Molecular bases, pathogenic mechanisms and possible therapeutic approach in Leber's Hereditary Optic Neuropathy

Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by a rapid loss of central vision and optic atrophy, due to the selective degeneration of retinal ganglion cells. The age of onset is around 20, and the degenerative process is fast and usually the second eye becomes affected in weeks or months. Even if this pathology is well known and has been well characterized, there are still open questions on its pathophysiology, such as the male prevalence, the incomplete penetrance and the tissue selectivity. This maternally inherited disease is caused by mutations in mitochondrial encoded genes of NADH ubiquinone oxidoreductase (complex I) of the respiratory chain. The 90% of LHON cases are caused by one of the three common mitochondrial DNA mutations (11778/ND4, 14484/ND6 and 3460/ND1) and the remaining 10% is caused by rare pathogenic mutations, reported in literature in one or few families. Moreover, there is also a small subset of patients reported with new putative pathogenic nucleotide changes, which awaits to be confirmed. We here clarify some molecular aspects of LHON, mainly the incomplete penetrance and the role of rare mtDNA mutations or variants on LHON expression, and attempt a possible therapeutic approach using the cybrids cell model. We generated novel structural models for mitochondrial encoded complex I subunits and a conservation analysis and pathogenicity prediction have been carried out for LHON reported mutations. This in-silico approach allowed us to locate LHON pathogenic mutations in defined and conserved protein domains and can be a useful tool in the analysis of novel mtDNA variants with unclear pathogenic/functional role. Four rare LHON pathogenic mutations have been identified, confirming that the ND1 and ND6 genes are mutational hot spots for LHON. All mutations were previously described at least once and we validated their pathogenic role, suggesting the need for their screening in LHON diagnostic protocols. Two novel mtDNA variants with a possible pathogenic role have been also identified in two independent branches of a large pedigree. Functional studies are necessary to define their contribution to LHON in this family. It also been demonstrated that the combination of mtDNA rare polymorphic variants is relevant in determining the maternal recurrence of myoclonus in unrelated LHON pedigrees. Thus, we suggest that particular mtDNA backgrounds and /or the presence of specific rare mutations may increase the pathogenic potential of the primary LHON mutations, thereby giving rise to the extraocular clinical features characteristic of the LHON “plus” phenotype. We identified the first molecular parameter that clearly discriminates LHON affected individuals from asymptomatic carriers, the mtDNA copy number. This provides a valuable mechanism for future investigations on variable penetrance in LHON. However, the increased mtDNA content in LHON individuals was not correlated to the functional polymorphism G1444A of PGC-1 alpha, the master regulator of mitochondrial biogenesis, but may be due to gene expression of genes involved in this signaling pathway, such as PGC-1 alpha/beta and Tfam. Future studies will be necessary to identify the biochemical effects of rare pathogenic mutations and to validate the novel candidate mutations here described, in terms of cellular bioenergetic characterization of these variants. Moreover, we were not able to induce mitochondrial biogenesis in cybrids cell lines using bezafibrate. However, other cell line models are available, such as fibroblasts harboring LHON mutations, or other approaches can be used to trigger the mitochondrial biogenesis.

Computer simulation of ordering and dynamics in liquid crystals in the bulk and close to the surface

The aim of this PhD thesis is to investigate the orientational and dynamical properties of liquid crystalline systems, at molecular level and using atomistic computer simulations, to reach a better understanding of material behavior from a microscopic point view. In perspective this should allow to clarify the relation between the micro and macroscopic properties with the objective of predicting or confirming experimental results on these systems. In this context, we developed four different lines of work in the thesis. The first one concerns the orientational order and alignment mechanism of rigid solutes of small dimensions dissolved in a nematic phase formed by the 4-pentyl,4 cyanobiphenyl (5CB) nematic liquid crystal. The orientational distribution of solutes have been obtained with Molecular Dynamics Simulation (MD) and have been compared with experimental data reported in literature. we have also verified the agreement between order parameters and dipolar coupling values measured in NMR experiments. The MD determined effective orientational potentials have been compared with the predictions of Maier­Saupe and Surface tensor models. The second line concerns the development of a correct parametrization able to reproduce the phase transition properties of a prototype of the oligothiophene semiconductor family: sexithiophene (T6). T6 forms two crystalline polymorphs largely studied, and possesses liquid crystalline phases still not well characterized, From simulations we detected a phase transition from crystal to liquid crystal at about 580 K, in agreement with available experiments, and in particular we found two LC phases, smectic and nematic. The crystal­smectic transition is associated to a relevant density variation and to strong conformational changes of T6, namely the molecules in the liquid crystal phase easily assume a bent shape, deviating from the planar structure typical of the crystal. The third line explores a new approach for calculating the viscosity in a nematic through a virtual exper- iment resembling the classical falling sphere experiment. The falling sphere is replaced by an hydrogenated silicon nanoparticle of spherical shape suspended in 5CB, and gravity effects are replaced by a constant force applied to the nanoparticle in a selected direction. Once the nanoparticle reaches a constant velocity, the viscosity of the medium can be evaluated using Stokes' law. With this method we successfully reproduced experimental viscosities and viscosity anisotropy for the solvent 5CB. The last line deals with the study of order induction on nematic molecules by an hydrogenated silicon surface. Gaining predicting power for the anchoring behavior of liquid crystals at surfaces will be a very desirable capability, as many properties related to devices depend on molecular organization close to surfaces. Here we studied, by means of atomistic MD simulations, the flat interface between an hydrogenated (001) silicon surface in contact with a sample of 5CB molecules. We found a planar anchoring of the first layers of 5CB where surface interactions are dominating with respect to the mesogen intermolecular interactions. We also analyzed the interface 5CB­vacuum, finding a homeotropic orientation of the nematic at this interface.

