Active fibre-reinforced composites with embedded shape memory alloys

This dissertation concerns active fibre-reinforced composites with embedded shape memory alloy wires. The structural application of active materials allows to develop adaptive structures which actively respond to changes in the environment, such as morphing structures, self-healing structures and power harvesting devices. In particular, shape memory alloy actuators integrated within a composite actively control the structural shape or stiffness, thus influencing the composite static and dynamic properties. Envisaged applications include, among others, the prevention of thermal buckling of the outer skin of air vehicles, shape changes in panels for improved aerodynamic characteristics and the deployment of large space structures. The study and design of active composites is a complex and multidisciplinary topic, requiring in-depth understanding of both the coupled behaviour of active materials and the interaction between the different composite constituents. Both fibre-reinforced composites and shape memory alloys are extremely active research topics, whose modelling and experimental characterisation still present a number of open problems. Thus, while this dissertation focuses on active composites, some of the research results presented here can be usefully applied to traditional fibre-reinforced composites or other shape memory alloy applications. The dissertation is composed of four chapters. In the first chapter, active fibre-reinforced composites are introduced by giving an overview of the most common choices available for the reinforcement, matrix and production process, together with a brief introduction and classification of active materials. The second chapter presents a number of original contributions regarding the modelling of fibre-reinforced composites. Different two-dimensional laminate theories are derived from a parent three-dimensional theory, introducing a procedure for the a posteriori reconstruction of transverse stresses along the laminate thickness. Accurate through the thickness stresses are crucial for the composite modelling as they are responsible for some common failure mechanisms. A new finite element based on the First-order Shear Deformation Theory and a hybrid stress approach is proposed for the numerical solution of the two-dimensional laminate problem. The element is simple and computationally efficient. The transverse stresses through the laminate thickness are reconstructed starting from a general finite element solution. A two stages procedure is devised, based on Recovery by Compatibility in Patches and three-dimensional equilibrium. Finally, the determination of the elastic parameters of laminated structures via numerical-experimental Bayesian techniques is investigated. Two different estimators are analysed and compared, leading to the definition of an alternative procedure to improve convergence of the estimation process. The third chapter focuses on shape memory alloys, describing their properties and applications. A number of constitutive models proposed in the literature, both one-dimensional and three-dimensional, are critically discussed and compared, underlining their potential and limitations, which are mainly related to the definition of the phase diagram and the choice of internal variables. Some new experimental results on shape memory alloy material characterisation are also presented. These experimental observations display some features of the shape memory alloy behaviour which are generally not included in the current models, thus some ideas are proposed for the development of a new constitutive model. The fourth chapter, finally, focuses on active composite plates with embedded shape memory alloy wires. A number of di®erent approaches can be used to predict the behaviour of such structures, each model presenting different advantages and drawbacks related to complexity and versatility. A simple model able to describe both shape and stiffness control configurations within the same context is proposed and implemented. The model is then validated considering the shape control configuration, which is the most sensitive to model parameters. The experimental work is divided in two parts. In the first part, an active composite is built by gluing prestrained shape memory alloy wires on a carbon fibre laminate strip. This structure is relatively simple to build, however it is useful in order to experimentally demonstrate the feasibility of the concept proposed in the first part of the chapter. In the second part, the making of a fibre-reinforced composite with embedded shape memory alloy wires is investigated, considering different possible choices of materials and manufacturing processes. Although a number of technological issues still need to be faced, the experimental results allow to demonstrate the mechanism of shape control via embedded shape memory alloy wires, while showing a good agreement with the proposed model predictions.

