Pubblicazioni dello IUSS

La responsabilità dell’operatore del settore alimentare alla luce dei requisiti generali imposti alle informazioni alimentari dal reg. (UE) n. 1169/2011.

2018-05-30T10:30:23+00:00

My research concerns a specific topic of the new Regulation (EU) n. 1169/2011 on the provision of food information to consumers, that is the responsibility of food business operator for the information given to the consumers in the light of the new «general food information requirements» provided in the Chapter III of the Regulation. Moving from some considerations about the major novelties brought in by the Regulation (EU) n. 1169/2011 and about the concept of responsibility, the first part of the research examines the new rules about the responsibility of the food business operator introduced by the art. 8 of the Reg. (EU) n. 1169/2011 and defines on which operator in the food supply chain are imposed determined duties to inform the consumers or to control the presence and accuracy of food informations. Then, the same section analyzes in which cases the food business operator fulfills the obligation, provided in the art. 6, Reg. (EU) n. 1169/2011, to give informations «in accordance» with the new Regulation and, consequently, when he can't be considered responsible. The third chapter focuses on the the possibility – only mentioned in the 5° Whereas of the Reg. (EU) n. 1169/2011 – to coordinate the specific provisions of the Regulation (Eu) n. 1169/2011, which prohibits unfair food information practices, with the general clauses laid down in the Directive n. 2005/29/EC concerning the Unfair business to consumer commercial pratices. The last part of the thesis, in closing, develops the topic of the enforcement of the food law provisions laid down in the Reg. (EU) n. 1169/2011 examining both the problem of the administrative sanctions applicable in the future to the infringements, both the individual and collective remedies granted to consumers under private law.

DESIGN FOR PEOPLE AFFECTED BY DUCHENNE MUSCULAR DYSTROPHY. Proposal for a new type of night AFO, Ankle Foot Orthosis, based on 3D indirect survey and 3D printing.

2018-05-30T10:30:26+00:00

The aim of this study is to investigate night Ankle Foot Orthoses, commonly prescribed to Duchenne Muscular Dystrophy patients to understand if there are margins to increase their comfort, aesthetic customization and psychological acceptance by the users, but even to improve their manufacturing process and to reduce costs. Duchenne is a rare form of muscular dystrophy affecting 1 on 3.500 male children that, at about 8 to 12 years old progressively become wheelchair bounded and with an expectation of life on the late 20 or 30 years old, since usually cardiac or pulmonary complications occur. Due to muscles’ weakening, Achilles tendon takes over on muscle tissue and starts to thicken and shrink, causing plantar flexion and retractions, while the function of AFOs is for applying a stretching force that can delay equine deformation of the feet. It is scientifically demonstrated that a constant use of night Ankle Foot Orthosis, together with physiotherapy, can extend the independent ambulation by up to two years and delay the occurrence of other complications. The PhD study was conducted from 2012 to 2014 thanks to a partnership between the Department of Architecture of Ferrara University and Parent Project Onlus for Duchenne and Becker. Moreover the thesis was endorsed by the Neuropsychiatric Department specialized in Duchenne of the Policlinico Gemelli in Rome, orthoses manufactures, experts in 3D survey, parametric design, and solid prototyping and, last but not least, by the direct contact with final users and their families. The core of the thesis was organized in three parts. In the first one, after a brief recognition on the disease, a market analysis on all the lower limb orthoses available on Italian, European and North American market was conducted. The elaborated interactive database was essential to understand the state of art, the Italian picture and the most advanced innovations and ongoing experimentations. All these data were a crucial tool in the design process. The second part focused on cultural and methodological approaches in the design of the AFO. After an overview on theories that frame the research, as Customer Centered and User Centered Design, as well as Universal Design, Inclusive Design, Design for All and Design for disabilities, a Quality Function Deployment process was chosen to translate theories into design directives. Relating user needs, technical requirements and comparison with the competitors, the scheme provides the guidelines for the design of a really innovative dorsal night AFO for DMD patients. The results of the research and future perspective are exposed in the third part. The analysis of the handcraft current processes of manufacturing suggested the opportunity of investigating the application of modern technologies aimed at the optimization of the process and the final product. Indirect survey techniques of photo-modelling or laser scanner are used to accurately reproduce the shape of the leg, while the user is sitting on a particular bench designed to acquire the foot in a stretching position and to entertain the child as he was on a rocking horse. The 3D virtual reconstruction of the limb, combined with 15 control points, is elaborated in an algorithm of parametric design to obtain a customized AFO that can be 3D printed with complete freedom of personalization to meet the tastes of the child. The results are highly promising and deserve to be further developed in future experimentations on field.

