University of Bologna

AMS Tesi di Dottorato
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    Study and experimental characterization of the laser welding process for the manufacturing of electric powertrain components in the automotive industry

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    The PhD project that will be presented in this thesis is focused on the study and optimization of the production process for the manufacturing of electrical powertrain components in the automotive field using the laser beam welding process (LBW). The objective is to define, through experimental activities, an optimized process condition for applications in the electrical field that can be generalized, that is, which guarantees its reproducibility as the types of connections vary and which represents the basis for extending the method to future applications in e-mobility sector. The work developed along two lines of research, the convergence of which made it possible to create prototypes of battery modules based on different types of lithium-ion cells and stator windings for electric motors. On the one hand, the different welding configurations involving the production of batteries based on pouch cells and therefore the welding of aluminum and copper in dissimilar configuration were studied, while for the prismatic cells only one configuration was analyzed. On the other hand, the welding of pure copper hairpins with rectangular shape in edge joint configuration was studied for the production of stator windings. The experimental tests carried out have demonstrated the feasibility of using the LBW process for the production of electric powertrain components entirely designed and developed internally as the types of materials and welding configurations vary; the methodologies required for the characterization methods, necessary for the end-of-line tests, for the evaluation of the properties of the different joint configurations and components (battery and electric motor) were also defined with the aim of obtaining the best performance. The entire doctorate program was conducted in collaboration with Ferrari Auto S.p.A. and the direct industrial application of the issues addressed has been faced

    Essay in Empirical Economics: Intangible Economy, Innovative Firms and Institution of Innovation

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    The present thesis is made up by three separate chapters covering topics related to international trade, intellectual property right, business groups and knowledge flows and finally, an attempt to identify promising and innovative young firms. The first paper focuses on the role of institutions, and it shows howdifferent types of institutions are important to determine comparative advantage for countries at different stage of development. The papers finds that intellectual property rights (IPR) protection changes export composition of OECD countries toward IP-intensive sectors, whereas contract enforcement is a driver of export of relation-specific inputs in non-OECD countries. However, better IPR quality encourages technology transfer by redirecting non-OECD imports toward IP-intensive industries. The second chapter studies how subsidiaries of Business Groups interact between each other. In particular, the paper highlights productivity gains that affiliates enjoy from intangible assets developed by other firms within the same group. The analysis shows that a key element to consider in order to understand these flows, is to take into account the hierarchical links between subsidiaries. This crucial step allows to show that within Business Groups knowledge flows upwards, i.e. subsidiaries in lower layers share their knowledge to subsidiaries in upper layers. The third chapter presents a novel dataset assembled during my experience at the OECD on innovative start-up. Combining information from two different data provider, Crunchbase and Dealroom, and implementing several cleaning and matching procedure, we managed to gather this dataset which covers almost the universe of innovative start-ups all over the world. This data are a key element that will be exploited in several work at the OECD, for example to study the determinants of start-ups success (innovation, scale-up) and how relevant are Killer Acquisitions in start-ups

    The copialettere of Francesco Guicciardini: diary of a lieutenancy before the sack of Rome

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    La tesi di dottorato ha come oggetto di ricerca un copialettere appartenuto a Francesco Guicciardini e rinvenuto da Roberto Ridolfi nei primi anni del Novecento. Il testimone si trova nelle filze XXI e XXII dell’Archivio Guicciardini e in un faldone delle carte Strozziane (ASF I 130) dell’Archivio di Stato di Firenze. Si tratta di un residuo di un codice cartaceo, composto da 151 carte, corrispondenti a 50 unità codicologiche di varia dimensione. Il codice è integralmente apografo, se non per tre sole note autografe di Francesco Guicciardini, e raccoglie la copia di ben 258 missive ‒ comprendenti lettere inviate, riassunti di lettere in entrata, istruzioni e carteggi tra altri corrispondenti ‒ tutte ascrivibili tra l’8 giugno 1526 e il 18 febbraio 1527, quando Guicciardini era impegnato, nelle vesti di luogotenente, nell’esercito pontificio. Sulla scorta degli studi pregressi, si propone uno studio di questo corpus epistolare, con il tentativo di definirne un’attribuzione e una datazione certe. Un esame quantitativo e qualitativo delle varianti tra le missive conservate all’interno del copialettere e il loro modello, le lettere minute, ha infatti mostrato una complessa riorganizzazione della struttura epistolare e una profonda rielaborazione formale del dettato a livello sintattico, morfologico e lessicale. L’insieme di tali fattori, avallati da un’ulteriore collazione tra l’esemplare del copialettere, delle minute e degli originali, anch’essi frutto di un’operazione di copia, ha potuto confermare la paternità guicciardiniana del codice. La ricerca prosegue con un raffronto tra il copialettere e alcuni brani tratti dal secondo libro dei Commentari della luogotenenza, poi confluiti nel XVII libro della Storia d’Italia, per tentare di comprendere le modalità di utilizzo di questa specialissima compagine epistolare.The object of the doctoral thesis is a copialettere that belonged to Francesco Guicciardini and was found by Roberto Ridolfi in the early twentieth century. The witness is located in the Guicciardini Archive and in the State Archive of Florence (Carte Strozziane, ASF I 130). It is a residue of a paper codex, composed of 151 papers, corresponding to 50 codicological units of various sizes. The codex is entirely apograph, with the exception of only three autograph notes by Francesco Guicciardini, and contains copies of 258 letters - including sent letters, summaries of incoming letters, instructions and correspondence between other correspondents - all of which can be dated between 8 June 1526 and 18 February 1527, when Guicciardini was serving as lieutenant in the papal army. On the basis of previous researches, a study of this corpus of correspondence is proposed, with the attempt to define a precise attribution and dating. A quantitative and qualitative examination of the variants between the letters preserved in the letter-copies and their model, the minute letters, has in fact shown a complex reorganisation of the epistolary structure and a profound formal reworking of the dictation at syntactic, morphological and lexical levels. The combination of these factors, supported by a further collation between the copialettere, the minute letters and the originals, which are also the result of a copying operation, was able to confirm Guicciardini's authorship of the codex. The research continues with a comparison between the copialettere and some passages from the second book of the Commentari della luogotenenza, later included in the seventeenth book of the Storia d'Italia, in an attempt to understand how this very special epistolary collection was used

