization, while the C-terminal domain containing the GCN5-related N-acetyltransferase (GNAT) motif is crucial for the enzymatic activity and mediates oligomer formation. Notably, AlphaFold modelling demonstrates structural similarity between SidF and SidL. Enzymatic assays showed that SidF can utilize acetyl-CoA as a donor, previously thought to be a substrate of SidL but not SidF, and selectively uses N5-hydroxy-L-ornithine as an acceptor. This study elucidates the structure of SidF and reveals its role in siderophore biosynthesis. We propose SidF as the unknown transacetylase complementing SidL activity, highlighting its central role in A. fumigatus siderophore biosynthesis. Investigation of this uncharacterized GNAT protein enhances our understanding of fungal virulence and holds promise for its potential application in developing antifungal therapies
Three Essays on Inequality, Inflation, and the Calibration of AB-SFC Models
No full textQuesta tesi presenta tre saggi su disuguaglianza, inflazione e calibrazione di modelli agent-based stock-flow consistent (AB-SFC).
Il primo capitolo offre una revisione approfondita della letteratura teorica ed empirica relativa alla relazione tra inflazione e disuguaglianza. Successivamente, l’analisi si concentra sui meccanismi attraverso cui l’inflazione incide sulla distribuzione del reddito e della ricchezza, identificando canali distributivi distinti. La rassegna evidenzia come il contesto istituzionale e la natura degli shock inflazionistici siano determinanti fondamentali degli esiti distributivi, contribuendo a spiegare l’eterogeneità riscontrata nei risultati empirici. Questo impone una riflessione approfondita sulla progettazione e l’attuazione delle politiche di targeting dell’inflazione da parte delle banche centrali.
Il secondo capitolo utilizza un framework macroeconomico ibrido AB-SFC per analizzare le conseguenze distributive di uno shock inflazionistico derivante da un aumento del prezzo degli input intermedi. L’analisi mette in luce effetti redistributivi significativi sia in termini di distribuzione funzionale sia interpersonale del reddito, con implicazioni per la stabilità macro-finanziaria. Inoltre, in presenza di concentrazione di mercato, i markup nei settori sistemicamente rilevanti rappresentano il principale motore della redistribuzione e della persistenza dello shock inflazionistico.
Il terzo capitolo propone una metodologia sistematica di calibrazione per modelli ibridi AB-SFC, volta a migliorarne la coerenza con i conti nazionali e con i dati reali. In primo luogo, il capitolo sviluppa e calibra un modello aggregato stock-flow consistent per l’economia statunitense. Successivamente, il modello viene esteso mediante l’integrazione di un settore delle famiglie disaggregato, caratterizzato da elementi agent-based, calibrando le dotazioni iniziali delle famiglie sulla base di dati campionari. Il capitolo si conclude analizzando le implicazioni di tale integrazione per le dinamiche del modello.This dissertation comprises three essays on inequality, inflation and the calibration of agent-based stock-flow consistent (AB-SFC) models.
The first chapter provides an in-depth review of the theoretical and empirical literature concerning the relationship between inflation and inequality. Subsequently, the analysis focuses on the mechanisms through which inflation affects the distribution of income and wealth, identifying several distinct distributional channels. The review reveals that institutional settings and the source of inflationary shocks are key determinants of distributional outcomes, which helps to explain the heterogeneity in empirical findings. This calls for careful consideration of how central banks design and implement inflation-targeting policies.
The second chapter uses a hybrid AB-SFC macroeconomic framework to investigate the distributional consequences of an inflationary shock resulting from an increase in the price of intermediate inputs. The analysis reveals significant redistributive effects in terms of both functional and inter-personal income distribution, with implications for macro-financial stability. Furthermore, in the presence of market concentration, markups in systemically significant sectors primarily drive redistribution and persistence of the inflationary episode.