Procedura per il riconoscimento delle unita’ elementari negli aggregati urbani attraverso la comprensione dei processi tipologici

2018-05-30T10:30:27+00:00

Seismic events in recent years have caused heavy damage to historic city centers. This calls for an effective planning aimed at reaching an adequate decrease of the vulnerability of city centers buildings. A deep knowledge of the structure of the urban environment ‐ and, to a lesser extent, of the buildings the urban environment is made up of ‐ is the essential precondition for effectively intervening on the urban fabric. Currently, the most used means of knowledge are Vulnerability Assessment Forms, whose goal is to assess not only the damage suffered by a building in the aftermath of an earthquake, but also its habitability standards. These forms, which are supposed to assess the buildings as a whole, in most cases only analyzes single buildings or cadastral units, since there is no well‐defined procedure on how to identify single units within the urban fabric. The identification of an Elementary Unit (i.e. the smallest independent unit within the fabric) is the crucial point of this delicate process. This identification process, though, is based on weak and misleading definitions, e.g. those that have been used up to today to fill in the Assessment Forms. This work of research aims at clearly defining both the idea itself of Elementary Unit and a procedure to identify it. This procedure could be extensively used not only in emergency situations, but also for the regular preventive territory management. This goal can be reached through a constant phenomenological examination of the urban fabric buildings carried out using Muratori‐inspired typological analysis tools. By studying the transformation process of the basic building types, it is possible to identify the Elementary Units the urban fabric is made up of. Once the urban fabric structure has been comprehended, this work will present a clear and most valid definition of Elementary Unit, which will simplify any later examination of the urban fabric – from the identification of “subjects” for AeDES Forms, to the drafting of Reconstruction Plans. The case study of Ferrara offers a chance to verify the validity of the process of identification of buildings within the urban fabric, designed on a real example. This will, in turn, prove the validity of the term “Elementary Unit” and its strong connection with the concept of building type and the typological development.

I LIMITI DELLA RIQUALIFICAZIONE EDILIZIA. Contributo alla selezione di indicatori ausiliari relativi alle modalità di intervento sui fabbricati residenziali del trentennio successivo al secondo dopoguerra.

2018-05-30T10:30:27+00:00

The growing awareness of the importance to limit soil sealing process is one of the reasons to definitely shift the building activity on the existent stock. Approximately a third of the European housing stock was built during the thirty years after WW-II. A huge part of these buildings presents different kind of obsolescence. This declining performance process makes necessary to take a decision about how buildings can meet actual requirements. A decision must be taken in order to choose the preferable intervention in a sustainable and lifespan conscious design perspective. Renovation and demolition are both possible for multi-storey apartment buildings that do not present historical or testimonial quality. By the analysis of some case studies the research illustrates which are the most incidental parameters in the decision-making process and selects some indicators that could be defined as the limits of renovation project. Aware that from a sustainable viewpoint diffused demolition are not preferable, these indicators represent the conditions in which demolition could nevertheless be a preferable option.

An innovative methodology for the analysis of microparticle deposits in transonic and subsonic blades for the assessment of compressor degradation

2018-05-30T10:30:27+00:00

Solid particle ingestion is one of the principal degradation mechanisms in the compressor section of heavy-duty gas turbines. Usually, foulants in the ppm range not captured by the air filtration system cause deposits on blading and result in a severe performance drop of the compressor. It is of great interest to the manufacturer and industry to determine which areas of the compressor airfoils are affected by these contaminants as a function of the location of the power unit. The aim of this work is the estimation of the actual deposits on the blade surface in terms of location and quantity. Particle trajectory simulations use a stochastic Lagrangian tracking method which solves the equations of motion separately from the continuous phase. Then, a transonic rotor and subsonic rotor are considered as a case study for the numerical investigation. The compressor rotor numerical model and the discrete phase treatment have been validated against the experimental and numerical data available in literature. The size of the particles, their concentrations and the filtration efficiency are specified in order to perform a realistic quantitative analysis of the fouling phenomena in an axial compressor. This study combines the impact/adhesion characteristic of the particles obtained through a Computational Fluid Dynamics (CFD) numerical simulation and the real size distribution of the contaminants in the air swallowed by the compressor. The kinematic characteristics (velocity and angle) of the impact of micrometric and sub-micrometric particles with the blade surface of an axial transonic and subsonic rotor are shown. The blade zones affected by particle impact are extensively analyzed. This work has the goal of combining the kinematic characteristics of particle impact on the blade with fouling phenomenon through the use of a quantity called ‘sticking probability’ adopted from literature. The analysis shows that particular fluid-dynamic phenomena such as separation, shock waves and tip leakage vortex strongly influence pattern deposition. The combination of the smaller particles (0.15 ― 0.25) μm and the larger ones (1.00 ― 1.50) μm determines the highest amounts of deposits on the leading edge of the compressor airfoil. The blade zones affected by deposits are clearly reported by using easy-to-use contaminant maps realized on the blade surface in terms of contaminant mass per unit of time. From these analyses, some guidelines for proper installation and management of the power plant (in terms of filtration systems and washing strategies) can be drawn.

