Mitochondrial respiratory supercomplex association limits production of reactive oxygen species from Complex I

Evidence accumulated in the last ten years has demonstrated that a large proportion of the mitochondrial respiratory chain complexes in a variety of organisms is arranged in supramolecular assemblies called supercomplexes or respirasomes. Besides conferring a kinetic advantage (substrate channeling) and being required for the assembly and stability of Complex I, indirect considerations support the view that supercomplexes may also prevent excessive formation of reactive oxygen species (ROS) from the respiratory chain. Following this line of thought we have decided to directly investigate ROS production by Complex I under conditions in which the complex is arranged as a component of the supercomplex I1III2 or it is dissociated as an individual enzyme. The study has been addressed both in bovine heart mitochondrial membranes and in reconstituted proteoliposomes composed of complexes I and III in which the supramolecular organization of the respiratory assemblies is impaired by: (i) treatment either of bovine heart mitochondria or liposome-reconstituted supercomplex I-III with dodecyl maltoside; (ii) reconstitution of Complexes I and III at high phospholipids to protein ratio. The results of this investigation provide experimental evidence that the production of ROS is strongly increased in either model; supporting the view that disruption or prevention of the association between Complex I and Complex III by different means enhances the generation of superoxide from Complex I . This is the first demonstration that dissociation of the supercomplex I1III2 in the mitochondrial membrane is a cause of oxidative stress from Complex I. Previous work in our laboratory demonstrated that lipid peroxidation can dissociate the supramolecular assemblies; thus, here we confirm that preliminary conclusion that primary causes of oxidative stress may perpetuate reactive oxygen species (ROS) generation by a vicious circle involving supercomplex dissociation as a major determinant.

La governance del sociosanitario in Emilia Romagna: Esperienze e prospettive

In un contesto dominato da invecchiamento della popolazione, prevalenza della cronicità e presenza crescente di pazienti multiproblematici e non autosufficienti è indispensabile spostare il baricentro delle cure dall'acuzie alla cronicità, e quindi assicurare la continuità e la coerenza fra i diversi setting di cura, sia sanitari che socio-sanitari (ospedale, servizi sanitari territoriali, domicilio, strutture residenziali di Long term care). Dall'analisi della letteratura emerge che il maggiore ostacolo a realizzare questa continuità è rappresentato dalla presenza, caratteristica del sistema di welfare italiano, di molteplici attori e strutture con competenze, obiettivi e funzioni diverse e separate, e la raccomandazione di lavorare per l'integrazione contemporaneamente su più livelli: - normativo-istituzionale - programmatorio - professionale e gestionale Il sistema della "governance" realizzato in Emilia-Romagna per l'integrazione socio-sanitaria è stato valutato alla luce di queste raccomandazioni, seguendo il modello della Realist evaluation per i Social complex interventions: enucleando le "teorie" alla base dell'intervento ed analizzando i diversi step della sua implementazione. Alla luce di questa valutazione, il modello della "governance" è risultato coerente con le indicazioni delle linee guida, ed effettivamente capace di produrre risultati al fine della continuità e della coerenza fra cure sanitarie e assistenza sociale e sanitaria complessa. Resta da realizzare una valutazione complessiva dell'impatto su efficacia, costi e soddisfazione dei pazienti.

New Metal Tetrazolate Complexes: Design, Synthesis, Characterization and Applications

