InSAR deformation measurements of the earthquake cycle in transcurrent tectonic domains, analytical and analog modeling

I applied the SBAS-DInSAR method to the Mattinata Fault (MF) (Southern Italy) and to the Doruneh Fault System (DFS) (Central Iran). In the first case, I observed limited internal deformation and determined the right lateral kinematic pattern with a compressional pattern in the northern sector of the fault. Using the Okada model I inverted the observed velocities defining a right lateral strike slip solution for the MF. Even if it fits the data within the uncertainties, the modeled slip rate of 13-15 mm yr-1 seems too high with respect to the geological record. Concerning the Western termination of DFS, SAR data confirms the main left lateral transcurrent kinematics of this fault segment, but reveal a compressional component. My analytical model fits successfully the observed data and quantifies the slip in ~4 mm yr-1 and ~2.5 mm yr-1 of pure horizontal and vertical displacement respectively. The horizontal velocity is compatible with geological record. I applied classic SAR interferometry to the October–December 2008 Balochistan (Central Pakistan) seismic swarm; I discerned the different contributions of the three Mw > 5.7 earthquakes determining fault positions, lengths, widths, depths and slip distributions, constraining the other source parameters using different Global CMT solutions. A well constrained solution has been obtained for the 09/12/2008 aftershock, whereas I tested two possible fault solutions for the 28-29/10/08 mainshocks. It is not possible to favor one of the solutions without independent constraints derived from geological data. Finally I approached the study of the earthquake-cycle in transcurrent tectonic domains using analog modeling, with alimentary gelatins like crust analog material. I successfully joined the study of finite deformation with the earthquake cycle study and sudden dislocation. A lot of seismic cycles were reproduced in which a characteristic earthquake is recognizable in terms of displacement, coseismic velocity and recurrence time.

Wireless Networks for Body-Centric Communications

Progress in miniaturization of electronic components and design of wireless systems paved the way towards ubiquitous and pervasive communications, enabling anywhere and anytime connectivity. Wireless devices present on, inside, around the human body are becoming commonly used, leading to the class of body-centric communications. The presence of the body with all its peculiar characteristics has to be properly taken into account in the development and design of wireless networks in this context. This thesis addresses various aspects of body-centric communications, with the aim of investigating network performance achievable in different scenarios. The main original contributions pertain to the performance evaluation for Wireless Body Area Networks (WBANs) at the Medium Access Control layer: the application of Link Adaptation to these networks is proposed, Carrier Sense Multiple Access with Collision Avoidance algorithms used for WBAN are extensively investigated, coexistence with other wireless systems is examined. Then, an analytical model for interference in wireless access network is developed, which can be applied to the study of communication between devices located on humans and fixed nodes of an external infrastructure. Finally, results on experimental activities regarding the investigation of human mobility and sociality are presented.

Non-Linear Analysis and Design of Synchronous Bearingless Multiphase Permanent Magnet Machines and Drives

A two-dimensional model to analyze the distribution of magnetic fields in the airgap of a PM electrical machines is studied. A numerical algorithm for non-linear magnetic analysis of multiphase surface-mounted PM machines with semi-closed slots is developed, based on the equivalent magnetic circuit method. By using a modular structure geometry, whose the basic element can be duplicated, it allows to design whatever typology of windings distribution. In comparison to a FEA, permits a reduction in computing time and to directly changing the values of the parameters in a user interface, without re-designing the model. Output torque and radial forces acting on the moving part of the machine can be calculated. In addition, an analytical model for radial forces calculation in multiphase bearingless Surface-Mounted Permanent Magnet Synchronous Motors (SPMSM) is presented. It allows to predict amplitude and direction of the force, depending on the values of torque current, of levitation current and of rotor position. It is based on the space vectors method, letting the analysis of the machine also during transients. The calculations are conducted by developing the analytical functions in Fourier series, taking all the possible interactions between stator and rotor mmf harmonic components into account and allowing to analyze the effects of electrical and geometrical quantities of the machine, being parametrized. The model is implemented in the design of a control system for bearingless machines, as an accurate electromagnetic model integrated in a three-dimensional mechanical model, where one end of the motor shaft is constrained to simulate the presence of a mechanical bearing, while the other is free, only supported by the radial forces developed in the interactions between magnetic fields, to realize a bearingless system with three degrees of freedom. The complete model represents the design of the experimental system to be realized in the laboratory.