Geochemical and Isotopic Investigation on the Po river waters from Monviso spurces to its Delta: natural and anthropogenic components

2018-05-30T10:30:27+00:00

The Po river cross east-west the whole Northern Italy and flows within a densely populated area characterized by intense agriculture and industrial activities. In spite of its importance, systematic geochemical and isotopic investigations of its water are rare and never reported for the whole basin scale.

The aim of this study was to fill this knowledge gap investigating the Po river water through a chemical and multi-isotopic approach that includes oxygen, hydrogen, carbon, nitrogen sulphur and strontium isotope data.

The Po river flows within the Padanian plain, which is a sedimentary basin bound to the N by the Alpine mountains, to the SW by the Apennine hills and to the E by the Adriatic Sea and cover an area of more than 71,000 km2 (a quarter of the national territory). From the geological point of view the basin was characterized by a marine sedimentation in the Pliocene to Early Pleistocene, followed by fluvial sedimentation that enhanced during the glaciation periods. Within the plain the most important fluvial system is represented by the Po river which is progressively fed by many tributaries (and groundwater flows) from both the Alps and the Apennines. The Alpine streams are mainly fed by snow melting and show a seasonal peak flow during the spring-early summer period, while the Apennines streams have a rainy, and therefore intermittent, influence showing a minimum seasonal flow (drought) during the summer. These tributaries account for the annual regime of the Po river which is characterized by two low-level hydrometric periods (winter and summer) and two flood periods (late fall and spring). The first flood period reflects the intense late fall rains, while the second is due to snow melt from the higher sectors of the. The average discharge rate is 1,500 m3/s and maximum peak flows of 10,300 m3/s at section of Occhiobello, which is located in the lower reach of the river (close to the city of Ferrara), right upstream of the deltaic system.

The isotopic compositions (δ18O - δD ) demonstrate that the predominant part of the runoff derives from the Alpine sector of the catchment through important tributaries such as Dora Baltea, Ticino, Adda and Tanaro rivers, whereas the contribution of the Apennines tributaries is less important. Geochemical and isotopic data show that the Po river water attains a homogeneous composition at ca. 100 km from the spring. The average composition measured at Occhiobello is characterized by δ18O 9.6‰, δD 64.0‰, TDS (Total Dissolved Solids) 260 mg/L, chloride 15 mg/L and by a general Ca–HCO3 hydrochemical facies, which is maintained for most of the river stream, only varying in the terminal part where the river is diverted in a complex deltaic system affected by more significant evaporation and mixing with saline water evidenced by higher TDS and chloride content (up to 8,000 mg/L and 4,000 mg/L, respectively). The comparison of the data presented in this thesis with historical chemical analyses of Po river (available for the past fifty years) indicates that the major components (i.e. Ca2+, Mg2+, Na+, K+, HCO3, Cl, SO4) of the runoff water remained constant over the last decades suggesting that they reflect natural compositions unaffected by anthropogenic activities; in contrast, nitrate drastically increases from less than 1 mg/L to an average value of 9 mg/L as result of diffuse contamination. Coherently, δ13C (between -11.4‰ and -4.4‰) and δ34S (between 4.2‰ and 8.0‰) and also the 87Sr/86Sr (between 0.70896 and 0.70974) are compatible with the weathering and dissolution processes that involve the lithologies outcropping in the basin, while extremely variable δ15N (between -4.1‰ and 18.0‰) indicates contribution from pollutants of urban origin as well as components released by the agricultural and zootechnical activities. These observations confirm that although the origin of the main constituents of the Po river water is geogenic, anthropogenic contributions are also effective. The data also highlight an evolution of the dissolved nitrogen species that appear extremely reactive, especially in the deltaic part of the river, which is characterized by denitrification processes. Geochemical and isotopic maps have been drawn to visualize spatial gradients, which reflect the evolution of the river water composition at progressive distance from the source; more detailed maps were focused on the deltaic part in order to visualize the processes occurring in the transitional zone toward the Adriatic Sea.

It has to be noted that the presented data represent a snapshot of the nowadays river condition, and that future monitoring will be useful to highlight a) progressive involvement of further anthropogenic components and b) on-going environmental (climatic) changes. For these reasons this research contribute to integrate the GLObal River Chemistry (GLORICH) database (Hartmann et al. 2014, Proc Earth Plan Sci ) which is a useful tool to monitor earth surface processes at extensive scales and high resolution, and also to implement existing isotopic hydro-archives that provide additional information that cannot routinely be recovered from elementary chemistry alone (Bowen et al. 2009, Earth Plan Sc).

