Cognitive and affective processes in social actions and decisions

The question of how we make, and how we should make judgments and decisions has occupied thinkers for many centuries. This thesis has the aim to add new evidences to clarify the brain’s mechanisms for decisions. The cognitive and the emotional processes of social actions and decisions are investigated with the aim to understand which brain areas are mostly involved. Four experimental studies are presented. A specific kind of population is involved in the first study (as well as in study III) concerning patients with lesion of ventromedial prefrontal cortex (vmPFC). This region is collocated in the ventral surface of frontal lobe, and it seems have an important role in social and moral decision in forecasting the negative emotional consequences of choice. In study I, it is examined whether emotions, specifically social emotions subserved by the vmPFC, affect people’s willingness to trust others. In study II is observed how incidental emotions could encourage trusting behaviour, especially when individuals are not aware of emotive stimulation. Study III has the aim to gather a direct psychophysiological evidence, both in healthy and neurologically impaired individuals, that emotions are crucially involved in shaping moral judgment, by preventing moral violations. Study IV explores how the moral meaning of a decision and its subsequent action can modulate the basic component of action such as sense of agency.

Spatial and temporal variability and ecological processes in the epibenthic assemblages of the northern Adriatic Sea

Several coralligenous reefs occur in the soft bottoms of the northern Adriatic continental shelf. Mediterranean coralligenous habitats are characterised by high species diversity and are intrinsically valuable for their biological diversity and for the ecological processes they support. The conservation and management of these habitats require quantifying spatial and temporal variability of their benthic assemblages. This PhD thesis aims to give a relevant contribution to the knowledge of the structure and dynamics of the epibenthic assemblages on the coralligenous subtidal reefs occurring in the northern Adriatic Sea. The epibenthic assemblages showed a spatial variation larger compared to temporal changes, with a temporal persistence of reef-forming organisms. Assemblages spatial heterogeneity has been related to morphological features and geographical location of the reefs, together with variation in the hydrological conditions. Manipulative experiments help to understand the ecological processes structuring the benthic assemblages and maintaining their diversity. In this regards a short and long term experiment on colonization patterns of artificial substrata over a 3-year period has been performed in three reefs, corresponding to the three main types of assemblages detected in the previous study. The first colonisers, largely depending by the different larval supply, played a key role in determining the heterogeneity of the assemblages in the early stage of colonisation. Lateral invasion, from the surrounding assemblages, was the driver in structuring the mature assemblages. These complex colonisation dynamics explained the high heterogeneity of the assemblages dwelling on the northern Adriatic biogenic reefs. The buildup of these coralligenous reefs mainly depends by the bioconstruction-erosion processes that has been analysed through a field experiment. Bioconstruction, largely due to serpulid polychaetes, prevailed on erosion processes and occurred at similar rates in all sites. Similarly, the total energy contents in the benthic communities do not differ among sites, despite being provided by different species. Therefore, we can hypothesise that both bioconstruction processes and energetic storage may be limited by the availability of resources. Finally the major contribution of the zoobenthos compared to the phytobenthos to the total energetic content of assemblages suggests that the energy flow in these benthic habitats is primarily supported by planktonic food web trough the filter feeding invertebrates.

Integration of cognitive and affective processes in perception and decision-making

The relationship between emotion and cognition is a topic that raises great interest in research. Recently, a view of these two processes as interactive and mutually influencing each other has become predominant. This dissertation investigates the reciprocal influences of emotion and cognition, both at behavioral and neural level, in two specific fields, such as attention and decision-making. Experimental evidence on how emotional responses may affect perceptual and attentional processes has been reported. In addition, the impact of three factors, such as personality traits, motivational needs and social context, in modulating the influence that emotion exerts on perception and attention has been investigated. Moreover, the influence of cognition on emotional responses in decision-making has been demonstrated. The current experimental evidence showed that cognitive brain regions such as the dorsolateral prefrontal cortex are causally implicated in regulation of emotional responses and that this has an effect at both pre and post decisional stages. There are two main conclusions of this dissertation: firstly, emotion exerts a strong influence on perceptual and attentional processes but, at the same time, this influence may also be modulated by other factors internal and external to the individuals. Secondly, cognitive processes may modulate emotional prepotent responses, by serving a regulative function critical to driving and shaping human behavior in line with current goals.

Model reduction of stochastic groundwater flow and transport processes

This work presents a comprehensive methodology for the reduction of analytical or numerical stochastic models characterized by uncertain input parameters or boundary conditions. The technique, based on the Polynomial Chaos Expansion (PCE) theory, represents a versatile solution to solve direct or inverse problems related to propagation of uncertainty. The potentiality of the methodology is assessed investigating different applicative contexts related to groundwater flow and transport scenarios, such as global sensitivity analysis, risk analysis and model calibration. This is achieved by implementing a numerical code, developed in the MATLAB environment, presented here in its main features and tested with literature examples. The procedure has been conceived under flexibility and efficiency criteria in order to ensure its adaptability to different fields of engineering; it has been applied to different case studies related to flow and transport in porous media. Each application is associated with innovative elements such as (i) new analytical formulations describing motion and displacement of non-Newtonian fluids in porous media, (ii) application of global sensitivity analysis to a high-complexity numerical model inspired by a real case of risk of radionuclide migration in the subsurface environment, and (iii) development of a novel sensitivity-based strategy for parameter calibration and experiment design in laboratory scale tracer transport.

Eruptive and depositional processes of widely dispersed volcanic ash: Insights from the Brown Tuffs (Aeolian Islands)

This is a multidisciplinary study of the Brown Tuffs (BT) ash deposits of the Aeolian Islands in northern Sicily and representing the most voluminous and widely distributed tephra deposit in this region. A large dataset of major and minor elements of the BT glass has defined a range from K-series basaltic-andesites and trachy-andesites through to tephri-phonolites and trachytes that is consistent with the Vulcano magmatic system. Combined with stratigraphic information and new radiocarbon ages, four stratigraphic macro-units are defined: the Lower (80-56 ky; LBT), Intermediate (56-27 ky; IBT), Intermediate-upper (26-24 ky; IBT-upper) and Upper BT (24-6 ky; UBT). Glass compositional data provide constraints on proximal-distal correlations of the BT with deep-sea tephra layers in the Tyrrhenian and Adriatic Seas and new insights on the definition of the dispersal area of the BT eruptions. Sedimentological evidence of massive to stratified deposits and shear-related structures, coupled with grain-size and componentry analyses, have allowed to interpret the BT as the result of laterally-spreading, concentrated ash-rich PDCs, with a high potential of erosion of the substratum. Shear-structures similar to those observed in the field in the BT deposits have been reproduced by small-medium scale laboratory experiments carried out on ash granular flows, which have also allowed to describe the behaviour of ash-rich PDcs and their mobility depending on variations of slope-ratio, grain size and flow channelization. The resulting integrated dataset provides a contribution to the knowledge of the BT eruptions and insights on long-term hazard assessment in the study area. The eruptive dynamics of the BT may have a role in characterizing the whole magmatic system of the La Fossa Caldera on Vulcano, in the light of the geochemical link highlighted between the UBT macrounit and the early products of the La Fossa cone.