Effect of Laser Shock Peening on Fatigue Crack Propagation of Aeronautical Structures

Laser Shock Peening (LSP) is a surface enhancement treatment which induces a significant layer of beneficial compressive residual stresses up to several mm underneath the surface of metal components in order to improve the detrimental effects of crack growth behavior rate in it. The aim of this thesis is to predict the crack growth behavior of thin Aluminum specimens with one or more LSP stripes defining a compressive residual stress area. The LSP treatment has been applied as crack retardation stripes perpendicular to the crack growing direction, with the objective of slowing down the crack when approaching the LSP patterns. Different finite element approaches have been implemented to predict the residual stress field left by the laser treatment, mostly by means of the commercial software Abaqus/Explicit. The Afgrow software has been used to predict the crack growth behavior of the component following the laser peening treatment and to detect the improvement in fatigue life comparing to the specimen baseline. Furthermore, an analytical model has been implemented on the Matlab software to make more accurate predictions on fatigue life of the treated components. An educational internship at the Research and Technologies Germany- Hamburg department of Airbus helped to achieve knowledge and experience to write this thesis. The main tasks of the thesis are the following: -To up to date Literature Survey related to laser shock peening in metallic structures -To validate the FE models developed against experimental measurements at coupon level -To develop design of crack growth slow down in centered and edge cracked tension specimens based on residual stress engineering approach using laser peened patterns transversal to the crack path -To predict crack growth behavior of thin aluminum panels -To validate numerical and analytical results by means of experimental tests.

