Le massif des Béni Snassen situé au Nord-Est du Maroc, se présente en un vaste dôme anticlinal essentiellement composé de terrains calcaires mésozoïques reposant sur un socle granito-schisteux paléozoïque. Par sa nature lithologique et par sa karstification ce massif contient des ressources hydrogéologiques d'une grande importance d'un point de vue économique (alimentation en eau, irrigation...) dans une zone en plein développement touristique, agricole et urbain. Ce travail a permis de mesurer la vulnérabilité des ressources karstiques en eau du massif afin de mettre en place des mesures de protection et de préservation de la ressource et fournir aux acteurs du territoire des outils et un support d'aide à la gestion et l'exploitation durables de cette ressource en eau. Pour répondre à cette problématique il a été nécessaire de croiser grâce aux " Systèmes d'Information Géographique " des données environnementales, anthropiques et territoriales. Cette approche a permis de spatialiser, croiser, superposer et pondérer les différentes couches d'information selon deux entrées : (i) l'entrée environnementale a permis de combiner le contexte géologique, l'évolution géomorphologique, la structuration hydrogéologique et les données bio-pédologique et climatique ; (ii) l'entrée anthropique pose les usages actuels et permet de prendre en compte les modes de réponse (en termes d'aménagement, de protection...) pour préserver la qualité de la ressource en eau. Les activités anthropiques fragilisent le système par la dégradation et la surexploitation des ressources naturelles (défrichement, coupe de bois, incendies, activités agro-pastorales non adaptées, etc.), mais aussi favorisent sa protection par le renforcement du milieu (construction des terrasses agricoles, reboisement, restauration, etc.).

The present study, being part of a wide research program carried by the University of Bologna (Dipartimento di Scienze della Terra e Geo-Ambientali and Dipartimento di Archeologia) together with the Soprintendenze of Emilia-Romagna and Veneto, is aimed at examining the manufacturing and circulation of Greek Italic amphorae in the Adriatic area. This represents an essential step for the historical and archaeological reconstructions and in particular for: - the identification of local manufacturing though the archaeometric comparisons between ceramic samples and raw materials - the reconstruction of the ancient routes connecting different areas of the Roman world The examined archaeologic sites are representative of the main manufacturing areas in the Adriatic region both along the Italian and Albanian coasts: Adria, Cattolica, Rimini, Spina , Suasa and Phoinike. Notably, the Adriatic region not only represents the manufacturing area, but also coincides with the source area where the raw materials were collected. Archaeometric analyses of representative samples from the different areas of interests, were performed adapting the analytical tecniques used in mineralogy, petrography and geochemistry, to the study of ancient archaeological finds. These data were combined with the ones obtained from the analysis of clays, aimed at characterizing the nature of the raw materials. As a whole, an integration of these data with the available archaeologic observations led to significant advances in the scientific knowledge about of the main types of amphoric manufacturing and distribution in the Adriatic region. In particular, a local manufacturing is suggested for all the archaeological finds from Cattolica and for the main part of the archaeological finds from Suasa. Moreover, the occurrence of commercial routes between the sites of Rimini and Suasa and between Adria, Spina and Suasa is evidenced. On the contrary, for the amphorae from Phoinike a provenance from the examined sites is very unlikely.

Univ., Diss.--Bern, 1995.

Proteins are one of the most studied biological molecules of the last decades. A great amount of experimental techniques provide to researchers direct or indirect informations on proteins structure and function. In silico simulations can be used as a “computational microscope” giving the possibility to observe protein dynamic properties at atomistic resolution. In this work, various applications of computational methods to biological systems are presented. In particular, all-atom Molecular Dynamics (MD) simulations were employed to investigate the behaviour of proteins at atomstic resolution. The term “Molecular Dynamics” is usually referred to computational methods used for the simulation of classical many-body systems. These techniques are applied to microscopic systems and they represent a powerful approach for the study of physical processes, providing a tool for their interpretation. They have been widely used in the past decades to elucidate a large variety of molecular processes in different fields such as solid state physics, material science, chemistry, biochemistry and biophysics. Here, all-atom MD simulations were employed to observe equilibrium properties of several biologically relevant proteins. This allowed us to direct perform a comparison of molecular mechanisms occurring at the atomistic level as obtained from in silico studies with experimental data, which usually describe processes at larger length and time scales. These MD simulations were also meant as a starting point for the construction of simplified models, as they were processed through coarse-graining procedures to extrapolate crucial systems features, such as informative protein sites, on the basis of information theory approaches. Specifically we studied the dynamics of pembrolizumab, a humanized immunoglobulin of type G4 (IgG4) used as a therapeutic antibody. It is employed for the treatment of lung cancer, melanoma, stomach and head cancer and Hodgkin’s lymphoma. This antibody interacts with the programmed cell death protein 1 (PD-1) receptor, blocking the suppression of the immune response during cancer development. The studied systems are three: the apo state of pembrolizumab, the holo state (i.e. pembrolizumab bound to PD-1) and the glycosylated apo configuration. Each configuration was simulated for 2μs, for a total of 6μs. The analysis of the trajectories was carried out by combining standard structural analysis techniques and information theory-based measures of correlation. From MD trajectories we could extract valuable informations on the connectivity that exists among the structural domains that compose the antibody structure. Moreover, it was possible to infer which regions are involved in the structural rearrangement in the case of the antigen binding. We could observe that the presence of the antigen reduces the conformational variability of the molecule giving a greater stability to it. The second studied system is the P53 protein complex. In this case we focused on the tetramerization domain (TD) region that is composed by 2 identical dimers and has the function of bringing together the four monomers of the p53 complex. Starting from the observation that in case of the mutation of residue R337 several pathologies are developed in humans, we constructed computational models to reproduce the dynamics of the mutants and investigate their behaviour in silico. We performed simulations for a total of 16 μs divided in 8 different cases. In the first part of the study the wild type (WT) protein was compared to the R337C and the R337H mutant in three different protonation states: delta protonated Histidine, epsilon protonated Histidine ad double protonated Histidine. In the second part of the study we highlighted the differences between the WT configuration and three rationally designed mutants: R337D-352D, 337R-D352R, R337D-D352R. In this part of the investigation, the importance of the electrostatic interaction between residues R337 and D352 in the stability of the tetramerization do- main was discussed. Furthermore, we matched the obtained computational results of p53 tetramerization domain with functional experiments in yeasts (performed in collaboration with the CIBIO department) of all the simulated forms. The third simulated protein is the zinc sensing transcriptional repressor (CzrA), an homodimeric protein that binds DNA in Staphylococcus aureus. All-atom MD simulations of two different configurations were performed for a total of 4μs, the first one is the WT apo protein while the second is the WT holo system, where the protein is complexed with two Zn ions. In this case, in addition to standard analysis techniques, we applied the mapping entropy minimization protocol to highlight the most informative protein regions, from the perspective of information theory. Finally, our in silico results were compared to available NMR data of the protein itself.