Characterization of pyrolysis and oxidation processes of biomaterials, biomasses and biofuels

The urgent need for alternative solutions mitigating the impacts of human activities on the environment has strongly opened new challenges and opportunities in view of the energy transition. Indeed, the automotive industry is going through a revolutionary moment in its quest to reduce its carbon footprint, with biofuels being one of the viable alternatives. The use of different classes of biofuels as fuel additives/standalone components has attracted the attention of many researchers. Despite their beneficial effects, biofuel’s combustion can also result in the production of undesirable pollutants, requiring complete characterization of the phenomena occurring during their production and consumption. Industrial scale-up of biomass conversion is challenging owing to the complexity of its chemistry and transport phenomena involved in the process. In this view, the role of solid-phase and gas-phase chemistry is paramount. Thus, this study is devoted to detailed analysis of physical-chemical phenomena characterizing biomass pyrolysis and biofuel oxidation. The pyrolysis mechanism has been represented by 20 reactions whereas, the gas-phase kinetic models; manually upgraded model (KiBo_MU) and automated model (KiBo_AG), comprises 141 species and 453 reactions, and 631 species and 28329 reactions, respectively. The accuracy of the kinetic models was tested against experimental data and the models captured experimental trends very well. While the development and validation of detailed kinetic mechanisms is the main deliverable of this project, the realized procedure integrating schematic classifications with methodologies for the identification of common decomposition pathways and intermediates represents an additional source of novelty. Besides, the fundamentally oriented nature of the adopted method allows the identification of most relevant reactions and species under the operating conditions different industrial applications, paving the way for reduced kinetic mechanisms. Ultimately, the resulting detailed mechanisms can be used to integrate with more complex fluid dynamics model to accurately reproduce the behavior of real systems and reactors.

Innovation in aquaculture. Modeling the adoption and implementation processes of innovations in the Italian aquaculture sector

Since the turn of the century, fisheries have maintained a steady growth rate, while aquaculture has experienced a more rapid expansion. Aquaculture can offer EU consumers more diverse, healthy, and sustainable food options, some of which are more popular elsewhere. To develop the sector, the EU is investing heavily. The EU supports innovative projects that promote the sustainable development of seafood sectors and food security. Priority 3 promotes sector development through innovation dissemination. This doctoral dissertation examined innovation transfer in the Italian aquaculture sector, specifically the adoption of innovative tools, using a theoretical model to better understand the complexity of these processes. The work focused on innovation adoption, emphasising that it is the end of a well-defined process. The Awareness Knowledge Adoption Implementation Effectiveness (AKAIE) model was created to better analyse post-adoption phases and evaluate technology adoption implementation and impact. To identify AKAIE drivers and barriers, aquaculture actors were consulted. "Perceived complexity"—barriers to adoption that are strongly influenced by contextual factors—has been used to examine their perspectives (i.e. socio-economic, institutional, cultural ones). The new model will contextualise the sequence based on technologies, entrepreneur traits, corporate and institutional contexts, and complexity perception, the sequence's central node. Technology adoption can also be studied by examining complexity perceptions along the AKAIE sequence. This study proposes a new model to evaluate the diffusion of a given technology, offering the policy maker the possibility to be able to act promptly across the process. The development of responsible policies for evaluating the effectiveness of innovation is more necessary than ever, especially to orient strategies and interventions in the face of major scenarios of change.

Non-Markovian stochastic processes and their applications: from anomalous diffusion to time series analysis

This work provides a forward step in the study and comprehension of the relationships between stochastic processes and a certain class of integral-partial differential equation, which can be used in order to model anomalous diffusion and transport in statistical physics. In the first part, we brought the reader through the fundamental notions of probability and stochastic processes, stochastic integration and stochastic differential equations as well. In particular, within the study of H-sssi processes, we focused on fractional Brownian motion (fBm) and its discrete-time increment process, the fractional Gaussian noise (fGn), which provide examples of non-Markovian Gaussian processes. The fGn, together with stationary FARIMA processes, is widely used in the modeling and estimation of long-memory, or long-range dependence (LRD). Time series manifesting long-range dependence, are often observed in nature especially in physics, meteorology, climatology, but also in hydrology, geophysics, economy and many others. We deepely studied LRD, giving many real data examples, providing statistical analysis and introducing parametric methods of estimation. Then, we introduced the theory of fractional integrals and derivatives, which indeed turns out to be very appropriate for studying and modeling systems with long-memory properties. After having introduced the basics concepts, we provided many examples and applications. For instance, we investigated the relaxation equation with distributed order time-fractional derivatives, which describes models characterized by a strong memory component and can be used to model relaxation in complex systems, which deviates from the classical exponential Debye pattern. Then, we focused in the study of generalizations of the standard diffusion equation, by passing through the preliminary study of the fractional forward drift equation. Such generalizations have been obtained by using fractional integrals and derivatives of distributed orders. In order to find a connection between the anomalous diffusion described by these equations and the long-range dependence, we introduced and studied the generalized grey Brownian motion (ggBm), which is actually a parametric class of H-sssi processes, which have indeed marginal probability density function evolving in time according to a partial integro-differential equation of fractional type. The ggBm is of course Non-Markovian. All around the work, we have remarked many times that, starting from a master equation of a probability density function f(x,t), it is always possible to define an equivalence class of stochastic processes with the same marginal density function f(x,t). All these processes provide suitable stochastic models for the starting equation. Studying the ggBm, we just focused on a subclass made up of processes with stationary increments. The ggBm has been defined canonically in the so called grey noise space. However, we have been able to provide a characterization notwithstanding the underline probability space. We also pointed out that that the generalized grey Brownian motion is a direct generalization of a Gaussian process and in particular it generalizes Brownain motion and fractional Brownain motion as well. Finally, we introduced and analyzed a more general class of diffusion type equations related to certain non-Markovian stochastic processes. We started from the forward drift equation, which have been made non-local in time by the introduction of a suitable chosen memory kernel K(t). The resulting non-Markovian equation has been interpreted in a natural way as the evolution equation of the marginal density function of a random time process l(t). We then consider the subordinated process Y(t)=X(l(t)) where X(t) is a Markovian diffusion. The corresponding time-evolution of the marginal density function of Y(t) is governed by a non-Markovian Fokker-Planck equation which involves the same memory kernel K(t). We developed several applications and derived the exact solutions. Moreover, we considered different stochastic models for the given equations, providing path simulations.