Statistical properties of Radio Halos and the re-acceleration model

Galaxy clusters occupy a special position in the cosmic hierarchy as they are the largest bound structures in the Universe. There is now general agreement on a hierarchical picture for the formation of cosmic structures, in which galaxy clusters are supposed to form by accretion of matter and merging between smaller units. During merger events, shocks are driven by the gravity of the dark matter in the diffuse barionic component, which is heated up to the observed temperature. Radio and hard-X ray observations have discovered non-thermal components mixed with the thermal Intra Cluster Medium (ICM) and this is of great importance as it calls for a “revision” of the physics of the ICM. The bulk of present information comes from the radio observations which discovered an increasing number of Mpcsized emissions from the ICM, Radio Halos (at the cluster center) and Radio Relics (at the cluster periphery). These sources are due to synchrotron emission from ultra relativistic electrons diffusing through µG turbulent magnetic fields. Radio Halos are the most spectacular evidence of non-thermal components in the ICM and understanding the origin and evolution of these sources represents one of the most challenging goal of the theory of the ICM. Cluster mergers are the most energetic events in the Universe and a fraction of the energy dissipated during these mergers could be channelled into the amplification of the magnetic fields and into the acceleration of high energy particles via shocks and turbulence driven by these mergers. Present observations of Radio Halos (and possibly of hard X-rays) can be best interpreted in terms of the reacceleration scenario in which MHD turbulence injected during these cluster mergers re-accelerates high energy particles in the ICM. The physics involved in this scenario is very complex and model details are difficult to test, however this model clearly predicts some simple properties of Radio Halos (and resulting IC emission in the hard X-ray band) which are almost independent of the details of the adopted physics. In particular in the re-acceleration scenario MHD turbulence is injected and dissipated during cluster mergers and thus Radio Halos (and also the resulting hard X-ray IC emission) should be transient phenomena (with a typical lifetime <» 1 Gyr) associated with dynamically disturbed clusters. The physics of the re-acceleration scenario should produce an unavoidable cut-off in the spectrum of the re-accelerated electrons, which is due to the balance between turbulent acceleration and radiative losses. The energy at which this cut-off occurs, and thus the maximum frequency at which synchrotron radiation is produced, depends essentially on the efficiency of the acceleration mechanism so that observations at high frequencies are expected to catch only the most efficient phenomena while, in principle, low frequency radio surveys may found these phenomena much common in the Universe. These basic properties should leave an important imprint in the statistical properties of Radio Halos (and of non-thermal phenomena in general) which, however, have not been addressed yet by present modellings. The main focus of this PhD thesis is to calculate, for the first time, the expected statistics of Radio Halos in the context of the re-acceleration scenario. In particular, we shall address the following main questions: • Is it possible to model “self-consistently” the evolution of these sources together with that of the parent clusters? • How the occurrence of Radio Halos is expected to change with cluster mass and to evolve with redshift? How the efficiency to catch Radio Halos in galaxy clusters changes with the observing radio frequency? • How many Radio Halos are expected to form in the Universe? At which redshift is expected the bulk of these sources? • Is it possible to reproduce in the re-acceleration scenario the observed occurrence and number of Radio Halos in the Universe and the observed correlations between thermal and non-thermal properties of galaxy clusters? • Is it possible to constrain the magnetic field intensity and profile in galaxy clusters and the energetic of turbulence in the ICM from the comparison between model expectations and observations? Several astrophysical ingredients are necessary to model the evolution and statistical properties of Radio Halos in the context of re-acceleration model and to address the points given above. For these reason we deserve some space in this PhD thesis to review the important aspects of the physics of the ICM which are of interest to catch our goals. In Chapt. 1 we discuss the physics of galaxy clusters, and in particular, the clusters formation process; in Chapt. 2 we review the main observational properties of non-thermal components in the ICM; and in Chapt. 3 we focus on the physics of magnetic field and of particle acceleration in galaxy clusters. As a relevant application, the theory of Alfv´enic particle acceleration is applied in Chapt. 