This final thesis is aimed at summarizing the research program I have carried out during my PhD studies, that has been dealing with the design, the preparation, characterization and applications of new Re(I), Ru(II), and Ir(III) metal complexes containing anionic ligands such as 5-aryl tetrazolates [R-CN4]- or their neutral analogues, N-alkyltetrazoles [R-CN4-R1]. Chapter 1 consists of a brief introduction on tetrazoles and metal-tetrazolato complexes, and on the photophysical properties of d6 transition metal complexes. In chapter 2, the synthesis, characterization and study of the photophysical properties of new luminescent Ir(III)-tetrazolate complexes are discussed. Moreover, the application of one of the new Ir(III)-CN complexes as emissive core in the fabrication of an OLED device is reported. In chapter 3, the study of the antimicrobial activity of new Ru(II)-alkyltetrazole complexes is reported. When the pentatomic ring was substituted with a long alkyl residue, antimicrobial activity toward Deinococcus radiodurans was observed. In chapter 4, a new family of luminescent Re(I)-tetrazolate complexes is reported. In this study, different N-alkyl tetrazoles play the role of diimine (diim) ligands in the preparation of new Re(I) tricarbonyl complexes. In addition, absorption and emission titration experiments were performed to study their interaction with Bovine Serum Albumin (BSA). In chapter 5, the synthesis and characterization of new luminescent Re(I)-tetrazolate complexes are discussed. The use of sulfonated diimine ligands in the preparation of new Re(I) tricarbonyl complexes led to the first example Re(I) complexes for the luminescent staining of proteins. In chapter 6, the synthesis, a new family of Ir(III)-NO2 tetrazole complexes displaying unexpected photophysical properties are discussed. Moreover, the possibility to tune the luminescent output of such systems upon chemical modification of the pending nitro group was verified by performing reduction tests with sodium dithionite; this represents encouraging evidence for their possible application as hypoxia-responsive luminescent probes in bioimaging.

Assessing the state of Nephrops norvegicus and management measures in the Central Adriatic Sea

Nephrops norvegicus is a sedentary bottom-dwelling crustacean that represents one of the main commercial species exploited in the Adriatic Sea (Central Mediterranean). An evaluation of the status of this important resource is thus extremely important in order to manage it in a sustainable way. The evaluation of N. norvegicus is complicated by several issues, mainly: (i) the complex biology and behaviour of the species itself, (ii) the presence of subpopulations with different biological traits within the same stock unit. Relevant concentration of N.norvegicus occurs within the Pomo/Jabuka Pits area which is characterised by peculiar oceanographic and geophysical conditions. This area represented for a long time an important fishing ground shared by Italian and Croatian fleets and recently a Fishery Restricted Area (FRA) was established there. The aim of the present study is to perform for the first time an evaluation of the status of the N.norvegicus subpopulation inhabiting the Pomo/Jabuka Pits also accounting for the possible effects on it of the management measures. To achieve this, the principal fisheryindependent and fishery-dependent dataset available for the study area were firstly analysed and then treated. Data collected by the CNR-IRBIM of Ancona through both indirect (“UWTV”) and direct (trawling) methods were refined by means of a revision of the time series and related biases, and a modelling approach accounting for environmental and fishery effects, respectively. Commercial data for both Italy and Croatia were treated in order to obtain landings and length distributions for the Pomo area only; an historical reconstruction of data starting from 1970 was carried out for both countries. The obtained information was used as input for a Bayesian length-based stock assessment model developed through the CASAL software; the flexibility of this model is recommended for N.norvegicus and similar species allowing to deal with sex- and fleet-based integrated assessment method

Respiratory chain complex I dysfunction in tumorigenesis

Diseases due to mutations in mitochondrial DNA probably represent the most common form of metabolic disorders, including cancer, as highlighted in the last years. Approximately 300 mtDNA alterations have been identified as the genetic cause of mitochondrial diseases and one-third of these alterations are located in the coding genes for OXPHOS proteins. Despite progress in identification of their molecular mechanisms, little has been done with regard to the therapy. Recently, a particular gene therapy approach, namely allotopic expression, has been proposed and optimized, although the results obtained are rather controversial. In fact, this approach consists in synthesis of a wild-type version of mutated OXPHOS protein in the cytosolic compartment and in its import into mitochondria, but the available evidence is based only on the partial phenotype rescue and not on the demonstration of effective incorporation of the functional protein into respiratory complexes. In the present study, we took advantage of a previously analyzed cell model bearing the m.3571insC mutation in MTND1 gene for the ND1 subunit of respiratory chain complex I. This frame-shift mutation induces in fact translation of a truncated ND1 protein then degraded, causing complex I disassembly, and for this reason not in competition with that allotopically expressed. We show here that allotopic ND1 protein is correctly imported into mitochondria and incorporated in complex I, promoting its proper assembly and rescue of its function. This result allowed us to further confirm what we have previously demonstrated about the role of complex I in tumorigenesis process. Injection of the allotopic clone in nude mice showed indeed that the rescue of complex I assembly and function increases tumor growth, inducing stabilization of HIF1α, the master regulator of tumoral progression, and consequently its downstream gene expression activation.