Effects of environmental complexity on neurogenesis in the hippocampal dentate gyrus

Introduction. Postnatal neurogenesis in the hippocampal dentate gyrus, can be modulated by numerous determinants, such as hormones, transmitters and stress. Among the factors positively interfering with neurogenesis, the complexity of the environment appears to play a particularly striking role. Adult mice reared in an enriched environment produce more neurons and exhibit better performance in hippocampus-specific learning tasks. While the effects of complex environments on hippocampal neurogenesis are well documented, there is a lack of information on the effects of living under socio-sensory deprivation conditions. Due to the immaturity of rats and mice at birth, studies dealing with the effects of environmental enrichment on hippocampal neurogenesis were carried out in adult animals, i.e. during a period of relatively low rate of neurogenesis. The impact of environment is likely to be more dramatic during the first postnatal weeks, because at this time granule cell production is remarkably higher than at later phases of development. The aim of the present research was to clarify whether and to what extent isolated or enriched rearing conditions affect hippocampal neurogenesis during the early postnatal period, a time window characterized by a high rate of precursor proliferation and to elucidate the mechanisms underlying these effects. The experimental model chosen for this research was the guinea pig, a precocious rodent, which, at 4-5 days of age can be independent from maternal care. Experimental design. Animals were assigned to a standard (control), an isolated, or an enriched environment a few days after birth (P5-P6). On P14-P17 animals received one daily bromodeoxyuridine (BrdU) injection, to label dividing cells, and were sacrificed either on P18, to evaluate cell proliferation or on P45, to evaluate cell survival and differentiation. Methods. Brain sections were processed for BrdU immunhistochemistry, to quantify the new born and surviving cells. The phenotype of the surviving cells was examined by means of confocal microscopy and immunofluorescent double-labeling for BrdU and either a marker of neurons (NeuN) or a marker of astrocytes (GFAP). Apoptotic cell death was examined with the TUNEL method. Serial sections were processed for immunohistochemistry for i) vimentin, a marker of radial glial cells, ii) BDNF (brain-derived neurotrofic factor), a neurotrophin involved in neuron proliferation/survival, iii) PSA-NCAM (the polysialylated form of the neural cell adhesion molecule), a molecule associated with neuronal migration. Total granule cell number in the dentate gyrus was evaluated by stereological methods, in Nissl-stained sections. Results. Effects of isolation. In P18 isolated animals we found a reduced cell proliferation (-35%) compared to controls and a lower expression of BDNF. Though in absolute terms P45 isolated animals had less surviving cells than controls, they showed no differences in survival rate and phenotype percent distribution compared to controls. Evaluation of the absolute number of surviving cells of each phenotype showed that isolated animals had a reduced number of cells with neuronal phenotype than controls. Looking at the location of the new neurons, we found that while in control animals 76% of them had migrated to the granule cell layer, in isolated animals only 55% of the new neurons had reached this layer. Examination of radial glia cells of P18 and P45 animals by vimentin immunohistochemistry showed that in isolated animals radial glia cells were reduced in density and had less and shorter processes. Granule cell count revealed that isolated animals had less granule cells than controls (-32% at P18 and -42% at P45). Effects of enrichment. In P18 enriched animals there was an increase in cell proliferation (+26%) compared to controls and a higher expression of BDNF. Though in both groups there was a decline in the number of BrdU-positive cells by P45, enriched animals had more surviving cells (+63) and a higher survival rate than controls. No differences were found between control and enriched animals in phenotype percent distribution. Evaluation of the absolute number of cells of each phenotype showed that enriched animals had a larger number of cells of each phenotype than controls. Looking at the location of cells of each phenotype we found that enriched animals had more new neurons in the granule cell layer and more astrocytes and cells with undetermined phenotype in the hilus. Enriched animals had a higher expression of PSA-NCAM in the granule cell layer and hilus Vimentin immunohistochemistry showed that in enriched animals radial glia cells were more numerous and had more processes.. Granule cell count revealed that enriched animals had more granule cells than controls (+37% at P18 and +31% at P45). Discussion. Results show that isolation rearing reduces hippocampal cell proliferation but does not affect cell survival, while enriched rearing increases both cell proliferation and cell survival. Changes in the expression of BDNF are likely to contribute to he effects of environment on precursor cell proliferation. The reduction and increase in final number of granule neurons in isolated and enriched animals, respectively, are attributable to the effects of environment on cell proliferation and survival and not to changes in the differentiation program. As radial glia cells play a pivotal role in neuron guidance to the granule cell layer, the reduced number of radial glia cells in isolated animals and the increased number in enriched animals suggests that the size of radial glia population may change dynamically, in order to match changes in neuron production. The high PSA-NCAM expression in enriched animals may concur to favor the survival of the new neurons by facilitating their migration to the granule cell layer. Conclusions. By using a precocious rodent we could demonstrate that isolated/enriched rearing conditions, at a time window during which intense granule cell proliferation takes place, lead to a notable decrease/increase of total granule cell number. The time-course and magnitude of postnatal granule cell production in guinea pigs are more similar to the human and non-human primate condition than in rats and mice. Translation of current data to humans would imply that exposure of children to environments poor/rich of stimuli may have a notably large impact on dentate neurogenesis and, very likely, on hippocampus dependent memory functions.

