An efficient Jeans modelling of axisymmetric galaxies with multiple stellar components

Dynamical models of stellar systems represent a powerful tool to study their internal structure and dynamics, to interpret the observed morphological and kinematical fields, and also to support numerical simulations of their evolution. We present a method especially designed to build axisymmetric Jeans models of galaxies, assumed as stationary and collisionless stellar systems. The aim is the development of a rigorous and flexible modelling procedure of multicomponent galaxies, composed of different stellar and dark matter distributions, and a central supermassive black hole. The stellar components, in particular, are intended to represent different galaxy structures, such as discs, bulges, halos, and can then have different structural (density profile, flattening, mass, scale-length), dynamical (rotation, velocity dispersion anisotropy), and population (age, metallicity, initial mass function, mass-to-light ratio) properties. The theoretical framework supporting the modelling procedure is presented, with the introduction of a suitable nomenclature, and its numerical implementation is discussed, with particular reference to the numerical code JASMINE2, developed for this purpose. We propose an approach for efficiently scaling the contributions in mass, luminosity, and rotational support, of the different matter components, allowing for fast and flexible explorations of the model parameter space. We also offer different methods of the computation of the gravitational potentials associated of the density components, especially convenient for their easier numerical tractability. A few galaxy models are studied, showing internal, and projected, structural and dynamical properties of multicomponent galaxies, with a focus on axisymmetric early-type galaxies with complex kinematical morphologies. The application of galaxy models to the study of initial conditions for hydro-dynamical and $N$-body simulations of galaxy evolution is also addressed, allowing in particular to investigate the large number of interesting combinations of the parameters which determine the structure and dynamics of complex multicomponent stellar systems.

Exploring the internal kinematics of Galactic Globular Cluster cores

Globular clusters (GCs) are traditionally described as simple quasi-relaxed non-rotating stellar systems, characterized by spherical symmetry and isotropy in velocity space. However, recent studies have shown deviations from isotropic velocity distributions and significant internal rotation in many GCs, suggesting that their internal structure and kinematics are more complex than previously thought. The aim of this thesis is to investigate the internal kinematics of Galactic Globular Clusters (GGCs) as part of the Multi-Instrument Kinematic Survey (MIKiS), which exploits the capabilities of different ESO-VLT spectrographs to obtain comprehensive velocity dispersion (VD) and rotation profiles of GGCs. Moreover, this thesis has the particular goal of unraveling the kinematics of GC cores, which are still largely unexplored, by taking advantage of the exceptional spatial resolution of the adaptive-optics assisted integral-field spectrograph MUSE/NFM. The thesis presents a thorough kinematic study of three GGCs NGC 1904, NGC 6440, and NGC 6569. By combining the data sets acquired with four different spectrographs, we obtained the radial velocity (RV) of more than 1000 individual stars in each cluster, sampling from the innermost to the outermost regions. This allowed us to obtain the entire VD profile of each cluster and exclude the presence of an intermediate-mass black hole in the core of NGC 1904, at odds with previous findings obtained from integrated-light spectra. The studies also revealed signatures of internal rotation in each of the GCs studied. These results, supported by those of N-body simulations, prove that GCs were born with a significant initial rotation that they gradually lost through internal two-body relaxation and angular momentum loss carried away by escaping stars. Furthermore, we derived the structural parameters of NGC 6440 and NGC 6569, obtaining a comprehensive overview of the internal kinematics and structure of these GCs, which is necessary to properly reconstruct the evolutionary history of these systems.

Numerical simulations of the spine for patient-specific models of severe scoliosis