Optimization Methods for Image Regularization from Poisson Data

2018-05-30T10:30:26+00:00

This work regards optimization techniques for image restoration problems in presence of Poisson noise. In several imaging applications (e.g. Astronomy, Microscopy, Medical Imaging) such noise is predominant; hence regularization techniques are needed in order to obtain satisfying restored images. In a variational framework, the image restoration problem consists in finding a minimum of a functional, which is the sum of two terms,: the fit–to–data and the regularization one. The trade–off between these two terms is measured by a regularization parameter. The estimation of such a parameter is very difficult due to the presence of Poisson noise. In this thesis we investigate three models regarding this parameter: a Discrepancy Model, Constrained Model and the Bregman procedure. The former two provide an estimation for the regularization parameter, but in some cases, such as low counts images, they do not allow to obtain satisfactory results. On the other hand, in presence of such images the Bregman procedure provides reliable results and, moreover, it allows to use an overestimation of the regularization parameter, giving satisfying restored images; furthermore, this procedure permits to gain a contrast enhancement on the final result. In the first part of the work, the basics on image restoration problems are recalled, and a survey on the state–of–the–art methods is given, with an original contribution regarding scaling techniques in ε–subgradient methods. Then, the Discrepancy and the Constrained Models are analyzed from both theoretical and practical point of view, developing suitable numerical techniques for their solution; furthermore, an inexact version of the Bregman procedure is introduced: such a version allows to have a minor computational cost and maintains the same theoretical features of the exact version. Finally, in the last part, a wide experimentation shows the computational efficiency of the inexact Bregman procedure; furthermore, the three models are compared, showing that in high counts images they provide similar results, while in case of low counts images the Bregman procedure provides reliable restored images. This last consideration is evident not only on test problems, but also in problems coming from Astronomy imaging, particularly in case of High Dynamic Range images, as shown in the final part of the experimental section.

Study of coherent interactions between charged particle beams and crystals for beam steering and intense electromagnetic radiation generation.

2018-05-30T10:30:26+00:00

The work presented in this thesis has been devoted to the investigation of new schemes for beam steering and high-intense electromagnetic radiation generation through coherent interactions of charged particle beams with crystals. A series of experiments was carried out in two different laboratories, i.e., the Super Proton Synchrotron (SPS) at CERN in Geneve and the MAinzer MIkrotron (MAMI) of the University of Mainz in Germany, by different international and national collaborations, namely the UA9 experiment., the European CUTE project and the INFN COHERENT and ICE-RAD experiments. The experimental data have been analysed and critically compared with simulations. First of all, the possibility of combining the efficient deflection and the intense electromagnetic radiation production of ultrarelativistic electrons through channeling or volume reflection in bent silicon crystals was investigated. Interesting results were obtained in a wide range of beam energies, spanning from 0.855 GeV available at MAMI to hundreds of GeV accessible at the H4 extracted beamline of SPS. It has been demonstrated the possibility to use bent crystals for efficient deflection of electron beams in the subGeV energy range. This range of energies was still unexplored due to the lack of properly sized bent crystal for negative beams steering. Secondly, it has been shown that the radiation accompanying single (VR) and multiple (MVROC) volume reflection in a bent crystal has peculiar characteristics, such as higher intensity than for bremsstrahlung in an amorphous material and a wide angular acceptance, that make this kind of radiation quite interesting for applications. On the very high-energy side, crystal-aided collimation through radiation accompanying VR and MVROC has been proposed for the future electronpositron colliders, e.g., the International Linear Collider. On the other hand, in the subGeVGeV energy range, which is accessible by most electron accelerators worldwide, the radiation accompanying VR can be exploited as an high-intensity X- or γ-sourse with poor emittance beams. In addition to the studies carried out with electrons, the investigation of new schemes for manipulation of charged beams trajectories was carried out at the H8 beamline of SPS with the usage of 400 GeV/c protons. Firstly, a periodically bent crystal was realized via the superficial grooving method and tested at the H8 line. The effectiveness of this method in achieving perfectly periodic structures was demonstrated. On the strength of these results, it has been proposed to test the crystal sample as a positron-based crystalline undulator in the energy range of 10-20 GeV, as a source of intense MeV photons. Finally, it has been experimentally demonstrated that even a straight crystal, i.e., a crystal mirror, may be used for the steering of ultrarelativistic protons in place of a bent crystal. Unlike the traditional scheme relying on mm-long curved crystals, particle mirroring enables beam steering in high-energy accelerators via interactions with μm-thin straight crystal. The main advantage of mirroring is the interaction with a minimal amount of material along the beam, thereby decreasing unwanted nuclear interactions. Summarizing, all the experimental studies presented in this thesis lead us to consider crystals, either bent or unbent, as reliable tools in particle accelerator physics for different applications within a wide energy range.

Studio anatomo-funzionale integrato della sostanza bianca cerebrale e computazione di un atlante funzionale sottocorticale

2018-05-30T10:30:25+00:00

Over the last 20 years the study of brain functions experienced a huge impulse due to the technical improvements in the imaging and neurosurgical cortico-subcortical direct electrical stimulation (DES) procedures. Particularly, functional MRI (fMRI), DES and diffusion tensor imaging (DTI) allowed the in vivo study of functional organization and white matter (WM) connections. The integration of data provided by these different techniques opened a new door in the study of the brain, leading neuroscientists and neurosurgeons in the connectomic era. This conceptual evolution renewed the interest also for the structural study of brain connections with blunt dissection, in order to improve and confirm data provided by DTI.