4 where we report the most important results from calculations we have done in the framework of the re-acceleration scenario. In this Chapter we show that a fraction of the energy of fluid turbulence driven in the ICM by the cluster mergers can be channelled into the injection of Alfv´en waves at small scales and that these waves can efficiently re-accelerate particles and trigger Radio Halos and hard X-ray emission. The main part of this PhD work, the calculation of the statistical properties of Radio Halos and non-thermal phenomena as expected in the context of the re-acceleration model and their comparison with observations, is presented in Chapts.5, 6, 7 and 8. In Chapt.5 we present a first approach to semi-analytical calculations of statistical properties of giant Radio Halos. The main goal of this Chapter is to model cluster formation, the injection of turbulence in the ICM and the resulting particle acceleration process. We adopt the semi–analytic extended Press & Schechter (PS) theory to follow the formation of a large synthetic population of galaxy clusters and assume that during a merger a fraction of the PdV work done by the infalling subclusters in passing through the most massive one is injected in the form of magnetosonic waves. Then the processes of stochastic acceleration of the relativistic electrons by these waves and the properties of the ensuing synchrotron (Radio Halos) and inverse Compton (IC, hard X-ray) emission of merging clusters are computed under the assumption of a constant rms average magnetic field strength in emitting volume. The main finding of these calculations is that giant Radio Halos are naturally expected only in the more massive clusters, and that the expected fraction of clusters with Radio Halos is consistent with the observed one. In Chapt. 6 we extend the previous calculations by including a scaling of the magnetic field strength with cluster mass. The inclusion of this scaling allows us to derive the expected correlations between the synchrotron radio power of Radio Halos and the X-ray properties (T, LX) and mass of the hosting clusters. For the first time, we show that these correlations, calculated in the context of the re-acceleration model, are consistent with the observed ones for typical µG strengths of the average B intensity in massive clusters. The calculations presented in this Chapter allow us to derive the evolution of the probability to form Radio Halos as a function of the cluster mass and redshift. The most relevant finding presented in this Chapter is that the luminosity functions of giant Radio Halos at 1.4 GHz are expected to peak around a radio power » 1024 W/Hz and to flatten (or cut-off) at lower radio powers because of the decrease of the electron re-acceleration efficiency in smaller galaxy clusters. In Chapt. 6 we also derive the expected number counts of Radio Halos and compare them with available observations: we claim that » 100 Radio Halos in the Universe can be observed at 1.4 GHz with deep surveys, while more than 1000 Radio Halos are expected to be discovered in the next future by LOFAR at 150 MHz. This is the first (and so far unique) model expectation for the number counts of Radio Halos at lower frequency and allows to design future radio surveys. Based on the results of Chapt. 6, in Chapt.7 we present a work in progress on a “revision” of the occurrence of Radio Halos. We combine past results from the NVSS radio survey (z » 0.05 − 0.2) with our ongoing GMRT Radio Halos Pointed Observations of 50 X-ray luminous galaxy clusters (at z » 0.2−0.4) and discuss the possibility to test our model expectations with the number counts of Radio Halos at z » 0.05 − 0.4. The most relevant limitation in the calculations presented in Chapt. 5 and 6 is the assumption of an “averaged” size of Radio Halos independently of their radio luminosity and of the mass of the parent clusters. This assumption cannot be released in the context of the PS formalism used to describe the formation process of clusters, while a more detailed analysis of the physics of cluster mergers and of the injection process of turbulence in the ICM would require an approach based on numerical (possible MHD) simulations of a very large volume of the Universe which is however well beyond the aim of this PhD thesis. On the other hand, in Chapt.8 we report our discovery of novel correlations between the size (RH) of Radio Halos and their radio power and between RH and the cluster mass within the Radio Halo region, MH. In particular this last “geometrical” MH − RH correlation allows us to “observationally” overcome the limitation of the “average” size of Radio Halos. Thus in this Chapter, by making use of this “geometrical” correlation and of a simplified form of the re-acceleration model based on the results of Chapt. 5 and 6 we are able to discuss expected correlations between the synchrotron power and the thermal cluster quantities relative to the radio emitting region. This is a new powerful tool of investigation and we show that all the observed correlations (PR − RH, PR − MH, PR − T, PR − LX, . . . ) now become well understood in the context of the re-acceleration model. In addition, we find that observationally the size of Radio Halos scales non-linearly with the virial radius of the parent cluster, and this immediately means that the fraction of the cluster volume which is radio emitting increases with cluster mass and thus that the non-thermal component in clusters is not self-similar.