Rafael Moneo: la complessità del vuoto. Dalle matrici formali dell'opera di Oteiza e Chillida

The experience of void, essential to the production of forms and to make use them, can be considered as the base of the activities that attend to the formative processes. If void and matter constitutes the basic substances of architecture. Their role in the definition of form, the symbolic value and the constructive methods of it defines the quality of the space. This job inquires the character of space in the architecture of Moneo interpreting the meaning of the void in the Basque culture through the reading of the form matrices in the work of Jorge Oteiza and Eduardo Chillida. In the tie with the Basque culture a reading key is characterized by concurring to put in relation some of the theoretical principles expressed by Moneo on the relationship between place and time, in an unique and specific vision of the space. In the analysis of the process that determines the genesis of the architecture of Moneo emerges a trajectory whose direction is constructed on two pivos: on the one hand architecture like instrument of appropriation of the place, gushed from an acquaintance process who leans itself to the reading of the relations that define the place and of the resonances through which measuring it, on the other hand the architecture whose character is able to represent and to extend the time in which he is conceived, through the autonomy that is conferred to them from values. Following the trace characterized from this hypothesis, that is supported on the theories elaborated from Moneo, surveying deepens the reading of the principles that construct the sculptural work of Oteiza and Chillida, features from a search around the topic of the void and to its expression through the form. It is instrumental to the definition of a specific area that concurs to interpret the character of the space subtended to a vision of the place and the time, affine to the sensibility of Moneo and in some way not stranger to its cultural formation. The years of the academic formation, during which Moneo enters in contact with the Basque artistic culture, seem to be an important period in the birth of that knowledge that will leads him to the formulation of theories tied to the relationship between time, place and architecture. The values expressed through the experimental work of Oteiza and Chillida during years '50 are valid bases to the understanding of such relationships. In tracing a profile of the figures of Oteiza and Chillida, without the pretension that it is exhaustive for the reading of the complex historical period in which they are placed, but with the needs to put the work in a context, I want to be evidenced the important role carried out from the two artists from the Basque cultural area within which Moneo moves its first steps. The tie that approaches Moneo to the Basque culture following the personal trajectory of the formative experience interlaces to that one of important figures of the art and the Spanish architecture. One of the more meaningful relationships is born just during the years of his academic formation, from 1958 to the 1961, when he works like student in the professional office of the architect Francisco Sáenz de Oiza, who was teaching architectural design at the ETSAM. In these years many figures of Basque artists alternated at the professional office of Oiza that enjoys the important support of the manufacturer and maecenas Juan Huarte Beaumont, introduced to he from Oteiza. The tie between Huarte and Oteiza is solid and continuous in the years and it realizes in a contribution to many of the initiatives that makes of Oteiza a forwarder of the Basque culture. In the four years of collaboration with Oiza, Moneo has the opportunity to keep in contact with an atmosphere permeated by a constant search in the field of the plastic art and with figures directly connected to such atmosphere. It’s of a period of great intensity as in the production like in the promotion of the Basque art. The collective “Blanco y Negro”, than is held in 1959 at the Galería Darro to Madrid, is only one of the many times of an exhibition of the work of Oteiza and Chillida. The end of the Fifties is a period of international acknowledgment for Chillida that for Oteiza. The decade of the Fifties consecrates the hypotheses of a mythical past of the Basque people through the spread of the studies carried out in the antecedent years. The archaeological discoveries that join to a context already rich of signs of the prehistoric era, consolidate the knowledge of a strong cultural identity. Oteiza, like Chillida and other contemporary artists, believe in a cosmogonist conception belonging to the Basques, connected to their matriarchal mythological past. The void in its meaning of absence, in the Basque culture, thus as in various archaic and oriental religions, is equivalent to the spiritual fullness as essential condition to the revealing of essence. Retracing the archaic origins of the Basque culture emerges the deep meaning that the void assumes as key element in the religious interpretation of the passage from the life to the death. The symbology becomes rich of meaningful characters who derive from the fact that it is a chthonic cult. A representation of earth like place in which divine manifest itself but also like connection between divine and human, and this manipulation of the matter of which the earth it is composed is the tangible projection of the continuous search of the man towards God. The search of equilibrium between empty and full, that characterizes also the development of the form in architecture, in the Basque culture assumes therefore a peculiar value that returns like constant in great part of the plastic expressions, than in this context seem to be privileged regarding the other expressive forms. Oteiza and Chillida develop two original points of view in the representation of the void through the form. Both use of rigorous systems of rules sensitive to the physics principles and the characters of the matter. The last aim of the Oteiza’s construction is the void like limit of the knowledge, like border between known and unknown. It doesn’t means to reduce the sculptural object to an only allusive dimension because the void as physical and spiritual power is an active void, that possesses that value able to reveal the being through the trace of un-being. The void in its transcendental manifestation acts at the same time from universal and from particular, like in the atomic structure of the matter, in which on one side it constitutes the inner structure of every atom and on the other one it is necessary condition to the interaction between all the atoms. The void can be seen therefore as the action field that concurs the relations between the forms but is also the necessary condition to the same existence of the form. In the construction of Chillida the void represents that counterpart structuring the matter, inborn in it, the element in absence of which wouldn’t be variations neither distinctive characters to define the phenomenal variety of the world. The physics laws become the subject of the sculptural representation, the void are the instrument that concurs to catch up the equilibrium. Chillida dedicate himself to experience the space through the senses, to perceive of the qualities, to tell the physics laws which forge the matter in the form and the form arranges the places. From the artistic experience of the two sculptors they can be transposed, to the architectonic work of Moneo, those matrices on which they have constructed their original lyric expressions, where the void is absolute protagonist. An ambit is defined thus within which the matrices form them drafts from the work of Oteiza and Chillida can be traced in the definition of the process of birth and construction of the architecture of Moneo, but also in the relation that the architecture establishes with the place and in the time. The void becomes instrument to read the space constructed in its relationships that determine the proportions, rhythms, and relations. In this way the void concurs to interpret the architectonic space and to read the value of it, the quality of the spaces constructing it. This because it’s like an instrument of the composition, whose role is to maintain to the separation between the elements putting in evidence the field of relations. The void is that instrument that serves to characterize the elements that are with in the composition, related between each other, but distinguished. The meaning of the void therefore pushes the interpretation of the architectonic composition on the game of the relations between the elements that, independent and distinguished, strengthen themselves in their identity. On the one hand if void, as measurable reality, concurs all the dimensional changes quantifying the relationships between the parts, on the other hand its dialectic connotation concurs to search the equilibrium that regulated such variations. Equilibrium that therefore does not represent an obtained state applying criteria setting up from arbitrary rules but that depends from the intimate nature of the matter and its embodiment in the form. The production of a form, or a formal system that can be finalized to the construction of a building, is indissolubly tied to the technique that is based on the acquaintance of the formal vocation of the matter, and what it also can representing, meaning, expresses itself in characterizing the site. For Moneo, in fact, the space defined from the architecture is above all a site, because the essence of the site is based on the construction. When Moneo speaks about “birth of the idea of plan” like essential moment in the construction process of the architecture, it refers to a process whose complexity cannot be born other than from a deepened acquaintance of the site that leads to the comprehension of its specificity. Specificity arise from the infinite sum of relations, than for Moneo is the story of the oneness of a site, of its history, of the cultural identity and of the dimensional characters that that they are tied to it beyond that to the physical characteristics of the site. This vision is leaned to a solid made physical structure of perceptions, of distances, guideline and references that then make that the process is first of all acquaintance, appropriation. Appropriation that however does not happen for directed consequence because does not exist a relationship of cause and effect between place and architecture, thus as an univocal and exclusive way does not exist to arrive to a representation of an idea. An approach that, through the construction of the place where the architecture acquires its being, searches an expression of its sense of the truth. The proposal of a distinction for areas like space, matter, spirit and time, answering to the issues that scan the topics of the planning search of Moneo, concurs a more immediate reading of the systems subtended to the composition principles, through which is related the recurrent architectonic elements in its planning dictionary. From the dialectic between the opposites that is expressed in the duality of the form, through the definition of a complex element that can mediate between inside and outside as a real system of exchange, Moneo experiences the form development of the building deepening the relations that the volume establishes in the site. From time to time the invention of a system used to answer to the needs of the program and to resolve the dual character of the construction in an only gesture, involves a deep acquaintance of the professional practice. The technical aspect is the essential support to which the construction of the system is indissolubly tied. What therefore arouses interest is the search of the criteria and the way to construct that can reveal essential aspects of the being of the things. The constructive process demands, in fact, the acquaintance of the formative properties of the matter. Property from which the reflections gush on the relations that can be born around the architecture through the resonance produced from the forms. The void, in fact, through the form is in a position to constructing the site establishing a reciprocity relation. A reciprocity that is determined in the game between empty and full and of the forms between each other, regarding around, but also with regard to the subjective experience. The construction of a background used to amplify what is arranged on it and to clearly show the relations between the parts and at the same time able to tie itself with around opening the space of the vision, is a system that in the architecture of Moneo has one of its more effective applications in the use of the platform used like architectonic element. The spiritual force of this architectonic gesture is in the ability to define a place whose projecting intention is perceived and shared with who experience and has lived like some instrument to contact the cosmic forces, in a delicate process that lead to the equilibrium with them, but in completely physical way. The principles subtended to the construction of the form taken from the study of the void and the relations that it concurs, lead to express human values in the construction of the site. The validity of these principles however is tested from the time. The time is what Moneo considers as filter that every architecture is subordinate to and the survival of architecture, or any of its formal characters, reveals them the validity of the principles that have determined it. It manifests thus, in the tie between the spatial and spiritual dimension, between the material and the worldly dimension, the state of necessity that leads, in the construction of the architecture, to establish a contact with the forces of the universe and the intimate world, through a process that translate that necessity in elaboration of a formal system.

