Spectral-Element and Adjoint 3D Full-Wave Tomography for the Lithosphere of Central Italy

The primary objective of this thesis is to obtain a better understanding of the 3D velocity structure of the lithosphere in central Italy. To this end, I adopted the Spectral-Element Method to perform accurate numerical simulations of the complex wavefields generated by the 2009 Mw 6.3 L’Aquila event and by its foreshocks and aftershocks together with some additional events within our target region. For the mainshock, the source was represented by a finite fault and different models for central Italy, both 1D and 3D, were tested. Surface topography, attenuation and Moho discontinuity were also accounted for. Three-component synthetic waveforms were compared to the corresponding recorded data. The results of these analyses show that 3D models, including all the known structural heterogeneities in the region, are essential to accurately reproduce waveform propagation. They allow to capture features of the seismograms, mainly related to topography or to low wavespeed areas, and, combined with a finite fault model, result into a favorable match between data and synthetics for frequencies up to ~0.5 Hz. We also obtained peak ground velocity maps, that provide valuable information for seismic hazard assessment. The remaining differences between data and synthetics led us to take advantage of SEM combined with an adjoint method to iteratively improve the available 3D structure model for central Italy. A total of 63 events and 52 stations in the region were considered. We performed five iterations of the tomographic inversion, by calculating the misfit function gradient - necessary for the model update - from adjoint sensitivity kernels, constructed using only two simulations for each event. Our last updated model features a reduced traveltime misfit function and improved agreement between data and synthetics, although further iterations, as well as refined source solutions, are necessary to obtain a new reference 3D model for central Italy tomography.

La Ricostruzione 3D di Bologna nel XVI Secolo

Il lavoro presentato ha come oggetto la ricostruzione tridimensionale della città di Bologna nella sua fase rinascimentale. Tale lavoro vuole fornire un modello 3D delle architetture e degli spazi urbani utilizzabile sia per scopi di ricerca nell’ambito della storia delle città sia per un uso didattico-divulgativo nel settore del turismo culturale. La base del lavoro è una fonte iconografica di grande importanza: l’affresco raffigurante Bologna risalente al 1575 e situato in Vaticano; questa è una veduta a volo d’uccello di grandi dimensioni dell’intero tessuto urbano bolognese all’interno della terza cerchia di mura. In esso sono rappresentate in maniera particolareggiata le architetture civili e ecclesiastiche, gli spazi ortivi e cortilivi interni agli isolati e alcune importanti strutture urbane presenti in città alla fine del Cinquecento, come l’area portuale e i canali interni alla città, oggi non più visibili. La ricostruzione tridimensionale è stata realizzata tramite Blender, software per la modellazione 3D opensource, attraverso le fasi di modellazione, texturing e creazione materiali (mediante campionamento delle principali cromie presenti nell’affresco), illuminazione e animazione. Una parte della modellazione è stata poi testata all’interno di un GIS per verificare l’utilizzo delle geometrie 3D come elementi collegabili ad altre fonti storiche relative allo sviluppo urbano e quindi sfruttabili per la ricerca storica. Grande attenzione infine è stata data all’uso dei modelli virtuali a scopo didattico-divulgativo e per il turismo culturale. La modellazione è stata utilizzata all’interno di un motore grafico 3D per costruire un ambiente virtuale interattivo nel quale un utente anche non esperto possa muoversi per esplorare gli spazi urbani della Bologna del Cinquecento. In ultimo è stato impostato lo sviluppo di un’applicazione per sistemi mobile (Iphone e Ipad) al fine di fornire uno strumento per la conoscenza della città storica in mobilità, attraverso la comparazione dello stato attuale con quello ricostruito virtualmente.

L'area dei Lungarni di Pisa nel tardo Medioevo (XIV-XV secolo). un tentativo di ricostruzione in 3D.