Two fluid numerical model for coastal applications

Wave breaking is an important coastal process, influencing hydro-morphodynamic processes such as turbulence generation and wave energy dissipation, run-up on the beach and overtopping of coastal defence structures. During breaking, waves are complex mixtures of air and water (“white water”) whose properties affect velocity and pressure fields in the vicinity of the free surface and, depending on the breaker characteristics, different mechanisms for air entrainment are usually observed. Several laboratory experiments have been performed to investigate the role of air bubbles in the wave breaking process (Chanson & Cummings, 1994, among others) and in wave loading on vertical wall (Oumeraci et al., 2001; Peregrine et al., 2006, among others), showing that the air phase is not negligible since the turbulent energy dissipation involves air-water mixture. The recent advancement of numerical models has given valuable insights in the knowledge of wave transformation and interaction with coastal structures. Among these models, some solve the RANS equations coupled with a free-surface tracking algorithm and describe velocity, pressure, turbulence and vorticity fields (Lara et al. 2006 a-b, Clementi et al., 2007). The single-phase numerical model, in which the constitutive equations are solved only for the liquid phase, neglects effects induced by air movement and trapped air bubbles in water. Numerical approximations at the free surface may induce errors in predicting breaking point and wave height and moreover, entrapped air bubbles and water splash in air are not properly represented. The aim of the present thesis is to develop a new two-phase model called COBRAS2 (stands for Cornell Breaking waves And Structures 2 phases), that is the enhancement of the single-phase code COBRAS0, originally developed at Cornell University (Lin & Liu, 1998). In the first part of the work, both fluids are considered as incompressible, while the second part will treat air compressibility modelling. The mathematical formulation and the numerical resolution of the governing equations of COBRAS2 are derived and some model-experiment comparisons are shown. In particular, validation tests are performed in order to prove model stability and accuracy. The simulation of the rising of a large air bubble in an otherwise quiescent water pool reveals the model capability to reproduce the process physics in a realistic way. Analytical solutions for stationary and internal waves are compared with corresponding numerical results, in order to test processes involving wide range of density difference. Waves induced by dam-break in different scenarios (on dry and wet beds, as well as on a ramp) are studied, focusing on the role of air as the medium in which the water wave propagates and on the numerical representation of bubble dynamics. Simulations of solitary and regular waves, characterized by both spilling and plunging breakers, are analyzed with comparisons with experimental data and other numerical model in order to investigate air influence on wave breaking mechanisms and underline model capability and accuracy. Finally, modelling of air compressibility is included in the new developed model and is validated, revealing an accurate reproduction of processes. Some preliminary tests on wave impact on vertical walls are performed: since air flow modelling allows to have a more realistic reproduction of breaking wave propagation, the dependence of wave breaker shapes and aeration characteristics on impact pressure values is studied and, on the basis of a qualitative comparison with experimental observations, the numerical simulations achieve good results.

An advanced analytical study on linseed oil paint binder

Drying oils, and in particular linseed oil, were the most common binding media employed in painting between XVI and XIX centuries. Artists usually operated some pre-treatments on the oils to obtain binders with modified properties, such as different handling qualities or colour. Oil processing has a key role on the subsequent ageing of and degradation of linseed oil paints. In this thesis a multi-analytical approach was adopted to investigate the drying, polymerization and oxidative degradation of the linseed oil paints. In particular, thermogravimetry analysis (TGA), yielding information on the macromolecular scale, were compared with gas-chromatography mass-spectrometry (GC-MS) and direct exposure mass spectrometry (DEMS) providing information on the molecular scale. The study was performed on linseed oils and paint reconstructions prepared according to an accurate historical description of the painting techniques of the 19th century. TGA revealed that during ageing the molecular weight of the oils changes and that higher molecular weight fractions formed. TGA proved to be an excellent tool to compare the oils and paint reconstructions. This technique is able to highlight the different physical behaviour of oils that were processed using different methods and of paint layers on the basis of the different processed oil and /or the pigment used. GC/MS and DE-MS were used to characterise the soluble and non-polymeric fraction of the oils and paint reconstructions. GC/MS allowed us to calculate the ratios of palmitic to stearic acid (P/S), and azelaic to palmitic acid (A/P) and to evaluate effects produced by oil pre-treatments and the presence of different pigments. This helps to understand the role of the pre-treatments and of the pigments on the oxidative degradation undergone by siccative oils during ageing. DE-MS enabled the various molecular weight fractions of the samples to be simultaneously studied, and thus helped to highlight the presence of oxidation and hydrolysis reactions, and the formation of carboxylates that occur during ageing and with the changing of the oil pre-treatments and the pigments. The combination of thermal analysis with molecular techniques such as GC-MS, DEMS and FTIR enabled a model to be developed, for unravelling some crucial issues: 1) how oil pre-treatments produce binders with different physical-chemical qualities, and how this can influence the ageing of an oil paint film; 2) which is the role of the interaction between oil and pigments in the ageing and degradation process.

The bursting behavior of gas slugs: laboratory and analytical insights into Strombolian volcanic eruptions.