Expression of the repressor element-1 silencing transcription factor (REST) is regulated by IGF-I and PKC in human neuroblastoma cells

The repressor element 1-silencing transcription factor (REST) was first identified as a protein that binds to a 21-bp DNA sequence element (known as repressor element 1 (RE1)) resulting in transcriptional repression of the neural-specific genes [Chong et al., 1995; Schoenherr and Anderson, 1995]. The original proposed role for REST was that of a factor responsible for restricting neuronal gene expression to the nervous system by silencing expression of these genes in non-neuronal cells. Although it was initially thought to repress neuronal genes in non-neuronal cells, the role of REST is complex and tissue dependent. In this study I investigated any role played by REST in the induction and patterning of differentiation of SH-SY5Y human neuroblastoma cells exposed to IGF-I. and phorbol 12- myristate 13-acetate (PMA) To down-regulate REST expression we developed an antisense (AS) strategy based on the use of phosphorothioate oligonucleotides (ODNs). In order to evaluate REST mRNA levels, we developed a real-time PCR technique and REST protein levels were evaluated by western blotting. Results showed that nuclear REST is increased in SH-SY5Y neuroblastoma cells cultured in SFM and exposed to IGF-I for 2-days and it then declines in 5-day-treated cells concomitant with a progressive neurite extension. Also the phorbol ester PMA was able to increase nuclear REST levels after 3-days treatment concomitant to neuronal differentiation of neuroblastoma cells, whereas, at later stages, it is down-regulated. Supporting these data, the exposure to PKC inhibitors (GF10923X and Gö6976) and PMA (16nM) reverted the effects observed with PMA alone. REST levels were related to morphological differentiation, expression of growth coneassociated protein 43 (GAP-43; a gene not regulated by REST) and of synapsin I and βIII tubulin (genes regulated by REST), proteins involved in the early stage of neuronal development. We observed that differentiation of SH-SY5Y cells by IGF-I and PMA was accompanied by a significant increase of these neuronal markers, an effect that was concomitant with REST decrease. In order to relate the decreased REST expression with a progressive neurite extension, I investigated any possible involvement of the ubiquitin–proteasome system (UPS), a multienzymatic pathway which degrades polyubiquinated soluble cytoplasmic proteins [Pickart and Cohen, 2004]. For this purpose, SH-SY5Y cells are concomitantly exposed to PMA and the proteasome inhibitor MG132. In SH-SY5Y exposed to PMA and MG 132, we observed an inverse pattern of expression of synapsin I and β- tubulin III, two neuronal differentiation markers regulated by REST. Their cytoplasmic levels are reduced when compared to cells exposed to PMA alone, as a consequence of the increase of REST expression by proteasome inhibitor. The majority of proteasome substrates identified to date are marked for degradation by polyubiquitinylation; however, exceptions to this principle, are well documented [Hoyt and Coffino, 2004]. Interestingly, REST degradation seems to be completely ubiquitin-independent. The expression pattern of REST could be consistent with the theory that, during early neuronal differentiation induced by IGF-I and PKC, it may help to repress the expression of several genes not yet required by the differentiation program and then it declines later. Interestingly, the observation that REST expression is progressively reduced in parallel with cell proliferation seems to indicate that the role of this transcription factor could also be related to cell survival or to counteract apotosis events [Lawinger et al., 2000] although, as shown by AS-ODN experiments, it does not seem to be directly involved in cell proliferation. Therefore, the decline of REST expression is a comparatively later event during maturation of neuroroblasts in vitro. Thus, we propose that REST is regulated by growth factors, like IGF-I, and PKC activators in a time-dependent manner: it is elevated during early steps of neural induction and could contribute to down-regulate genes not yet required by the differentiation program while it declines later for the acquisition of neural phenotypes, concomitantly with a progressive neurite extension. This later decline is regulated by the proteasome system activation in an ubiquitin-indipendent way and adds more evidences to the hypothesis that REST down-regulation contributes to differentiation and arrest of proliferation of neuroblastoma cells. Finally, the glycosylation pattern of the REST protein was analysed, moving from the observation that the molecular weight calculated on REST sequence is about 116 kDa but using western blotting this transcription factor appears to have distinct apparent molecular weight (see Table 1.1): this difference could be explained by post-translational modifications of the proteins, like glycosylation. In fact recently, several studies underlined the importance of O-glycosylation in modulating transcriptional silencing, protein phosphorylation, protein degradation by proteasome and protein–protein interactions [Julenius et al., 2005; Zachara and Hart, 2006]. Deglycosilating analysis showed that REST protein in SH-SY5Y and HEK293 cells is Oglycosylated and not N-glycosylated. Moreover, using several combination of deglycosilating enzymes it is possible to hypothesize the presence of Gal-β(1-3)-GalNAc residues on the endogenous REST, while β(1-4)-linked galactose residues may be present on recombinant REST protein expressed in HEK293 cells. However, the O-glycosylation process produces an immense multiplicity of chemical structures and monosaccharides must be sequentially hydrolyzed by a series of exoglycosidase. Further experiments are needed to characterize all the post-translational modification of the transcription factor REST.

