Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies

Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects

Infrastrutture per Monitoraggio e Controllo di Dispositivi Industrial IoT basate su Soluzioni Eclipse Foundation

L'obiettivo di questo studio è quello di realizzare un'infrastruttura per ambienti industriali che permetta di monitorare e controllare dispositivi appartenenti al mondo dell'Internet of Things, basata su due tecnologie offerte dall'Eclipse Foundation. L'elaborato offre in primo luogo una panoramica sul mondo dell'IIoT e un'analisi approfondita delle piattaforme Eclipse Kura, utilizzata per la realizzazione di un gateway IoT ed Eclipse Kapua utilizzata per la realizzazione di una piattaforma Cloud. Successivamente il focus si sposta sull'implementazione dell'infrastruttura, mostrando nel dettaglio la sua installazione, la sua configurazione e lo sviluppo di componenti aggiuntivi. Lo studio si conclude infine, con l'esecuzione di una serie di test e una valutazione del risultato ottenuto

Active Fault Tolerant Control for Overactuated Unmanned Vehicles

Motivato dalla crescente richiesta di sicurezza, disponibilità e affidabilità nei veicoli, lo scopo della presente tesi è sviluppare nuovi metodi per effettuare sia la diagnosi dei guasti che il controllo tollerante ai guasti per veicoli sovrattuati. In particolare, si considerano i guasti degli attuatori, poiché essi rappresentano una classe comune di guasti ed hanno conseguenze critiche se non affrontati tempestivamente. Per raggiungere l'obiettivo, si propongono metodi attivi, ovvero la diagnosi guasti attiva ed il controllo attivo tollerante ai guasti, poiché essi presentano migliori capacità di gestire guasti di severità arbitraria. Il primo passo consiste nel quantificare l'ampiezza del guasto. Per questo motivo, in questa tesi si illustrano diversi algoritmi per la diagnosi dei guasti applicata a due categorie di veicoli, in particolare i veicoli sottomarini a comando remoto ed i droni multirotore. I metodi sviluppati richiedono l'utilizzo di sole misure inerziali, quindi sono facilmente applicabili anche su veicoli con limitate disponibilità sensoriali. Dato un insieme di variabili misurate, la stima dei guasti dell'ingresso diventa più complessa all'aumentare del numero di attuatori. D'altronde, i veicoli sovrattuati sono caratterizzati dalla ridondanza di attuatori, quindi il compito non è banale: la diagnosi dei guasti attiva permette di distinguere tra diversi tipi di guasto, tramite l'introduzione di segnali opportuni nei canali di ingresso. Inoltre, poiché molti attuatori hanno un comportamento non lineare, i metodi lineari classici non raggiungono prestazioni soddisfacenti, quindi è necessario sviluppare soluzioni specifiche. Come secondo passo, supposto che una stima del guasto sia disponibile grazie al predetto algoritmo di rilevamento e diagnosi dei guasti, in questa tesi si propone di sfruttare gli algoritmi di allocazione dello sforzo di controllo per gestire i guasti, oltre che per soddisfare i vincoli degli ingressi e minimizzare una funzione di costo. L'algoritmo di allocazione ha un ruolo chiave in tale schema di controllo, in quanto permette di affrontare i guasti moltiplicativi senza il bisogno di riformulare la legge di controllo (tipicamente nonlineare); inoltre, esso permette di gestire la ridondanza in maniera dinamica. Il metoto proposto consiste nel formulare il problema di allocazione come un problema di ottimizzazione, per poi farlo ricadere in una classe di problemi per la quale sono disponibili in letteratura degli algoritmi di soluzione efficienti, come ad esempio avviene per i problemi convessi. Lo schema di controllo tollerante ai guasti discusso è poi applicato ai veicoli sottomarini a comando remoto, siano essi equipaggiati con propulsori fissi o azimutali (ossia orientabili), e ai droni multirotore, sia nel caso di eliche ad angolo di incidenza fisso, sia nel caso di angolo di incidenza variabile. I risultati forniti dalle simulazioni, realizzate in condizioni realistiche, mostrano l'efficacia del metodo, in termini di tolleranza ai guasti, di riduzione dell'errore di inseguimento della traiettoria e di miglioramento del consumo energetico.Motivated by the always increasing need for safety, availability, and reliability of vehicles, the objective of this thesis is to provide novel methods to perform both fault diagnosis and fault tolerant control for marine and aerial overactuated unmanned vehicles. In particular, actuator faults are considered, as they represent a common class of faults, and they entail severe consequences if not tackled in time. In order to reach the goal, active methods are developed, i.e., active fault diagnosis and active fault tolerant control, because of their superior capability to cope with faults of arbitrary magnitude. The first step is to estimate the fault magnitude. For this reason, several fault diagnosis algorithms are presented in this thesis to deal with two classes of vehicles, namely, remotely operated vehicles and multirotor drones. Such methods require inertial measurements only, thus they are well suited for vehicles with a limited amount of onboard sensors. Given a set of measured variables, input fault estimation becomes more challenging as the number of actuators increases. Overactuated vehicles are characterized by redundant actuators, thus the task is not trivial: active fault diagnosis makes possible to distinguish between various kinds of faults by injecting a test signal to the control inputs. Moreover, several actuators show a nonlinear behaviour, hence classical linear tools do not achieve satisfactory performances, and specific solutions must be designed. Secondly, provided that a suitable fault estimation is available thanks to a fault detection and diagnosis algorithm, this thesis proposes to exploit control allocation algorithms to manage faults, while satisfying input constraints and minimizing a cost function. In this active fault tolerant scheme, control allocation plays a central role, as it allows to cope with multiplicative faults without the need of redesigning the (possibly nonlinear) control law, and also makes possible to manage actuator redundancy dynamically. The method consists in formulating the control allocation problem as an optimization problem, and then recasting it to a class of optimization problems where efficient solvers are available in the literature, i.e., convex ones. Such fault tolerant methods are then applied to cope with actuator faults in remotely operated vehicles, whether they are equipped with fixed thrusters or azimuth (i.e., orientable) thrusters, and in multirotor drones, both in the case of fixed pitch and variable pitch propellers. Simulation results which mimic real world scenarios illustrate the effectiveness of the methods, in terms of fault tolerance, reduced tracking error, and improved energy consumption