The aim of this thesis is to study how explosive behavior and geophysical signals in a volcanic conduit are related to the development of overpressure in slug-driven eruptions. A first suite of laboratory experiments of gas slugs ascending in analogue conduits was performed. Slugs ascended into a range of analogue liquids and conduit diameters to allow proper scaling to the natural volcanoes. The geometrical variation of the slug in response to the explored variables was parameterised. Volume of gas slug and rheology of the liquid phase revealed the key parameters in controlling slug overpressure at bursting. Founded on these results, a theoretical model to calculate burst overpressure for slug-driven eruptions was developed. The dimensionless approach adopted allowed to apply the model to predict bursting pressure of slugs at Stromboli. Comparison of predicted values with measured data from Stromboli volcano showed that the model can explain the entire spectrum of observed eruptive styles at Stromboli – from low-energy puffing, through normal Strombolian eruptions, up to paroxysmal explosions – as manifestations of a single underlying physical process. Finally, another suite of laboratory experiments was performed to observe oscillatory pressure and forces variations generated during the expansion and bursting of gas slugs ascending in a conduit. Two end-member boundary conditions were imposed at the base of the pipe, simulating slug ascent in closed base (zero magma flux) and open base (constant flux) conduit. At the top of the pipe, a range of boundary conditions that are relevant at a volcanic vent were imposed, going from open to plugged vent. The results obtained illustrate that a change in boundary conditions in the conduit concur to affect the dynamic of slug expansion and burst: an upward flux at the base of the conduit attenuates the magnitude of the pressure transients, while a rheological stiffening in the top-most region of conduit changes dramatically the magnitude of the observed pressure transients, favoring a sudden, and more energetic pressure release into the overlying atmosphere. Finally, a discussion on the implication of changing boundary on the oscillatory processes generated at the volcanic scale is also given.

Pyrolysis of peptides and proteins. Analytical study and environmental applications

Analytical pyrolysis was used to investigate the formation of diketopiperazines (DKPs) which are cyclic dipeptides formed from the thermal degradation of proteins. A quali/quantitative procedure was developed combining microscale flash pyrolysis at 500 °C with gas chromatography-mass spectrometry (GC-MS) of DKPs trapped onto an adsorbent phase. Polar DKPs were silylated prior to GC-MS. Particular attention was paid to the identification of proline (Pro) containing DKPs due to their greater facility of formation. The GC-MS characteristics of more than 80 original and silylated DKPs were collected from the pyrolysis of sixteen linear dipeptides and four model proteins (e.g. bovine serum albumin, BSA). The structure of a novel DKP, cyclo(pyroglutamic-Pro) was established by NMR and ESI-MS analysis, while the structures of other novel DKPs remained tentative. DKPs resulted rather specific markers of amino acid sequence in proteins, even though the thermal degradation of DKPs should be taken into account. Structural information of DKPs gathered from the pyrolysis of model compounds was employed to the identification of these compounds in the pyrolysate of proteinaceous samples, including intrinsecally unfolded protein (IUP). Analysis of the liquid fraction (bio-oil) obtained from the pyrolysis of microalgae Nannochloropsis gaditana, Scenedesmus spp with a bench scale reactor showed that DKPs constituted an important pool of nitrogen-containing compounds. Conversely, the level of DKPs was rather low in the bio-oil of Botryococcus braunii. The developed micropyrolysis procedure was applied in combination with thermogravimetry (TGA) and infrared spectroscopy (FT-IR) to investigate surface interaction between BSA and synthetic chrysotile. The results showed that the thermal behavior of BSA (e.g. DKPs formation) was affected by the different form of doped synthetic chrysotile. The typical DKPs evolved from collagen were quantified in the pyrolysates of archaeological bones from Vicenne Necropolis in order to evaluate their conservation status in combination with TGA, FTIR and XRD analysis.