Lo scopo di questa ricerca è la ricostruzione dei Lungarni di Pisa nel Tardo Medioevo (XIV-XV secolo); lo studio intende sottolineare le trasformazioni urbanistiche che hanno cambiato il volto di Pisa nel corso del tempo e ricordare che l’area fluviale ebbe un ruolo di primo piano come baricentro commerciale ed economico della città, vocazione che si è in gran parte persa con l’età moderna e contemporanea. La metodologia seguita, affinata e perfezionata durante la partecipazione al progetto Nu.M.E. (Nuovo Museo Elettronico della Città di Bologna), si basa sull’analisi e il confronto di fonti eterogenee ma complementari, che includono precedenti studi di storia dell’urbanistica, un corpus di documentazione di epoca medievale (provvedimenti amministrativi come gli Statuti del Comune di Pisa, ma anche descrizioni di cronisti e viaggiatori), fonti iconografiche, tra cui vedute e mappe cinquecentesche o successive, e fonti materiali, come le persistenze medievali ancora osservabili all’interno degli edifici ed i reperti rinvenuti durante alcune campagne di scavo archeologiche. Il modello 3D non è concepito come statico e “chiuso”, ma è liberamente esplorabile all’interno di un engine tridimensionale; tale prodotto può essere destinato a livelli di utenza diversi, che includono sia studiosi e specialisti interessati a conoscere un maggior numero di informazioni e ad approfondire la ricerca, sia semplici cittadini appassionati di storia o utenti più giovani, come studenti di scuole medie superiori e inferiori.

Ruolo dell'Enantiomero (R)-9-HSA nel controllo della proliferazione in una linea di Adenocarcinoma del Colon umano

9-hydroxystearic acid (9-HSA) is an endogenous lipoperoxidation product and its administration to HT29, a colon adenocarcinoma cell line, induced a proliferative arrest in G0/G1 phase mediated by a direct activation of the p21WAF1 gene, bypassing p53. We have previously shown that 9-HSA controls cell growth and differentiation by inhibiting histone deacetylase 1 (HDAC1) activity, showing interesting features as a new anticancer drug. The interaction of 9-HSA with the catalytic site of the 3D model has been tested with a docking procedure: noticeably, when interacting with the site, the (R)-9-enantiomer is more stable than the (S) one. Thus, in this study, (R)- and (S)-9-HSA were synthesized and their biological activity tested in HT29 cells. At the concentration of 50 M (R)-9-HSA showed a stronger antiproliferative effect than the (S) isomer, as indicated by the growth arrest in G0/G1. The inhibitory effect of (S)-9-HSA on HDAC1, HDAC2 and HDAC3 activity was less effective than that of the (R)-9-HSA in vitro, and the inhibitory activity of both the (R)- and the (S)-9-HSA isomer, was higher on HDAC1 compared to HDAC2 and HDAC3, thus demonstrating the stereospecific and selective interaction of 9-HSA with HDAC1. In addition, histone hyperacetylation caused by 9-HSA treatment was examined by an innovative HPLC/ESI/MS method. Analysis on histones isolated from control and treated HT29 confirmed the higher potency of (R)-9-HSA compared to (S)-9-HSA, severely affecting H2A-2 and H4 acetylation. On the other side, it seemed of interest to determine whether the G0/G1 arrest of HT29 cell proliferation could be bypassed by the stimulation with the growth factor EGF. Our results showed that 9-HSA-treated cells were not only prevented from proliferating, but also showed a decreased [3H]thymidine incorporation after EGF stimulation. In this condition, HT29 cells expressed very low levels of cyclin D1, that didn’t colocalize with HDAC1. These results suggested that the cyclin D1/HDAC1 complex is required for proliferation. Furthermore, in the effort of understanding the possible mechanisms of this effect, we have analyzed the degree of internalization of the EGF/EGFR complex and its interactions with HDAC1. EGF/EGFR/HDAC1 complex quantitatively increases in 9-HSA-treated cells but not in serum starved cells after EGF stimulation. Our data suggested that 9-HSA interaction with the catalytic site of the HDAC1 disrupts the HDAC1/cyclin D1 complex and favors EGF/EGFR recruitment by HDAC1, thus enhancing 9-HSA antiproliferative effects. In conclusion 9-HSA is a promising HDAC inhibitor with high selectivity and specificity, capable of inducing cell cycle arrest and histone hyperacetylation, but also able to modulate HDAC1 protein interaction. All these aspects may contribute to the potency of this new antitumor agent.

