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Development of shape sensing and damage monitoring algorithms for digital twins of aeronautical structures
No full textGrowing demands for lighter, safer, and more efficient aeronautical structures are driving research toward condition-based and digital twin–oriented structural management, rather than relying on scheduled inspections. In this context, the ability to estimate the structural state in real time, in terms of both performance and integrity, represents a fundamental requirement. In this thesis, a Structural Health Monitoring framework for shape sensing and damage monitoring of aeronautical structures is developed, combining physics-based and data-driven approaches using a single network of Fiber Bragg Grating sensors.
In the first part, shape sensing methodologies based on the inverse Finite Element Method are developed. Since such a method requires a high number of sensors to accurately reconstruct the full displacement field, different strategies are proposed to preserve reconstruction accuracy while reducing the required sensor count, thus enabling practical applicability in real industrial scenarios. The proposed frameworks are validated through both numerical simulations and experimental testing on typical aeronautical structures.
In the second part, methods for structural damage monitoring are investigated, with a particular focus on detection and localization. The adopted approaches are vibration-based and rely on variations in strain mode shapes between baseline and current structural configurations. Fully automated methodologies are developed, both through the use of damage indices and neural networks. These frameworks are validated using numerical case studies and experimental data from a composite scale glider.
Overall, the work carried out in this thesis represents a relevant advancement toward the development of structural digital twins, supporting the transition toward next-generation aircraft
On the positivity of Ulrich bundles
No full textWe study the positivity properties of Ulrich bundles defined with respect to an ample and
globally generated polarization. First we prove a generalization of a theorem by Lopez on
the first Chern class. Then, under some additional assumptions on the polarization, we give
a description of its augmented base locus, which consequently leads to a characterization of
the V-bigness and of the ampleness of an Ulrich bundle in this setting. Finally we study the
normal generation of an Ulrich bundle focusing on curves, on surfaces with q=p_g=0 and
on hypersurfaces of dimension 2 and 3
I disturbi della forma del pensiero: dimensioni psicopatologiche e valore prognostico in acuto
No full textIntroduzione. La struttura dei disturbi della forma del pensiero (formal thought disorder, FTD) risulta controversa sia per numero che per composizione delle dimensioni sottese. Oltre alla disorganizzazione e povertà ideica, le evidenze suggeriscono la presenza di una o più dimensioni aggiuntive dalla caratterizzazione incerta. La Thought and Language Disorder Scale (TALD) ne rappresenta un valido strumento di valutazione, tuttavia la sua struttura è stata indagata solo in campioni misti, ovvero composti anche da controlli, limitandone l’affidabilità in popolazioni cliniche. Inoltre, il valore discriminante dei FTD tra differenti aree diagnostiche in contesti di acuzie appare controverso e poggia spesso su una classificazione presumibilmente riduttiva, che li distingue in positivi e negativi. Infine, in letteratura non è adeguatamente indagato il valore prognostico dei FTD rispetto a esiti di interesse clinico in acuto, quali: uso della contenzione fisica, trattamento sanitario obbligatorio (TSO), durata del ricovero e numero di successivi ricoveri.
Obiettivi. Alla luce di tali considerazioni, gli obiettivi del presente lavoro sono: indagare la struttura dimensionale della TALD e, più in generale, dei FTD in un campione clinico in acuto; confrontare i profili fenotipici dei FTD tra i principali gruppi diagnostici in acuto; esaminare il valore prognostico dei FTD rispetto agli esiti di interesse clinico in acuto.