Considering that DES is, since now, the only direct and specific method to explore the functional role of subcortical bundles, we aimed to a study integrating blunt dissection, according to the technique described by Klingler, DTI and DES during neurosurgical procedure for resection of lowgrade gliomas (LGGs). Aims of the study are:

l) definition of course and terminations of the main WM fascicles;

2) production of antomo-topographical data, including course and reciprocal relationships of different association, projection and connection bundles, in order to produce anatomofunctional details for the improvement of surgical approach to intra-axial lesions.

3) computation of the first functional atlas of the human WM and of a probabilistic map of WM resectability, using data provided by DES during awake surgery with intra-operative neuropsychological monitoring.

Phytochemicals: Design, Synthesis, Biological Evaluation and Novel Characterisation Methods.

2018-05-30T10:30:26+00:00

The collective theme of this thesis is: Phytochemicals: Design, Synthesis, Biological Evaluation and Novel Characterisation Methods. Contained within this general theme, the research described is divided into two research areas:

1. Development of new analytical methods for biopolymers (soluble fiber) characterisation.

2. Studies on the structure–activity relationship between selected food ingredients (and their semisynthetic analogues) and specific cell lines in order to understand the variables that enhance their bioavailability and biological activity against these targets.

In the context of the application of a new analytical methods, a new approach to bio-polymers (soluble fibre) determination was developed by means of High Performance Thin Layer Chromatography (HPTLC). Quality control is an important aspect in the food industry; however, the lack of rapid and efficient analytical methods frequently hinders adequate and expedient characterisation of foodstuffs. Furthermore, the presence of high levels of soluble fibres is often used to claim prebiotic activity for the food product. However, in the food industry it is common practice to provide technical data sheets wherein information on soluble fibres are given as a difference from other components (fat, protein, etc).

Given that the term “soluble fibre” is specific to certain structure classes e.g. inulins, fructo-oligosaccharides, it is obvious that the characterisation by mass difference is not sufficient to support such claims and a more precise analytical method should be employed. Thus a novel method based on High Performance Thin Layer Chromatography (HPTLC) was developed where samples of Adansonia digitata fruit pulp were used to demonstrate the application of this method to accurately evaluate its soluble fibre content and use this information to gain further insight into its reported prebiotic activity. High Performance Liquid Chromatography (HPLC) was used to validate the results. Samples of Adansonia digitata were also submitted to different enzymatic treatments in order to gain a deeper understanding of the cell wall composition. The polymers released after enzymatic breakdown were hydrolysed to their monomeric components and the resulting sugar mixture analysed through the newly-developed HPTLC method. It was shown that samples of Adansonia digitata dried fruit pulp contained only sucrose, glucose and fructose,

contrary to previous reports where soluble fibre content were assessed by mass difference.

This emphasised the need for more precise methods of composition assessment of fibrerich

foodstuffs and demonstrated our HPTLC method as a valid tool for soluble fibre

determination.

The second part of this thesis focuses on structure–activity relationship between food

ingredients and their semisynthetic analogues on selected targets. Within that research,

new polyphenol analogues were designed, synthesised and evaluated on different targets in

order to determine their potential application as multi-target compounds.

Polyphenols have attracted a strong interest in the field of medicinal chemistry due to their

reported anti-cancer, anti-inflammatory, anti-oxidant, anti-artherosclerotic properties, as

well as neuro- and cardio-protective activities. They have been used in prebiotics,

pharmaceuticals, cosmetics, nutraceuticals and can be extracted from renewable sources

such as tea leafs, grapes, cocoa seeds and vegetables. Unfortunately, due to their inherently

poor solubility profile in aqueous media and rapid in vivo metabolic breakdown, they have

not yet been extensively exploited to their full potential. The aim of this research, was to

find new carriers for those naturally occurring compounds that enhance their

bioavailability, increase their half-life in the blood and facilitate their transport across the

cell membrane which should consequently increase of their biological activity. In the past,

a number of new carriers have been evaluated to address enhance some of these properties

including pegylation, sugar conjugation or inclusion in liposomes. It was therefore decided

to expand the objectives of the project beyond these preliminary studies and thus new

linkers were chosen that were not only passive connection units, but could also serve as

active pharmacophores, thereby expanding the activity profile of the synthesised molecules

and enabling molecular diversity. This was realised by utilising triazole-containing linkers

as the key structural feature of the new analogues

The synthetic design of the new family of compounds was assisted by molecular modelling

and the newly prepared molecules were tested for their activity on eight strains of

dermatophytes and on 5-lipoxygenase (5-LO) – both the isolated enzyme and on cell based assays.

An overall summary of the outcomes and the proposed future works for the projects are presented before the final section which contains the experimental procedures and characterisation data for the new compounds synthesised through these investigations.