Metodi di ottimizzazione morfologica nel progetto preliminare di propulsori aeronautici avanzati

The aim of this Doctoral Thesis is to develop a genetic algorithm based optimization methods to find the best conceptual design architecture of an aero-piston-engine, for given design specifications. Nowadays, the conceptual design of turbine airplanes starts with the aircraft specifications, then the most suited turbofan or turbo propeller for the specific application is chosen. In the aeronautical piston engines field, which has been dormant for several decades, as interest shifted towards turboaircraft, new materials with increased performance and properties have opened new possibilities for development. Moreover, the engine’s modularity given by the cylinder unit, makes it possible to design a specific engine for a given application. In many real engineering problems the amount of design variables may be very high, characterized by several non-linearities needed to describe the behaviour of the phenomena. In this case the objective function has many local extremes, but the designer is usually interested in the global one. The stochastic and the evolutionary optimization techniques, such as the genetic algorithms method, may offer reliable solutions to the design problems, within acceptable computational time. The optimization algorithm developed here can be employed in the first phase of the preliminary project of an aeronautical piston engine design. It’s a mono-objective genetic algorithm, which, starting from the given design specifications, finds the engine propulsive system configuration which possesses minimum mass while satisfying the geometrical, structural and performance constraints. The algorithm reads the project specifications as input data, namely the maximum values of crankshaft and propeller shaft speed and the maximal pressure value in the combustion chamber. The design variables bounds, that describe the solution domain from the geometrical point of view, are introduced too. In the Matlab® Optimization environment the objective function to be minimized is defined as the sum of the masses of the engine propulsive components. Each individual that is generated by the genetic algorithm is the assembly of the flywheel, the vibration damper and so many pistons, connecting rods, cranks, as the number of the cylinders. The fitness is evaluated for each individual of the population, then the rules of the genetic operators are applied, such as reproduction, mutation, selection, crossover. In the reproduction step the elitist method is applied, in order to save the fittest individuals from a contingent mutation and recombination disruption, making it undamaged survive until the next generation. Finally, as the best individual is found, the optimal dimensions values of the components are saved to an Excel® file, in order to build a CAD-automatic-3D-model for each component of the propulsive system, having a direct pre-visualization of the final product, still in the engine’s preliminary project design phase. With the purpose of showing the performance of the algorithm and validating this optimization method, an actual engine is taken, as a case study: it’s the 1900 JTD Fiat Avio, 4 cylinders, 4T, Diesel. Many verifications are made on the mechanical components of the engine, in order to test their feasibility and to decide their survival through generations. A system of inequalities is used to describe the non-linear relations between the design variables, and is used for components checking for static and dynamic loads configurations. The design variables geometrical boundaries are taken from actual engines data and similar design cases. Among the many simulations run for algorithm testing, twelve of them have been chosen as representative of the distribution of the individuals. Then, as an example, for each simulation, the corresponding 3D models of the crankshaft and the connecting rod, have been automatically built. In spite of morphological differences among the component the mass is almost the same. The results show a significant mass reduction (almost 20% for the crankshaft) in comparison to the original configuration, and an acceptable robustness of the method have been shown. The algorithm here developed is shown to be a valid method for an aeronautical-piston-engine preliminary project design optimization. In particular the procedure is able to analyze quite a wide range of design solutions, rejecting the ones that cannot fulfill the feasibility design specifications. This optimization algorithm could increase the aeronautical-piston-engine development, speeding up the production rate and joining modern computation performances and technological awareness to the long lasting traditional design experiences.