Simulatore di interfaccia uomo-macchina per i controllo di UAV

Recent statistics have demonstrated that two of the most important causes of failures of the UAVs (Uninhabited Aerial Vehicle) missions are related to the low level of decisional autonomy of vehicles and to the man machine interface. Therefore, a relevant issue is to design a display/controls architecture which allows the efficient interaction between the operator and the remote vehicle and to develop a level of automation which allows the vehicle the decision about change in mission. The research presented in this paper focuses on a modular man-machine interface simulator for the UAV control, which simulates UAV missions, developed to experiment solution to this problem. The main components of the simulator are an advanced interface and a block defined automation, which comprehend an algorithm that implements the level of automation of the system. The simulator has been designed and developed following a user-centred design approach in order to take into account the operator’s needs in the communication with the vehicle. The level of automation has been developed following the supervisory control theory which says that the human became a supervisor who sends high level commands, such as part of mission, target, constraints, in then-rule, while the vehicle receives, comprehends and translates such commands into detailed action such as routes or action on the control system. In order to allow the vehicle to calculate and recalculate the safe and efficient route, in term of distance, time and fuel a 3D planning algorithm has been developed. It is based on considering UASs representative of real world systems as objects moving in a virtual environment (terrain, obstacles, and no fly zones) which replicates the airspace. Original obstacle avoidance strategies have been conceived in order to generate mission planes which are consistent with flight rules and with the vehicle performance constraints. The interface is based on a touch screen, used to send high level commands to the vehicle, and a 3D Virtual Display which provides a stereoscopic and augmented visualization of the complex scenario in which the vehicle operates. Furthermore, it is provided with an audio feedback message generator. Simulation tests have been conducted with pilot trainers to evaluate the reliability of the algorithm and the effectiveness and efficiency of the interface in supporting the operator in the supervision of an UAV mission. Results have revealed that the planning algorithm calculate very efficient routes in few seconds, an adequate level of workload is required to command the vehicle and that the 3D based interface provides the operator with a good sense of presence and enhances his awareness of the mission scenario and of the vehicle under his control.

Meta-models, environment and layers: agent-oriented engineering of complex systems

