Spinal cord injury: assessment of autonomic state-dependent control of cardiovascular system and body core temperature

Spinal cord injury (SCI) results not only in paralysis; but it is also associated with a range of autonomic dysregulation that can interfere with cardiovascular, bladder, bowel, temperature, and sexual function. The entity of the autonomic dysfunction is related to the level and severity of injury to descending autonomic (sympathetic) pathways. For many years there was limited awareness of these issues and the attention given to them by the scientific and medical community was scarce. Yet, even if a new system to document the impact of SCI on autonomic function has recently been proposed, the current standard of assessment of SCI (American Spinal Injury Association (ASIA) examination) evaluates motor and sensory pathways, but not severity of injury to autonomic pathways. Beside the severe impact on quality of life, autonomic dysfunction in persons with SCI is associated with increased risk of cardiovascular disease and mortality. Therefore, obtaining information regarding autonomic function in persons with SCI is pivotal and clinical examinations and laboratory evaluations to detect the presence of autonomic dysfunction and quantitate its severity are mandatory. Furthermore, previous studies demonstrated that there is an intimate relationship between the autonomic nervous system and sleep from anatomical, physiological, and neurochemical points of view. Although, even if previous epidemiological studies demonstrated that sleep problems are common in spinal cord injury (SCI), so far only limited polysomnographic (PSG) data are available. Finally, until now, circadian and state dependent autonomic regulation of blood pressure (BP), heart rate (HR) and body core temperature (BcT) were never assessed in SCI patients. Aim of the current study was to establish the association between the autonomic control of the cardiovascular function and thermoregulation, sleep parameters and increased cardiovascular risk in SCI patients.

Regulating State Aid: Inter-jurisdictional competition, public choice, and corporate governance

Depending on the regulatory regime they are subject to, governments may or may not be allowed to hand out state aid to private firms. The economic justification for state aid can address several issues present in the competition for capital and the competition for transfers from the state. First, there are principal-agent problems involved at several stages. Self-interested politicians might enter state aid deals that are the result of extensive rent-seeking activities of organized interest groups. Thus the institutional design of political systems will have an effect on the propensity of a jurisdiction to award state aid. Secondly, fierce competition for firm locations can lead to over-spending. This effect is stronger if the politicians do not take into account the entirety of the costs created by their participation in the firm location race. Thirdly, state aid deals can be incomplete and not in the interest of the citizens. This applies if there are no sanctions if firms do not meet their obligations from receiving aid, such as creating a certain number of jobs or not relocating again for a certain amount of time. The separation of ownership and control in modern corporations leads to principal-agent problems on the side of the aid recipient as well. Managers might receive personal benefits from subsidies, the use of which is sometimes less monitored than private finance. This can eventually be to the detriment of the shareholders. Overall, it can be concluded that state aid control should also serve the purpose of regulating the contracting between governments and firms. An extended mandate for supervision by the European Commission could include requirements to disincentive the misuse of state aid. The Commission should also focus on the corporate governance regime in place in the jurisdiction that awards the aid as well as in the recipient firm.

The dark side of the board: advances in chess Kriegspiel

While imperfect information games are an excellent model of real-world problems and tasks, they are often difficult for computer programs to play at a high level of proficiency, especially if they involve major uncertainty and a very large state space. Kriegspiel, a variant of chess making it similar to a wargame, is a perfect example: while the game was studied for decades from a game-theoretical viewpoint, it was only very recently that the first practical algorithms for playing it began to appear. This thesis presents, documents and tests a multi-sided effort towards making a strong Kriegspiel player, using heuristic searching, retrograde analysis and Monte Carlo tree search algorithms to achieve increasingly higher levels of play. The resulting program is currently the strongest computer player in the world and plays at an above-average human level.