Valorizzazione di cartografia storica attraverso moderne tecniche geomatiche: recupero metrico, elaborazione e consultazione in ambiente digitale

“Cartographic heritage” is different from “cartographic history”. The second term refers to the study of the development of surveying and drawing techniques related to maps, through time, i.e. through different types of cultural environment which were background for the creation of maps. The first term concerns the whole amount of ancient maps, together with these different types of cultural environment, which the history has brought us and which we perceive as cultural values to be preserved and made available to many users (public, institutions, experts). Unfortunately, ancient maps often suffer preservation problems of their analog support, mostly due to aging. Today, metric recovery in digital form and digital processing of historical cartography allow preserving map heritage. Moreover, modern geomatic techniques give us new chances of using historical information, which would be unachievable on analog supports. In this PhD thesis, the whole digital processing of recovery and elaboration of ancient cartography is reported, with a special emphasis on the use of digital tools in preservation and elaboration of cartographic heritage. It is possible to divide the workflow into three main steps, that reflect the chapter structure of the thesis itself: • map acquisition: conversion of the ancient map support from analog to digital, by means of high resolution scanning or 3D surveying (digital photogrammetry or laser scanning techniques); this process must be performed carefully, with special instruments, in order to reduce deformation as much as possible; • map georeferencing: reproducing in the digital image the native metric content of the map, or even improving it by selecting a large number of still existing ground control points; this way it is possible to understand the projection features of the historical map, as well as to evaluate and represent the degree of deformation induced by the old type of cartographic transformation (that can be unknown to us), by surveying errors or by support deformation, usually all errors of too high value with respect to our standards; • data elaboration and management in a digital environment, by means of modern software tools: vectorization, giving the map a new and more attractive graphic view (for instance, by creating a 3D model), superimposing it on current base maps, comparing it to other maps, and finally inserting it in GIS or WebGIS environment as a specific layer. The study is supported by some case histories, each of them interesting from the point of view of one digital cartographic elaboration step at least. The ancient maps taken into account are the following ones: • three maps of the Po river delta, made at the end of the XVI century by a famous land-surveyor, Ottavio Fabri (he is single author in the first map, co-author with Gerolamo Pontara in the second map, co-author with Bonajuto Lorini and others in the third map), who wrote a methodological textbook where he explains a new topographical instrument, the squadra mobile (mobile square) invented and used by himself; today all maps are preserved in the State Archive of Venice; • the Ichnoscenografia of Bologna by Filippo de’ Gnudi, made in the 1702 and today preserved in the Archiginnasio Library of Bologna; it is a scenographic view of the city, captured in a bird’s eye flight, but also with an icnographic value, as the author himself declares; • the map of Bologna by the periti Gregorio Monari and Antonio Laghi, the first map of the city derived from a systematic survey, even though it was made only ten years later (1711–1712) than the map by de’ Gnudi; in this map the scenographic view was abandoned, in favor of a more correct representation by means of orthogonal projection; today the map is preserved in the State Archive of Bologna; • the Gregorian Cadastre of Bologna, made in 1831 and updated until 1927, now preserved in the State Archive of Bologna; it is composed by 140 maps and 12 brogliardi (register volumes). In particular, the three maps of the Po river delta and the Cadastre were studied with respect to their acquisition procedure. Moreover, the first maps were analyzed from the georeferencing point of view, and the Cadastre was analyzed with respect to a possible GIS insertion. Finally, the Ichnoscenografia was used to illustrate a possible application of digital elaboration, such as 3D modeling. Last but not least, we must not forget that the study of an ancient map should start, whenever possible, from the consultation of the precious original analogical document; analysis by means of current digital techniques allow us new research opportunities in a rich and modern multidisciplinary context.