In silico methods, such as musculoskeletal modelling, may aid the selection of the optimal surgical treatment for highly complex pathologies such as scoliosis. Many musculoskeletal models use a generic, simplified representation of the intervertebral joints, which are fundamental to the flexibility of the spine. Therefore, to model and simulate the spine, a suitable representation of the intervertebral joint is crucial. The aim of this PhD was to characterise specimen-specific models of the intervertebral joint for multi-body models from experimental datasets. First, the project investigated the characterisation of a specimen-specific lumped parameter model of the intervertebral joint from an experimental dataset of a four-vertebra lumbar spine segment. Specimen-specific stiffnesses were determined with an optimisation method. The sensitivity of the parameters to the joint pose was investigate. Results showed the stiffnesses and predicted motions were highly depended on both the joint pose. Following the first study, the method was reapplied to another dataset that included six complete lumbar spine segments under three different loading conditions. Specimen-specific uniform stiffnesses across joint levels and level-dependent stiffnesses were calculated by optimisation. Specimen-specific stiffness show high inter-specimen variability and were also specific to the loading condition. Level-dependent stiffnesses are necessary for accurate kinematic predictions and should be determined independently of one another. Secondly, a framework to create subject-specific musculoskeletal models of individuals with severe scoliosis was developed. This resulted in a robust codified pipeline for creating subject-specific, severely scoliotic spine models from CT data. In conclusion, this thesis showed that specimen-specific intervertebral joint stiffnesses were highly sensitive to joint pose definition and the importance of level-dependent optimisation. Further, an open-source codified pipeline to create patient-specific scoliotic spine models from CT data was released. These studies and this pipeline can facilitate the specimen-specific characterisation of the scoliotic intervertebral joint and its incorporation into scoliotic musculoskeletal spine models.

Analisi degli aspetti di qualità nella gestione dei sistemi di drenaggio urbano attraverso modellazione numerica e indagini di campo

In order to protect river water quality, highly affected in urban areas by continuos as intermittent immissions, it is necessary to adopt measures to intercept and treat these polluted flows. In particular during rain events, river water quality is affected by CSOs activation. Built in order to protect the sewer system and the WWTP by increased flows due to heavy rains, CSOs divert excess flows to the receiving water body. On the basis of several scientific papers, and of direct evidences as well, that demonstrate the detrimental effect of CSOs discharges, also the legislative framework moved towards a stream standard point of view. The WFD (EU/69/2000) sets new goals for receiving water quality, and groundwater as well, through an integrated immission/emissions phylosophy, in which emission limits are associated with effluent standards, based on the receiving water characteristics and their specific use. For surface waters the objective is that of a “good” ecological and chemical quality status. A surface water is defined as of good ecological quality if there is only slight departure from the biological community that would be expected in conditions of minimal anthropogenic impact. Each Member State authority is responsible for preparing and implementing a River Basin Management Plan to achieve the good ecological quality, and comply with WFD requirements. In order to cope with WFD targets, and thus to improve urban receiving water quality, a CSOs control strategy need to be implemented. Temporarily storing the overflow (or at least part of it) into tanks and treating it in the WWTP, after the end of the storm, showed good results in reducing total pollutant mass spilled into the receiving river. Italian State Authority, in order to comply with WFD statements, sets general framework, and each Region has to adopt a Water Remediation Plan (PTA, Piano Tutela Acque), setting goals, methods, and terms, to improve river water quality. Emilia Romagna PTA sets 25% reduction up to 2008, and 50% reduction up to 2015 fo total pollutants masses delivered by CSOs spills. In order to plan remediation actions, a deep insight into spills dynamics is thus of great importance. The present thesis tries to understand spills dynamics through a numerical and an experimental approach. A four months monitoring and sampling campaign was set on the Bologna sewer network, and on the Navile Channel, that is the WWTP receiving water , and that receives flows from up to 28 CSOs during rain events. On the other hand, the full model of the sewer network, was build with the commercial software InfoWorks CS. The model was either calibrated with the data from the monitoring and sampling campaign. Through further model simulations interdependencies among masses spilled, rain characteristics and basin characteristics are looked for. The thesis can be seen as a basis for further insighs and for planning remediation actions.

Study of silicon-on-insulator multiple-gate MOS structures including band-gap engineering and self heating effects