Strategies and procedures for the development of intermodal freight transport in Europe: the role of motorways of the sea services and railway terminals

Since the birth of the European Union on 1957, the development of a single market through the integration of national freight transport networks has been one of the most important points in the European Union agenda. Increasingly congested motorways, rising oil prices and concerns about environment and climate change require the optimization of transport systems and transport processes. The best solution should be the intermodal transport, in which the most efficient transport options are used for the different legs of transport. This thesis examines the problem of defining innovative strategies and procedures for the sustainable development of intermodal freight transport in Europe. In particular, the role of maritime transport and railway transport in the intermodal chain are examined in depth, as these modes are recognized to be environmentally friendly and energy efficient. Maritime transport is the only mode that has kept pace with the fast growth in road transport, but it is necessary to promote the full exploitation of it by involving short sea shipping as an integrated service in the intermodal door-to-door supply chain and by improving port accessibility. The role of Motorways of the Sea services as part of the Trans-European Transport Network is is taken into account: a picture of the European policy and a state of the art of the Italian Motorways of the Sea system are reported. Afterwards, the focus shifts from line to node problems: the role of intermodal railway terminals in the transport chain is discussed. In particular, the last mile process is taken into account, as it is crucial in order to exploit the full capacity of an intermodal terminal. The difference between the present last mile planning models of Bologna Interporto and Verona Quadrante Europa is described and discussed. Finally, a new approach to railway intermodal terminal planning and management is introduced, by describing the case of "Terminal Gate" at Verona Quadrante Europa. Some proposals to favour the integrate management of "Terminal Gate" and the allocation of its capacity are drawn up.

Technical innovations for the diagnosis and the rehabilitation of motor and perceptive impairments of the child with Cerebral Palsy