Metodo. È stato reclutato un campione di 226 soggetti ricoverati presso il Servizio Psichiatrico di Diagnosi e Cura (SPDC) del Policlinico Umberto I con diagnosi di disturbo psicotico, bipolare e depressivo. I soggetti sono stati valutati all’ingresso tramite TALD per esaminare i FTD. Per indagare la struttura dei FTD è stata condotta un’analisi fattoriale esplorativa (EFA) con metodo dei minimi residui e rotazione promax. Il modello emerso è stato testato tramite analisi fattoriale confermativa (CFA)
sui precedenti studi di EFA della TALD, aggregando le matrici di correlazione riprodotte. È stata condotta un’analisi della varianza multivariata (MANOVA) con analisi post hoc per esaminare l’effetto della diagnosi sulle sottoscale della TALD, confrontandole tra gruppi diagnostici. Inoltre sono state effettuate una serie di analisi della covarianza (ANCOVA), controllando per la produzione verbale (logorrea, eloquio accelerato). Per indagare il valore prognostico dei FTD sono state condotte analisi di regressione per ciascun esito di interesse clinico in acuto; per il numero di nuovi ricoveri è stata condotta un’analisi binomiale negativa con offset per il periodo di osservazione.
Risultati. L’EFA individua quattro dimensioni indipendenti ma correlate a coppie, che spiegano complessivamente il 51,3% della varianza: la Disorganizzazione Ideica e la Schizofasia; la Povertà Ideica e il Deficit Soggettivo del Linguaggio. La bontà del modello mostra indici di fit adeguati alla CFA (χ2=212,0; SRMR=0,06; RMSEA=0,02; GFI=0,96; AGFI=0,95; CFI=0,99; NNFI=0,99).
La MANOVA mostra un effetto significativo della diagnosi sulle dimensioni TALD (V=0,371, F(2, 8) = 12,6, p < 0,001, parη2 = 0,185). I pazienti psicotici, rispetto a quelli con eccitamento maniacale, mostrano maggiori livelli di Povertà Ideica (F=6,3; p < 0.01) e Deficit Soggettivo del Linguaggio (F=9,7; p < 0,01), ma non di Disorganizzazione Ideica e Schizofasia. Quest’ultima tuttavia risulta significativamente maggiore controllando per ritmo e produzione verbale all’ANCOVA (t=1,98, p<0,05). Sia i pazienti con psicosi che quelli con eccitamento mostrano, a confronto con quelli depressi, livelli maggiori di Disorganizzazione Ideica (F=34,1; p < 0,01) e Schizofasia (F=9,3; p < 0,01) e inferiori di Deficit Soggettivo del Linguaggio (F=9,7; p < 0,01), senza differenze significative a livello di Povertà Ideica.
Le dimensioni TALD, nel loro insieme, mostrano una capacità predittiva significativa rispetto alla contenzione fisica (χ2=20,8; p < 0,001; R2=0,16), al TSO (χ2=16,0; p <0,01; R2=0,11), alla durata del ricovero (F=3,6; p < 0,001; R2=0,06) e al rischio di ulteriori ricoveri (χ2=10,52; p=0,03; pseudo-R2=0,05). Se analizzate assieme ad altri possibili predittori riportati in letteratura, solo la Disorganizzazione Ideica mantiene un effetto indipendente rispetto alla contenzione fisica (B=0,07, p=0,05, OR=1,07) e al rischio di successivi ricoveri (Beta=0,06; p=0,01; Exp(B)=1,05).
