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Longitudinal Micro CT-driven biomarkers as a tool to evaluate lung fibrosis progression and antifibrotic efficacy in a refined Bleomycin mouse model
Get PDFIdiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with no curative pharmacological treatment. Animal models play an essential role in revealing molecular mechanisms involved in the pathogenesis of the disease.
Bleomycin (BLM)-induced lung fibrosis is the most widely used and characterized model for anti-fibrotic drugs screening. However, several issues have been reported, such as the identification of an optimal BLM dose and administration scheme as well as gender-specificity. Moreover, the balance between disease resolution, an appropriate time window for therapeutic intervention and animal welfare remains critical aspects yet to be fully elucidated.
In this thesis, Micro CT imaging has been used as a tool to identify the ideal BLM dose regimen to induce sustained lung fibrosis in mice as well as to assess the anti-fibrotic effect of Nintedanib (NINT) treatment upon this BLM administration regimen.
In order to select the optimal BLM dose scheme, C57bl/6 male mice were treated with BLM via oropharyngeal aspiration (OA), following either double or triple BLM administration.
The triple BLM administration resulted in the most promising scheme, able to balance disease resolution, appropriate time-window for therapeutic intervention and animal welfare.
The fibrosis progression was longitudinally assessed by micro-CT every 7 days for 5 weeks after BLM administration and 5 animals were sacrificed at each timepoint for the BALF and histological evaluation. The antifibrotic effect of NINT was assessed following different treatment regimens in this model.
Herein, we have developed an optimized mouse model of pulmonary fibrosis, enabling three weeks of the therapeutic window to screen putative anti-fibrotic drugs. micro-CT scanning, allowed us to monitor the progression of lung fibrosis and the therapeutical response longitudinally in the same subject, drastically reducing the number of animals involved in the experiment
Modelling spillover effects in spatial stochastic frontier analysis
Get PDFIn the last two decades, authors have begun to expand classical stochastic frontier (SF) models in order to include also some spatial components. Indeed, firms tend to concentrate in clusters, taking advantage of positive agglomeration externalities due to cooperation, shared ideas and emulation, resulting in increased productivity levels. Until now scholars have introduced spatial dependence into SF models following two different paths: evaluating global and local spatial spillover effects related to the frontier or considering spatial cross-sectional correlation in the inefficiency and/or in the error term. In this thesis, we extend the current literature on spatial SF models introducing two novel specifications for panel data. First, besides considering productivity and input spillovers, we introduce the possibility to evaluate the specific spatial effects arising from each inefficiency determinant through their spatial lags aiming to capture also knowledge spillovers. Second, we develop a very comprehensive spatial SF model that includes both frontier and error-based spillovers in order to consider four different sources of spatial dependence (i.e. productivity and input spillovers related to the frontier function and behavioural and environmental correlation associated with the two error terms). Finally, we test the finite sample properties of the two proposed spatial SF models through simulations, and we provide two empirical applications to the Italian accommodation and agricultural sectors. From a practical perspective, policymakers, based on results from these models, can rely on precise, detailed and distinct insights on the spillover effects affecting the productive performance of neighbouring spatial units obtaining interesting and relevant suggestions for policy decisions
To learn about the theater of people with visual impairments: documents, studies, experiments, workshops, interviews.
Get PDFAttraverso questa tesi, si intente centrare l'attenzione del mondo accademico e di quello teatrale sugli apporti delle pratiche performative al posizionamento sociale e la qualità della vita delle persone cieche e ipovedenti.
Questa tesi tenta di fornire strumenti che avvicinino le persone con disabilità visive alla pratica delle attività teatrali basate su teorie scientifiche. Innanzitutto, a questo fine, ho reperito, sintetizzato e messo in reciproca relazione contributi di taglio psicologico, fisiologico e sociologico. Da questo lavoro esplorativo è risultato un quadro compressivo delle condizioni psicofisiche delle persone con disabilità visive. I loro aspetti psicologici presentano disturbi depressivi, ansie, problematiche circa la concezione di sé e l’autostima, rischi di suicidio, mentre quelli fisici includono stabilità posturale, coordinamento bilaterale e diverse forme di attività. A questi elementi vanno inoltre associati controllo dell'espressione, socialità e memoria.
Combinando questi insiemi di caratteristiche alle possibilità e alle dinamiche del laboratorio teatrale, si sono quindi elaborate, progettate e sperimentate diverse serie di esercizi teatrali per non vedenti e ipovedenti. Tuttavia, a causa degli impedimenti oggettivi causati dalla pandemia del Covid, questa parte sperimentale della ricerca è in gran parte restata allo stato embrionale.