The treatment of the Cerebral Palsy (CP) is considered as the “core problem” for the whole field of the pediatric rehabilitation. The reason why this pathology has such a primary role, can be ascribed to two main aspects. First of all CP is the form of disability most frequent in childhood (one new case per 500 birth alive, (1)), secondarily the functional recovery of the “spastic” child is, historically, the clinical field in which the majority of the therapeutic methods and techniques (physiotherapy, orthotic, pharmacologic, orthopedic-surgical, neurosurgical) were first applied and tested. The currently accepted definition of CP – Group of disorders of the development of movement and posture causing activity limitation (2) – is the result of a recent update by the World Health Organization to the language of the International Classification of Functioning Disability and Health, from the original proposal of Ingram – A persistent but not unchangeable disorder of posture and movement – dated 1955 (3). This definition considers CP as a permanent ailment, i.e. a “fixed” condition, that however can be modified both functionally and structurally by means of child spontaneous evolution and treatments carried out during childhood. The lesion that causes the palsy, happens in a structurally immature brain in the pre-, peri- or post-birth period (but only during the firsts months of life). The most frequent causes of CP are: prematurity, insufficient cerebral perfusion, arterial haemorrhage, venous infarction, hypoxia caused by various origin (for example from the ingestion of amniotic liquid), malnutrition, infection and maternal or fetal poisoning. In addition to these causes, traumas and malformations have to be included. The lesion, whether focused or spread over the nervous system, impairs the whole functioning of the Central Nervous System (CNS). As a consequence, they affect the construction of the adaptive functions (4), first of all posture control, locomotion and manipulation. The palsy itself does not vary over time, however it assumes an unavoidable “evolutionary” feature when during growth the child is requested to meet new and different needs through the construction of new and different functions. It is essential to consider that clinically CP is not only a direct expression of structural impairment, that is of etiology, pathogenesis and lesion timing, but it is mainly the manifestation of the path followed by the CNS to “re”-construct the adaptive functions “despite” the presence of the damage. “Palsy” is “the form of the function that is implemented by an individual whose CNS has been damaged in order to satisfy the demands coming from the environment” (4). Therefore it is only possible to establish general relations between lesion site, nature and size, and palsy and recovery processes. It is quite common to observe that children with very similar neuroimaging can have very different clinical manifestations of CP and, on the other hand, children with very similar motor behaviors can have completely different lesion histories. A very clear example of this is represented by hemiplegic forms, which show bilateral hemispheric lesions in a high percentage of cases. The first section of this thesis is aimed at guiding the interpretation of CP. First of all the issue of the detection of the palsy is treated from historical viewpoint. Consequently, an extended analysis of the current definition of CP, as internationally accepted, is provided. The definition is then outlined in terms of a space dimension and then of a time dimension, hence it is highlighted where this definition is unacceptably lacking. The last part of the first section further stresses the importance of shifting from the traditional concept of CP as a palsy of development (defect analysis) towards the notion of development of palsy, i.e., as the product of the relationship that the individual however tries to dynamically build with the surrounding environment (resource semeiotics) starting and growing from a different availability of resources, needs, dreams, rights and duties (4). In the scientific and clinic community no common classification system of CP has so far been universally accepted. Besides, no standard operative method or technique have been acknowledged to effectively assess the different disabilities and impairments exhibited by children with CP. CP is still “an artificial concept, comprising several causes and clinical syndromes that have been grouped together for a convenience of management” (5). The lack of standard and common protocols able to effectively diagnose the palsy, and as a consequence to establish specific treatments and prognosis, is mainly because of the difficulty to elevate this field to a level based on scientific evidence. A solution aimed at overcoming the current incomplete treatment of CP children is represented by the clinical systematic adoption of objective tools able to measure motor defects and movement impairments. A widespread application of reliable instruments and techniques able to objectively evaluate both the form of the palsy (diagnosis) and the efficacy of the treatments provided (prognosis), constitutes a valuable method able to validate care protocols, establish the efficacy of classification systems and assess the validity of definitions. Since the ‘80s, instruments specifically oriented to the analysis of the human movement have been advantageously designed and applied in the context of CP with the aim of measuring motor deficits and, especially, gait deviations. The gait analysis (GA) technique has been increasingly used over the years to assess, analyze, classify, and support the process of clinical decisions making, allowing for a complete investigation of gait with an increased temporal and spatial resolution. GA has provided a basis for improving the outcome of surgical and nonsurgical treatments and for introducing a new modus operandi in the identification of defects and functional adaptations to the musculoskeletal disorders. Historically, the first laboratories set up for gait analysis developed their own protocol (set of procedures for data collection and for data reduction) independently, according to performances of the technologies available at that time. In particular, the stereophotogrammetric systems mainly based on optoelectronic technology, soon became a gold-standard for motion analysis. They have been successfully applied especially for scientific purposes. Nowadays the optoelectronic systems have significantly improved their performances in term of spatial and temporal resolution, however many laboratories continue to use the protocols designed on the technology available in the ‘70s and now out-of-date. Furthermore, these protocols are not coherent both for the biomechanical models and for the adopted collection procedures. In spite of these differences, GA data are shared, exchanged and interpreted irrespectively to the adopted protocol without a full awareness to what extent these protocols are compatible and comparable with each other. Following the extraordinary advances in computer science and electronics, new systems for GA no longer based on optoelectronic technology, are now becoming available. They are the Inertial and Magnetic Measurement Systems (IMMSs), based on miniature MEMS (Microelectromechanical systems) inertial sensor technology. These systems are cost effective, wearable and fully portable motion analysis systems, these features gives IMMSs the potential to be used both outside specialized laboratories and to consecutive collect series of tens of gait cycles. The recognition and selection of the most representative gait cycle is then easier and more reliable especially in CP children, considering their relevant gait cycle variability. The second section of this thesis is focused on GA. In particular, it is firstly aimed at examining the differences among five most representative GA protocols in order to assess the state of the art with respect to the inter-protocol variability. The design of a new protocol is then proposed and presented with the aim of achieving gait analysis on CP children by means of IMMS. The protocol, named ‘Outwalk’, contains original and innovative solutions oriented at obtaining joint kinematic with calibration procedures extremely comfortable for the patients. The results of a first in-vivo validation of Outwalk on healthy subjects are then provided. In particular, this study was carried out by comparing Outwalk used in combination with an IMMS with respect to a reference protocol and an optoelectronic system. In order to set a more accurate and precise comparison of the systems and the protocols, ad hoc methods were designed and an original formulation of the statistical parameter coefficient of multiple correlation was developed and effectively applied. On the basis of the experimental design proposed for the validation on healthy subjects, a first assessment of Outwalk, together with an IMMS, was also carried out on CP children. The third section of this thesis is dedicated to the treatment of walking in CP children. Commonly prescribed treatments in addressing gait abnormalities in CP children include physical therapy, surgery (orthopedic and rhizotomy), and orthoses. The orthotic approach is conservative, being reversible, and widespread in many therapeutic regimes. Orthoses are used to improve the gait of children with CP, by preventing deformities, controlling joint position, and offering an effective lever for the ankle joint. Orthoses are prescribed for the additional aims of increasing walking speed, improving stability, preventing stumbling, and decreasing muscular fatigue. The ankle-foot orthosis (AFO), with a rigid ankle, are primarily designed to prevent equinus and other foot deformities with a positive effect also on more proximal joints. However, AFOs prevent the natural excursion of the tibio-tarsic joint during the second rocker, hence hampering the natural leaning progression of the whole body under the effect of the inertia (6). A new modular (submalleolar) astragalus-calcanear orthosis, named OMAC, has recently been proposed with the intention of substituting the prescription of AFOs in those CP children exhibiting a flat and valgus-pronated foot. The aim of this section is thus to present the mechanical and technical features of the OMAC by means of an accurate description of the device. In particular, the integral document of the deposited Italian patent, is provided. A preliminary validation of OMAC with respect to AFO is also reported as resulted from an experimental campaign on diplegic CP children, during a three month period, aimed at quantitatively assessing the benefit provided by the two orthoses on walking and at qualitatively evaluating the changes in the quality of life and motor abilities. As already stated, CP is universally considered as a persistent but not unchangeable disorder of posture and movement. Conversely to this definition, some clinicians (4) have recently pointed out that movement disorders may be primarily caused by the presence of perceptive disorders, where perception is not merely the acquisition of sensory information, but an active process aimed at guiding the execution of movements through the integration of sensory information properly representing the state of one’s body and of the environment. Children with perceptive impairments show an overall fear of moving and the onset of strongly unnatural walking schemes directly caused by the presence of perceptive system disorders. The fourth section of the thesis thus deals with accurately defining the perceptive impairment exhibited by diplegic CP children. A detailed description of the clinical signs revealing the presence of the perceptive impairment, and a classification scheme of the clinical aspects of perceptual disorders is provided. In the end, a functional reaching test is proposed as an instrumental test able to disclosure the perceptive impairment. References 1. Prevalence and characteristics of children with cerebral palsy in Europe. Dev Med Child Neurol. 2002 Set;44(9):633-640. 2. Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N, Dan B, et al. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol. 2005 Ago;47(8):571-576. 3. Ingram TT. A study of cerebral palsy in the childhood population of Edinburgh. Arch. Dis. Child. 1955 Apr;30(150):85-98. 4. Ferrari A, Cioni G. The spastic forms of cerebral palsy : a guide to the assessment of adaptive functions. Milan: Springer; 2009. 5. Olney SJ, Wright MJ. Cerebral Palsy. Campbell S et al. Physical Therapy for Children. 2nd Ed. Philadelphia: Saunders. 2000;:533-570. 6. Desloovere K, Molenaers G, Van Gestel L, Huenaerts C, Van Campenhout A, Callewaert B, et al. How can push-off be preserved during use of an ankle foot orthosis in children with hemiplegia? A prospective controlled study. Gait Posture. 2006 Ott;24(2):142-151.