Asset management of wastewater networks

Asset Management (AM) is a set of procedures operable at the strategic-tacticaloperational level, for the management of the physical asset’s performance, associated risks and costs within its whole life-cycle. AM combines the engineering, managerial and informatics points of view. In addition to internal drivers, AM is driven by the demands of customers (social pull) and regulators (environmental mandates and economic considerations). AM can follow either a top-down or a bottom-up approach. Considering rehabilitation planning at the bottom-up level, the main issue would be to rehabilitate the right pipe at the right time with the right technique. Finding the right pipe may be possible and practicable, but determining the timeliness of the rehabilitation and the choice of the techniques adopted to rehabilitate is a bit abstruse. It is a truism that rehabilitating an asset too early is unwise, just as doing it late may have entailed extra expenses en route, in addition to the cost of the exercise of rehabilitation per se. One is confronted with a typical ‘Hamlet-isque dilemma’ – ‘to repair or not to repair’; or put in another way, ‘to replace or not to replace’. The decision in this case is governed by three factors, not necessarily interrelated – quality of customer service, costs and budget in the life cycle of the asset in question. The goal of replacement planning is to find the juncture in the asset’s life cycle where the cost of replacement is balanced by the rising maintenance costs and the declining level of service. System maintenance aims at improving performance and maintaining the asset in good working condition for as long as possible. Effective planning is used to target maintenance activities to meet these goals and minimize costly exigencies. The main objective of this dissertation is to develop a process-model for asset replacement planning. The aim of the model is to determine the optimal pipe replacement year by comparing, temporally, the annual operating and maintenance costs of the existing asset and the annuity of the investment in a new equivalent pipe, at the best market price. It is proposed that risk cost provide an appropriate framework to decide the balance between investment for replacing or operational expenditures for maintaining an asset. The model describes a practical approach to estimate when an asset should be replaced. A comprehensive list of criteria to be considered is outlined, the main criteria being a visà- vis between maintenance and replacement expenditures. The costs to maintain the assets should be described by a cost function related to the asset type, the risks to the safety of people and property owing to declining condition of asset, and the predicted frequency of failures. The cost functions reflect the condition of the existing asset at the time the decision to maintain or replace is taken: age, level of deterioration, risk of failure. The process model is applied in the wastewater network of Oslo, the capital city of Norway, and uses available real-world information to forecast life-cycle costs of maintenance and rehabilitation strategies and support infrastructure management decisions. The case study provides an insight into the various definitions of ‘asset lifetime’ – service life, economic life and physical life. The results recommend that one common value for lifetime should not be applied to the all the pipelines in the stock for investment planning in the long-term period; rather it would be wiser to define different values for different cohorts of pipelines to reduce the uncertainties associated with generalisations for simplification. It is envisaged that more criteria the municipality is able to include, to estimate maintenance costs for the existing assets, the more precise will the estimation of the expected service life be. The ability to include social costs enables to compute the asset life, not only based on its physical characterisation, but also on the sensitivity of network areas to social impact of failures. The type of economic analysis is very sensitive to model parameters that are difficult to determine accurately. The main value of this approach is the effort to demonstrate that it is possible to include, in decision-making, factors as the cost of the risk associated with a decline in level of performance, the level of this deterioration and the asset’s depreciation rate, without looking at age as the sole criterion for making decisions regarding replacements.

On Reasonable Space and Time Cost Models for the λ-Calculus

Slot and van Emde Boas Invariance Thesis states that a time (respectively, space) cost model is reasonable for a computational model C if there are mutual simulations between Turing machines and C such that the overhead is polynomial in time (respectively, linear in space). The rationale is that under the Invariance Thesis, complexity classes such as LOGSPACE, P, PSPACE, become robust, i.e. machine independent. In this dissertation, we want to find out if it possible to define a reasonable space cost model for the lambda-calculus, the paradigmatic model for functional programming languages. We start by considering an unusual evaluation mechanism for the lambda-calculus, based on Girard's Geometry of Interaction, that was conjectured to be the key ingredient to obtain a space reasonable cost model. By a fine complexity analysis of this schema, based on new variants of non-idempotent intersection types, we disprove this conjecture. Then, we change the target of our analysis. We consider a variant over Krivine's abstract machine, a standard evaluation mechanism for the call-by-name lambda-calculus, optimized for space complexity, and implemented without any pointer. A fine analysis of the execution of (a refined version of) the encoding of Turing machines into the lambda-calculus allows us to conclude that the space consumed by this machine is indeed a reasonable space cost model. In particular, for the first time we are able to measure also sub-linear space complexities. Moreover, we transfer this result to the call-by-value case. Finally, we provide also an intersection type system that characterizes compositionally this new reasonable space measure. This is done through a minimal, yet non trivial, modification of the original de Carvalho type system.

Creazione e sviluppo di un sistema di controllo in tempo reale per un sistema fuel cell

The control of a proton exchange membrane fuel cell system (PEM FC) for domestic heat and power supply requires extensive control measures to handle the complicated process. Highly dynamic and non linear behavior, increase drastically the difficulties to find the optimal design and control strategies. The objective is to design, implement and commission a controller for the entire fuel cell system. The fuel cell process and the control system are engineered simultaneously; therefore there is no access to the process hardware during the control system development. Therefore the method of choice was a model based design approach, following the rapid control prototyping (RCP) methodology. The fuel cell system is simulated using a fuel cell library which allowed thermodynamic calculations. In the course of the development the process model is continuously adapted to the real system. The controller application is designed and developed in parallel and thereby tested and verified against the process model. Furthermore, after the commissioning of the real system, the process model can be also better identified and parameterized utilizing measurement data to perform optimization procedures. The process model and the controller application are implemented in Simulink using Mathworks` Real Time Workshop (RTW) and the xPC development suite for MiL (model-in-theloop) and HiL (hardware-in-the-loop) testing. It is possible to completely develop, verify and validate the controller application without depending on the real fuel cell system, which is not available for testing during the development process. The fuel cell system can be immediately taken into operation after connecting the controller to the process.