Infine, sono stati documentati con descrizioni e interviste due laboratori teatrali per non vedenti rappresentativi della realtà italiana. A questi ho aggiunto riferimenti su iniziative e istituzioni di carattere teatrale: New Life, Teatro Ciego, XINMU Laboratorio teatrale, EXTANT, Theater Breaking, CRE Outreach.
Si spera che, attraverso questo ricerca, non solo le persone con disabilità visive si famigliarizzino con le risorse offerte dalle pratiche formative, ma anche gli studiosi interessati possano sinteticamente accedere ad una complessiva e preliminare delle attività teatrali per i non vedenti, contribuendo, così, allo sviluppo sistematico della ricerca in questo campo.Through this thesis, we intend to focus the attention of the academic and theatrical world on the contributions of performative practices to the social positioning and quality of life of blind and visually impaired people.
This thesis is a first glance in providing tools that bring visually impaired people closer to the practice of theatrical activities based on scientific theories. To this aim, I have synthesized and put in mutual relation contributions of a psychological, physiological and sociological nature. This exploratory work resulted in a comprehensive picture of the psychophysical conditions of people with visual impairments. Their psychological aspects include depressive disorders, anxieties, problems with self-conception, self-esteem and suicide risks, while the physical ones include postural stability, bilateral coordination and different forms of activity. These elements must also be associated with control of expression, sociability, and memory.
By combining these sets of characteristics with the possibilities and dynamics of the theater laboratory, various series of theatrical exercises for the blind and visually impaired have therefore been elaborated, designed and tested. However, due to the objective impediments caused by the Covid pandemic, this experimental part of the research has largely remained in its embryonic state.
Finally, two theater workshops for the blind representative of the Italian reality were documented with descriptions and interviews. I added references to theatrical initiatives and institutions: New Life, Teatro Ciego, XINMU Theatre Workshop, EXTANT, Theater Breaking, CRE Outreach.
I hope that, through this research, not only people with visual impairments will familiarize themselves with the resources offered by training practices, but also that interested scholars will be able to synthetically access an overall and preliminary overview of theatrical activities for the blind, thus contributing to the systematic development of research in this field
Liver and spleen shear-wave elastography in the diagnosis and severity staging of Philadelphia-negative myeloproliferative diseases and myelofibrosis
Get PDFIntroduzione: La stiffness epato-splenica, misurata attraverso la transient elastography (TE), è stata associata con la fibrosi midollare nei pazienti con malattia mieloproliferativa (MPNs). La rigidità dei tessuti può essere valutata con la shear-wave elastography (SWE), con due tecniche: point (pSWE) e bidimensionale (2DSWE). Obiettivi dello studio sono: 1) identificare le differenze di TE fra i pazienti con MPNs, i cirrotici e volontari sani (HV); 2) valutare specifiche caratteristiche di TE in pazienti con MF, PV ed ET; 3) stabilire una correlazione con il grado di fibrosi midollare.
Metodi: in questo studio monocentrico, MPN, cirrotici ed HV hanno eseguito elastometria epato-splenica con pSWE e 2DSWE.
Risultati: 236 pazienti sono stati inclusi in questo studio: 64 con MF (27.1%), 33 con PV (14%), 46 con ET (19.4%), 75 HV (32%) e 18 (8%) cirrotici. Al confronto con gli HV, i pazienti con MF hanno maggiore stiffness splenica (pSWE 40.9 vs 26.3 kPa, p<0.001; 2DSWE 34.9 vs 20.1 kPa, p<0.001) ed epatica (pSWE 7.72 vs 5.52 kPa, p<0.001; 2DSWE 6.96 vs 5.01 kPa, p<0.001). Al confronto con i pazienti con PV ed ET, quelli con MF hanno maggiori valori di stiffness epatici (p<0.001) e splenici (p<0.001). In fibrosi di basso (0-1) (n=81 , 60.4%) vs alto grado (2-3) (n=42, 39.6%), sono evidenti valori di stiffness maggiori nei pazienti con fibrosi di alto grado sia per il fegato (pSWE 5.2 vs 6.65 kPa; 2DSWE 5.1 vs 6.05 kPa) che nella milza (pSWE 27.2 vs 37.9 kPa, 2DSWE 21.7 vs 30.75 kPa – p<0.001)
Conclusioni: La TE distingue i pazienti con MF sia dai sani che dalle altre MPNs. Valori di TE sono significativamente associati con caratteristiche rilevanti che includono la fibrosi midollare in tutte le MPNs. I valori di stiffness epatici e splenici sono pertanto rilevanti nella diagnosi e management delle MPNs.Introduction: Spleen and liver stiffness, investigated by transient elastography (TE), have been associated with marrow fibrosis in patients with Ph-negative myeloproliferative neoplasms (MPNs). Tissue stiffness can be assessed by shear wave elastography (SWE), the two most common techniques being point (pSWE) and bidimensional (2DSWE). Aims of this study are: 1) to identify TE differences between MPN pts, cirrhotics and healthy volunteers (HV); 2) to evaluate specific TE features in pts with MF, PV and ET; 3) to establish a correlation with bone marrow fibrosis grade.