    Treatment of actinic keratosis with nicotinamide-associated photodynamic therapy versus treatment with photodynamic therapy alone: ​​an observational study.

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    Le cheratosi attiniche (actinic keratosis, AK) sono le neoformazioni epiteliali di più comune riscontro nella pratica clinica dermatologica. La maggior parte delle terapie attualmente utilizzate per le AK sono terapie “di campo”, ossia volte a trattare l’intero campo di cancerizzazione, cioè l’insieme delle lesioni, sia cliniche sia subcliniche, che si sviluppano in seguito all’accumulo di modificazioni pre-neoplastiche in una regione di epitelio in seguito all’esposizione a lungo termine ad agenti cancerogeni, in questo caso i raggi ultravioletti. La terapia fotodinamica (photodynamic therapy, PDT), che può essere svolta nella modalità “convenzionale” (utilizzando una luce rossa) oppure “daylight” (utilizzando la luce naturale), è una metodica ampiamente utilizzata nella terapia di AK multiple e campo di cancerizzazione. La recente letteratura ha mostrato come la nicotinamide (forma attiva della vitamina B3) possa essere in grado di ridurre l’insorgenza di nuove AK e tumori cutanei non-melanoma, potendo favorire il processo di riparazione del DNA e ridurre l’immunosoppressione legata all’esposizione cronica agli UV. Pochi studi si sono concentrati sui possibili legami fra PDT e trattamento con nicotinamide, ed in particolare sul loro effetto combinato nel trattamento delle AK. Questo studio è volto a comparare gli outcomes di due differenti trattamenti, ossia la PDT associata a nicotinamide per os, rispetto alla sola PDT, per il trattamento di AK multiple e del campo di cancerizzazione nel distretto testa-collo.Actinic keratosis (AK) is the most common epithelial neoformation in the clinical practice. Most of the treatments of AK are “field” therapies, i.e. aimed at treating the “field of cancerization”, which consists of all the lesions, both clinical and subclinical, that develop after the accumulation of pre-neoplastic modifications due to long-term exposure to carcinogens, in this case ultraviolet (UV) radiation. Photodynamic therapy (PDT), which can be performed with the conventional technique (using red light) or with the daylight technique (using natural radiation), is widely used for the treatment of multiple AKs and field of cancerization. The recent literature has shown that nicotinamide (the active form of vitamin B3), may reduce the onset of new AKs and non-melanoma skin cancer, since it can promote DNA repair process and reduce the immunosuppression linked to UV-exposure. Only few studies have focused on the possible associations between PDT and nicotinamide, and in particular on the combined effect of PDT and nicotinamide in the treatment of AK. This study aims to compare the efficacy of two different treatments, i.e. PDT associated with systemic nicotinamide and PDT alone, for the treatment of multiple AKs and field of cancerization in the head and neck district

    Clinical and pathophysiological characterization of patients with acutely decompensated cirrhosis and acute-on-chronic liver failure