Effective field theories and their phenomenological applications

Effective field theories (EFTs) are ubiquitous in theoretical physics and in particular in field theory descriptions of quantum systems probed at energies much lower than one or few characterizing scales. More recently, EFTs have gained a prominent role in the study of fundamental interactions and in particular in the parametriasation of new physics beyond the Standard Model, which would occur at scales Λ, much larger than the electroweak scale. In this thesis, EFTs are employed to study three different physics cases. First, we consider light-by-light scattering as a possible probe of new physics. At low energies it can be described by dimension-8 operators, leading to the well-known Euler-Heisenberg Lagrangian. We consider the explicit dependence of matching coefficients on type of particle running in the loop, confirming the sensitiveness to the spin, mass, and interactions of possibly new particles. Second, we consider EFTs to describe Dark Matter (DM) interactions with SM particles. We consider a phenomenologically motivated case, i.e., a new fermion state that couples to the Hypercharge through a form factor and has no interactions with photons and the Z boson. Results from direct, indirect and collider searches for DM are used to constrain the parameter space of the model. Third, we consider EFTs that describe axion-like particles (ALPs), whose phenomenology is inspired by the Peccei-Quinn solution to strong CP problem. ALPs generically couple to ordinary matter through dimension-5 operators. In our case study, we investigate the rather unique phenomenological implications of ALPs with enhanced couplings to the top quark.

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.

Algorithms for UAS insertion in civil air space

One of the most interesting challenge of the next years will be the Air Space Systems automation. This process will involve different aspects as the Air Traffic Management, the Aircrafts and Airport Operations and the Guidance and Navigation Systems. The use of UAS (Uninhabited Aerial System) for civil mission will be one of the most important steps in this automation process. In civil air space, Air Traffic Controllers (ATC) manage the air traffic ensuring that a minimum separation between the controlled aircrafts is always provided. For this purpose ATCs use several operative avoidance techniques like holding patterns or rerouting. The use of UAS in these context will require the definition of strategies for a common management of piloted and piloted air traffic that allow the UAS to self separate. As a first employment in civil air space we consider a UAS surveillance mission that consists in departing from a ground base, taking pictures over a set of mission targets and coming back to the same ground base. During all mission a set of piloted aircrafts fly in the same airspace and thus the UAS has to self separate using the ATC avoidance as anticipated. We consider two objective, the first consists in the minimization of the air traffic impact over the mission, the second consists in the minimization of the impact of the mission over the air traffic. A particular version of the well known Travelling Salesman Problem (TSP) called Time-Dependant-TSP has been studied to deal with traffic problems in big urban areas. Its basic idea consists in a cost of the route between two clients depending on the period of the day in which it is crossed. Our thesis supports that such idea can be applied to the air traffic too using a convenient time horizon compatible with aircrafts operations. The cost of a UAS sub-route will depend on the air traffic that it will meet starting such route in a specific moment and consequently on the avoidance maneuver that it will use to avoid that conflict. The conflict avoidance is a topic that has been hardly developed in past years using different approaches. In this thesis we purpose a new approach based on the use of ATC operative techniques that makes it possible both to model the UAS problem using a TDTSP framework both to use an Air Traffic Management perspective. Starting from this kind of mission, the problem of the UAS insertion in civil air space is formalized as the UAS Routing Problem (URP). For this reason we introduce a new structure called Conflict Graph that makes it possible to model the avoidance maneuvers and to define the arc cost function of the departing time. Two Integer Linear Programming formulations of the problem are proposed. The first is based on a TDTSP formulation that, unfortunately, is weaker then the TSP formulation. Thus a new formulation based on a TSP variation that uses specific penalty to model the holdings is proposed. Different algorithms are presented: exact algorithms, simple heuristics used as Upper Bounds on the number of time steps used, and metaheuristic algorithms as Genetic Algorithm and Simulated Annealing. Finally an air traffic scenario has been simulated using real air traffic data in order to test our algorithms. Graphic Tools have been used to represent the Milano Linate air space and its air traffic during different days. Such data have been provided by ENAV S.p.A (Italian Agency for Air Navigation Services).