Aspects of Integrability in Gauge/String Correspondence

In this thesis, we present our work about some generalisations of ideas, techniques and physical interpretations typical for integrable models to one of the most outstanding advances in theoretical physics of nowadays: the AdS/CFT correspondences. We have undertaken the problem of testing this conjectured duality under various points of view, but with a clear starting point - the integrability - and with a clear ambitious task in mind: to study the finite-size effects in the energy spectrum of certain string solutions on a side and in the anomalous dimensions of the gauge theory on the other. Of course, the final desire woul be the exact comparison between these two faces of the gauge/string duality. In few words, the original part of this work consists in application of well known integrability technologies, in large parte borrowed by the study of relativistic (1+1)-dimensional integrable quantum field theories, to the highly non-relativisic and much complicated case of the thoeries involved in the recent conjectures of AdS5/CFT4 and AdS4/CFT3 corrspondences. In details, exploiting the spin chain nature of the dilatation operator of N = 4 Super-Yang-Mills theory, we concentrated our attention on one of the most important sector, namely the SL(2) sector - which is also very intersting for the QCD understanding - by formulating a new type of nonlinear integral equation (NLIE) based on a previously guessed asymptotic Bethe Ansatz. The solutions of this Bethe Ansatz are characterised by the length L of the correspondent spin chain and by the number s of its excitations. A NLIE allows one, at least in principle, to make analytical and numerical calculations for arbitrary values of these parameters. The results have been rather exciting. In the important regime of high Lorentz spin, the NLIE clarifies how it reduces to a linear integral equations which governs the subleading order in s, o(s0). This also holds in the regime with L ! 1, L/ ln s finite (long operators case). This region of parameters has been particularly investigated in literature especially because of an intriguing limit into the O(6) sigma model defined on the string side. One of the most powerful methods to keep under control the finite-size spectrum of an integrable relativistic theory is the so called thermodynamic Bethe Ansatz (TBA). We proposed a highly non-trivial generalisation of this technique to the non-relativistic case of AdS5/CFT4 and made the first steps in order to determine its full spectrum - of energies for the AdS side, of anomalous dimensions for the CFT one - at any values of the coupling constant and of the size. At the leading order in the size parameter, the calculation of the finite-size corrections is much simpler and does not necessitate the TBA. It consists in deriving for a nonrelativistc case a method, invented for the first time by L¨uscher to compute the finite-size effects on the mass spectrum of relativisic theories. So, we have formulated a new version of this approach to adapt it to the case of recently found classical string solutions on AdS4 × CP3, inside the new conjecture of an AdS4/CFT3 correspondence. Our results in part confirm the string and algebraic curve calculations, in part are completely new and then could be better understood by the rapidly evolving developments of this extremely exciting research field.

Modellazione multibody di veicoli ferroviari: sviluppo ed implementazione di modelli innovativi per l'analisi del contatto ruota - rotaia