Traditional software engineering approaches and metaphors fall short when applied to areas of growing relevance such as electronic commerce, enterprise resource planning, and mobile computing: such areas, in fact, generally call for open architectures that may evolve dynamically over time so as to accommodate new components and meet new requirements. This is probably one of the main reasons that the agent metaphor and the agent-oriented paradigm are gaining momentum in these areas. This thesis deals with the engineering of complex software systems in terms of the agent paradigm. This paradigm is based on the notions of agent and systems of interacting agents as fundamental abstractions for designing, developing and managing at runtime typically distributed software systems. However, today the engineer often works with technologies that do not support the abstractions used in the design of the systems. For this reason the research on methodologies becomes the basic point in the scientific activity. Currently most agent-oriented methodologies are supported by small teams of academic researchers, and as a result, most of them are in an early stage and still in the first context of mostly \academic" approaches for agent-oriented systems development. Moreover, such methodologies are not well documented and very often defined and presented only by focusing on specific aspects of the methodology. The role played by meta- models becomes fundamental for comparing and evaluating the methodologies. In fact a meta-model specifies the concepts, rules and relationships used to define methodologies. Although it is possible to describe a methodology without an explicit meta-model, formalising the underpinning ideas of the methodology in question is valuable when checking its consistency or planning extensions or modifications. A good meta-model must address all the different aspects of a methodology, i.e. the process to be followed, the work products to be generated and those responsible for making all this happen. In turn, specifying the work products that must be developed implies dening the basic modelling building blocks from which they are built. As a building block, the agent abstraction alone is not enough to fully model all the aspects related to multi-agent systems in a natural way. In particular, different perspectives exist on the role that environment plays within agent systems: however, it is clear at least that all non-agent elements of a multi-agent system are typically considered to be part of the multi-agent system environment. The key role of environment as a first-class abstraction in the engineering of multi-agent system is today generally acknowledged in the multi-agent system community, so environment should be explicitly accounted for in the engineering of multi-agent system, working as a new design dimension for agent-oriented methodologies. At least two main ingredients shape the environment: environment abstractions - entities of the environment encapsulating some functions -, and topology abstractions - entities of environment that represent the (either logical or physical) spatial structure. In addition, the engineering of non-trivial multi-agent systems requires principles and mechanisms for supporting the management of the system representation complexity. These principles lead to the adoption of a multi-layered description, which could be used by designers to provide different levels of abstraction over multi-agent systems. The research in these fields has lead to the formulation of a new version of the SODA methodology where environment abstractions and layering principles are exploited for en- gineering multi-agent systems.

Copper(I) phenanthroline complexes and supramolecular systems containing fullerenes: Photophysics, photochemistry and potential applications in sustainable energy technologies.

Chemistry can contribute, in many different ways to solve the challenges we are facing to modify our inefficient and fossil-fuel based energy system. The present work was motivated by the search for efficient photoactive materials to be employed in the context of the energy problem: materials to be utilized in energy efficient devices and in the production of renewable electricity and fuels. We presented a new class of copper complexes, that could find application in lighting techhnologies, by serving as luminescent materials in LEC, OLED, WOLED devices. These technologies may provide substantial energy savings in the lighting sector. Moreover, recently, copper complexes have been used as light harvesting compounds in dye sensitized photoelectrochemical solar cells, which offer a viable alternative to silicon-based photovoltaic technologies. We presented also a few supramolecular systems containing fullerene, e.g. dendrimers, dyads and triads.The most complex among these arrays, which contain porphyrin moieties, are presented in the final chapter. They undergo photoinduced energy- and electron transfer processes also with long-lived charge separated states, i.e. the fundamental processes to power artificial photosynthetic systems.

Paesaggi agrari. Nuove prospettive per i sistemi territoriali: agricoltura ecologica, saperi tradizionali, scambio locale

Il paesaggio, e così anche il paesaggio agrario, può essere considerato come segno del rapporto uomo/natura, come costrutto storico che testimonia il succedersi delle diverse civilizzazioni che l'hanno generato, ma anche come spazio per l'immaginazione territoriale, come progetto per il futuro del territorio. In questo lavoro si trattano le relazioni tra questa visione del paesaggio e le forme di produzione e consumo dei prodotti agricoli, nell'ambito delle trasformazioni che l'ambito rurale sta subendo a partire dagli ultimi decenni, tra pressione dell'urbano, da un lato, e abbandono e crisi dell'agricoltura, dall'altro. Particolare attenzione è riservata a quelle esperienze che, attraverso la produzione biologica e lo scambio locale, esprimono un nuovo progetto di territorio, che prende avvio dal contesto rurale ma che pervade anche le città, proponendo anche nuove relazioni tra città e campagna. Nelle reti della filiera corta e dell'economia solidale che si concretizzano soprattutto come esperienze “dal basso”, di autogestione e partecipazione, si diffondono insieme prodotti e valori. In quest'ottica la sostenibilità ambientale non appare più come una fonte di limitazioni e esternalità negative, per dirla con il linguaggio dell'economia, ma diventa un valore aggiunto di appartenenza collettiva (equilibri ecologici, paesaggio) e un'occasione per nuove relazioni sociali e territoriali.