Development of an X-ray spectrometric system and feasibility tests of Silicon Drift Detector for medical and space applications

The thesis work concerns X-ray spectrometry for both medical and space applications and is divided into two sections. The first section addresses an X-ray spectrometric system designed to study radiological beams and is devoted to the optimization of diagnostic procedures in medicine. A parametric semi-empirical model capable of efficiently reconstructing diagnostic X-ray spectra in 'middle power' computers was developed and tested. In addition, different silicon diode detectors were tested as real-time detectors in order to provide a real-time evaluation of the spectrum during diagnostic procedures. This project contributes to the field by presenting an improved simulation of a realistic X-ray beam emerging from a common X-ray tube with a complete and detailed spectrum that lends itself to further studies of added filtration, thus providing an optimized beam for different diagnostic applications in medicine. The second section describes the preliminary tests that have been carried out on the first version of an Application Specific Integrated Circuit (ASIC), integrated with large area position-sensitive Silicon Drift Detector (SDD) to be used on board future space missions. This technology has been developed for the ESA project: LOFT (Large Observatory for X-ray Timing), a new medium-class space mission that the European Space Agency has been assessing since February of 2011. The LOFT project was proposed as part of the Cosmic Vision Program (2015-2025).

Improvement of photon transport model by including coupled photon-electron transport and kernel refinement

The first part of this work deals with the inverse problem solution in the X-ray spectroscopy field. An original strategy to solve the inverse problem by using the maximum entropy principle is illustrated. It is built the code UMESTRAT, to apply the described strategy in a semiautomatic way. The application of UMESTRAT is shown with a computational example. The second part of this work deals with the improvement of the X-ray Boltzmann model, by studying two radiative interactions neglected in the current photon models. Firstly it is studied the characteristic line emission due to Compton ionization. It is developed a strategy that allows the evaluation of this contribution for the shells K, L and M of all elements with Z from 11 to 92. It is evaluated the single shell Compton/photoelectric ratio as a function of the primary photon energy. It is derived the energy values at which the Compton interaction becomes the prevailing process to produce ionization for the considered shells. Finally it is introduced a new kernel for the XRF from Compton ionization. In a second place it is characterized the bremsstrahlung radiative contribution due the secondary electrons. The bremsstrahlung radiation is characterized in terms of space, angle and energy, for all elements whit Z=1-92 in the energy range 1–150 keV by using the Monte Carlo code PENELOPE. It is demonstrated that bremsstrahlung radiative contribution can be well approximated with an isotropic point photon source. It is created a data library comprising the energetic distributions of bremsstrahlung. It is developed a new bremsstrahlung kernel which allows the introduction of this contribution in the modified Boltzmann equation. An example of application to the simulation of a synchrotron experiment is shown.

Development and characterisation of a neurogenic model of brain cancer

Primary glioblastoma (GB), the most common and aggressive adult brain tumour, is refractory to conventional therapies and characterised by poor prognosis. GB displays striking cellular heterogeneity, with a sub-population, called Glioblastoma Stem Cells (GSCs), intrinsically resistant to therapy, hence the high rate of recurrence. Alterations of the tumour suppressor gene PTEN are prevalent in primary GBM, resulting in the inhibition of the polarity protein Lgl1 due to aPKC hyperactivation. Dysregulation of this molecular axis is one of the mechanisms involved in GSC maintenance. After demonstrating that the PTEN/aPKC/Lgl axis is conserved in Drosophila, I deregulated it in different cells populations of the nervous system in order to individuate the cells at the root of neurogenic brain cancers. This analysis identified the type II neuroblasts (NBs) as the most sensitive to alterations of this molecular axis. Type II NBs are a sub-population of Drosophila stem cells displaying a lineage similar to that of the mammalian neural stem cells. Following aPKC activation in these stem cells, I obtained an adult brain cancer model in Drosophila that summarises many phenotypic traits of human brain tumours. Fly tumours are indeed characterised by accumulation of highly proliferative immature cells and keep growing in the adult leading the affected animals to premature death. With the aim to understand the role of cell polarity disruption in this tumorigenic process I carried out a molecular characterisation and transcriptome analysis of brain cancers from our fly model. In summary, the model I built and partially characterised in this thesis work may help deepen our knowledge on human brain cancers by investigating many different aspects of this complicate disease.