The wheel - rail contact analysis plays a fundamental role in the multibody modeling of railway vehicles. A good contact model must provide an accurate description of the global contact phenomena (contact forces and torques, number and position of the contact points) and of the local contact phenomena (position and shape of the contact patch, stresses and displacements). The model has also to assure high numerical efficiency (in order to be implemented directly online within multibody models) and a good compatibility with commercial multibody software (Simpack Rail, Adams Rail). The wheel - rail contact problem has been discussed by several authors and many models can be found in the literature. The contact models can be subdivided into two different categories: the global models and the local (or differential) models. Currently, as regards the global models, the main approaches to the problem are the so - called rigid contact formulation and the semi – elastic contact description. The rigid approach considers the wheel and the rail as rigid bodies. The contact is imposed by means of constraint equations and the contact points are detected during the dynamic simulation by solving the nonlinear algebraic differential equations associated to the constrained multibody system. Indentation between the bodies is not permitted and the normal contact forces are calculated through the Lagrange multipliers. Finally the Hertz’s and the Kalker’s theories allow to evaluate the shape of the contact patch and the tangential forces respectively. Also the semi - elastic approach considers the wheel and the rail as rigid bodies. However in this case no kinematic constraints are imposed and the indentation between the bodies is permitted. The contact points are detected by means of approximated procedures (based on look - up tables and simplifying hypotheses on the problem geometry). The normal contact forces are calculated as a function of the indentation while, as in the rigid approach, the Hertz’s and the Kalker’s theories allow to evaluate the shape of the contact patch and the tangential forces. Both the described multibody approaches are computationally very efficient but their generality and accuracy turn out to be often insufficient because the physical hypotheses behind these theories are too restrictive and, in many circumstances, unverified. In order to obtain a complete description of the contact phenomena, local (or differential) contact models are needed. In other words wheel and rail have to be considered elastic bodies governed by the Navier’s equations and the contact has to be described by suitable analytical contact conditions. The contact between elastic bodies has been widely studied in literature both in the general case and in the rolling case. Many procedures based on variational inequalities, FEM techniques and convex optimization have been developed. This kind of approach assures high generality and accuracy but still needs very large computational costs and memory consumption. Due to the high computational load and memory consumption, referring to the current state of the art, the integration between multibody and differential modeling is almost absent in literature especially in the railway field. However this integration is very important because only the differential modeling allows an accurate analysis of the contact problem (in terms of contact forces and torques, position and shape of the contact patch, stresses and displacements) while the multibody modeling is the standard in the study of the railway dynamics. In this thesis some innovative wheel – rail contact models developed during the Ph. D. activity will be described. Concerning the global models, two new models belonging to the semi – elastic approach will be presented; the models satisfy the following specifics: 1) the models have to be 3D and to consider all the six relative degrees of freedom between wheel and rail 2) the models have to consider generic railway tracks and generic wheel and rail profiles 3) the models have to assure a general and accurate handling of the multiple contact without simplifying hypotheses on the problem geometry; in particular the models have to evaluate the number and the position of the contact points and, for each point, the contact forces and torques 4) the models have to be implementable directly online within the multibody models without look - up tables 5) the models have to assure computation times comparable with those of commercial multibody software (Simpack Rail, Adams Rail) and compatible with RT and HIL applications 6) the models have to be compatible with commercial multibody software (Simpack Rail, Adams Rail). The most innovative aspect of the new global contact models regards the detection of the contact points. In particular both the models aim to reduce the algebraic problem dimension by means of suitable analytical techniques. This kind of reduction allows to obtain an high numerical efficiency that makes possible the online implementation of the new procedure and the achievement of performance comparable with those of commercial multibody software. At the same time the analytical approach assures high accuracy and generality. Concerning the local (or differential) contact models, one new model satisfying the following specifics will be presented: 1) the model has to be 3D and to consider all the six relative degrees of freedom between wheel and rail 2) the model has to consider generic railway tracks and generic wheel and rail profiles 3) the model has to assure a general and accurate handling of the multiple contact without simplifying hypotheses on the problem geometry; in particular the model has to able to calculate both the global contact variables (contact forces and torques) and the local contact variables (position and shape of the contact patch, stresses and displacements) 4) the model has to be implementable directly online within the multibody models 5) the model has to assure high numerical efficiency and a reduced memory consumption in order to achieve a good integration between multibody and differential modeling (the base for the local contact models) 6) the model has to be compatible with commercial multibody software (Simpack Rail, Adams Rail). In this case the most innovative aspects of the new local contact model regard the contact modeling (by means of suitable analytical conditions) and the implementation of the numerical algorithms needed to solve the discrete problem arising from the discretization of the original continuum problem. Moreover, during the development of the local model, the achievement of a good compromise between accuracy and efficiency turned out to be very important to obtain a good integration between multibody and differential modeling. At this point the contact models has been inserted within a 3D multibody model of a railway vehicle to obtain a complete model of the wagon. The railway vehicle chosen as benchmark is the Manchester Wagon the physical and geometrical characteristics of which are easily available in the literature. The model of the whole railway vehicle (multibody model and contact model) has been implemented in the Matlab/Simulink environment. The multibody model has been implemented in SimMechanics, a Matlab toolbox specifically designed for multibody dynamics, while, as regards the contact models, the CS – functions have been used; this particular Matlab architecture allows to efficiently connect the Matlab/Simulink and the C/C++ environment. The 3D multibody model of the same vehicle (this time equipped with a standard contact model based on the semi - elastic approach) has been then implemented also in Simpack Rail, a commercial multibody software for railway vehicles widely tested and validated. Finally numerical simulations of the vehicle dynamics have been carried out on many different railway tracks with the aim of evaluating the performances of the whole model. The comparison between the results obtained by the Matlab/ Simulink model and those obtained by the Simpack Rail model has allowed an accurate and reliable validation of the new contact models. In conclusion to this brief introduction to my Ph. D. thesis, we would like to thank Trenitalia and the Regione Toscana for the support provided during all the Ph. D. activity. Moreover we would also like to thank the INTEC GmbH, the society the develops the software Simpack Rail, with which we are currently working together to develop innovative toolboxes specifically designed for the wheel rail contact analysis.