Fixed-size LS-SVM LPV System Identification for Large Datasets

In this paper, we propose an efficient method for handling large datasets in linear parameter-varying (LPV) model identification. The method is based on least-squares support vector machine (LS-SVM) identification in the primal space. To make the identification computationally feasible, even for very large datasets, we propose estimating a finite-dimensional feature map. To achieve this, we propose a two-step method to reduce the computational effort. First, we define the training set as a fixed-size subsample of the entire dataset, considering collision entropy for subset selection. The second step involves approximating the feature map through the eigenvalue decomposition of the kernel matrices. This paper considers both autoregressive with exogenous input (ARX) and state-space (SS) model forms. By comparing the problem formulation in the primal and dual spaces in terms of accuracy and computational complexity, the main advantage of the proposed technique is the reduction in space and time complexity during the training stage, making it preferable for handling very large datasets. To validate our proposed primal approach, we apply it to estimate LPV models using provided inputs, outputs, and scheduling signals for two nonlinear benchmarks: the parallel Wiener-Hammerstein system and the Silverbox system. The performances of our proposed approach are compared with the dual LS-SVM approach and the kernel principal component regression

Fault Tolerant Control of a Variable Pitch Quadrotor

In this paper, we solve the fault tolerant tracking problem for a variable pitch quadrotor. Following the Disturbance Observer Based Control design paradigm, we face the observation problem for the blade pitch, and consequently the related fault and failure diagnosis problems. The control allocation algorithm solves the optimal redistribution problem of the control effort among the propellers in case of actuation failure. The optimization problem takes into account the energy consumption, the health condition of the actuators and the presence of input constraints, such as saturation and rate of change limits. In particular, we face the specific problem of lock-in-place servo failures, which reduce the number of the control actions in the system. Indeed, together with a fault detection and isolation module, lock-in-place servo failures can be managed in the control allocation algorithm while keeping the tracking capabilities. The proposed optimal fault tolerant accommodation algorithm can be coupled with most of the nonlinear control laws commonly applied to conventional multirotor systems. Numerical simulations with noise and constraints show the capability of the scheme to handle this class of failures