The third chapter proposes a systematic calibration methodology for hybrid AB-SFC models aimed at improving their consistency with national accounts and real-world data. First, the chapter develops and calibrates an aggregate stock-flow consistent model of the US economy. It then extends this model by incorporating a disaggregated household sector with agent-based features and calibrating initial household endowments using survey data. The chapter concludes by exploring the implications of this integration for model dynamics
Concomitant Thoracic Spinal Hemangioma and Dural Arteriovenous Fistula: Case Report and Technical Note
No full textBackground and Clinical Significance: The coexistence of spinal hemangiomas and dural arteriovenous fistula (SDAVF) is uncommon. Unclear imaging and progressive neurological impairment require early surgical management. Case Presentation: A 76-year-old woman presented with progressive thoracolumbar pain and worsening bladder dysfunction. Magnetic resonance imaging (MRI) of the thoracic spine revealed a round-shape expansive lesion at T11 with spinal cord edema and homogeneous contrast enhancement. Despite a chronic presentation, the subacute progression of bladder dysfunction and spinal cord edema warranted timely intervention. Intraoperatively, a vascular malformation resembling a dural arteriovenous fistula (SDAVF), unrecognized at pre-operative imaging, was found in association, and histological examination confirmed the diagnosis of hemangioma. The mechanism of coexistence remains unclear, although venous hypertension due to fistula could induce vascular malformations. Conclusions: This case emphasizes the importance of thorough imaging, timely intervention and intraoperative assessment in patients presenting with a suspicion of spinal hemangioma; it may also provide awareness of potentially associated concurrent lesions such as SDAVFs, unrecognized at pre-operative imaging, and technical insights during surgery
Identifying Hypothyroidism as Complication of Type 1 Diabetes from Continuous Glucose Monitoring Data
No full textRecent studies have shown that type 1 diabetes mellitus (T1DM) is an important risk factor for the development of hypothyroidism. In this regard, a timely intervention is fundamental to limit adverse effects. Providing real-time measurements of interstitial glucose, Continuous Glucose Monitoring (CGM) devices may represent a powerful source of data to feed machine-learning based algorithms for the discovery of hidden patterns related to the development of diabetes complications such as hypothyroidism. Aim of this study was to setup a machine-learning-based approach capable to identify subjects with hypothyroidism among those with T1DM, starting from CGM tracings. CGM data acquired during a period of 26 weeks and relating to 79 subjects with T1DM taken from the REPLACE-BG campaign database, of which 51 had hypothyroidism and 28 had T1DM with no other complication, were used. The CGM traces were pre-processed to handle the presence of missing data and 41 features were extracted with the use of AGATA software. The feature set was then reduced through Two-Step Decision Tree-Embedded Feature Selection (DT-EFS), leading to the inclusion of 8 final features. The best performing model was the decision tree, showing the following testing performances: area under receiver operating characteristics of 72.3%, accuracy of 71.4%, precision of 74.6%, F1 score of 70.1%, sensitivity of 71.4% and specificity of 69.5%. The 8 features identified herein describe the long-term variability of the subjects' glycemic trace which may suggests a possible connection with the presence of hypothyroidism in T1DM.Clinical Relevance-This establishes the possibility to automatically detect hypothyroidism in T1DM from clinically meaningful CGM glycemic patterns
Digital twins and AI integration in offshore renewable energy: A Review
No full textThe integration of digital twins and AI in offshore renewable energy systems represents a transformative approach to improve operational efficiency, scalability, and sustainability. This paper provides a review of innovative applications of digital twins and AI in the context of offshore wind energy and floating energy islands. It examines the existing literature and published case studies to highlight the challenges in this field. Digital twins are revolutionizing the design, monitoring, and maintenance of offshore platforms. By incorporating AI-driven analytics and predictive maintenance capabilities, these systems enable precise decision-making, reduce downtime, and extend the lifespan of infrastructure subjected to harsh marine environments. Case studies discussed include the application of digital twins for structural health monitoring in offshore wind farms, where significant reductions in maintenance costs were achieved through predictive analytics
The Fractional Pohozaev identity in RN
No full textIn this paper, we prove the Pohozaev identity for the following fractional nonlinear elliptic equation: (Formula presented.) where N≥2, s∈(0,1), (-Δ)s denotes the fractional Laplacian operator, and g:R→R is a locally Hölder continuous function. Our proof rests on a regularity result for bounded distributional solutions of the above equation, an integration by parts formula for Ds,2∩C2s+ε functions with locally bounded gradient and vector fields of class Cc0,1, and a limiting procedure