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.

A bayesian model for mixed responses and skew laten variable to measure HRQoL in children

The aim of the thesi is to formulate a suitable Item Response Theory (IRT) based model to measure HRQoL (as latent variable) using a mixed responses questionnaire and relaxing the hypothesis of normal distributed latent variable. The new model is a combination of two models already presented in literature, that is, a latent trait model for mixed responses and an IRT model for Skew Normal latent variable. It is developed in a Bayesian framework, a Markov chain Monte Carlo procedure is used to generate samples of the posterior distribution of the parameters of interest. The proposed model is test on a questionnaire composed by 5 discrete items and one continuous to measure HRQoL in children, the EQ-5D-Y questionnaire. A large sample of children collected in the schools was used. In comparison with a model for only discrete responses and a model for mixed responses and normal latent variable, the new model has better performances, in term of deviance information criterion (DIC), chain convergences times and precision of the estimates.

Designing and Programming Organizational Infrastructures for Agents situated in Artifact-based Environments

Actual trends in software development are pushing the need to face a multiplicity of diverse activities and interaction styles characterizing complex and distributed application domains, in such a way that the resulting dynamics exhibits some grade of order, i.e. in terms of evolution of the system and desired equilibrium. Autonomous agents and Multiagent Systems are argued in literature as one of the most immediate approaches for describing such a kind of challenges. Actually, agent research seems to converge towards the definition of renewed abstraction tools aimed at better capturing the new demands of open systems. Besides agents, which are assumed as autonomous entities purposing a series of design objectives, Multiagent Systems account new notions as first-class entities, aimed, above all, at modeling institutional/organizational entities, placed for normative regulation, interaction and teamwork management, as well as environmental entities, placed as resources to further support and regulate agent work. The starting point of this thesis is recognizing that both organizations and environments can be rooted in a unifying perspective. Whereas recent research in agent systems seems to account a set of diverse approaches to specifically face with at least one aspect within the above mentioned, this work aims at proposing a unifying approach where both agents and their organizations can be straightforwardly situated in properly designed working environments. In this line, this work pursues reconciliation of environments with sociality, social interaction with environment based interaction, environmental resources with organizational functionalities with the aim to smoothly integrate the various aspects of complex and situated organizations in a coherent programming approach. Rooted in Agents and Artifacts (A&A) meta-model, which has been recently introduced both in the context of agent oriented software engineering and programming, the thesis promotes the notion of Embodied Organizations, characterized by computational infrastructures attaining a seamless integration between agents, organizations and environmental entities.

Emerging contaminants in agricultural ecosystems: impact of selected pharmaceutical on water and soil ecology and pratical implications