Thermochronologic and geodynamic evolution of the Pontides: Sakarya terrane (Karakaya Complex) and Istanbul terrane, Turkey.

An integrated array of analytical methods -including clay mineralogy, vitrinite reflectance, Raman spectroscopy on carbonaceous material, and apatite fission-track analysis- was employed to constrain the thermal and thermochronological evolution of selected portions of the Pontides of northern Turkey. (1) A multimethod investigation was applied for the first time to characterise the thermal history of the Karakaya Complex, a Permo-Triassic subduction-accretion complex cropping out throughout the Sakarya Zone. The results indicate two different thermal regimes: the Lower Karakaya Complex (Nilüfer Unit) -mostly made of metabasite and marble- suffered peak temperatures of 300-500°C (greenschist facies); the Upper Karakaya Complex (Hodul and the Orhanlar Units) –mostly made of greywacke and arkose- yielded heterogeneous peak temperatures (125-376°C), possibly the result of different degree of involvement of the units in the complex dynamic processes of the accretionary wedge. Contrary to common belief, the results of this study indicate that the entire Karakaya Complex suffered metamorphic conditions. Moreover, a good degree of correlation among the results of these methods demonstrate that Raman spectroscopy on carbonaceous material can be applied successfully to temperature ranges of 200-330°C, thus extending the application of this method from higher grade metamorphic contexts to lower grade metamorphic conditions. (2) Apatite fission-track analysis was applied to the Sakarya and the İstanbul Zones in order to constrain the exhumation history and timing of amalgamation of these two exotic terranes. AFT ages from the İstanbul and Sakarya terranes recorded three distinct episodes of exhumation related to the complex tectonic evolution of the Pontides. (i) Paleocene - early Eocene ages (62.3-50.3 Ma) reflect the closure of the İzmir-Ankara ocean and the ensuing collision between the Sakarya terrane and the Anatolide-Tauride Block. (ii) Late Eocene - earliest Oligocene (43.5-32.3 Ma) ages reflect renewed tectonic activity along the İzmir-Ankara. (iii) Late Oligocene- Early Miocene ages reflect the onset and development of the northern Aegean extension. The consistency of AFT ages, both north and south of the tectonic contact between the İstanbul and Sakarya terranes, suggest that such terranes were amalgamated in pre-Cenozoic times. (3) Fission-track analysis was also applied to rock samples from the Marmara region, in an attempt to constrain the inception and development of the North Anatolian Fault system in the region. The results agree with those from the central Pontides. The youngest AFT ages (Late Oligocene - early Miocene) were recorded in the western portion of the Marmara Sea region and reflect the onset and development of northern Aegean extension. Fission-track data from the eastern Marmara Sea region indicate rapid Early Eocene exhumation induced by the development of the İzmir-Ankara orogenic wedge. Thermochronological data along the trace of the Ganos Fault –a segment of the North Anatolian Fault system- indicate the presence of a tectonic discontinuity active by Late Oligocene time, i.e. well before the arrival of the North Anatolian Fault system in the area. The integration of thermochronologic data with preexisting structural data point to the existence of a system of major E-W-trending structural discontinuities active at least from the Late Oligocene. In the Early Pliocene, inception of the present-day North Anatolian Fault system in the Marmara region occurred by reactivation of these older tectonic structures. 


Complex higher spins, Weyl invariance and tractors

In this thesis work I analyze higher spin field theories from a first quantized perspective, finding in particular new equations describing complex higher spin fields on Kaehler manifolds. They are studied by means of worldline path integrals and canonical quantization, in the framework of supersymmetric spinning particle theories, in order to investigate their quantum properties both in flat and curved backgrounds. For instance, by quantizing a spinning particle with one complex extended supersymmetry, I describe quantum massless (p,0)-forms and find a worldline representation for their effective action on a Kaehler background, as well as exact duality relations. Interesting results are found also in the definition of the functional integral for the so called O(N) spinning particles, that will allow to study real higher spins on curved spaces. In the second part, I study Weyl invariant field theories by using a particular mathematical framework known as tractor calculus, that enable to maintain at each step manifest Weyl covariance.