Studies of OPA1 pathogenic mechanisms in Dominant Optic Atrophy and novel protein function in mitochondrial DNA stability

The mitochondrion is an essential cytoplasmic organelle that provides most of the energy necessary for eukaryotic cell physiology. Mitochondrial structure and functions are maintained by proteins of both mitochondrial and nuclear origin. These organelles are organized in an extended network that dynamically fuses and divides. Mitochondrial morphology results from the equilibrium between fusion and fission processes, controlled by a family of “mitochondria-shaping” proteins. It is becoming clear that defects in mitochondrial dynamics can impair mitochondrial respiration, morphology and motility, leading to apoptotic cell death in vitro and more or less severe neurodegenerative disorders in vivo in humans. Mutations in OPA1, a nuclear encoded mitochondrial protein, cause autosomal Dominant Optic Atrophy (DOA), a heterogeneous blinding disease characterized by retinal ganglion cell degeneration leading to optic neuropathy (Delettre et al., 2000; Alexander et al., 2000). OPA1 is a mitochondrial dynamin-related guanosine triphosphatase (GTPase) protein involved in mitochondrial network dynamics, cytochrome c storage and apoptosis. This protein is anchored or associated on the inner mitochondrial membrane facing the intermembrane space. Eight OPA1 isoforms resulting from alternative splicing combinations of exon 4, 4b and 5b have been described (Delettre et al., 2001). These variants greatly vary among diverse organs and the presence of specific isoforms has been associated with various mitochondrial functions. The different spliced exons encode domains included in the amino-terminal region and contribute to determine OPA1 functions (Olichon et al., 2006). It has been shown that exon 4, that is conserved throughout evolution, confers functions to OPA1 involved in maintenance of the mitochondrial membrane potential and in the fusion of the network. Conversely, exon 4b and exon 5b, which are vertebrate specific, are involved in regulation of cytochrome c release from mitochondria, and activation of apoptosis, a process restricted to vertebrates (Olichon et al., 2007). While Mgm1p has been identified thanks to its role in mtDNA maintenance, it is only recently that OPA1 has been linked to mtDNA stability. Missense mutations in OPA1 cause accumulation of multiple deletions in skeletal muscle. The syndrome associated to these mutations (DOA-1 plus) is complex, consisting of a combination of dominant optic atrophy, progressive external ophtalmoplegia, peripheral neuropathy, ataxia and deafness (Amati- Bonneau et al., 2008; Hudson et al., 2008). OPA1 is the fifth gene associated with mtDNA “breakage syndrome” together with ANT1, PolG1-2 and TYMP (Spinazzola et al., 2009). In this thesis we show for the first time that specific OPA1 isoforms associated to exon 4b are important for mtDNA stability, by anchoring the nucleoids to the inner mitochondrial membrane. Our results clearly demonstrate that OPA1 isoforms including exon 4b are intimately associated to the maintenance of the mitochondrial genome, as their silencing leads to mtDNA depletion. The mechanism leading to mtDNA loss is associated with replication inhibition in cells where exon 4b containing isoforms were down-regulated. Furthermore silencing of exon 4b associated isoforms is responsible for alteration in mtDNA-nucleoids distribution in the mitochondrial network. In this study it was evidenced that OPA1 exon 4b isoform is cleaved to provide a 10kd peptide embedded in the inner membrane by a second transmembrane domain, that seems to be crucial for mitochondrial genome maintenance and does correspond to the second transmembrane domain of the yeasts orthologue encoded by MGM1 or Msp1, which is also mandatory for this process (Diot et al., 2009; Herlan et al., 2003). Furthermore in this thesis we show that the NT-OPA1-exon 4b peptide co-immuno-precipitates with mtDNA and specifically interacts with two major components of the mitochondrial nucleoids: the polymerase gamma and Tfam. Thus, from these experiments the conclusion is that NT-OPA1- exon 4b peptide contributes to the nucleoid anchoring in the inner mitochondrial membrane, a process that is required for the initiation of mtDNA replication and for the distribution of nucleoids along the network. These data provide new crucial insights in understanding the mechanism involved in maintenance of mtDNA integrity, because they clearly demonstrate that, besides genes implicated in mtDNA replications (i.e. polymerase gamma, Tfam, twinkle and genes involved in the nucleotide pool metabolism), OPA1 and mitochondrial membrane dynamics play also an important role. Noticeably, the effect on mtDNA is different depending on the specific OPA1 isoforms down-regulated, suggesting the involvement of two different combined mechanisms. Over two hundred OPA1 mutations, spread throughout the coding region of the gene, have been described to date, including substitutions, deletions or insertions. Some mutations are predicted to generate a truncated protein inducing haploinsufficiency, whereas the missense nucleotide substitutions result in aminoacidic changes which affect conserved positions of the OPA1 protein. So far, the functional consequences of OPA1 mutations in cells from DOA patients are poorly understood. Phosphorus MR spectroscopy in patients with the c.2708delTTAG deletion revealed a defect in oxidative phosphorylation in muscles (Lodi et al., 2004). An energetic impairment has been also show in fibroblasts with the severe OPA1 R445H mutation (Amati-Bonneau et al., 2005). It has been previously reported by our group that OPA1 mutations leading to haploinsufficiency are associated in fibroblasts to an oxidative phosphorylation dysfunction, mainly involving the respiratory complex I (Zanna et al., 2008). In this study we have evaluated the energetic efficiency of a panel of skin fibroblasts derived from DOA patients, five fibroblast cell lines with OPA1 mutations causing haploinsufficiency (DOA-H) and two cell lines bearing mis-sense aminoacidic substitutions (DOA-AA), and compared with control fibroblasts. Although both types of DOA fibroblasts maintained a similar ATP content when incubated in a glucose-free medium, i.e. when forced to utilize the oxidative phosphorylation only to produce ATP, the mitochondrial ATP synthesis through complex I, measured in digitonin-permeabilized cells, was significantly reduced in cells with OPA1 haploinsufficiency only, whereas it was similar to controls in cells with the missense substitutions. Furthermore, evaluation of the mitochondrial membrane potential (DYm) in the two fibroblast lines DOA-AA and in two DOA-H fibroblasts, namely those bearing the c.2819-2A>C mutation and the c.2708delTTAG microdeletion, revealed an anomalous depolarizing response to oligomycin in DOA-H cell lines only. This finding clearly supports the hypothesis that these mutations cause a significant alteration in the respiratory chain function, which can be unmasked only when the operation of the ATP synthase is prevented. Noticeably, oligomycin-induced depolarization in these cells was almost completely prevented by preincubation with cyclosporin A, a well known inhibitor of the permeability transition pore (PTP). This results is very important because it suggests for the first time that the voltage threshold for PTP opening is altered in DOA-H fibroblasts. Although this issue has not yet been addressed in the present study, several are the mechanisms that have been proposed to lead to PTP deregulation, including in particular increased reactive oxygen species production and alteration of Ca2+ homeostasis, whose role in DOA fibroblasts PTP opening is currently under investigation. Identification of the mechanisms leading to altered threshold for PTP regulation will help our understanding of the pathophysiology of DOA, but also provide a strategy for therapeutic intervention.