Toward a 3D in vitro model based on decellularized thymus to maintain adult thymic ephitelial cells functionality

During my PhD,I have been develop an innovative technique to reproduce in vitro the 3D thymic microenvironment, to be used for growth and differentiation of thymocytes, and possible transplantation replacement in conditions of depressed thymic immune regulation. The work has been developed in the laboratory of Tissue Engineering at the University Hospital in Basel, Switzerland, under the tutorship of Prof.Ivan Martin. Since a number of studies have suggested that the 3D structure of the thymic microenvironment might play a key role in regulating the survival and functional competence of thymocytes, I’ve focused my effort on the isolation and purification of the extracellular matrix of the mouse thymus. Specifically, based on the assumption that TEC can favour the differentiation of pre-T lymphocytes, I’ve developed a specific decellularization protocol to obtain the intact, DNA-free extracellular matrix of the adult mouse thymus. Two different protocols satisfied the main characteristics of a decellularized matrix, according to qualitative and quantitative assays. In particular, the quantity of DNA was less than 10% in absolute value, no positive staining for cells was found and the 3D structure and composition of the ECM were maintained. In addition, I was able to prove that the decellularized matrixes were not cytotoxic for the cells themselves, and were able to increase expression of MHC II antigens compared to control cells grown in standard conditions. I was able to prove that TECs grow and proliferate up to ten days on top the decellularized matrix. After a complete characterization of the culture system, these innovative natural scaffolds could be used to improve the standard culture conditions of TEC, to study in vitro the action of different factors on their differentiation genes, and to test the ability of TECs to induce in vitro maturation of seeded T lymphocytes.

A new 3D modelling paradigm for discrete model

Until few years ago, 3D modelling was a topic confined into a professional environment. Nowadays technological innovations, the 3D printer among all, have attracted novice users to this application field. This sudden breakthrough was not supported by adequate software solutions. The 3D editing tools currently available do not assist the non-expert user during the various stages of generation, interaction and manipulation of 3D virtual models. This is mainly due to the current paradigm that is largely supported by two-dimensional input/output devices and strongly affected by obvious geometrical constraints. We have identified three main phases that characterize the creation and management of 3D virtual models. We investigated these directions evaluating and simplifying the classic editing techniques in order to propose more natural and intuitive tools in a pure 3D modelling environment. In particular, we focused on freehand sketch-based modelling to create 3D virtual models, interaction and navigation in a 3D modelling environment and advanced editing tools for free-form deformation and objects composition. To pursuing these goals we wondered how new gesture-based interaction technologies can be successfully employed in a 3D modelling environments, how we could improve the depth perception and the interaction in 3D environments and which operations could be developed to simplify the classical virtual models editing paradigm. Our main aims were to propose a set of solutions with which a common user can realize an idea in a 3D virtual model, drawing in the air just as he would on paper. Moreover, we tried to use gestures and mid-air movements to explore and interact in 3D virtual environment, and we studied simple and effective 3D form transformations. The work was carried out adopting the discrete representation of the models, thanks to its intuitiveness, but especially because it is full of open challenges.

3D probability tomography: theoretical developments and applications to high-resolution geophysical prospecting

The theory of the 3D multipole probability tomography method (3D GPT) to image source poles, dipoles, quadrupoles and octopoles, of a geophysical vector or scalar field dataset is developed. A geophysical dataset is assumed to be the response of an aggregation of poles, dipoles, quadrupoles and octopoles. These physical sources are used to reconstruct without a priori assumptions the most probable position and shape of the true geophysical buried sources, by determining the location of their centres and critical points of their boundaries, as corners, wedges and vertices. This theory, then, is adapted to the geoelectrical, gravity and self potential methods. A few synthetic examples using simple geometries and three field examples are discussed in order to demonstrate the notably enhanced resolution power of the new approach. At first, the application to a field example related to a dipole–dipole geoelectrical survey carried out in the archaeological park of Pompei is presented. The survey was finalised to recognize remains of the ancient Roman urban network including roads, squares and buildings, which were buried under the thick pyroclastic cover fallen during the 79 AD Vesuvius eruption. The revealed anomaly structures are ascribed to wellpreserved remnants of some aligned walls of Roman edifices, buried and partially destroyed by the 79 AD Vesuvius pyroclastic fall. Then, a field example related to a gravity survey carried out in the volcanic area of Mount Etna (Sicily, Italy) is presented, aimed at imaging as accurately as possible the differential mass density structure within the first few km of depth inside the volcanic apparatus. An assemblage of vertical prismatic blocks appears to be the most probable gravity model of the Etna apparatus within the first 5 km of depth below sea level. Finally, an experimental SP dataset collected in the Mt. Somma-Vesuvius volcanic district (Naples, Italy) is elaborated in order to define location and shape of the sources of two SP anomalies of opposite sign detected in the northwestern sector of the surveyed area. The modelled sources are interpreted as the polarization state induced by an intense hydrothermal convective flow mechanism within the volcanic apparatus, from the free surface down to about 3 km of depth b.s.l..