Methods: In this monocentric study, MPN and cirrhotic pts and HV received elastometric evaluation of spleen and liver stiffness by pSWE and 2DSWE.
Results: A total of 236 pts were included in this study: MPN pts were affected by MF (64, 27.1%), PV (33, 14%) or ET (46, 19.4%), in addition to 75 (32%) healthy controls and 18 (8%) cirrhotic volunteers. Compared to HV, MF patients had greater spleen (pSWE 40.9 vs 26.3 kPa, p<0.001; 2DSWE 34.9 vs 20.1 kPa, p<0.001), and liver stiffness (pSWE 7.72 vs 5.52 kPa, p<0.001; 2DSWE 6.96 vs 5.01 kPa, p<0.001). Compared to PV and ET pts, MF pts had higher spleen (p<0.001) and liver stiffness (p<0.001). In low (0-1) (n=81 , 60.4%) versus high grade fibrosis (2-3) (n=42, 39.6%), is evident a higher stiffness in patients with higher grades of bone marrow fibrosis both for liver (pSWE 5.2 vs 6.65 kPa; 2DSWE 5.1 vs 6.05 kPa) and spleen (pSWE 27.2 vs 37.9 kPa, 2DSWE 21.7 vs 30.75 kPa – p<0.001 in both tests).
Conclusions: TE evaluation distinguishes MF pts from HV and ET/PV. TE data were significantly associated with prognostically relevant features including marrow fibrosis in all MPNs. Overall, spleen/liver stiffness may help in MPN diagnosis and may provide clinical guidance
Identification of resistance factors to the main wheat diseases in the Mediterranean area
Get PDFSeveral diseases challenge bread and durum wheat productions worldwide. The importance of these cereals requires adequate protection to pathogens that can cause strong yield and grain quality losses. The main work of this thesis was related to phenotype GDP (Global Durum Panel) in the Mediterranean region (Italy, Egypt, Lebanon, Morocco and Turkey) and Argentina across three years (2019-2021) for yellow rust resistance (infection type and severity). GWAS shows in particular, loci in chromosome 1B, 2B, 4B, 5A, 6A, 7B showed high significance across nurseries/years, with various patterns of GxE. The second chapter is about Zymoseptoria tritici, agent of STB (Septoria Tritici Blotch), a foliar pathogen that yearly causes high damages if not controlled. In recent years research in durum wheat breeding is focused on the identification of novel, underexploited resistance genes to be subsequently and conveniently moved into the pre-breeding and breeding stream. The plants were phenotyped for disease height characters, infection type at the flag leaf and infection type at the level of the canopy below the flag leaf. This experiment opens up a rich scenario of analysis and opportunities to investigate and discover new loci of resistance to STB. Third chapter is about Fusarium head blight (FHB) is a fungal disease caused by pathogens belonging to the genus Fusarium. In particular, Fusarium culmorum and Fusarium graminearum species cause severe grain yield losses and accumulation of mycotoxins in wheat that compromise food safety. Over 250 QTL/genes for FHB resistance have been identified in bread wheat, such as Fhb 1 and Fhb 5 but only a small number of FHB resistance loci have been mapped in durum wheat. The aim of this work is to find loci of partial resistance to FHB already present in durum and bread wheat germplasm and therefore easily cumulative
Advanced studies on two animal models, murine and fish. RadKI21A626T mouse model: new insights into molecular mechanisms of enteric neuro-epithelial pathology. European sea bass: study of the effects of essential oils in different diets on the gastric system.
Get PDFMy PhD research period was focused on the anatomical, physiological and functional study of the gastrointestinal system on two different animal models.
In two different contexts, the purpose of these two lines of research was contribute to understand how a specific genetic mutation or the adoption of a particular dietary supplement can affect gastrointestinal function.