Pharmaceuticals are useful tools to prevent and treat human and animal diseases. Following administration, a significant fraction of pharmaceuticals is excreted unaltered into faeces and urine and may enter the aquatic ecosystem and agricultural soil through irrigation with recycled water, constituting a significant source of emerging contaminants into the environment. Understanding major factors influencing their environmental fate is consequently needed to value the risk, reduce contamination, and set up bioremediation technologies. The antiviral drug Tamiflu (oseltamivir carboxylate, OC) has received recent attention due to the potential use as a first line defence against H5N1 and H1N1 influenza viruses. Research has shown that OC is not removed during conventional wastewater treatments, thus having the potential to enter surface water bodies. A series of laboratory experiments investigated the fate and the removal of OC in surface water systems in Italy and Japan and in a municipal wastewater treatment plant. A preliminary laboratory study investigated the persistence of the active antiviral drug in water samples from an irrigation canal in northern Italy (Canale Emiliano Romagnolo). After an initial rapid decrease, OC concentration slowly decreased during the remaining incubation period. Approximately 65% of the initial OC amount remained in water at the end of the 36-day incubation period. A negligible amount of OC was lost both from sterilized water and from sterilized water/sediment samples, suggesting a significant role of microbial degradation. Stimulating microbial processes by the addition of sediments resulted in reduced OC persistence. Presence of OC (1.5 μg mL-1) did not significantly affect the metabolic potential of the water microbial population, that was estimated by glyphosate and metolachlor mineralization. In contrast, OC caused an initial transient decrease in the size of the indigenous microbial population of water samples. A second laboratory study focused on basic processes governing the environmental fate of OC in surface water from two contrasting aquatic ecosystems of northern Italy, the River Po and the Venice Lagoon. Results of this study confirmed the potential of OC to persist in surface water. However, the addition of 5% of sediments resulted in rapid OC degradation. The estimated half-life of OC in water/sediment of the River Po was 15 days. After three weeks of incubation at 20 °C, more than 8% of 14C-OC evolved as 14CO2 from water/sediment samples of the River Po and Venice Lagoon. OC was moderately retained onto coarse sediments from the two sites. In water/sediment samples of the River Po and Venice Lagoon treated with 14C-OC, more than 30% of the 14C-residues remained water-extractable after three weeks of incubation. The low affinity of OC to sediments suggests that the presence of sediments would not reduce its bioavailability to microbial degradation. Another series of laboratory experiments investigated the fate and the removal of OC in two surface water ecosystems of Japan and in the municipal wastewater treatment plant of the city of Bologna, in Northern Italy. The persistence of OC in surface water ranged from non-detectable degradation to a half-life of 53 days. After 40 days, less than 3% of radiolabeled OC evolved as 14CO2. The presence of sediments (5%) led to a significant increase of OC degradation and of mineralization rates. A more intense mineralization was observed in samples of the wastewater treatment plant when applying a long incubation period (40 days). More precisely, 76% and 37% of the initial radioactivity applied as 14C-OC was recovered as 14CO2 from samples of the biological tank and effluent water, respectively. Two bacterial strains growing on OC as sole carbon source were isolated and used for its removal from synthetic medium and environmental samples, including surface water and wastewater. Inoculation of water and wastewater samples with the two OC-degrading strains showed that mineralization of OC was significantly higher in both inoculated water and wastewater, than in uninoculated controls. Denaturing gradient gel electrophoresis and quantitative PCR analysis showed that OC would not affect the microbial population of surface water and wastewater. The capacity of the ligninolytic fungus Phanerochaete chrysosporium to degrade a wide variety of environmentally persistent xenobiotics has been largely reported in literature. In a series of laboratory experiments, the efficiency of a formulation using P. chrysosporium was evaluated for the removal of selected pharmaceuticals from wastewater samples. Addition of the fungus to samples of the wastewater treatment plant of Bologna significantly increased (P < 0.05) the removal of OC and three antibiotics, erythromycin, sulfamethoxazole, and ciprofloxacin. Similar effects were also observed in effluent water. OC was the most persistent of the four pharmaceuticals. After 30 days of incubation, approximately two times more OC was removed in bioremediated samples than in controls. The highest removal efficiency of the formulation was observed with the antibiotic ciprofloxacin. The studies included environmental aspects of soil contamination with two emerging veterinary contaminants, such as doramectin and oxibendazole, wich are common parasitic treatments in cattle farms.

Percorsi di gender performance: fotografia tra arte e moda dagli anni Novanta ad oggi