Dynamic identification of structures: experimental assessment of modal parameteres through methods in frequency domain, in time-frequency domain and model updating

Among the experimental methods commonly used to define the behaviour of a full scale system, dynamic tests are the most complete and efficient procedures. A dynamic test is an experimental process, which would define a set of characteristic parameters of the dynamic behaviour of the system, such as natural frequencies of the structure, mode shapes and the corresponding modal damping values associated. An assessment of these modal characteristics can be used both to verify the theoretical assumptions of the project, to monitor the performance of the structural system during its operational use. The thesis is structured in the following chapters: The first introductive chapter recalls some basic notions of dynamics of structure, focusing the discussion on the problem of systems with multiply degrees of freedom (MDOF), which can represent a generic real system under study, when it is excited with harmonic force or in free vibration. The second chapter is entirely centred on to the problem of dynamic identification process of a structure, if it is subjected to an experimental test in forced vibrations. It first describes the construction of FRF through classical FFT of the recorded signal. A different method, also in the frequency domain, is subsequently introduced; it allows accurately to compute the FRF using the geometric characteristics of the ellipse that represents the direct input-output comparison. The two methods are compared and then the attention is focused on some advantages of the proposed methodology. The third chapter focuses on the study of real structures when they are subjected to experimental test, where the force is not known, like in an ambient or impact test. In this analysis we decided to use the CWT, which allows a simultaneous investigation in the time and frequency domain of a generic signal x(t). The CWT is first introduced to process free oscillations, with excellent results both in terms of frequencies, dampings and vibration modes. The application in the case of ambient vibrations defines accurate modal parameters of the system, although on the damping some important observations should be made. The fourth chapter is still on the problem of post processing data acquired after a vibration test, but this time through the application of discrete wavelet transform (DWT). In the first part the results obtained by the DWT are compared with those obtained by the application of CWT. Particular attention is given to the use of DWT as a tool for filtering the recorded signal, in fact in case of ambient vibrations the signals are often affected by the presence of a significant level of noise. The fifth chapter focuses on another important aspect of the identification process: the model updating. In this chapter, starting from the modal parameters obtained from some environmental vibration tests, performed by the University of Porto in 2008 and the University of Sheffild on the Humber Bridge in England, a FE model of the bridge is defined, in order to define what type of model is able to capture more accurately the real dynamic behaviour of the bridge. The sixth chapter outlines the necessary conclusions of the presented research. They concern the application of a method in the frequency domain in order to evaluate the modal parameters of a structure and its advantages, the advantages in applying a procedure based on the use of wavelet transforms in the process of identification in tests with unknown input and finally the problem of 3D modeling of systems with many degrees of freedom and with different types of uncertainty.