Design and optimization of components and processes for plasma sources in advanced material treatments

The research activities described in the present thesis have been oriented to the design and development of components and technological processes aimed at optimizing the performance of plasma sources in advanced in material treatments. Consumables components for high definition plasma arc cutting (PAC) torches were studied and developed. Experimental activities have in particular focussed on the modifications of the emissive insert with respect to the standard electrode configuration, which comprises a press fit hafnium insert in a copper body holder, to improve its durability. Based on a deep analysis of both the scientific and patent literature, different solutions were proposed and tested. First, the behaviour of Hf cathodes when operating at high current levels (250A) in oxidizing atmosphere has been experimentally investigated optimizing, with respect to expected service life, the initial shape of the electrode emissive surface. Moreover, the microstructural modifications of the Hf insert in PAC electrodes were experimentally investigated during first cycles, in order to understand those phenomena occurring on and under the Hf emissive surface and involved in the electrode erosion process. Thereafter, the research activity focussed on producing, characterizing and testing prototypes of composite inserts, combining powders of a high thermal conductibility (Cu, Ag) and high thermionic emissivity (Hf, Zr) materials The complexity of the thermal plasma torch environment required and integrated approach also involving physical modelling. Accordingly, a detailed line-by-line method was developed to compute the net emission coefficient of Ar plasmas at temperatures ranging from 3000 K to 25000 K and pressure ranging from 50 kPa to 200 kPa, for optically thin and partially autoabsorbed plasmas. Finally, prototypal electrodes were studied and realized for a newly developed plasma source, based on the plasma needle concept and devoted to the generation of atmospheric pressure non-thermal plasmas for biomedical applications.

Salinity Effect on Horticultural Crops: Morphological, Physiological, and Biomolecular Elements of Salinity Stress Response

Among abiotic stresses, high salinity stress is the most severe environmental stress. High salinity exerts its negative impact mainly by disrupting the ionic and osmotic equilibrium of the cell. In saline soils, high levels of sodium ions lead to plant growth inhibition and even death. Salt tolerance in plants is a multifarious phenomenon involving a variety of changes at molecular, organelle, cellular, tissue as well as whole plant level. In addition, salt tolerant plants show a range of adaptations not only in morphological or structural features but also in metabolic and physiological processes that enable them to survive under extreme saline environments. The main objectives of my dissertation were understanding the main physiological and biomolecular features of plant responses to salinity in different genotypes of horticultural crops that are belonging to different families Solanaceae (tomato) and Cucurbitaceae (melon) and Brassicaceae (cabbage and radish). Several aspects of crop responses to salinity have been addressed with the final aim of combining elements of functional stress response in plants by using several ways for the assessment of plant stress perception that ranging from destructive measurements (eg. leaf area, relative growth rate, leaf area index, and total plant fresh and dry weight), to physiological determinations (eg. stomatal conductance, leaf gas exchanges, water use efficiency, and leaf water relation), to the determination of metabolite accumulation in plant tissue (eg. Proline and protein) as well as evaluation the role of enzymatic antioxidant capacity assay in scavenging reactive oxygen species that have been generated under salinized condition, and finally assessing the gene induction and up-down regulation upon salinization (eg. SOS pathway).