Comparison between analytical and numerical methods for the assessment of masonry arch bridges: Case study of Clemente Bridge on Savio river

This research has focused on the study of the behavior and of the collapse of masonry arch bridges. The latest decades have seen an increasing interest in this structural type, that is still present and in use, despite the passage of time and the variation of the transport means. Several strategies have been developed during the time to simulate the response of this type of structures, although even today there is no generally accepted standard one for assessment of masonry arch bridges. The aim of this thesis is to compare the principal analytical and numerical methods existing in literature on case studies, trying to highlight values and weaknesses. The methods taken in exam are mainly three: i) the Thrust Line Analysis Method; ii) the Mechanism Method; iii) the Finite Element Methods. The Thrust Line Analysis Method and the Mechanism Method are analytical methods and derived from two of the fundamental theorems of the Plastic Analysis, while the Finite Element Method is a numerical method, that uses different strategies of discretization to analyze the structure. Every method is applied to the case study through computer-based representations, that allow a friendly-use application of the principles explained. A particular closed-form approach based on an elasto-plastic material model and developed by some Belgian researchers is also studied. To compare the three methods, two different case study have been analyzed: i) a generic masonry arch bridge with a single span; ii) a real masonry arch bridge, the Clemente Bridge, built on Savio River in Cesena. In the analyses performed, all the models are two-dimensional in order to have results comparable between the different methods taken in exam. The different methods have been compared with each other in terms of collapse load and of hinge positions.

New synthetic bile acid analogue agonists of FXR and TGR5 receptors: Analytical methodologies for the study of their physico-chemical properties, pharmacokinetic activity and metabolism.

This thesis reports an integrated analytical approach for the study of physicochemical and biological properties of new synthetic bile acid (BA) analogues agonists of FXR and TGR5 receptors. Structure-activity data were compared with those previous obtained using the same experimental protocols on synthetic and natural occurring BA. The new synthetic BA analogues are classified in different groups according also to their potency as a FXR and TGR5 agonists: unconjugated and steroid modified BA and side chain modified BA including taurine or glycine conjugates and pseudo-conjugates (sulphonate and sulphate analogues). In order to investigate the relationship between structure and activity the synthetic analogues where admitted to a physicochemical characterization and to a preliminary screening for their pharmacokinetic and metabolism using a bile fistula rat model. Sensitive and accurate analytical methods have been developed for the quali-quantitative analysis of BA in biological fluids and sample used for physicochemical studies. Combined High Performance Liquid Chromatography Electrospray tandem mass spectrometry with efficient chromatographic separation of all studied BA and their metabolites have been optimized and validated. Analytical strategies for the identification of the BA and their minor metabolites have been developed. Taurine and glycine conjugates were identified in MS/MS by monitoring the specific ion transitions in multiple reaction monitoring (MRM) mode while all other metabolites (sulphate, glucuronic acid, dehydroxylated, decarboxylated or oxo) were monitored in a selected-ion reaction (SIR) mode with a negative ESI interface by the following ions. Accurate and precise data where achieved regarding the main physicochemical properties including solubility, detergency, lipophilicity and albumin binding . These studies have shown that minor structural modification greatly affect the pharmacokinetics and metabolism of the new analogues in respect to the natural BA and on turn their site of action, particularly where their receptor are located in the enterohepatic circulation.

Model reduction of stochastic groundwater flow and transport processes

This work presents a comprehensive methodology for the reduction of analytical or numerical stochastic models characterized by uncertain input parameters or boundary conditions. The technique, based on the Polynomial Chaos Expansion (PCE) theory, represents a versatile solution to solve direct or inverse problems related to propagation of uncertainty. The potentiality of the methodology is assessed investigating different applicative contexts related to groundwater flow and transport scenarios, such as global sensitivity analysis, risk analysis and model calibration. This is achieved by implementing a numerical code, developed in the MATLAB environment, presented here in its main features and tested with literature examples. The procedure has been conceived under flexibility and efficiency criteria in order to ensure its adaptability to different fields of engineering; it has been applied to different case studies related to flow and transport in porous media. Each application is associated with innovative elements such as (i) new analytical formulations describing motion and displacement of non-Newtonian fluids in porous media, (ii) application of global sensitivity analysis to a high-complexity numerical model inspired by a real case of risk of radionuclide migration in the subsurface environment, and (iii) development of a novel sensitivity-based strategy for parameter calibration and experiment design in laboratory scale tracer transport.