Studio, sintesi e caratterizzazione di nuovi materiali microporosi funzionalizzati per la realizzazione di processi reattivi e separativi in sistemi dinamici

2018-05-30T10:30:25+00:00

This PhD program has focused on the study, preparation and characterization of new functionalized microporous materials for applications in chromatographic and chromatographic-like flow systems, including the possibility of performing chemical transformations in flow-mode (flow chemistry). The work has been multidisciplinary in nature, including elements of analytical and organic chemistry, material science and process modeling. The materials prepared in this work have been used for different purposes. They have been employed, on the one hand, for the preparation of packed-bed microreactors to perform advanced stereoselective chemical transformations by means of organocatalysts anchored to solid supports (polystyrene and silica gel based) and, on the other, as new stationary phases for chromatographic separations. In the case of organocatalyst-functionalized silicon packed-bed microreactors, we followed the idea that mechanisms of chiral induction due to organocatalysts (asymmetric synthesis) might be exploited for chiral discrimination (chiral chromatography) with their immobilized counterparts. The new materials have been thoroughly characterized in terms of chemico-physical, geometric and thermodynamic properties by investigating the mass transfer phenomena in packed beds, by measuring the adsorption isotherms of different substrates on different porous materials and by characterizing some of their fundamental properties such as porosity, superficial area, functionalization degree, etc. In addition, their dynamic behavior in reactive systems has been studied and modeled to understand not only the thermodynamics but also the kinetics of the process and to optimize, based on this information, the experimental conditions as to maximize production yield. Microreactors and the possibility of performing flow-chemistry through them satisfy the fundamental criteria of green chemistry, allowing for the realization of sustainable processes in terms of environmental impact and cost. The activities of my work have produced seven papers on international peer-reviewed journals. These publications are included at the end of my dissertation. One additional paper is in preparation.

Novel Ligands and assays for ociceptin/orphanin FQ and classical opioid receptors

2018-05-30T10:30:25+00:00

The aim of the present study was twofold: pharmacologically characterize novel ligands and set-up and validate novel in vitro assays for nociceptin/orphanin FQ (N/OFQ) peptide (NOP) and classical opioid receptors. NOP and opioid receptors are 7TM receptors coupled with inhibitory G proteins; receptor activation leads to the inhibition of cAMP formation and calcium currents, and opening of potassium channels. Via these cellular inhibitory mechanisms, the N/OFQ – NOP receptor and classical opioid systems regulate a variety of biological functions both in the central nervous system and in the periphery. The calcium mobilization assay has been and still is broadly used as primary screening for novel molecules in academic and industrial in vitro pharmacology laboratories. The use of chimeric G proteins allows to extend the calcium mobilization assay to virtually all types of G protein coupled receptors. This approach was previously used in our laboratories for characterizing NOP receptor ligands. In the frame of the present study, the calcium mobilization assay has been extended and validated for classical opioid receptors using a panel of standard opioid receptor agonists and antagonist. This test was used for investigating the pharmacological profile of novel opioid ligands including a series of morphine and oxymorphone analogues and novel cyclic endomorphin-2 derivatives. Calcium mobilization studies together with classical in vitro assays such as receptor binding, [35S]GTPγS binding and bioassays with isolated organs were applied to novel NOP receptor ligands including i) 3 different series of spiroxatrine derivatives; ii) the antagonist NiK-21273; iii) [X5]N/OFQ(1-13)-NH2 derivatives; iv) three tetrabranched derivatives of N/OFQ generated with an innovative chemical approach named peptide welding technology. Recent data demonstrated that biased agonists, i.e. receptor ligands able to select which signaling pathways become activated upon binding to the receptor, may display advantages over unbiased ligands. In particular, in the field of opioids, G-protein (vs arrestin) biased agonists for the mu receptor displayed an increased therapeutic index associated to reduced tolerance liability. No data are yet available about biased agonism in the NOP receptor field. Therefore a novel bioluminescence resonance energy transfer (BRET) based assay was set-up for the NOP receptor. This method that allows to study both NOP/G-protein and NOP/β-arrestin interactions has been validated using a large panel of NOP ligands encompassing full and partial agonist as well as antagonist activity. The comparison of data achieved investigating NOP/G-protein and NOP/β-arrestin interaction allowed us to perform the very first study of biased agonism in the NOP receptor field. In summary the studies performed in the frame of my PhD project extend our knowledge on the pharmacological profile of NOP and classical opioid receptors, provided to the scientific community novel compounds, pharmacologically characterized in detail, to be used as research tools and possibly as drug prototypes, and made available novel pharmacological assays useful for selecting fully innovative drugs such NOP receptor biased agonists.

Scale-dependent approaches in conservation biogeography of a cosmopolitan raptor: the Osprey.