Design and testing of innovative, artificial intelligence-based techniques to model and control the combustion process and to reduce the Co2 emissions in modern, high-performance, gasoline direct injection engines

This work deals with the development of calibration procedures and control systems to improve the performance and efficiency of modern spark ignition turbocharged engines. The algorithms developed are used to optimize and manage the spark advance and the air-to-fuel ratio to control the knock and the exhaust gas temperature at the turbine inlet. The described work falls within the activity that the research group started in the previous years with the industrial partner Ferrari S.p.a. . The first chapter deals with the development of a control-oriented engine simulator based on a neural network approach, with which the main combustion indexes can be simulated. The second chapter deals with the development of a procedure to calibrate offline the spark advance and the air-to-fuel ratio to run the engine under knock-limited conditions and with the maximum admissible exhaust gas temperature at the turbine inlet. This procedure is then converted into a model-based control system and validated with a Software in the Loop approach using the engine simulator developed in the first chapter. Finally, it is implemented in a rapid control prototyping hardware to manage the combustion in steady-state and transient operating conditions at the test bench. The third chapter deals with the study of an innovative and cheap sensor for the in-cylinder pressure measurement, which is a piezoelectric washer that can be installed between the spark plug and the engine head. The signal generated by this kind of sensor is studied, developing a specific algorithm to adjust the value of the knock index in real-time. Finally, with the engine simulator developed in the first chapter, it is demonstrated that the innovative sensor can be coupled with the control system described in the second chapter and that the performance obtained could be the same reachable with the standard in-cylinder pressure sensors.

Neurogeometry of stereo vision

This work aims to develop a neurogeometric model of stereo vision, based on cortical architectures involved in the problem of 3D perception and neural mechanisms generated by retinal disparities. First, we provide a sub-Riemannian geometry for stereo vision, inspired by the work on the stereo problem by Zucker (2006), and using sub-Riemannian tools introduced by Citti-Sarti (2006) for monocular vision. We present a mathematical interpretation of the neural mechanisms underlying the behavior of binocular cells, that integrate monocular inputs. The natural compatibility between stereo geometry and neurophysiological models shows that these binocular cells are sensitive to position and orientation. Therefore, we model their action in the space R3xS2 equipped with a sub-Riemannian metric. Integral curves of the sub-Riemannian structure model neural connectivity and can be related to the 3D analog of the psychophysical association fields for the 3D process of regular contour formation. Then, we identify 3D perceptual units in the visual scene: they emerge as a consequence of the random cortico-cortical connection of binocular cells. Considering an opportune stochastic version of the integral curves, we generate a family of kernels. These kernels represent the probability of interaction between binocular cells, and they are implemented as facilitation patterns to define the evolution in time of neural population activity at a point. This activity is usually modeled through a mean field equation: steady stable solutions lead to consider the associated eigenvalue problem. We show that three-dimensional perceptual units naturally arise from the discrete version of the eigenvalue problem associated to the integro-differential equation of the population activity.

Cancers of unknown primary site (CUPs) as a model of metastatic process.

Cancers of unknown primary site (CUPs) are a rare group of metastatic tumours, with a frequency of 3-5%, with an overall survival of 6-10 month. The identification of tumour primary site is usually reached by a combination of diagnostic investigations and immunohistochemical testing of the tumour tissue. In CUP patients, these investigations are inconclusive. Since international guidelines for treatment are based on primary site indication, CUP treatment requires a blind approach. As a consequence, CUPs are usually empiric treated with poorly effective. In this study, we applied a set of microRNAs using EvaGreen-based Droplet Digital PCR in a retrospective and prospective collection of formalin-fixed paraffin-embedded tissue samples. We assessed miRNA expression of 155 samples including primary tumours (N=94), metastases of known origin (N=10) and metastases of unknown origin (N=50). Then, we applied the shrunken centroids predictive algorithm to obtain the CUP’s site(s)-of-origin. The molecular test was successfully applied to all CUP samples and provided a site-of-origin identification for all samples, potentially within a one-week time frame from sample inclusion. In the second part of the study we derived two CUP cell lines, and corresponding patient-derived xenografts (PDXs). CUP cell lines and PDXs underwent histological, molecular, and genomic characterization confirming the features of the original tumour. Tissues-of-origin prediction was obtained from the tumour microRNA expression profile and confirmed by single cell RNA sequencing. Genomic testing analysis identified FGFR2 amplification in both models. Drug-screening assays were performed to test the activity of FGFR2-targeting drug and the combination treatment with the MEK inhibitor trametinib, which proved to be synergic and exceptionally active, both in vitro and in vivo. In conclusion, our study demonstrated that miRNA expression profiling could be employed as diagnostic test. Then we successfully derived two CUP models from patients, used for therapy tests, bringing personalized therapy closer to CUP patients.