Discussione e conclusioni. Questo è il primo studio che esamina la struttura fattoriale della TALD in un campione interamente clinico, in acuto. La struttura emersa appare complessivamente coerente con gli studi di analisi fattoriale della TALD e dei FTD in genere, ma se ne differenzia per la distinzione dei FTD positivi in Disorganizzazione Ideica e Schizofasia, che corrobora un dato sostenuto a livello teorico-concettuale, ma con evidenze empiriche limitate. Il confronto tra gruppi diagnostici suggerisce che in acuto tali dimensioni siano scarsamente discriminative, confutando l’ipotesi classica che i FTD siano un elemento distintivo della schizofrenia. In tal senso, è suggestiva la mancanza di differenze significative in termini di Disorganizzazione Ideica tra psicosi e mania e di Povertà Ideica tra psicosi e depressione. La capacità della Schizofasia di discriminare tra disturbi psicotici ed eccitamento maniacale in acuto rimane incerta, ma è meritevole di approfondimento da parte della ricerca futura per le sue implicazioni clinico-diagnostiche. La Disorganizzazione Ideica mostra un valore prognostico indipendente rispetto al rischio di contenzione fisica e di riospedalizzazione; globalmente, i dati suggeriscono che la sua valutazione possa essere utilmente inclusa all’interno di modelli predittivi globali per la valutazione del rischio di esiti di interesse in acuto. Tra i possibili limiti, il più rilevante è rappresentato dall’attuale numerosità del campione, in funzione dell’analisi fattoriale, che impone la necessaria cautela nell’interpretazione dei dati e la prosecuzione della raccolta al fine di incrementare la solidità metodologica dello studio
Monkeypox virus (MPXV): induction and sensitivity to Interferon antiviral effects
No full textIntroduction
Monkeypox (mpox) is a zoonotic viral disease caused by the monkeypox virus (MPXV), which belongs to the Orthopoxvirus genus. This genus also includes the variola virus (VARV), which causes smallpox. In May 2022, an unprecedented multi-country outbreak of MPXV clade II primarily affected men who have sex with men (MSM), though not exclusively. Despite decades of human infection, the interaction between MPXV and innate immunity remains poorly understood. Interferons (IFNs) represent the first line of host antiviral defense. Members of the Poxviridae family have demonstrated the capacity to counteract type I IFNs (IFN-I, e.g. IFN-α and IFN-β) and IFN-γ. In light of these considerations, the objective of this PhD thesis was to analyze the expression of type I and II IFNs in clinical samples obtained from various anatomical regions of MPXV-infected patients, as well as the kinetics of type I IFN induction and the activation of the downstream IFN pathway following MPXV infection in different cellular models that are susceptible to MPXV infection. Furthermore, to better characterize the interplay between MPXV infection and the IFN response, the sensitivity of MPXV to treatment with different IFN-I/II preparations was evaluated.
Material and methods
Skin lesions (SL, n=9), anal canal brushing (ACB, n=5), nasopharyngeal swabs (NPS, n=4) and peripheral blood mononuclear cells (PBMC, n=3) were collected from male patients infected with MPXV. MPXV DNA was quantified in SL, ACB and NPS using the Bioperfectus Monkeypox Virus Real-Time PCR Kit (BioPerfectus Technologies Co., Jiangsu, China). PBMCs were obtained from sex- and age-matched healthy donors (HDs). The induction of IFN-I and the expression of IFN-related genes (STAT1, STAT2, ISG15, ISG56, IDO and PKR) were analyzed in the IFN-competent, MPXV-permissive adenocarcinoma epithelial cell line (A549). The sensitivity of MPXV to IFN-I/II was evaluated in A549 cells, as well as in Henrietta Lacks (HeLa) cells and African green monkey kidney epithelial (VeroE6) cells, which are known to be susceptible to MPXV infection in vitro. IFN-I induction was evaluated through the stimulation of A549 cells with UV-inactivated vesicular stomatitis virus (VSV) of the Indiana strain, which is known for its ability to induce IFN. IFN preparations were also tested against well-established IFN-sensitive viruses: VSV and encephalomyocarditis virus (EMCV). All MPXV experiments were conducted in the Biosafety Level 3 facility at INMI “Lazzaro Spallanzani” in Rome using isolate hMPXV/Italy/UN-INMI-Pt2/2022 (GenBank accession number ON745215.1). MPXV growth kinetics in A549 cells was determined using real-time PCR and gene expression analysis using RT-real-time PCR. Statistical analyses were performed using IBM SPSS Statistics 27.0.1 and graphs were created using GraphPad Prism 8.0.1.