2018-05-30T10:30:25+00:00

Being a cosmopolitan and migratory species, the osprey Pandion haliaetus provides a good opportunity to explore how behavioural adaptations in different populations, that evolved under different ecological conditions and are widely spaced, can be the proximate causes of geographical distribution, genetic divergence, population connectivity, migratory strategies and foraging ecology. According to this, a multi-scale integrated approach has been adopted for the osprey: through an interdisciplinary framework made by molecular ecology, trophic ecology as assessed via stable isotopic analyses, spatial ecology through the use of novel biotelemetry tools, as well as population dynamics, fish censuses and assessments of levels of human disturbance, we: a) evidenced the existence of four different lineages at global scale that should be treated as Evolutionary Significant Units (ESUs) and deserve specific management; b) revealed population connectivity in the Western Palearctic; c) disentangled the migratory behaviour and winter ecology of Mediterranean ospreys and compared it with northern European populations, in an evolutionary context; d) stressed the need of adequate management measures to be adopted for three local populations of the Mediterranean basin (Corsica, Morocco and Italy). Overall, this work has led to some important advances with respect to the conservation biogeography of ospreys at different scales. Those insights are particularly valuable with respect to the effective management of this emblematic species.

HLA-G molecules in infection and autoimmune diseases

2018-05-30T10:30:24+00:00

Human leukocyte antigen-G (HLA-G) is a non-classical HLA class I molecule that differs from classical HLA class I molecules for low allelic polymorphism and restricted tissue distribution. In physiological conditions HLA-G molecules are expressed on trophoblast at the fetal-maternal interface and other sites of immune privilege, such as thymus and cornea, where have an important role in the maintenance of a tolerogenic condition. In fact, HLA-G regulates the immune response through its immune-modulatory and anti-inflammatory function on both innate and adaptive immunity. HLA-G molecules are expressed as membrane bound and soluble isoforms (mHLA-G, sHLA-G) that bind and activate immune-inhibitory receptors (ILT2, ILT4, KIR2DL4) expressed on immune cells. Recently, HLA-G molecule has been shown to have an important implication in different pathological situations, such as infections and autoimmune diseases, where HLA-G shows aberrant expression and specific HLA-G gene polymorphisms correlate with disease severity and outcome. Moreover, HLA-G could be up-modulated and used as a immune-escape mechanism by virus and tumours. On the basis of this knowledge, HLA-G may exhibit two distinct effects in pathological conditions: it could be protective in Th1-based inflammatory and autoimmune diseases or it could be detrimental in tumors or infectious diseases. The aim of this thesis is to investigate the role of HLA-G mlecules in different pathological conditions: microbial infections and autoimmune diseases.

Archeologia dell'Architettura e Tecnologie per lo studio dell'insediamento umano medievale e post-medievale: le chiese rurali della bassa valle del Cedrino (Sardegna).

2018-05-30T10:30:24+00:00

The aim of the research is the study of the ruins of many rural churches using some technologies, like 3D reliefs and a Geographic Information System (GIS). The churches are distributed throughout the lower valley of the Cedrino river, a hilly zone located in the central east coast of the island of Sardinia. The territory considers Loculi, Irgoli, Onifai, Galtellì, and Orosei municipalities. Most of these churches have been built during the medieval period, which makes it possible to estimate the human medieval settlement and to make a complete documentation of each church. Until today none of circa 20 sites has ever been investigated from an archaeological study. The research has provided a multi-scale study: from artefacts to landscape. The detailed scale has consisted in reading the masonry structures preserved and making an analytic documentation of buildings using 3D reliefs, where possible; the regional scale has been studied by storing data in a GIS and using those data for territorial analyses. The application of the three-dimensionality in the study of historical buildings is still relatively new. In order to resolve critical issues related to the methodology required in the archaeological-architectonic studies, further investigations are still necessary. In recent years, the development of 3D models in Archaeology and Cultural Heritage showed a growing trend, but in several cases during the data collection, as well as the historical analysis, archaeological knowledge is lacking. The information obtained from 3D models is limited to visualizations and virtual reconstruction. In this research, both the interior and the exterior of a selected sacred building have been surveyed by an integrated approach using a terrestrial laser scanner and photogrammetry. The use of multiple techniques was an essential requirement to produce complete 3D models of monuments, but also it was the best compromise among geometric resolution, costs, and time. Other monument have been documented by a photogrammetric approach called Structure from Motion. These models have been used to develop and verify the interpretations and archaeological analyses through the possibility to carry out geometric measurements, correlate surfaces with volumes, visualize the relation between inner and external walls. Finally, we have elaborated technical drawings for very high-precision documentation. All of the archaeological data collected during the surveys have been stored in the GIS to create an archive that can be connected to existing databases and implemented with data from different sources, such as information from surveys in remote-sensing landscapes archaeology and computerization of data from previous studies. The knowledge acquired will be the basis for the realization of preserving proposals and the enhancement of the cultural resource of “rural churches” involving and making local communities aware in its own history.

La donazione al limite. La fenomenologia di Husserl di fronte alle questioni-limite dell’esperienza.