Functional gastrointestinal disorders are chronic conditions characterized by symptoms for which no organic cause can be found. Although symptoms are generally mild, a small subset of cases shows severe manifestations. This subset of patients may also have recurrent intestinal sub-occlusive episodes, but in absence of mechanical causes. This condition is referred to as chronic intestinal pseudo-obstruction, a rare, intractable chronic disease. Some mutations have been associated with CIPO. A novel causative RAD21 missense mutation was identified in a large consanguineous family, segregating a recessive form of CIPO. The present thesis was aimed to elucidate the mechanisms leading to neuropathy underlying CIPO via a recently developed conditional KI mouse carrying the RAD21 mutation. The experimental studies are based on the characterization and functional analysis of the conditional KI Rad21A626T mouse model.
On the other hand aquaculture is increasing the global supply of foods. The species selected and feeds used affects the nutrients available from aquaculture, with a need to improve feed efficiency, both for economic and environmental reasons, but this will require novel innovative approaches.
Nutritional strategies focused on the use of botanicals have attracted interest in animal production. Previous research indicates the positive results of using essential oils (EOs) as natural feed additives for several farmed animals. Therefore, the present study was designed to compare the effects of feed EO supplementation in two different forms (natural and composed of active ingredients obtained by synthesis) on the gastric mucosa in European sea bass
Development of numerical tools for the simulation, design and optimization of a Helicon Plasma Thruster
Get PDFThis work thesis focuses on the Helicon Plasma Thruster (HPT) as a candidate for generating thrust for small satellites and CubeSats. Two main topics are addressed: the development of a Global Model (GM) and a 3D self-consistent numerical tool. The GM is suitable for preliminary analysis of HPTs with noble gases such as argon, neon, krypton, and xenon, and alternative propellants such as air and iodine. A lumping methodology is developed to reduce the computational cost when modelling the excited species in the plasma chemistry. A 3D self-consistent numerical tool is also developed that can treat discharges with a generic 3D geometry and model the actual plasma-antenna coupling. The tool consists of two main modules, an EM module and a FLUID module, which run iteratively until a steady state solution is converged. A third module is available for solving the plume with a simplified semi-analytical approach, a PIC code, or directly by integration of the fluid equations. Results obtained from both the numerical tools are benchmarked against experimental measures of HPTs or Helicon reactors, obtaining very good qualitative agreement with the experimental trend for what concerns the GM, and an excellent agreement of the physical trends predicted against the measured data for the 3D numerical strategy
Investigating the learning potential of the Second Quantum Revolution: development of an approach for secondary school students
Get PDFIn recent years we have witnessed important changes: the Second Quantum Revolution is in the spotlight of many countries, and it is creating a new generation of technologies.
To unlock the potential of the Second Quantum Revolution, several countries have launched strategic plans and research programs that finance and set the pace of research and development of these new technologies (like the Quantum Flagship, the National Quantum Initiative Act and so on).
The increasing pace of technological changes is also challenging science education and institutional systems, requiring them to help to prepare new generations of experts.
This work is placed within physics education research and contributes to the challenge by developing an approach and a course about the Second Quantum Revolution. The aims are to promote quantum literacy and, in particular, to value from a cultural and educational perspective the Second Revolution.
The dissertation is articulated in two parts. In the first, we unpack the Second Quantum Revolution from a cultural perspective and shed light on the main revolutionary aspects that are elevated to the rank of principles implemented in the design of a course for secondary school students, prospective and in-service teachers. The design process and the educational reconstruction of the activities are presented as well as the results of a pilot study conducted to investigate the impact of the approach on students' understanding and to gather feedback to refine and improve the instructional materials.
The second part consists of the exploration of the Second Quantum Revolution as a context to introduce some basic concepts of quantum physics. We present the results of an implementation with secondary school students to investigate if and to what extent external representations could play any role to promote students’ understanding and acceptance of quantum physics as a personal reliable description of the world
High power density electrical machines with hairpin windings
Get PDFNowadays, electrical machines are seeing an ever-increasing development and extensive research is currently being dedicated to the improvement of their efficiency and torque/power density. Compared to conventional random windings, hairpin winding inherently features lower DC resistance, higher fill factor, better thermal performance, improved reliability, and an automated manufacturing process. However, several challenges need to be addressed, including electromagnetic, thermal, and manufacturing aspects. Of these, the high ohmic losses at high-frequency operations due to skin and proximity effects are the most severe, resulting in low efficiency or high-temperature values.