I progetti di Oswald Mathias Ungers per la città di Treviri. Questioni di composizione architettonica

Abstract This PhD thesis focuses on two projects carried out by Oswald Mathias Ungers in the city of Trier. More specifi cally, this study focuses on the relationship between composition principles, architectural forms, historical context and the nature of the city where these buildings have been built. The works carried out by Ungers in Trier are unique experiences - if taken in this master’s works context - and each one of them refl ects - in its specifi c project and architectural composition theme - the results - in terms of design - of a complex research on the fundamentals of architecture carried out by Ungers in more than fi ve decades of his activity. The theoretical and compositional experiment aspect is one of the main subjects to defi ne these buildings in terms of architecture. This aspect is so crucial that it is possible to consider them as an example of radical and specifi c experiences, referred to a specifi c place and based on a specifi c theoretical corpus. More specifi cally, this study focuses on the design activity carried out by Ungers in this city, mainly between the 80s and 90s and in the fi rst decade of the 21st century. It puts forward an interpretation that does not only defi ne the essential features, elements and questions lying behind these two architectures, but fi rst and foremost analyzes the theoretical, methodological and compositional relationship between Ungers and Trier, his adopted city. An increasingly closer relationship between the architect and his city highlights the wider relationship network established between the place and the projects carried out by Ungers in this city and makes it possible to understand the importance of Trier in the work of this architect, in his education and in his way to see, think and make architecture. The projects analyzed - the Thermen am Forum Museum (1988-1996) and the Kaiserthermen entrance hall (2003-2007) - were analyzed in terms of their architectural composition in an attempt to highlight the poetry of these architectures and to fi nd out their progressive, rational - and therefore transmissible - character. This study is an attempt to assess and unveil the compositional themes characterizing these projects while detecting the compositional principles lying behind the works and verifying the design process through which such principles were translated into architecture. Looking at these works as architectural composition examples makes it possible to clarify Ungers’ hermeneutic relationship established with the city’s history and structure. More specifi cally, the main subject of this thesis is the relationship between the architect, his city and history in the architectural solutions offered by two exemplary case studies, which were both built and placed in the historical city center of Trier and both connected with the ancient core of the city. The Thermen am Forum Museum and the Kaiserthermen entrance hall projects are - though being developed at different times of Ungers’ architectural life and though being extremely different in terms of approach to their context, due to their architectural image - two works that can be compared with the historical heritage of the city and this makes them ideal examples of the relationship between architectural forms, history and environment.

The stratigraphic record of the quaternary sea level fluctuations and the impact of the post-glacial sea level rise (Termination I) in the Adriatic basin (Mediterranean sea)