Actuator Fault Tolerant Control of Variable Pitch Quadrotor Vehicles

Variable pitch quadrotors can experience actuation faults and failures of two main types: one type related to the rotor system and the other one related to the blade pitch servo. In this paper, we face the fault tolerant attitude tracking problem for a variable pitch quadrotor, in case of partial loss of effectiveness of the rotor system or lock-in-place of the blade pitch servo. The proposed solution is based on the combination of the Disturbance Observer Based Control design paradigm together with that of Active Fault Diagnosis. In detail, an observer is designed for estimating the thrust produced by each rotor. An active diagnosis scheme is adopted to discriminate which fault/failure is affecting the system. Finally, a control allocation algorithm solves the optimal redistribution problem of the control effort among the rotors, subject to different constraints. The proposed overall optimal fault tolerant control scheme can be coupled with most of the nonlinear control laws commonly applied to conventional, fixed pitch, quadrotor systems. Numerical simulations show the capability of the proposed scheme to handle both loss of effectiveness of the rotor system or lock-in-place of the blade pitch servo

Fault Tolerant Control for Remotely Operated Vehicles with Thruster Faults using Nonlinear Disturbance Observers

In this paper, a disturbance observer based control strategy is developed to provide fault tolerance to thruster faults for a remotely operated vehicle. The scheme relies on the vehicle’s position, orientation and velocity information only, without the need for additional measurements from the thrusters such as voltage, current, and rotation speed. Because the system is over-actuated, a bank of observers is designed for purposes of fault detection and isolation. A nonlinear disturbance observer is designed to restructure itself, according to the fault isolation outcome, to estimate the fault magnitude. The fault estimation is finally exploited by the control law using an active fault tolerant control strategy. The solution is designed for the cases where at most one faulty thruster is expected. The fault tolerant control strategy is tested in simulation, where a severe thruster fault is injected

L’ortolano Emberiza hortulana nella Regione Marche: analisi della distribuzione e preferenze ambientali

The Ortolan bunting Emberiza hortulana is one of many species of passerines in great decline in most of Europe. Even in Italy, the species is considered to be in decline, for this reason it is protected for conservation purposes, although it still not appear to be at risk. However, recent studies have shown an increase of breeding pairs in the central eastern portion of the Italian peninsula. In the Marche Region a study was conducted, through the implementation of 2100 points counts, with the aim of verifying the actual presence of Ortolan bunting and study their habitat preferences. The species was found to be moderately widespread, being present in 11.5% of the total point counts monitored. The species presence was correlated positively with farmlands and shrubs, but it seems avoid urban structures like roads and buildings

Design of debris removal missions performed by robotic graspers

The well known increase of the orbiting debris, leading to a critical condition in which additional launches could be precluded, calls for mitigation and removal practices. First, and maybe easier to accomplish with respect to other concepts under study, some missions should be probably carried out in a close fiiture to grasp large unused orbiting objects, like upper stages or idle spacecraft that already ended their operational lifetime. The focus on large objects, even if they are a limited subset of orbiting spent bodies, helps in two ways: The reduction of the cross section for possible impacts, and, more remarkably, the reduction of the number and size of additional debris to be generated in a possible collision. As a result, these targets can justify the cost and the complexity of removal missions which, even if almost traditional in the approach and not-too-far from current operational capabilities, still pose significant technical problems. The paper aims to present the operational sequence of a removal mission to be performed by a robotic spacecraft. The issues relevant for the different phases are discussed, with a special focus on the grasping operations, when the robotic arms of the servicing spacecraft, after the determination of the relative kinematic state of the target, should carcfully embraces and precisely catch, in a safe area, the orbiting body. Such an approach should bypass obstacles like solar panels and avoid the break-up of the target, possibly degraded due to its long exposure to space environment. The results of simulations under reasonable, engineering hypothesis for the mission's scenario are presented, with the estimate of torques and forces to be exerted by the robotic arms. The attitude issues for the servicing spacecraft, as well as the vibration behaviour for an accurate end-effector positioning during robotic arms manoeuvres are considered. The confidence in the findings of these numerical studies is strengthened by the know-how gained with the related experimental activities performed during recent years in the labs at Sapienza Universita' di Roma by means of dedicated, small test-beds. Copyright © (2012) by the International Astronautical Federation

Fault-Tolerant Disturbance Observer Based Control for Altitude and Attitude Tracking of a Quadrotor

This paper presents an attitude and altitude fault-tolerant tracking control for a quadrotor using the Disturbance Observer Based Control (DOBC). A Newton-Euler model of the quadrotor is described and the fault-tolerant control problem is treated for small angles. An appropriate estimation gain is proposed for the considered system, which allows to impose desired closed loop performances. These closed loop performances are analysed, showing the boundedness properties, and highlighting the trade off between fault estimation and control effort. Numerical simulations are provided for testing the effectiveness of the proposed DOBC solution, which is compared with the classical backstepping controller in case of multiple actuation faults