My project explores and compares different forms of gender performance in contemporary art and visual culture according to a perspective centered on photography. Thanks to its attesting power this medium can work as a ready-made. In fact during the 20th century it played a key role in the cultural emancipation of the body which (using a Michel Foucault’s expression) has now become «the zero point of the world». Through performance the body proves to be a living material of expression and communication while photography ensures the recording of any ephemeral event that happens in time and space. My questioning approach considers the gender constructed imagery from the 1990s to the present in order to investigate how photography’s strong aura of realism promotes and allows fantasies of transformation. The contemporary fascination with gender (especially for art and fashion) represents a crucial issue in the global context of postmodernity and is manifested in a variety of visual media, from photography to video and film. Moreover the internet along with its digital transmission of images has deeply affected our world (from culture to everyday life) leading to a postmodern preference for performativity over the more traditional and linear forms of narrativity. As a consequence individual borders get redefined by the skin itself which (dissected through instant vision) turns into a ductile material of mutation and hybridation in the service of identity. My critical assumptions are taken from the most relevant changes occurred in philosophy during the last two decades as a result of the contributions by Jacques Lacan, Michel Foucault, Jacques Derrida, Gilles Deleuze who developed a cross-disciplinary and comparative approach to interpret the crisis of modernity. They have profoundly influenced feminist studies so that the category of gender has been reassessed in contrast with sex (as a biological connotation) and in relation to history, culture, society. The ideal starting point of my research is the year 1990. I chose it as the approximate historical moment when the intersection of race, class and gender were placed at the forefront of international artistic production concerned with identity, diversity and globalization. Such issues had been explored throughout the 1970s but it was only from the mid-1980s onward that they began to be articulated more consistently. Published in 1990, the book "Gender trouble: feminism and the subversion of identity" by Judith Butler marked an important breakthrough by linking gender to performance as well as investigating the intricate connections between theory and practice, embodiment and representation. It inspired subsequent research in a variety of disciplines, art history included. In the same year Teresa de Lauretis launched the definition of queer theory to challenge the academic perspective in gay and lesbian studies. In the meantime the rise of Third Wave Feminism in the US introduced a racially and sexually inclusive vision over the global situation in order to reflect on subjectivity, new technologies and popular culture in connection with gender representation. These conceptual tools have enabled prolific readings of contemporary cultural production whether fine arts or mass media. After discussing the appropriate framework of my project and taking into account the postmodern globalization of the visual, I have turned to photography to map gender representation both in art and in fashion. Therefore I have been creating an archive of images around specific topics. I decided to include fashion photography because in the 1990s this genre moved away from the paradigm of an idealized and classical beauty toward a new vernacular allied with lifestyles, art practices, pop and youth culture; as one might expect the dominant narrative modes in fashion photography are now mainly influenced by cinema and snapshot. These strategies originate story lines and interrupted narratives using models’ performance to convey a particular imagery where identity issues emerge as an essential part of fashion spectacle. Focusing on the intersections of gender identities with socially and culturally produced identities, my approach intends to underline how the fashion world has turned to current trends in art photography and in some case turned to the artists themselves. The growing fluidity of the categories that distinguish art from fashion photography represents a particularly fruitful moment of visual exchange. Varying over time the dialogue between these two fields has always been vital; nowadays it can be studied as a result of this close relationship between contemporary art world and consumer culture. Due to the saturation of postmodern imagery the feedback between art and fashion has become much more immediate and then increasingly significant for anyone who wants to investigate the construction of gender identity through performance. In addition to that a lot of magazines founded in the 1990s bridged the worlds of art and fashion because some of their designers and even editors were art-school graduates encouraging innovation. The inclusion of art within such magazines aimed at validating them as a form of art in themselves supporting a dynamic intersection for music, fashion, design and youth culture: an intersection that also contributed to create and spread different gender stereotypes. This general interest in fashion produced many exhibitions of and about fashion itself at major international venues such as the Victoria and Albert Museum in London, the Metropolitan Museum of Art and the Solomon R. Guggenheim Museum in New York. Since then this celebrated success of fashion has been regarded as a typical element of postmodern culture. Owing to that I have also based my analysis on some important exhibitions dealing with gender performance like "Féminin-Masculin" at the Centre Pompidou of Paris (1995), "Rrose is a Rrose is a Rrose. Gender performance in photography" at the Solomon R. Guggenheim Museum of New York (1997), "Global Feminisms" at the Brooklyn Museum (2007), "Female Trouble" at the Pinakothek der Moderne in München together with the workshops dedicated to "Performance: gender and identity" in June 2005 at the Tate Modern of London. Since 2003 in Italy we have had Gender Bender - an international festival held annually in Bologna - to explore the gender imagery stemming from contemporary culture. In few days this festival offers a series of events ranging from visual arts, performance, cinema, literature to conferences and music. Being aware that any method of research is neither race nor gender neutral I have traced these critical paths to question gender identity in a multicultural perspective taking account of the political implications too. In fact, if visibility may be equated with exposure, we can also read these images as points of intersection of visibility with social power. Since gender assignations rely so heavily on the visual, the postmodern dismantling of gender certainty through performance has wide-ranging effects that need to be analyzed. In some sense this practice can even contest the dominance of visual within postmodernism. My visual map in contemporary art and fashion photography includes artists like Nan Goldin, Cindy Sherman, Hellen van Meene, Rineke Dijkstra, Ed Templeton, Ryan McGinley, Anne Daems, Miwa Yanagi, Tracey Moffat, Catherine Opie, Tomoko Sawada, Vanessa Beecroft, Yasumasa Morimura, Collier Schorr among others.