Ecological Wisdom Study of the Han Dynasty Settlement Site in Sanyangzhuang Based on Landscape Archaeology
No full textThis study systematically investigates settlement sites that record living patterns of ancient humans, aiming to reveal the interactive mechanisms of human–environment relationships. The core issues of landscape archeology research are the surface spatial structure, human spatial cognition, and social practice activities. This article takes the Han Dynasty settlement site in Sanyangzhuang, Neihuang County, Anyang City, Henan Province, as a typical case. It comprehensively uses ArcGIS 10.8 spatial analysis and remote sensing image interpretation techniques to construct spatial distribution models of elevation, slope, and aspect in the study area, and analyzes the process of the Yellow River’s ancient course changes. A regional historical geographic information system was constructed by integrating multiple data sources, including archeological excavation reports, excavated artifacts, and historical documents. At the same time, the sequences of temperature and dry–wet index changes in the study area during the Qin and Han dynasties were quantitatively reconstructed, and a climate evolution map for this period was created based on ancient climate proxy indicators. Drawing on three dimensions of settlement morphology, architectural spatial organization, and agricultural technology systems, this paper provides a deep analysis of the site’s spatial cognitive logic and the ecological wisdom it embodies. The results show the following: (1) The Sanyangzhuang Han Dynasty settlement site reflects the efficient utilization strategy and environmental adaptation mechanism of ancient settlements for land resources, presenting typical scattered characteristics. Its formation mechanism is closely related to the evolution of social systems in the Western Han Dynasty. (2) In terms of site selection, settlements consider practicality and ceremony, which can not only meet basic living needs, but also divide internal functional zones based on the meaning implied by the orientation of the constellations. (3) The widespread use of iron farming tools has promoted the innovation of cultivation techniques, and the implementation of the substitution method has formed an ecological regulation system to cope with seasonal climate change while ensuring agricultural yield. The above results comprehensively reflect three types of ecological wisdom: “ecological adaptation wisdom of integrating homestead and farmland”, “spatial cognitive wisdom of analogy, heaven, law, and earth”, and “agricultural technology wisdom adapted to the times”. This study not only deepens our understanding of the cultural value of the Han Dynasty settlement site in Sanyangzhuang, but also provides a new theoretical perspective, an important paradigm reference, and a methodological reference for the study of ancient settlement ecological wisdom
Erythroid-stimulating agents in VEXAS syndrome: A retrospective study from an Italian multicentre cohort
No full textDecoding the Dynamic Behavior of Twin Church Bell Towers Through Ambient Vibration Analysis
No full textItaly is home to numerous monumental structures of great historical and architectural value that require preservation. To ensure their protection, it is crucial to adopt minimally invasive yet effective techniques capable of assessing their current structural performance and monitoring their health. Among the most suitable methods is ambient vibration monitoring, which analyzes accelerometric recordings under operational conditions to determine the dynamic properties of the structure. This study presents the results of short-term monitoring conducted on the two towers of the San Francesco church in Ascoli Piceno. Modal identification allowed for the determination of frequencies, mode shapes, and damping ratios. These data were then used to calibrate the Finite Element Model of the complex by adjusting the elastic parameters of the masonry, aligning the numerical mode shapes and frequencies with the experimental results
Isotope Effects in High-Performance Liquid Chromatography: First Baseline Separation of Isotopomers on Achiral and Chiral Columns
No full textIn this study, the feasibility of very challenging separation of isotopomers by high-performance liquid chromatography in a common setup is successfully demonstrated with the examples of deuterated amphetamine and methamphetamine. Understanding the effect of various factors, such as analyte structure, location of heavy atoms within the structure, separation mode (i.e., surface chemistry of the stationary phase), mobile phase components and their additives, pH of the mobile phase, and separation temperature, that enabled baseline separation of isotopomers with high selectivity is discussed. The results reported here are significant for both the analytical separation of isotopomers and their preparative-scale separation. The understanding and fine-tuning of the mechanisms underpinning isotopomer retention and discrimination enabled the reversal of isotopomer elution order on specific chiral columns. The simultaneous separation of isotopomers and their enantiomers was observed on polysaccharide-based chiral columns. Molecular modeling was used to provide a reasonable explanation of the separation mechanism of the isotopomers