Geometric and Combinatorial Aspects of NonEquilibrium Statistical Mechanics

Non-Equilibrium Statistical Mechanics is a broad subject. Grossly speaking, it deals with systems which have not yet relaxed to an equilibrium state, or else with systems which are in a steady non-equilibrium state, or with more general situations. They are characterized by external forcing and internal fluxes, resulting in a net production of entropy which quantifies dissipation and the extent by which, by the Second Law of Thermodynamics, time-reversal invariance is broken. In this thesis we discuss some of the mathematical structures involved with generic discrete-state-space non-equilibrium systems, that we depict with networks in all analogous to electrical networks. We define suitable observables and derive their linear regime relationships, we discuss a duality between external and internal observables that reverses the role of the system and of the environment, we show that network observables serve as constraints for a derivation of the minimum entropy production principle. We dwell on deep combinatorial aspects regarding linear response determinants, which are related to spanning tree polynomials in graph theory, and we give a geometrical interpretation of observables in terms of Wilson loops of a connection and gauge degrees of freedom. We specialize the formalism to continuous-time Markov chains, we give a physical interpretation for observables in terms of locally detailed balanced rates, we prove many variants of the fluctuation theorem, and show that a well-known expression for the entropy production due to Schnakenberg descends from considerations of gauge invariance, where the gauge symmetry is related to the freedom in the choice of a prior probability distribution. As an additional topic of geometrical flavor related to continuous-time Markov chains, we discuss the Fisher-Rao geometry of nonequilibrium decay modes, showing that the Fisher matrix contains information about many aspects of non-equilibrium behavior, including non-equilibrium phase transitions and superposition of modes. We establish a sort of statistical equivalence principle and discuss the behavior of the Fisher matrix under time-reversal. To conclude, we propose that geometry and combinatorics might greatly increase our understanding of nonequilibrium phenomena.

Development of predictive energy management strategies for hybrid electric vehicles supported by connectivity

Nowadays, the spreading of the air pollution crisis enhanced by greenhouse gases emission is leading to the worsening of the global warming. In this context, the transportation sector plays a vital role, since it is responsible for a large part of carbon dioxide production. In order to address these issues, the present thesis deals with the development of advanced control strategies for the energy efficiency optimization of plug-in hybrid electric vehicles (PHEVs), supported by the prediction of future working conditions of the powertrain. In particular, a Dynamic Programming algorithm has been developed for the combined optimization of vehicle energy and battery thermal management. At this aim, the battery temperature and the battery cooling circuit control signal have been considered as an additional state and control variables, respectively. Moreover, an adaptive equivalent consumption minimization strategy (A-ECMS) has been modified to handle zero-emission zones, where engine propulsion is not allowed. Navigation data represent an essential element in the achievement of these tasks. With this aim, a novel simulation and testing environment has been developed during the PhD research activity, as an effective tool to retrieve routing information from map service providers via vehicle-to-everything connectivity. Comparisons between the developed and the reference strategies are made, as well, in order to assess their impact on the vehicle energy consumption. All the activities presented in this doctoral dissertation have been carried out at the Green Mobility Research Lab} (GMRL), a research center resulting from the partnership between the University of Bologna and FEV Italia s.r.l., which represents the industrial partner of the research project.

Il controllo sugli aiuti di Stato e i nuovi orizzonti della fiscalita europea

la tesi esamina l’applicazione del controllo sugli aiuti di Stato in materia fiscale tramite la disamina della giurisprudenza della Corte di giustizia. Il lavoro intende fornire una nuova prospettiva di analisi, valorizzando l’interazione tra la nozione di ‘aiuto fiscale’ ex art. 107(1) TFUE e le categorie tributarie nazionali, sottese all’applicazione del “test in tre fasi” coniato dalla Corte per identificare la presenza di un ‘vantaggio selettivo’. Facendo applicazione di tale prospettiva di analisi, la ricerca propone una nuova categorizzazione della ‘selettività fiscale’, tramite la quale vengono affrontate le tematiche più controverse legate all’applicazione dell’istituto. Infine, considerando i numerosi progetti di riforma della fiscalità diretta attualmente al vaglio delle Istituzioni europee, la tesi si confronta con il “futuro” del controllo sugli aiuti di Stato, identificato nella necessaria interazione con una cornice normativa armonizzata.