2018-05-30T10:30:24+00:00

The aim of the research is to accurately analyze the concept of givenness in the phenomenology of Edmund Husserl in all its aspects. Initially, we present the general problem of the givenness in relation to the classical themes of phenomenology, such as the evidence and intuition. This allows us to highlight the idea of a primacy of givenness; the givenness is not a product of the phenomenology, but its essential basis. The phenomenological analysis must therefore follow, first of all, "what is given"; in this way the analysis can reach the dimension of passivity, and become a real "archeology", whose task is to study the original and ultimate layers of the constitution. Phenomenological archeology leave the realm of intuition to try to explain, from a phenomenological point of view, all those events that take place in a "limit" of the possibility of experience, or as "limit of possibility of givenness". Therefore, the analysis must face the difficult issue of the non-givenness, of what is no longer available within the phenomenological reduction. To do this, archeology proceeds through the method of deconstruction and "reconstruction". The limitquestions that we analyze presuppose the reconstructive phenomenology. In the first chapter we study the original temporality and the stream of consciousness as a "living present" in his original givenness. The second chapter focuses specifically on the phenomenology of non-givenness, through the analysis of the birth, death and dreamless sleep. In the third chapter, we seek to shed light on the givenness in the sphere of otherness, abnormality and animality. Finally, we analyze the unconscious, from a phenomenological point of view, such as "limit" of the affective force of consciousness, and in its pulsional life. The final section highlights the difference between the "ultimate questions" of phenomenology - metaphysical and teleological questions - and the limit-problems that need an archaeological and reconstructive approach.

Responsiveness of local governments to financial and institutional reforms: evidence from Italy

2018-05-30T10:30:23+00:00

This thesis proposes three distinct contribution to the field of economic analysis on local government. In particular, each of the three studies focuses on a specific Italian policy reform allowing us to analyze how it affects local fiscal policy decisions. In the first chapter we investigate the impact on expenditure of tax on principal dwellings before 2008 and the impact on expenditure of the grant which, after 2008, compensated for the abolition of the tax on principal dwellings. We setup a theoretical model in which the introduction of a political bias against taxation gives rise to the flypaper effect. If the public good is very important with respect to private consumption then an increase in the municipal size implies a decrease in the extent of the flypaper effect; the opposite happens if the public good is not important with respect to private consumption. We then test the hypotheses coming from the model by using data on Italian municipalities, focusing on two groups of expenditure: the principal expenditure, which are those essential to guarantee the minimum standard daily life of a municipality and the rest, defined as residual expenditure. We find that the flypaper effect holds for both kinds of expenditure, but decreases with respect to population in the case of principal expenditure and increases with respect to population in the case of residual expenditure. In the second chapter we setup a model in which the residents of two neighboring municipalities can use the services provided by public infrastructures located in both jurisdictions. If services are either complements or substitutes in use, the municipalities strategically interact when investing in infrastructures; moreover, when they differ in population size, the small municipality reacts more to the expenditure of its neighbor than the big one. The theoretical predictions are then tested by estimating the determinants of the stock of public infrastructures of the municipalities belonging to the Autonomous Province of Trento, in Italy. By introducing a spatial lag-error component, we find that municipalities positively react to an increase in infrastructures by their neighbors, but the effect tends to vanish above a given population threshold. Finally, in chapter 3 we use data for all Italian municipalities from 2001 to 2007 to empirically test the extent to which two different electoral rules, which hold for small and large municipalities, affect fiscal policy decisions at local level. Municipalities with fewer than 15,000 inhabitants elect their mayors in accordance with a single-ballot plurality rule where only one list can support her/him, while the rest of the municipalities uses a runoff plurality rule where multiple lists can support her/him. Per capita total taxes, charges and current expenditure in large municipalities are lower than in small ones if the mayor of the large municipality does not need a broad coalition to be elected, otherwise the use of a single- or double-ballot rule does not make any difference in the policy outcome.

Il procedimento per l’approvazione degli atti normativi del Governo.

2018-05-30T10:30:23+00:00

The thesis focuses on the relationship between better regulation rules and the law making process of the Government. The thesis, made of four chapters, aims to link the inefficient regulation of the law making process with the poor quality of the final output, both for the primary regulation and for the bills to be submitted to the Parliament. It is hold to be true that the government drafting process should consider appropriate time in order to assess the consequences of the bill, should involve the stakeholders and, in general, should consent an aware evaluation of the policies to be drafted. The first chapter consists in a description of the high importance and of the large amount of the regulation drafted by the Italian Government. The second chapter summarizes and describes the current regulation of the drafting process of the executive. In the procedures analysis, three phases are identified: the work scheduling, the preliminary activities, and the cabinet approval. Each of the reported phase end with a formal act, namely the definition of the agenda, the submission to the cabinet and the cabinet approval. In the third chapter, various performance indicators to measure the compliance to the law making process rules are proposed and, in particular, the implementation of the regulatory impact analysis is highlighted. Moreover, data are presented in order to demonstrate the poor attention of the Government to the quality of regulation and to the transparency of the procedures. In the fourth chapter, the possibility to determine the constitutionality of a law basing on the respect of the law making rules is presented. Finally, it is suggested that the head of the State could deny the authorization to the publication of an act drafted in violation of the law making rules.