Results
The expression of IFN-α, IFN-β, IFN-ω, and IFN-γ was analyzed in different clinical samples taken from male patients infected with MPXV. The expression of IFNs was compared between PBMC from MPXV patients and healthy donors (HD), while the results for other anatomical districts are descriptive. IFN-I were expressed at higher levels in PBMC from MPXV patients than in HD, while IFN-γ expression was comparable between the two groups. Levels of IFN-I mRNA varied depending on the anatomical district, with higher levels observed in the ACB and SL [p<0.05 (IFN-α: NPS vs SL; NPS vs ACB; IFN-β: NPS vs SL; ACB vs PBMC; IFN-ω: NPS vs SL; NPS vs ACB; SL vs PBMC), and p<0.01 (IFN-β: SL vs PBMC). Furthermore, IFN-γ expression was higher in SL (*p<0.05, ACB vs PBMC; ***p<0.001, NPS vs SL; SL vs ACB). Furthermore, levels of IFN-I transcripts were inversely related to MPXV DNA cycle threshold (Ct) levels. Conversely, there was a trend towards higher IFN-γ expression in samples with a higher MPXV-DNA Ct value, suggesting a potential anti-MPXV activity. In vitro, MPXV infection induces delayed expression of IFN-I between 48 and 72 hours, compared to UV-inactivated VSV. Furthermore, their expression was not associated with decreased MPXV replication. We then investigated MPXV sensitivity to the antiviral effects of various IFN preparations, including the IFN-α2b subtype, the natural IFN-αN1 preparation (comprising all IFN-α subtypes), IFN-ω, IFN-β, and IFN-γ. Our results showed that MPXV was resistant to both IFN-α preparations and IFN-ω, and displayed moderate sensitivity to IFN-β. The strongest efficacy was obtained with IFN-γ, with a reduction in viral titer observed at lower concentrations compared to IFN-I To further understand the interaction between MPXV and the IFN pathway, we analyzed the expression of selected genes in the downstream IFN pathway that are known to be involved in controlling and causing poxvirus infection. These genes include STAT1, STAT2, ISG15, ISG56, IDO and PKR. We examined their expression in MPXV-infected cells, in cells treated with IFN and in cells infected with MPXV and treated with IFN. As expected, all the IFN preparations induced significant expression of all the examined genes. Conversely, MPXV infection did not result in a significant increase in gene expression. Furthermore, treatment of MPXV-infected cells with IFNs did not induce high levels of expression of the analyzed genes, with only a few exceptions: ISG15 for IFN-I, and high induction of IDO for IFN-γ.
Conclusions
In conclusion, these results suggest that MPXV can counteract IFN production and interfere with downstream signaling pathways. MPXV also displays resistance to the antiviral effects of IFN-I, but not IFN-γ. The protective role of IFN-γ is further supported by its inverse correlation with MPXV DNA levels in clinical samples, as well as its ability to induce IDO expression in MPXV-infected cells in vitro. These findings shed light on the unique role of IFN-γ in host defense against MPXV and suggest its potential as a therapeutic agent for managing MPXV infection
Greater good from a distance: how psychological distance shapes utilitarian behavior
No full textThis research explores whether utilitarianism and deontology can be understood within the Construal Level Theory framework. We explore whether utilitarianism (vs. deontology), focused on the “greater good for the greatest number” as its objective, aligns with a high (vs. low) level of construal, focused on primary features and the goal of an event. We conducted an experimental study (N = 890) in which the level of construal was manipulated through social distance (high vs. low). Then measured the reported probability of participants taking utilitarian actions in three moral dilemmas and their perception of morality and appropriateness of the act itself. Although our manipulation did not affect the likelihood of taking action, a high construal level led to a more positive evaluation of morality and appropriateness of taking action. These findings add new knowledge to the role of construal level in influencing moral decision-making and moral judgments
Quantificazione oggettiva dell’infiammazione del vitreo anteriore attraverso l’utilizzo dell’OCT Swept-Source
No full textScopo: Valutare l’infiammazione nel vitreo anteriore (VA) utilizzando la tomografia a coerenza ottica del segmento anteriore (SS-ASOCT) e correlarla con le caratteristiche dell'uveite e la classificazione clinica dell'infiammazione intraoculare.