Methodological improvement of 3D fluoroscopic analysis for the robust quantification of 3D kinematics of human joints

3D video-fluoroscopy is an accurate but cumbersome technique to estimate natural or prosthetic human joint kinematics. This dissertation proposes innovative methodologies to improve the 3D fluoroscopic analysis reliability and usability. Being based on direct radiographic imaging of the joint, and avoiding soft tissue artefact that limits the accuracy of skin marker based techniques, the fluoroscopic analysis has a potential accuracy of the order of mm/deg or better. It can provide fundamental informations for clinical and methodological applications, but, notwithstanding the number of methodological protocols proposed in the literature, time consuming user interaction is exploited to obtain consistent results. The user-dependency prevented a reliable quantification of the actual accuracy and precision of the methods, and, consequently, slowed down the translation to the clinical practice. The objective of the present work was to speed up this process introducing methodological improvements in the analysis. In the thesis, the fluoroscopic analysis was characterized in depth, in order to evaluate its pros and cons, and to provide reliable solutions to overcome its limitations. To this aim, an analytical approach was followed. The major sources of error were isolated with in-silico preliminary studies as: (a) geometric distortion and calibration errors, (b) 2D images and 3D models resolutions, (c) incorrect contour extraction, (d) bone model symmetries, (e) optimization algorithm limitations, (f) user errors. The effect of each criticality was quantified, and verified with an in-vivo preliminary study on the elbow joint. The dominant source of error was identified in the limited extent of the convergence domain for the local optimization algorithms, which forced the user to manually specify the starting pose for the estimating process. To solve this problem, two different approaches were followed: to increase the optimal pose convergence basin, the local approach used sequential alignments of the 6 degrees of freedom in order of sensitivity, or a geometrical feature-based estimation of the initial conditions for the optimization; the global approach used an unsupervised memetic algorithm to optimally explore the search domain. The performances of the technique were evaluated with a series of in-silico studies and validated in-vitro with a phantom based comparison with a radiostereometric gold-standard. The accuracy of the method is joint-dependent, and for the intact knee joint, the new unsupervised algorithm guaranteed a maximum error lower than 0.5 mm for in-plane translations, 10 mm for out-of-plane translation, and of 3 deg for rotations in a mono-planar setup; and lower than 0.5 mm for translations and 1 deg for rotations in a bi-planar setups. The bi-planar setup is best suited when accurate results are needed, such as for methodological research studies. The mono-planar analysis may be enough for clinical application when the analysis time and cost may be an issue. A further reduction of the user interaction was obtained for prosthetic joints kinematics. A mixed region-growing and level-set segmentation method was proposed and halved the analysis time, delegating the computational burden to the machine. In-silico and in-vivo studies demonstrated that the reliability of the new semiautomatic method was comparable to a user defined manual gold-standard. The improved fluoroscopic analysis was finally applied to a first in-vivo methodological study on the foot kinematics. Preliminary evaluations showed that the presented methodology represents a feasible gold-standard for the validation of skin marker based foot kinematics protocols.

3D nanostructured microcarriers for cell therapy in regenerative medicine

Supercritical Emulsion Extraction technology (SEE-C) was proposed for the production of poly-lactic-co-glycolic acid microcarriers. SEE-C operating parameters as pressure, temperature and flow rate ratios were analyzed and the process performance was optimized in terms of size distribution and encapsulation efficiency. Microdevices loaded with bovine serum insulin were produced with different sizes (2 and 3 µm) or insulin charges (3 and 6 mg/g) and with an encapsulation efficiency of 60%. The microcarriers were characterized in terms of insulin release profile in two different media (PBS and DMEM) and the diffusion and degradation constants were also estimated by using a mathematical model. PLGA microdevices were also used in a cultivation of embryonic ventricular myoblasts (cell line H9c2 obtained from rat) in a FBS serum free medium to monitor cell viability and growth in dependence of insulin released. Good cell viability and growth were observed on 3 µm microdevices loaded with 3 mg/g of insulin. PLGA microspheres loaded with growth factors (GFs) were charged into alginate scaffold with human Mesenchimal Steam Cells (hMSC) for bone tissue engineering with the aim of monitoring the effect of the local release of these signals on cells differentiation. These “living” 3D scaffolds were incubated in a direct perfusion tubular bioreactor to enhance nutrient transport and exposing the cells to a given shear stress. Different GFs such as, h-VEGF, h-BMP2 and a mix of two (ratio 1:1) were loaded and alginate beads were recovered from dynamic (tubular perfusion system bioreactor) and static culture at different time points (1st, 7th, 21st days) for the analytical assays such as, live/dead; alkaline phosphatase; osteocalcin; osteopontin and Van Kossa Immunoassay. The immunoassay confirmed always a better cells differentiation in the bioreactor with respect to the static culture and revealed a great influence of the BMP-2 released in the scaffold on cell differentiation.