Theoretical and implementation aspects in the mechanization of the metatheory of programming languages

Interactive theorem provers are tools designed for the certification of formal proofs developed by means of man-machine collaboration. Formal proofs obtained in this way cover a large variety of logical theories, ranging from the branches of mainstream mathematics, to the field of software verification. The border between these two worlds is marked by results in theoretical computer science and proofs related to the metatheory of programming languages. This last field, which is an obvious application of interactive theorem proving, poses nonetheless a serious challenge to the users of such tools, due both to the particularly structured way in which these proofs are constructed, and to difficulties related to the management of notions typical of programming languages like variable binding. This thesis is composed of two parts, discussing our experience in the development of the Matita interactive theorem prover and its use in the mechanization of the metatheory of programming languages. More specifically, part I covers: - the results of our effort in providing a better framework for the development of tactics for Matita, in order to make their implementation and debugging easier, also resulting in a much clearer code; - a discussion of the implementation of two tactics, providing infrastructure for the unification of constructor forms and the inversion of inductive predicates; we point out interactions between induction and inversion and provide an advancement over the state of the art. In the second part of the thesis, we focus on aspects related to the formalization of programming languages. We describe two works of ours: - a discussion of basic issues we encountered in our formalizations of part 1A of the Poplmark challenge, where we apply the extended inversion principles we implemented for Matita; - a formalization of an algebraic logical framework, posing more complex challenges, including multiple binding and a form of hereditary substitution; this work adopts, for the encoding of binding, an extension of Masahiko Sato's canonical locally named representation we designed during our visit to the Laboratory for Foundations of Computer Science at the University of Edinburgh, under the supervision of Randy Pollack.

Human bone: the tissue characteristics determining its mechanical behaviour

The present thesis illustrates the research carried out during the PhD studies in Bioengineering. The research was aimed to characterise the human bone tissue, with particular regard to the differences between cortical and trabecular bone. The bone tissue characteristics that affect its mechanical properties were verified or identified, using an experimental approach, to corroborate or refute hypotheses based on the state of the art in bone tissue biomechanics. The studies presented in the present PhD thesis were designed to investigate aspects of bone tissue biomechanics, which were in need of a more in-depth examination since the data found in the literature was contradictory or scarce. In particular, the work was focalised on the characterisation of the basic structure of the bone tissue (groups of lamellae), its composition, its spatial organisation (trabecular bone microarchitecture) and their influence on the mechanical properties. In conclusion, the present thesis integrates eight different studies on the characterisation of bone tissue. A more in-depth examination of some of the aspects of bone tissue biomechanics where the data found in the literature was contradictory or scarce was performed. Bone tissue was investigated at several scales, from its composition up to its spatial organization, to determine which parameters influence the mechanical behaviour of the tissue. It was found that although the composition and real density of bone tissue are similar, the differences in structure at different levels cause differences between the two types of bone tissue (cortical and trabecular) in mechanical properties. However, the apparent density can still be considered a good predictor of the mechanical properties of both cortical and trabecular bone. Finally, it was found that the bone tissue characteristics might change when a pathology is present, as demonstrated for OA.

L'autovalutazione in età evolutiva: metacognizione e stili attributivi

The aim of the research is to study the capacity for self-evaluation of 271 primary school student undergoing tests involving mathematics and formal reasoning. Subjects were asked to estimate the number of correct answers and subsequently to compare their performance with that of their peers. The results demonstrate that all the subjects in all tests showed a significant negative relationship among real score and self - evaluation indices. Analyzing comparative assessments, the results reported in literature by Kruger and Dunning were confirmed: poor performers tend to significantly overestimate their own performance whilst top performers tend to underestimate it. This can be interpreted as a demonstration that the accuracy of comparative self-evaluations depends on a number of variables: cognitive and metacognitive factors and aspects associated with self-representation. To verify these aspects we examined bias in self evaluation from an attributional perspective too. Our conclusion is that cognitive and metacognitive processes work as “submerged” in highly subjective representations, allowing dynamics related to safeguarding the image one has of oneself to play a role.