Metodi: Sono stati inclusi in questo studio osservazionale, trasversale, 140 occhi di 96 pazienti: 40 con uveite ATTIVA, 40 con uveite INATTIVA e 60 CONTROLLI. Tutti gli occhi sono stati sottoposti a classificazione clinica dell'infiammazione intraoculare (conteggio delle cellule della camera anteriore (CA) e valutazione dell’opacità vitreale) e a imaging del VA con SS-ASOCT. Le cellule osservate nel VA tramite OCT sono state contate manualmente utilizzando ImageJ. La variazione della riflettività vitreale è stata misurata indirettamente calcolando l'intensità relativa vitreo/epitelio pigmentato dell'iride (VIT/IPE). Questi parametri basati sull'OCT sono stati confrontati tra i gruppi e correlati con la classificazione clinica dell'infiammazione.
Risultati: Il numero medio [DS] di cellule OCT del VA era significativamente più alto (entrambi ) nell'uveite ATTIVA (12 [9,8]) rispetto all'uveite INATTIVA (4,5 [3,5]) e ai CONTROLLI (4 [3,1]). Nell'uveite ATTIVA, il numero di cellule OCT del VA era significativamente e positivamente correlato con le cellule della CA (), l'intensità relativa VIT/IPE (), la classificazione anatomica dell'uveite (UVEITE INTERMEDIA, ) e la classificazione clinica della foschia vitreale (). L'intensità relativa media [DS] VIT/IPE del VA è aumentata dai CONTROLLI (0,12 [0,01]) all'uveite INATTIVA (0,15 [0,01]) all'uveite ATTIVA (0,17 [0,02]), ma senza differenze statisticamente significative.
Conclusioni: Siamo stati in grado di visualizzare e valutare oggettivamente i cambiamenti che si verificano nel VA in occhi con uveite per mezzo di un SS-ASOCT disponibile in commercio. Le cellule OCT nel VA potrebbero rappresentare uno strumento aggiuntivo nella valutazione oggettiva dell'infiammazione intraoculare
Introduzione a Percorsi in Civiltà dell’Asia e dell’Africa V
No full textCon la presente miscellanea, giunge al quinto volume l’iniziativa edi-toriale che il nostro corso di Dottorato in Civiltà dell’Asia e dell’Africa sta portando avanti già da alcuni anni: inaugurata nel 2021 e in conti-nuità con una precedente esperienza di pubblicazioni1, essa è finaliz-zata a valorizzare e diffondere i risultati delle ricerche effettuate da un gruppo selezionato di propri iscritti. Infatti, uno degli obiettivi che la nostra istituzione accademica persegue da tempo e che continuerà a prefiggersi anche in futuro è quello di aiutare i giovani studiosi a otti-mizzare la divulgazione delle conoscenze acquisite durante il proprio iter formativo
Exploring the endonuclease MUS81 as a new factor impacting on cancer chemosensitivity
No full textBackground:
The use of PARP inhibitors (PARPi) has resulted in significant prolongation of disease-free survival, particularly in patients with cancers characterized by Homologous Recombination Repair (HRR) deficiency. However, 20% of these eligible patients do not respond to PARPi or could develop PARPi resistance; to overcome this variety of problems, research is now considering the possibility of combining PARPi with other therapeutic approaches. Over recent years, our lab has actively investigated the activation and roles of the human MUS81, a structure specific endonuclease involved in the resolution of DNA replication intermediates during G2/M phase. Its role in maintaining genome stability makes it a potential target for cancer therapy.
Aim:
PARPi in combination with MUS81 depletion could counteract chemoresistance in breast cancer; this hypothesis is rooted in the idea that MUS81 loss can induce defects that evoke PARP activation.