The progresses of electron devices integration have proceeded for more than 40 years following the well–known Moore’s law, which states that the transistors density on chip doubles every 24 months. This trend has been possible due to the downsizing of the MOSFET dimensions (scaling); however, new issues and new challenges are arising, and the conventional ”bulk” architecture is becoming inadequate in order to face them. In order to overcome the limitations related to conventional structures, the researchers community is preparing different solutions, that need to be assessed. Possible solutions currently under scrutiny are represented by: • devices incorporating materials with properties different from those of silicon, for the channel and the source/drain regions; • new architectures as Silicon–On–Insulator (SOI) transistors: the body thickness of Ultra-Thin-Body SOI devices is a new design parameter, and it permits to keep under control Short–Channel–Effects without adopting high doping level in the channel. Among the solutions proposed in order to overcome the difficulties related to scaling, we can highlight heterojunctions at the channel edge, obtained by adopting for the source/drain regions materials with band–gap different from that of the channel material. This solution allows to increase the injection velocity of the particles travelling from the source into the channel, and therefore increase the performance of the transistor in terms of provided drain current. The first part of this thesis work addresses the use of heterojunctions in SOI transistors: chapter 3 outlines the basics of the heterojunctions theory and the adoption of such approach in older technologies as the heterojunction–bipolar–transistors; moreover the modifications introduced in the Monte Carlo code in order to simulate conduction band discontinuities are described, and the simulations performed on unidimensional simplified structures in order to validate them as well. Chapter 4 presents the results obtained from the Monte Carlo simulations performed on double–gate SOI transistors featuring conduction band offsets between the source and drain regions and the channel. In particular, attention has been focused on the drain current and to internal quantities as inversion charge, potential energy and carrier velocities. Both graded and abrupt discontinuities have been considered. The scaling of devices dimensions and the adoption of innovative architectures have consequences on the power dissipation as well. In SOI technologies the channel is thermally insulated from the underlying substrate by a SiO2 buried–oxide layer; this SiO2 layer features a thermal conductivity that is two orders of magnitude lower than the silicon one, and it impedes the dissipation of the heat generated in the active region. Moreover, the thermal conductivity of thin semiconductor films is much lower than that of silicon bulk, due to phonon confinement and boundary scattering. All these aspects cause severe self–heating effects, that detrimentally impact the carrier mobility and therefore the saturation drive current for high–performance transistors; as a consequence, thermal device design is becoming a fundamental part of integrated circuit engineering. The second part of this thesis discusses the problem of self–heating in SOI transistors. Chapter 5 describes the causes of heat generation and dissipation in SOI devices, and it provides a brief overview on the methods that have been proposed in order to model these phenomena. In order to understand how this problem impacts the performance of different SOI architectures, three–dimensional electro–thermal simulations have been applied to the analysis of SHE in planar single and double–gate SOI transistors as well as FinFET, featuring the same isothermal electrical characteristics. In chapter 6 the same simulation approach is extensively employed to study the impact of SHE on the performance of a FinFET representative of the high–performance transistor of the 45 nm technology node. Its effects on the ON–current, the maximum temperatures reached inside the device and the thermal resistance associated to the device itself, as well as the dependence of SHE on the main geometrical parameters have been analyzed. Furthermore, the consequences on self–heating of technological solutions such as raised S/D extensions regions or reduction of fin height are explored as well. Finally, conclusions are drawn in chapter 7.

Computational investigations of ion conduction mechanisms using enhanced sampling methods

Proper ion channels’ functioning is a prerequisite for a normal cell and disorders involving ion channels, or channelopathies, underlie many human diseases. Long QT syndromes (LQTS) for example may arise from the malfunctioning of hERG channel, caused either by the binding of drugs or mutations in HERG gene. In the first part of this thesis I present a framework to investigate the mechanism of ion conduction through hERG channel. The free energy profile governing the elementary steps of ion translocation in the pore was computed by means of umbrella sampling simulations. Compared to previous studies, we detected a different dynamic behavior: according to our data hERG is more likely to mediate a conduction mechanism which has been referred to as “single-vacancy-like” by Roux and coworkers (2001), rather then a “knock-on” mechanism. The same protocol was applied to a model of hERG presenting the Gly628Ser mutation, found to be cause of congenital LQTS. The results provided interesting insights about the reason of the malfunctioning of the mutant channel. Since they have critical functions in viruses’ life cycle, viral ion channels, such as M2 proton channel, are considered attractive targets for antiviral therapy. A deep knowledge of the mechanisms that the virus employs to survive in the host cell is of primary importance in the identification of new antiviral strategies. In the second part of this thesis I shed light on the role that M2 plays in the control of electrical potential inside the virus, being the charge equilibration a condition required to allow proton influx. The ion conduction through M2 was simulated using metadynamics technique. Based on our results we suggest that a potential anion-mediated cation-proton exchange, as well as a direct anion-proton exchange could both contribute to explain the activity of the M2 channel.