Three dimensional seismic imaging and earthquake locations in a complex, segmented fault region in Southern Apennines (Italy)

The southern Apennines of Italy have been experienced several destructive earthquakes both in historic and recent times. The present day seismicity, characterized by small-to-moderate magnitude earthquakes, was used like a probe to obatin a deeper knowledge of the fault structures where the largest earthquakes occurred in the past. With the aim to infer a three dimensional seismic image both the problem of data quality and the selection of a reliable and robust tomographic inversion strategy have been faced. The data quality has been obtained to develop optimized procedures for the measurements of P- and S-wave arrival times, through the use of polarization filtering and to the application of a refined re-picking technique based on cross-correlation of waveforms. A technique of iterative tomographic inversion, linearized, damped combined with a strategy of multiscale inversion type has been adopted. The retrieved P-wave velocity model indicates the presence of a strong velocity variation along a direction orthogonal to the Apenninic chain. This variation defines two domains which are characterized by a relatively low and high velocity values. From the comparison between the inferred P-wave velocity model with a portion of a structural section available in literature, the high velocity body was correlated with the Apulia carbonatic platforms whereas the low velocity bodies was associated to the basinal deposits. The deduced Vp/Vs ratio shows that the ratio is lower than 1.8 in the shallower part of the model, while for depths ranging between 5 km and 12 km the ratio increases up to 2.1 in correspondence to the area of higher seismicity. This confirms that areas characterized by higher values are more prone to generate earthquakes as a response to the presence of fluids and higher pore-pressures.

Use of behavioural patterns to analyze transport stress in piglets and young bulls. The influence of individual coping characteristics in stress response.

In modern farm systems the economic interests make reducing the risks related to transport practice an important goal. An increasing attention is directed to the welfare of animals in transit, also considering the new existing facilities. In recent years the results coming from the study of animal farm behaviour were used as tool to assess the welfare. In this thesis were analyzed behavioural patterns, jointly with blood variables, to evaluate the stress response of piglets and young bulls during transport. Since the animal behaviour could be different between individuals and these differences can affect animal responses to aversive situations, the individual behavioural characteristics were taken in account. Regarding young bulls, selected to genetic evaluation, the individual behaviour was investigated before, during and after transport, while for piglets was adopted a tested methodology classification and behavioural tests to observe their coping characteristics. The aim of this thesis was to analyse the behavioural and physiological response of young bulls and piglets to transport practice and to investigate if coping characteristics may affect how piglets cope with aversive situations. The thesis is composed by four experimental studies. The first one aims to identify the best existent methodology classification of piglets coping style between those that were credited in literature. The second one investigated the differences in response to novel situations of piglets with different coping styles. The last studies evaluated the stress response of piglets and young bulls to road transportation. The results obtained show that transport did not affect the behaviour and homeostasis of young animals which respond in a different way from adults. However the understanding of individual behavioural characteristic and the use of behavioural patterns, in addition to blood analyses, need to be more investigated in order to be useful tools to assess the animal response in aversive situation.

Analisi critica di modelli previsionali per le frane in Emilia Romagna

Questa tesi di dottorato è inserita nell’ambito della convenzione tra ARPA_SIMC (che è l’Ente finanziatore), l’Agenzia Regionale di Protezione Civile ed il Dipartimento di Scienze della Terra e Geologico - Ambientali dell’Ateneo di Bologna. L’obiettivo principale è la determinazione di possibili soglie pluviometriche di innesco per i fenomeni franosi in Emilia Romagna che possano essere utilizzate come strumento di supporto previsionale in sala operativa di Protezione Civile. In un contesto geologico così complesso, un approccio empirico tradizionale non è sufficiente per discriminare in modo univoco tra eventi meteo innescanti e non, ed in generale la distribuzione dei dati appare troppo dispersa per poter tracciare una soglia statisticamente significativa. È stato quindi deciso di applicare il rigoroso approccio statistico Bayesiano, innovativo poiché calcola la probabilità di frana dato un certo evento di pioggia (P(A|B)) , considerando non solo le precipitazioni innescanti frane (quindi la probabilità condizionata di avere un certo evento di precipitazione data l’occorrenza di frana, P(B|A)), ma anche le precipitazioni non innescanti (quindi la probabilità a priori di un evento di pioggia, P(A)). L’approccio Bayesiano è stato applicato all’intervallo temporale compreso tra il 1939 ed il 2009. Le isolinee di probabilità ottenute minimizzano i falsi allarmi e sono facilmente implementabili in un sistema di allertamento regionale, ma possono presentare limiti previsionali per fenomeni non rappresentati nel dataset storico o che avvengono in condizioni anomale. Ne sono esempio le frane superficiali con evoluzione in debris flows, estremamente rare negli ultimi 70 anni, ma con frequenza recentemente in aumento. Si è cercato di affrontare questo problema testando la variabilità previsionale di alcuni modelli fisicamente basati appositamente sviluppati a questo scopo, tra cui X – SLIP (Montrasio et al., 1998), SHALSTAB (SHALlow STABility model, Montgomery & Dietrich, 1994), Iverson (2000), TRIGRS 1.0 (Baum et al., 2002), TRIGRS 2.0 (Baum et al., 2008).