Numerical and Analytical Methods for Laser-Plasma Acceleration Physics

Theories and numerical modeling are fundamental tools for understanding, optimizing and designing present and future laser-plasma accelerators (LPAs). Laser evolution and plasma wave excitation in a LPA driven by a weakly relativistically intense, short-pulse laser propagating in a preformed parabolic plasma channel, is studied analytically in 3D including the effects of pulse steepening and energy depletion. At higher laser intensities, the process of electron self-injection in the nonlinear bubble wake regime is studied by means of fully self-consistent Particle-in-Cell simulations. Considering a non-evolving laser driver propagating with a prescribed velocity, the geometrical properties of the non-evolving bubble wake are studied. For a range of parameters of interest for laser plasma acceleration, The dependence of the threshold for self-injection in the non-evolving wake on laser intensity and wake velocity is characterized. Due to the nonlinear and complex nature of the Physics involved, computationally challenging numerical simulations are required to model laser-plasma accelerators operating at relativistic laser intensities. The numerical and computational optimizations, that combined in the codes INF&RNO and INF&RNO/quasi-static give the possibility to accurately model multi-GeV laser wakefield acceleration stages with present supercomputing architectures, are discussed. The PIC code jasmine, capable of efficiently running laser-plasma simulations on Graphics Processing Units (GPUs) clusters, is presented. GPUs deliver exceptional performance to PIC codes, but the core algorithms had to be redesigned for satisfying the constraints imposed by the intrinsic parallelism of the architecture. The simulation campaigns, run with the code jasmine for modeling the recent LPA experiments with the INFN-FLAME and CNR-ILIL laser systems, are also presented.

New analytical LC-mass spectrometry methodologies for the quali-quantitative determination of natural substances and drugs in complex matrices

This thesis reports an integrated analytical and physicochemical approach for the study of natural substances and new drugs based on mass spectrometry techniques combined with liquid chromatography. In particular, Chapter 1 concerns the study of Berberine a natural substance with pharmacological activity for the treatment of hepatobiliary and intestinal diseases. The first part focused on the relationships between physicochemical properties, pharmacokinetics and metabolism of Berberine and its metabolites. For this purpose a sensitive HPLC-ES-MS/MS method have been developed, validated and used to determine these compounds during their physicochemical properties studies and plasma levels of berberine and its metabolites including berberrubine(M1), demethylenberberine(M3), and jatrorrhizine(M4) in humans. Data show that M1, could have an efficient intestinal absorption by passive diffusion due to a keto-enol tautomerism confirmed by NMR studies and its higher plasma concentration. In the second part of Chapter 1, a comparison between M1 and BBR in vivo biodistribution in rat has been studied. In Chapter 2 a new HPLC-ES-MS/MS method for the simultaneous determination and quantification of glucosinolates, as glucoraphanin, glucoerucin and sinigrin, and isothiocyanates, as sulforaphane and erucin, has developed and validated. This method has been used for the analysis of functional foods enriched with vegetable extracts. Chapter 3 focused on a physicochemical study of the interaction between the bile acid sequestrants used in the treatment of hypercholesterolemia including colesevelam and cholestyramine with obeticolic acid (OCA), potent agonist of nuclear receptor farnesoid X (FXR). In particular, a new experimental model for the determination of equilibrium binding isotherm was developed. Chapter 4 focused on methodological aspects of new hard ionization coupled with liquid chromatography (Direct-EI-UHPLC-MS) not yet commercially available and potentially useful for qualitative analysis and for “transparent” molecules to soft ionization techniques. This method was applied to the analysis of several steroid derivatives.