Stereotactict body radiotherapy (SBRT)

Purpose: evaluation and comparison of volumetric modulated RapidarcTM radiotherapy (RA-IMRT) vs linac based Stereotactic body radiotherapy (SBRT) in the salvage treatment of isolated lymph node recurrences in patients affected by gynaecological cancer. Materials and Methods From January 2010 to September 2011, 15 patients affected by isolated lymph nodes recurrence of gynaecological cancer underwent salvage radiotherapy after conventional imaging staging with CT and 18-FDG-PET/CT. Two different radiotherapy techniques were used in this study: RA-IMRT (RapidarcTM implemented radiotherapy Varian Medical System, Palo Alto, CA, USA) or SBRT (BrainLAB, Feldkirchen, Germany). Five patients underwent CT scan and all patients underwent 18FDG-PET/CT for pre-treatment evaluation and staging. The mean total dose delivered was 54.3 Gy (range 50-60 Gy with conventional fractionation and 27.4 Gy (range 12-40 Gy hypofractionation) for RA-IMRT and SBRT respectively. The mean number of fractions was 27.6 fractions (range 25-31) and 3-4 fractions , the mean overall treatment duration was 40.5 days (range 36-45) and 6.5 days (range 5-8 days) for RA-IMRT and SBRT respectively. Results: At the time of the analysis, October 2011, the overall survival was 92.3 % (80% for RA-IMRT and 100% for SBRT). Six patients are alive with no evidence of disease and also six patients are alive with clinically evident disease in other sites (40% and 50% patients RA-IMRT vs SBRT respectively, one patient died for systemic progression of disease and two patient were not evaluable at this time. Conclusions: Our preliminary results showed that, the use of RA-IMRT and SBRT are an excellent local therapy for isolated lymph nodes recurrences of gynaecological cancer with a good toxicity profile and local control rate, even if any long term survivors would be expected. New treatment modalities like Cyberknife are also being implemented.

From fall-risk assessment to fall detection: inertial sensors in the clinical routine and daily life

Falls are caused by complex interaction between multiple risk factors which may be modified by age, disease and environment. A variety of methods and tools for fall risk assessment have been proposed, but none of which is universally accepted. Existing tools are generally not capable of providing a quantitative predictive assessment of fall risk. The need for objective, cost-effective and clinically applicable methods would enable quantitative assessment of fall risk on a subject-specific basis. Tracking objectively falls risk could provide timely feedback about the effectiveness of administered interventions enabling intervention strategies to be modified or changed if found to be ineffective. Moreover, some of the fundamental factors leading to falls and what actually happens during a fall remain unclear. Objectively documented and measured falls are needed to improve knowledge of fall in order to develop more effective prevention strategies and prolong independent living. In the last decade, several research groups have developed sensor-based automatic or semi-automatic fall risk assessment tools using wearable inertial sensors. This approach may also serve to detect falls. At the moment, i) several fall-risk assessment studies based on inertial sensors, even if promising, lack of a biomechanical model-based approach which could provide accurate and more detailed measurements of interests (e.g., joint moments, forces) and ii) the number of published real-world fall data of older people in a real-world environment is minimal since most authors have used simulations with healthy volunteers as a surrogate for real-world falls. With these limitations in mind, this thesis aims i) to suggest a novel method for the kinematics and dynamics evaluation of functional motor tasks, often used in clinics for the fall-risk evaluation, through a body sensor network and a biomechanical approach and ii) to define the guidelines for a fall detection algorithm based on a real-world fall database availability.

Iterative regularization methods for ill-posed problems

This Ph.D thesis focuses on iterative regularization methods for regularizing linear and nonlinear ill-posed problems. Regarding linear problems, three new stopping rules for the Conjugate Gradient method applied to the normal equations are proposed and tested in many numerical simulations, including some tomographic images reconstruction problems. Regarding nonlinear problems, convergence and convergence rate results are provided for a Newton-type method with a modified version of Landweber iteration as an inner iteration in a Banach space setting.

Plasticity in body and peripersonal space representations

A successful interaction with objects in the environment requires integrating information concerning object-location with the shape, dimension and position of body parts in space. The former information is coded in a multisensory representation of the space around the body, i.e. peripersonal space (PPS), whereas the latter is enabled by an online, constantly updated, action-orientated multisensory representation of the body (BR) that is critical for action. One of the critical features of these representations is that both PPS and BR are not fixed, but they dynamically change depending on different types of experience. In a series of experiment, I studied plastic properties of PPS and BR in humans. I have developed a series of methods to measure the boundaries of PPS representation (Chapter 4), to study its neural correlates (Chapter 3) and to assess BRs. These tasks have been used to study changes in PPS and BR following tool-use (Chapter 5), multisensory stimulation (Chapter 6), amputation and prosthesis implantation (Chapter 7) or social interaction (Chapter 8). I found that changes in the function (tool-use) and the structure (amputation and prosthesis implantation) of the physical body elongate or shrink both PPS and BR. Social context and social interaction also shape PPS representation. Such high degree of plasticity suggests that our sense of body in space is not given at once, but it is constantly constructed and adapted through experience.