About stabilization of non-minimum phase systems by output feedback

This thesis work has been motivated by an internal benchmark dealing with the output regulation problem of a nonlinear non-minimum phase system in the case of full-state feedback. The system under consideration structurally suffers from finite escape time, and this condition makes the output regulation problem very hard even for very simple steady-state evolution or exosystem dynamics, such as a simple integrator. This situation leads to studying the approaches developed for controlling Non-minimum phase systems and how they affect feedback performances. Despite a lot of frequency domain results, only a few works have been proposed for describing the performance limitations in a state space system representation. In particular, in our opinion, the most relevant research thread exploits the so-called Inner-Outer Decomposition. Such decomposition allows splitting the Non-minimum phase system under consideration into a cascade of two subsystems: a minimum phase system (the outer) that contains all poles of the original system and an all-pass Non-minimum phase system (the inner) that contains all the unavoidable pathologies of the unstable zero dynamics. Such a cascade decomposition was inspiring to start working on functional observers for linear and nonlinear systems. In particular, the idea of a functional observer is to exploit only the measured signals from the system to asymptotically reconstruct a certain function of the system states, without necessarily reconstructing the whole state vector. The feature of asymptotically reconstructing a certain state functional plays an important role in the design of a feedback controller able to stabilize the Non-minimum phase system.

Understanding the role of microglial extracellular vesicles (EVs) in neuroinflammation spreading: an in vitro study

Neuroinflammation is a crucial pathogenic mechanism that commonly underlies most neurodegenerative diseases. Microglia, the immune cells of the brain, play a critical role that changes depending on the stage of neuropathology: at early phases of brain diseases microglia display the neuroprotective phenotype which is switched to the classically activated pro-inflammatory subtype at later stages, contributing to neurodegeneration. The microglial phenotypic shift is characterized by a change in the release of bioactive molecules both soluble and through extracellular vesicles. Our in vitro studies aim to understand whether different types of activation could determine change in vesicles content, in particular miRNAs, and whether this could influence the activation state of control microglial cells. Microglial polarization has been induced in two different in vitro models: N9, microglial murine cell line, have been treated by using LPS towards a proinflammatory/neurotoxic phenotype or ATP towards antinflammatory/neuroprotective status; HMC3, human microglial cell line, have been activated using IFN-+ATP. We demonstrated that conditioned media/exosomes obtained from donor microglia were able to promote a pro-inflammatory phenotype in control cells, leading us to prove the existence of a neuroinflammation spreading process mediated by extracellular vesicles of microglia with a crucial role of miRNAs. Increased expression of miRNA-34a observed in N9 model underlines a possible contribution in the diffusion of proinflammatory activation of microglia. Thus, we tried to downregulate miR-34a expression using cleaving sequences of anti-mir-34a DNAzyme delivered by DNA nanostructures aimed to confirm the involvement of miR-34a in microglia polarization towards the neurotoxic phenotype. In conclusion, this thesis work reveal a new inflammation spreading mechanism that involves release of vesicles containing specific cargos by donor polarized microglia, particularly miRNAs, able to influence the phenotypic shift in unpolarized microglia: this process deserves to be deeply investigated as potential therapeutic target to counteract neurodegenerative diseases.

Modulation Techniques for Multi-Phase Converters and Control Strategies for Multi-Phase Electric Drives