The modern stratigraphy of clastic continental margins is the result of the interaction between several geological processes acting on different time scales, among which sea level oscillations, sediment supply fluctuations and local tectonics are the main mechanisms. During the past three years my PhD was focused on understanding the impact of each of these process in the deposition of the central and northern Adriatic sedimentary successions, with the aim of reconstructing and quantifying the Late Quaternary eustatic fluctuations. In the last few decades, several Authors tried to quantify past eustatic fluctuations through the analysis of direct sea level indicators, among which drowned barrier-island deposits or coral reefs, or indirect methods, such as Oxygen isotope ratios (δ18O) or modeling simulations. Sea level curves, obtained from direct sea level indicators, record a composite signal, formed by the contribution of the global eustatic change and regional factors, as tectonic processes or glacial-isostatic rebound effects: the eustatic signal has to be obtained by removing the contribution of these other mechanisms. To obtain the most realistic sea level reconstructions it is important to quantify the tectonic regime of the central Adriatic margin. This result has been achieved integrating a numerical approach with the analysis of high-resolution seismic profiles. In detail, the subsidence trend obtained from the geohistory analysis and the backstripping of the borehole PRAD1.2 (the borehole PRAD1.2 is a 71 m continuous borehole drilled in -185 m of water depth, south of the Mid Adriatic Deep - MAD - during the European Project PROMESS 1, Profile Across Mediterranean Sedimentary Systems, Part 1), has been confirmed by the analysis of lowstand paleoshorelines and by benthic foraminifera associations investigated through the borehole. This work showed an evolution from inner-shelf environment, during Marine Isotopic Stage (MIS) 10, to upper-slope conditions, during MIS 2. Once the tectonic regime of the central Adriatic margin has been constrained, it is possible to investigate the impact of sea level and sediment supply fluctuations on the deposition of the Late Pleistocene-Holocene transgressive deposits. The Adriatic transgressive record (TST - Transgressive Systems Tract) is formed by three correlative sedimentary bodies, deposited in less then 14 kyr since the Last Glacial Maximum (LGM); in particular: along the central Adriatic shelf and in the adjacent slope basin the TST is formed by marine units, while along the northern Adriatic shelf the TST is represented by costal deposits in a backstepping configuration. The central Adriatic margin, characterized by a thick transgressive sedimentary succession, is the ideal site to investigate the impact of late Pleistocene climatic and eustatic fluctuations, among which Meltwater Pulses 1A and 1B and the Younger Dryas cold event. The central Adriatic TST is formed by a tripartite deposit bounded by two regional unconformities. In particular, the middle TST unit includes two prograding wedges, deposited in the interval between the two Meltwater Pulse events, as highlighted by several 14C age estimates, and likely recorded the Younger Dryas cold interval. Modeling simulations, obtained with the two coupled models HydroTrend 3.0 and 2D-Sedflux 1.0C (developed by the Community Surface Dynamics Modeling System - CSDMS), integrated by the analysis of high resolution seismic profiles and core samples, indicate that: 1 - the prograding middle TST unit, deposited during the Younger Dryas, was formed as a consequence of an increase in sediment flux, likely connected to a decline in vegetation cover in the catchment area due to the establishment of sub glacial arid conditions; 2 - the two-stage prograding geometry was the consequence of a sea level still-stand (or possibly a fall) during the Younger Dryas event. The northern Adriatic margin, characterized by a broad and gentle shelf (350 km wide with a low angle plunge of 0.02° to the SE), is the ideal site to quantify the timing of each steps of the post LGM sea level rise. The modern shelf is characterized by sandy deposits of barrier-island systems in a backstepping configuration, showing younger ages at progressively shallower depths, which recorded the step-wise nature of the last sea level rise. The age-depth model, obtained by dated samples of basal peat layers, is in good agreement with previous published sea level curves, and highlights the post-glacial eustatic trend. The interval corresponding to the Younger Dyas cold reversal, instead, is more complex: two coeval coastal deposits characterize the northern Adriatic shelf at very different water depths. Several explanations and different models can be attempted to explain this conundrum, but the problem remains still unsolved.

Celti e Reti tra V e I sec. a.C. Oggetti tipo LaTène all'interno della cerchia culturale Fritzens-Sanzeno (arco alpino centro-orientale)

The study of the objects LaTène type found in middle-eastern alpine region (Trentino Alto Adige-Südtirol, Engadina, North Tirol, Voralberg and Villach basin) is aimed to a better comprehension of the complex net of relationships established among the Celts, settled both in the central Europe territories and, since the IV century b.C., in the Po Plain, and the local populations. The ancient authors, who called the inhabitants of this area Raeti, propose for this territory the usual pattern according to which, the population of a region was formed consequently to a migration or was caused by the hunting of pre-existing peoples. The archaeologists, in the last thirty years, recognized a cultural facies typical of the middle-eastern alpine territory during the second Iron Age, and defined that as Fritzens-Sanzeno culture (from the sites of Fritzens, Inn valley, and Sanzeno, Non Valley). The so-called Fritzens-Sanzeno culture spread out without breaks from the material culture of the final Bronze Age and the first Iron Age. This local substratum, characterized by a ceramic repertoire strongly standardized, by peculiar architectural solutions and by a particular typology of rural sacred places (Brandopferplätze), accepted, above all during the second Iron Age, the strong influences coming from the Etruscan world and from the Celtic one (evident in the presence of objects of ornament, of glass artefacts, of elements of the weaponry and of coins). The objects LaTène type become, with different degrees of reliability, important markers of the relationships existing between the Celts and the Raeti, although the ways of interaction (cultural influence, people's movements, commercial exchanges, gifts among élites etc.) is not still clear. The revision of published data and the study of unpublished materials allows to define a rich and articulated picture both to chronological level and to territorial one.