Computational Methods in Biophysics and Medicinal Chemistry: Applications and Challenges

In this thesis I described the theory and application of several computational methods in solving medicinal chemistry and biophysical tasks. I pointed out to the valuable information which could be achieved by means of computer simulations and to the possibility to predict the outcome of traditional experiments. Nowadays, computer represents an invaluable tool for chemists. In particular, the main topics of my research consisted in the development of an automated docking protocol for the voltage-gated hERG potassium channel blockers, and the investigation of the catalytic mechanism of the human peptidyl-prolyl cis-trans isomerase Pin1.

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.

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

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

Large Eddy Simulations applied to wind loading and pollutant dispersion

The application of Computational Fluid Dynamics based on the Reynolds-Averaged Navier-Stokes equations to the simulation of bluff body aerodynamics has been thoroughly investigated in the past. Although a satisfactory accuracy can be obtained for some urban physics problems their predictive capability is limited to the mean flow properties, while the ability to accurately predict turbulent fluctuations is recognized to be of fundamental importance when dealing with wind loading and pollution dispersion problems. The need to correctly take into account the flow dynamics when such problems are faced has led researchers to move towards scale-resolving turbulence models such as Large Eddy Simulations (LES). The development and assessment of LES as a tool for the analysis of these problems is nowadays an active research field and represents a demanding engineering challenge. This research work has two objectives. The first one is focused on wind loads assessment and aims to study the capabilities of LES in reproducing wind load effects in terms of internal forces on structural members. This differs from the majority of the existing research, where performance of LES is evaluated only in terms of surface pressures, and is done with a view of adopting LES as a complementary design tools alongside wind tunnel tests. The second objective is the study of LES capabilities in calculating pollutant dispersion in the built environment. The validation of LES in this field is considered to be of the utmost importance in order to conceive healthier and more sustainable cities. In order to validate the numerical setup adopted, a systematic comparison between numerical and experimental data is performed. The obtained results are intended to be used in the drafting of best practice guidelines for the application of LES in the urban physics field with a particular attention to wind load assessment and pollution dispersion problems.

mHealth-based Methods for Neuromotor Assessment and Rehabilitation

Recent years observed massive growth in wearable technology, everything can be smart: phones, watches, glasses, shirts, etc. These technologies are prevalent in various fields: from wellness/sports/fitness to the healthcare domain. The spread of this phenomenon led the World-Health-Organization to define the term 'mHealth' as "medical and public health practice supported by mobile devices, such as mobile phones, patient monitoring devices, personal digital assistants, and other wireless devices". Furthermore, mHealth solutions are suitable to perform real-time wearable Biofeedback (BF) systems: sensors in the body area network connected to a processing unit (smartphone) and a feedback device (loudspeaker) to measure human functions and return them to the user as (bio)feedback signal. During the COVID-19 pandemic, this transformation of the healthcare system has been dramatically accelerated by new clinical demands, including the need to prevent hospital surges and to assure continuity of clinical care services, allowing pervasive healthcare. Never as of today, we can say that the integration of mHealth technologies will be the basis of this new era of clinical practice. In this scenario, this PhD thesis's primary goal is to investigate new and innovative mHealth solutions for the Assessment and Rehabilitation of different neuromotor functions and diseases. For the clinical assessment, there is the need to overcome the limitations of subjective clinical scales. Creating new pervasive and self-administrable mHealth solutions, this thesis investigates the possibility of employing innovative systems for objective clinical evaluation. For rehabilitation, we explored the clinical feasibility and effectiveness of mHealth systems. In particular, we developed innovative mHealth solutions with BF capability to allow tailored rehabilitation. The main goal that a mHealth-system should have is improving the person's quality of life, increasing or maintaining his autonomy and independence. To this end, inclusive design principles might be crucial, next to the technical and technological ones, to improve mHealth-systems usability.