The ever-increasing spread of automation in industry puts the electrical engineer in a central role as a promoter of technological development in a sector such as the use of electricity, which is the basis of all the machinery and productive processes. Moreover the spread of drives for motor control and static converters with structures ever more complex, places the electrical engineer to face new challenges whose solution has as critical elements in the implementation of digital control techniques with the requirements of inexpensiveness and efficiency of the final product. The successfully application of solutions using non-conventional static converters awake an increasing interest in science and industry due to the promising opportunities. However, in the same time, new problems emerge whose solution is still under study and debate in the scientific community During the Ph.D. course several themes have been developed that, while obtaining the recent and growing interest of scientific community, have much space for the development of research activity and for industrial applications. The first area of research is related to the control of three phase induction motors with high dynamic performance and the sensorless control in the high speed range. The management of the operation of induction machine without position or speed sensors awakes interest in the industrial world due to the increased reliability and robustness of this solution combined with a lower cost of production and purchase of this technology compared to the others available in the market. During this dissertation control techniques will be proposed which are able to exploit the total dc link voltage and at the same time capable to exploit the maximum torque capability in whole speed range with good dynamic performance. The proposed solution preserves the simplicity of tuning of the regulators. Furthermore, in order to validate the effectiveness of presented solution, it is assessed in terms of performance and complexity and compared to two other algorithm presented in literature. The feasibility of the proposed algorithm is also tested on induction motor drive fed by a matrix converter. Another important research area is connected to the development of technology for vehicular applications. In this field the dynamic performances and the low power consumption is one of most important goals for an effective algorithm. Towards this direction, a control scheme for induction motor that integrates within a coherent solution some of the features that are commonly required to an electric vehicle drive is presented. The main features of the proposed control scheme are the capability to exploit the maximum torque in the whole speed range, a weak dependence on the motor parameters, a good robustness against the variations of the dc-link voltage and, whenever possible, the maximum efficiency. The second part of this dissertation is dedicated to the multi-phase systems. This technology, in fact, is characterized by a number of issues worthy of investigation that make it competitive with other technologies already on the market. Multiphase systems, allow to redistribute power at a higher number of phases, thus making possible the construction of electronic converters which otherwise would be very difficult to achieve due to the limits of present power electronics. Multiphase drives have an intrinsic reliability given by the possibility that a fault of a phase, caused by the possible failure of a component of the converter, can be solved without inefficiency of the machine or application of a pulsating torque. The control of the magnetic field spatial harmonics in the air-gap with order higher than one allows to reduce torque noise and to obtain high torque density motor and multi-motor applications. In one of the next chapters a control scheme able to increase the motor torque by adding a third harmonic component to the air-gap magnetic field will be presented. Above the base speed the control system reduces the motor flux in such a way to ensure the maximum torque capability. The presented analysis considers the drive constrains and shows how these limits modify the motor performance. The multi-motor applications are described by a well-defined number of multiphase machines, having series connected stator windings, with an opportune permutation of the phases these machines can be independently controlled with a single multi-phase inverter. In this dissertation this solution will be presented and an electric drive consisting of two five-phase PM tubular actuators fed by a single five-phase inverter will be presented. Finally the modulation strategies for a multi-phase inverter will be illustrated. The problem of the space vector modulation of multiphase inverters with an odd number of phases is solved in different way. An algorithmic approach and a look-up table solution will be proposed. The inverter output voltage capability will be investigated, showing that the proposed modulation strategy is able to fully exploit the dc input voltage either in sinusoidal or non-sinusoidal operating conditions. All this aspects are considered in the next chapters. In particular, Chapter 1 summarizes the mathematical model of induction motor. The Chapter 2 is a brief state of art on three-phase inverter. Chapter 3 proposes a stator flux vector control for a three- phase induction machine and compares this solution with two other algorithms presented in literature. Furthermore, in the same chapter, a complete electric drive based on matrix converter is presented. In Chapter 4 a control strategy suitable for electric vehicles is illustrated. Chapter 5 describes the mathematical model of multi-phase induction machines whereas chapter 6 analyzes the multi-phase inverter and its modulation strategies. Chapter 7 discusses the minimization of the power losses in IGBT multi-phase inverters with carrier-based pulse width modulation. In Chapter 8 an extended stator flux vector control for a seven-phase induction motor is presented. Chapter 9 concerns the high torque density applications and in Chapter 10 different fault tolerant control strategies are analyzed. Finally, the last chapter presents a positioning multi-motor drive consisting of two PM tubular five-phase actuators fed by a single five-phase inverter.