Towards the 3D attenuation imaging of active volcanoes: methods and tests on real and simulated data

The purpose of my PhD thesis has been to face the issue of retrieving a three dimensional attenuation model in volcanic areas. To this purpose, I first elaborated a robust strategy for the analysis of seismic data. This was done by performing several synthetic tests to assess the applicability of spectral ratio method to our purposes. The results of the tests allowed us to conclude that: 1) spectral ratio method gives reliable differential attenuation (dt*) measurements in smooth velocity models; 2) short signal time window has to be chosen to perform spectral analysis; 3) the frequency range over which to compute spectral ratios greatly affects dt* measurements. Furthermore, a refined approach for the application of spectral ratio method has been developed and tested. Through this procedure, the effects caused by heterogeneities of propagation medium on the seismic signals may be removed. The tested data analysis technique was applied to the real active seismic SERAPIS database. It provided a dataset of dt* measurements which was used to obtain a three dimensional attenuation model of the shallowest part of Campi Flegrei caldera. Then, a linearized, iterative, damped attenuation tomography technique has been tested and applied to the selected dataset. The tomography, with a resolution of 0.5 km in the horizontal directions and 0.25 km in the vertical direction, allowed to image important features in the off-shore part of Campi Flegrei caldera. High QP bodies are immersed in a high attenuation body (Qp=30). The latter is well correlated with low Vp and high Vp/Vs values and it is interpreted as a saturated marine and volcanic sediments layer. High Qp anomalies, instead, are interpreted as the effects either of cooled lava bodies or of a CO2 reservoir. A pseudo-circular high Qp anomaly was detected and interpreted as the buried rim of NYT caldera.

Soil-structure interaction during tunnelling in urban area: observations and 3D numerical modelling

This work illustrates a soil-tunnel-structure interaction study performed by an integrated,geotechnical and structural,approach based on 3D finite element analyses and validated against experimental observations.The study aims at analysing the response of reinforced concrete framed buildings on discrete foundations in interaction with metro lines.It refers to the case of the twin tunnels of the Milan (Italy) metro line 5,recently built in coarse grained materials using EPB machines,for which subsidence measurements collected along ground and building sections during tunnelling were available.Settlements measured under freefield conditions are firstly back interpreted using Gaussian empirical predictions. Then,the in situ measurements’ analysis is extended to include the evolving response of a 9 storey reinforced concrete building while being undercrossed by the metro line.In the finite element study,the soil mechanical behaviour is described using an advanced constitutive model. This latter,when combined with a proper simulation of the excavation process, proves to realistically reproduce the subsidence profiles under free field conditions and to capture the interaction phenomena occurring between the twin tunnels during the excavation. Furthermore, when the numerical model is extended to include the building, schematised in a detailed manner, the results are in good agreement with the monitoring data for different stages of the twin tunnelling. Thus, they indirectly confirm the satisfactory performance of the adopted numerical approach which also allows a direct evaluation of the structural response as an outcome of the analysis. Further analyses are also carried out modelling the building with different levels of detail. The results highlight that, in this case, the simplified approach based on the equivalent plate schematisation is inadequate to capture the real tunnelling induced displacement field. The overall behaviour of the system proves to be mainly influenced by the buried portion of the building which plays an essential role in the interaction mechanism, due to its high stiffness.