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    In the last decade, our understanding of the pathophysiological mechanisms underlying decompensated cirrhosis has greatly increased. Moreover, acute-on-chronic liver failure (ACLF) was defined as a distinct syndrome with specific features. Our research activities aimed to provide a contribution in characterizing patients with acutely decompensated cirrhosis and ACLF from a clinical and a pathophysiological perspective. As a first project, we addressed the clinical issue of predicting in-hospital development of ACLF in patients hospitalized for acute decompensation of cirrhosis. As a second contribution, we performed a reassessment of the whole metabolomic dataset obtained from 831 patients enrolled in the CANONIC study, focusing on amino acids, with the aim to uncover alterations in amino acids metabolic pathways. As a third perspective, we performed a GWAS on 270 patients with acute decompensation and ACLF included in the first clinical study. We categorized patients in 4 groups, according to their clinical presentation and their clinical course. We then performed two comparisons: group 1 vs group 4 (i.e., the most severe vs the mildest clinical courses), and group 1 vs group 2 (i.e., patients with different 1-year outcomes from a common clinical presentation with ACLF or bacterial infection). Three SNPs (rs9354118 on chromosome 6q16.1; rs1146878 on chromosome 13q22.2; rs6479397 on chromosome 9q22.31) were significantly associated with the selected phenotypes, but all of them were located in non-codifying DNA regions. However, their potential role as candidate Cis-Regulatory Elements (cCREs) opened interesting hypotheses on effects on the expression of neighboring genes. Indeed, four of them (FUT9 and UFL1 for SNP rs9354118, LMO7 and ACOD1 for rs1146878) are involved in the modulation of immune system activation and systemic inflammation. The results of the GWAS did not confirm previous findings reported in literature and presented some limitations. However, it provided the basis for further research in this still open issue

    Genome-wide analysis of G-type lectin genes in Fragaria vesca and functional characterization of FaMBL1 gene in defense response of F. × ananassa to fungal pathogens

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    Strawberry (Fragaria × ananassa) is an important soft fruit but easily to be infected by pathogens. Anthracnose and gray mold are two of the most destructive diseases of strawberry which lead to serious fruit rot. The first chapter introduced strawberry anthracnose caused by Colletotrichum acutatum. The infection strategy, disease cycle and management of C. acutatum on strawberry were reported. Likewise, the second chapter summarized the infection strategy of Botrytis cinerea and the defense responses of strawberry. As we already know white unripe strawberry fruits are more resistant to C. acutatum than red ripe fruits. During the interaction between strawberry white/red fruit and C. acutaum, a mannose binding lectin gene, FaMBL1, was found to be the most up-regulated gene and induced exclusively in white fruit. FaMBL1 belongs to the G-type lectin family which has important roles in plant development and defense process. To get insight into the role of FaMBL1, genome-wide identification was carried out on G-type lectin gene family in Fragaria vesca and the results were showed in chapter 3. G-type lectin genes make up a large family in F. vesca. Active expression upon biotic/abiotic stresses suggested a potential role of G-lectin genes in strawberry defenses. Hence, stable transgenic strawberry plants with FaMBL1 gene overexpressed were generated. Transformed strawberry plants were screened and identified. The results were showed in chapter 4, content of disease-related phytohormone, jasmonic acid, was found decreased in overexpressing lines compared with wild type (WT). Petioles inoculated by C. fioriniae of overexpressing lines had lower disease incidence than WT. Leaves of overexpressing lines challenged by B. cinerea showed remarkably smaller lesion diameters compared with WT. The chitinase 2-1 (FaChi2-1) showed higher expression in overexpressing lines than in WT during the interaction with B. cinerea, which could be related with the lower susceptibility of overexpressing lines

    Development of numerical methodologies to predict the liquid fuel sprays - wall interaction to optimize the mixing process of direct injection spark ignition engines

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    Nowadays the development of new Internal Combustion Engines is mainly driven by the need to reduce tailpipe emissions of pollutants, Green-House Gases and avoid the fossil fuels wasting. The design of dimension and shape of the combustion chamber together with the implementation of different injection strategies e.g., injection timing, spray targeting, higher injection pressure, play a key role in the accomplishment of the aforementioned targets. As far as the match between the fuel injection and evaporation and the combustion chamber shape is concerned, the assessment of the interaction between the liquid fuel spray and the engine walls in gasoline direct injection engines is crucial. The use of numerical simulations is an acknowledged technique to support the study of new technological solutions such as the design of new gasoline blends and of tailored injection strategies to pursue the target mixture formation. The current simulation framework lacks a well-defined best practice for the liquid fuel spray interaction simulation, which is a complex multi-physics problem. This thesis deals with the development of robust methodologies to approach the numerical simulation of the liquid fuel spray interaction with walls and lubricants. The accomplishment of this task was divided into three tasks: i) setup and validation of spray-wall impingement three-dimensional CFD spray simulations; ii) development of a one-dimensional model describing the liquid fuel – lubricant oil interaction; iii) development of a machine learning based algorithm aimed to define which mixture of known pure components mimics the physical behaviour of the real gasoline for the simulation of the liquid fuel spray interaction