Methods:
We knocked-out MUS81 by Crispr/Cas9 in cancer-derived, HRR-proficient, breast epithelial cells and in healthy mammary epithelial cells and investigated on the parylation levels, phenotype and possible PARPi sensitization.
Results:
MUS81 KO results in elevated parylation and DNA damage accumulation in breast cancer cells; these results correlate with more NAD+ consumption, due to an accentuated PARP activation. Cancer cells undergo metabolic alteration and rewiring when MUS81 is knocked out, while there is no effect on NAD+ levels in healthy breast epithelial cells with MUS81 loss. MUS81 KO sensitized greatly the HRR+ cancer cells to the PARP inhibitor Olaparib, while in normal epithelial cell line we had not found significant reduction in terms of cell viability.
Conclusions:
MUS81 depletion sensitize breast cancer cell to PARPi independently of their HRR status. This makes MUS81 a promising and critical target, since its depletion in combination with PARPi has shown efficacy exclusively on cancer cells, with minimal toxicity in healthy cells.
Results:
MUS81 KO results in elevated parylation and DNA damage accumulation in breast cancer cells; these results correlate with more NAD+ consumption, due to an accentuated PARP activation. Cancer cells undergo metabolic alteration and rewiring when MUS81 is knocked out, while there is no effect on NAD+ levels in healthy breast epithelial cells with MUS81 loss. MUS81 KO sensitized greatly the HRR+ cancer cells to the PARP inhibitor Olaparib, while in normal epithelial cell line we had not found significant reduction in terms of cell viability.
Conclusions:
MUS81 depletion sensitize breast cancer cell to PARPi independently of their HRR status. This makes MUS81 a promising and critical target, since its depletion in combination with PARPi has shown efficacy exclusively on cancer cells, with minimal toxicity in healthy cells
The Artifice Among Languages. Automating Geometric Processes Through AI
No full textThis paper explores the application of Artificial Intelligence (AI) in design and geometric analysis processes in the CAD environment, with reference to Descriptive Geometry. Although the use of AI in academia is constantly growing, the implementation of artificial intelligence tools for solving geometric problems remains limited. In this context, this research proposes an experimental approach to automate the creation and manipulation of NURBS geometric entities, focusing on the ellipse as a case study. This document details the process of converting curves generated by the ’Archimedes Compass’ in a 3D space into NURBS ellipses. The conversion is achieved through programming in Python and facilitated by ChatGPT. The analysis shows how the mathematical exactness typical of NURBS may not always be compatible with the requirements of certain geometric procedures, making integration with dedicated algorithms and AI tools necessary. In a broader perspective, the work shows the potential of textual programming and AI in simplifying and generalising complex processes, enabling new levels of precision and flexibility in virtual modelling. Finally, the results obtained and possible future perspectives in different areas of drawing and geometric representation are discussed
A new Incompressible SPH model for simulating wave–structure impacts
No full textThe simulation of free-surface flows in hydraulics presents a number of challenges due to the inherent complexity of handling a fluid volume that continuously deforms and evolves over time. In this context, the Smoothed Particle Hydrodynamics (SPH) method, based on a Lagrangian approach that represents the fluid through a set of moving particles, proves to be more suitable than traditional grid-based methods. However, compared to these latter approaches, the SPH method also exhibits certain drawbacks, including increased difficulty in the treatment of boundary conditions and a higher computational cost. This thesis proposes a numerical model for simulating free-surface flows based on the Incompressible SPH (ISPH) approach. The model employs a boundary treatment technique that, to the best of our knowledge, has never been applied within this specific framework. During the development of this technique, several intrinsic advantages were identified when compared to other methods available in the literature. A series of numerical tests were carried out to assess the validity of the proposed model. The results obtained, consistent with those reported in the literature, confirmed the effectiveness of the developed numerical model in reproducing the analyzed free-surface flow phenomena