In this work, the hairpin winding challenges were highlighted at high-frequency operations and at showing the limits of applicability of these standard approaches. Afterward, a multi-objective design optimization is proposed aiming to enhance the exploitation of the hairpin technology in electrical machines. Efficiency and volume power density are considered as main design objectives. Subsequently, a changing paradigm is made for the design of electric motors equipped with hairpin windings, where it is proven that a temperature-oriented approach would be beneficial when designing this type of pre-formed winding. Furthermore, the effect of the rotor topology on AC losses is also considered.
After providing design recommendations and FE electromagnetic and thermal evaluations, experimental tests are also performed for validation purposes on a motorette wound with pre-formed conductors. The results show that operating the machine at higher temperatures could be beneficial to efficiency, particularly in high-frequency operations where AC losses are higher at low operating temperatures. The last part of the thesis focuses on comparing the main electromagnetic performance metrics for a conventional hairpin winding, wound onto a benchmark stator with a semi-closed slot opening design, and a continuous hairpin winding, in which the slot opening is open. Lastly, the adoption of semi-magnetic slot wedges is investigated to improve the overall performance of the motor
Sustainable pavements for rural scenarios: laboratory and in-situ characterization of recycled materials and innovative construction solutions
Get PDFGrowing need for infrastructure has led to expanding research on advances in road pavement materials. Finding solutions that are sustainable, environmentally friendly and cost-efficient is a priority. Focusing such efforts on low-traffic and rural roads can contribute with a significant progress in the vital circulatory system of transport for rural and agricultural areas. An important alternative material for pavement construction is recycled aggregates from solid wastes, including waste from civil engineering activities, mainly construction and demolition. A literature review on studies is made; it is performed a planned set of laboratory testing procedures aimed to fully characterize and assess the potential in-situ mechanical performance and chemical impact. Furthermore, monitoring the full-scale response of the selected materials in a real field construction site, including the production, laying and compaction operations. Moreover, a novel single-phase solution for the construction of semi-flexible paving layers to be used as alternative material to common concrete and bituminous layers is experimented and introduced, aiming the production and laying of a single-phase laid material instead of a traditional two phases grouted macadam. Finally, on a parallel research work for farming pavements, the possible use of common geotechnical anti-erosive products for the improvement of soil bearing capacity of paddock areas in cattle husbandries of bio-farms is evaluated. this thesis has clearly demonstrated the feasibility of using the sustainable recycled aggregates for low-traffic rural roads and the pavements of farming and agriculture areas. The pavement layers constructed with recycled aggregates provided satisfying performance under heavy traffic conditions in experimental pavements. This, together with the fact that these aggregates can be available in most areas and in large quantities, provides great impetus towards shifting from traditional materials to more sustainable alternatives. The chemical and environmental stability of these materials proves their soundness to be utilized in farming environments.La Trovare soluzioni innovative che siano sostenibili, rispettose dell'ambiente ed efficienti in termini di costi è oggi una priorità. Concentrare tali sforzi sulle strade a basso traffico e rurali può contribuire ad uno sviluppo significativo nel sistema dei trasporti per le aree agricole. Un importante materiale alternativo per la costruzione di pavimentazioni è l’aggregato riciclato, compresi i rifiuti provenienti da attività di ingegneria civile. L'utilizzo di tale materiale alternativo richiede l'adozione di metodi tecnici e procedure di valutazione adeguati, in particolare per le applicazioni su strade rurali a basso traffico. In questa tesi, viene inizialmente effettuata una revisione completa della letteratura sugli studi precedentemente svolti su specifiche, analisi, test e casi di studio di aggregati riciclati. Viene eseguita una serie pianificata di test di laboratorio volte a caratterizzare e valutare le potenziali prestazioni meccaniche in situ e l'impatto chimico/ambientale. Il monitoraggio della risposta su vasta scala dei materiali in cantiere reale, comprese le operazioni di produzione, posa e compattazione, è stato effettuato sperimentata e introdotta una nuova soluzione monofase per la realizzazione di manti semi-flessibili da utilizzare come materiale alternativo ai comuni manti cementizi e bituminosi, finalizzata alla produzione e alla posa in opera di un materiale prodotto in un’unica fase, invece di un tradizionale macadam stuccato in due fasi. Questa tesi ha dimostrato la fattibilità dell'utilizzo di aggregati riciclati sostenibili per strade rurali a basso traffico e pavimentazioni di aree agricole.Questo, insieme al fatto che questi aggregati possono essere disponibili nella maggior parte delle aree e in grandi quantità, fornisce un grade risultato per incentivare il passaggio dai materiali tradizionali ad alternative più sostenibili. Oltre alle notevoli prestazioni portanti, la stabilità chimica e ambientale di questi materiali, sulla base delle misure di lisciviazione