    Applied biomaterials from sustainable sources

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    If we look back in time at the history of humanity, we can state that our generation is living an era of outstanding efficiency and progress because of globalization and global competition, even if this is resulting in the rapid depletion of energy sources and raw materials. The environmental impact of non-biodegradable plastic wastes is of increasing global concern: nowadays, imagining a world without synthetic plastics seems impossible, though their large-scale production and their extensive use have only spread since the end of the World War II. In recent years, the demand for sustainable materials has increased significantly and, with a view to circular economy, research has also focused on the enhancement and subsequent reuse of waste materials produced by industrial processing, intensive farming and the agricultural sector. Plastic polymers have been the most practical and economical solution for decades due to their low cost, prompt availability and excellent optical, mechanical and barrier properties. Biodegradable polymers could replace them in many applications, thus reducing the problems of traditional plastics disposability and the dependence on petroleum. Natural biopolymers are in fact characterized by a high biocompatibility and biodegradability and have already prompted research in the field of regenerative medicine. During my PhD, my goal was to use natural polymers from sustainable sources as raw materials to produce biomaterials, which are materials designed to interface with biological systems to evaluate, support or replace any tissue, organ, or function of the body. I focused on the use of the most abundant biopolymers in nature to produce biomaterials in the form of films, scaffolds and cements. After a complete characterization, the materials were proposed for suitable applications in different fields, from tissue engineering to cosmetics and food packaging. Some of the obtained results were published on international scientific and peer-reviewed journals

    Hypothermic Oxygenated Perfusion in Extended Criteria Donor Liver Transplantation – a randomized trial

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    I fegati provenienti dai donatori a criteri estesi sono associati a un rischio elevato di dysfunction dopo trapianto. La HOPE potrebbe ridurre l’incidenza di tale complicanza, benché i dati emersi da studi prospettici siano carenti. In questo studio monocentrico randomizzato i pazienti da sottoporre a trapianto di fegato con graft proveniente da donatore marginale sono stati randomizzati a ricevere un fegato dopo HOPE o a riceverne uno conservato in statica ipotermica (gruppo SCS). L’endpoint primario era la valutazione dell’incidenza dell’early allograft dysfunction. Gli endpoint secondari includevano la valutazione della sopravvivenza del ricevente e del graft, così come le complicanze post-trapianto. I pazienti del gruppo HOPE avevano un tasso significativamente più basso di EAD. L’analisi di sopravvivenza confermava che quei pazienti avevano una sopravvivenza del graft superiore, con inferiori tassi di re-ricovero e di complicanze post-operatorie, in particolare di natura cardio-vascolare.Liver grafts from extended criteria brain death donors are associated with higher dysfunction rates after transplantation. HOPE of the liver can reduce the incidence of graft dysfunction and failure in ECD grafts, although data from prospective studies are very limited. In this monocentric, open-label, randomized study, patients undergoing transplantation from an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage alone (SCS group). The primary endpoint was the incidence of early graft dysfunction. The secondary endpoints included graft and patient survival and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of early graft dysfunction. The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival, with lower re-admission and overall complication rates, in particular cardio-vascular adverse events

    The effect of morphine on endothelial differentiation of Vascular Mesenchimal Stromal Cells (vMSC)

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    In the field of illicit drug use, there is a great variability in prevalence mortality rates attributable to heroin overdose, but most studies on longitudinal trends of overdose deaths show increases across time. The most serious effect of opiates is the respiratory depression and pulmonary edema, whose cause is thought to be damage to the capillary endothelium, both ischemic and/or related to the direct toxic effect of the substance on entothelial cells. Tissue regeneration and repair are essential after endothelial cell injury and are related to the activity of human vascular mesenchimal stromal/stem cells (vMSCs), a versatile class of multipotent adult stem cells capable of self-renewal. The expression of opioid receptors on vMSCs has already been demonstrated; as a matter of fact, also an opiate-related impairment of vMSCs function might be a part of the pathophysiology of endothelial cell injury. The aim of this study was to assess the effect of in-vitro opiate exposure on the phisiologial activity and maintenance of human vMSCs. Cell viability, proliferative potential, oxidative stress and pro-senescence effect were evaluated in association with the ultrastructural analysis by transmission electron microscopy. In vitro vascular differentiation was also assessed, both by investigating the expression of the endothelial marker CD31 by immunofluorescence in cells exposed to VEGF and morphine sulphate; and by a tubular in vitro assay on geltrex matrix. Results showed clear cell impairment, including viability decrease, cytostatic and senescence effect as well as a state of cell cycle arrest and loss of replicative capacity for the highest concentrations tested. Although the results obtained must be considered only introductive to the related forensic issue, the forensic perpsectives have to consider the value of experimental data to assurge toward scientific evidence for application in caseworks and to provide a robust interpretation to the judicial questions in the forensic arena

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