MACPF/CDCs proteins are a huge family of pore-forming proteins present from the bacteria to the human genera. Cholesterol-dependent cytolysins (CDCs) are a family of toxins that participate in bacterial infection pathway at the membrane level. Great interest in this family is due to their similarity, in structure and in pore-forming mechanism, with some human immune system proteins (MACPF). We focused our attention particularly on two bacterial CDCs, Perfringolysin O and Listeriolysin O, and on the human protein Perforin, which is involved in the apoptotic pathway facilitating Granzyme release. In the literature, two possible configurations of CDCs and Perforin pores are proposed: ring and arc structures that could have different implications on the biological mechanism of action of these pore-forming proteins. By electrophysiological measurements and atomic force microscopy technique on different artificial membrane, we are able to enrich the ring and the arc fraction and demonstrate that both kinds of pore are active, i.e. conduct ions. Thus, my PhD work underlines two physiological structures which are involved in several ways, more than merely by disrupting membrane integrity, in pathogenic attack (bacterial CDCs proteins) as well as in immune response (human Perforin proteins).

Photocatalytic water splitting using solar energy could contribute to the solution of environmental and energy issues related to the hydrogen production. Key research area in this field is the development of photo-catalyst able to provide high energy conversion efficiency. TiO2 has been mostly preferred material as the photo-electrode due to many advantages, mainly related to the cost factor and stability. We have studied on hydrogen production by water splitting in photo-electrochemical cells prepared by using photoanodes made by two different kinds of TiO2: one deposited by RF sputtering and the other one by sol-gel method. Depositions were performed on electrical conducting ITO whose electrical properties plays vital role to reduce the photon energy loss. The photoanodes have been characterised by several techniques to infer on their optical and compositional properties. The observed differences in hydrogen production have been attributed to the peculiarities in absorption properties of the two TiO2 films that in the case of sputter-deposited films are more prone to absorb radiation also because of the produced defects during the deposition process. Metals like Cr and Fe were doped in TiO2 by RF magnetron sputtering and sol-gel methods to increase the efficiency of hydrogen production by water splitting by sensitizing the doped-TiO2 in visible light spectrum. The doping method, dopant concentration, charge transfer from metal dopants to TiO2, and type of dopants used for modification of TiO2 were investigated for their ability to enhance photocatalytic activity. UV-Visible spectra show that the sputter-metaldoped- TiO2 films are much more efficient than the chemically-prepared samples to induce red shift of the absorption edge for absorbing visible light. In addition, we proved that dopant atoms must be located, at low concentration, near the ITO-TiO2 interface to avoid the formation of recombination centers for photo-generated electron-hole pairs. H2 production rate is higher with Fe-doped TiO2 (15.5 μmole/h) than with Cr-doped TiO2 (5.3 μmole/h) because Fe ions trap both electrons and holes thus avoiding recombination. On the other hand, Cr can only trap one type of charge carrier. To increase the light conversion efficiency and reduce the recombination processes of Cr-doped TiO2, a multilayer structure of ITO/Cr-doped-TiO2 (9 at.%) was developed. When the multilayer films were exposed to visible light, we observed that the photocurrent increases as function of the number of bilayers by reaching the maximum with 6-bilayers of ITO/Crdoped-TiO2. The enhanced photocurrent is attributed to: 1) higher absorption of visible light by Cr-doped-TiO2, 2) number of space-charge layers in form of ITO/TiO2 interfaces in multilayer films, and 3) generation of photoelectrons just in/or near to the spacecharge layer by decreasing the Cr-doped-TiO2 layer thickness. The superior photocatalytic efficiency of the 6-bilayers film implies higher hydrogen production rate through water splitting: we obtained indeed 24.4 μmole/h of H2 production rate, a value about two times higher than that of pure TiO2 (12.5 μmole/h). Similar experiment we performed by doing TiO2 with vanadium metal. With 6-ilayers vanadium doped TiO2 film Shows higher hydrogen production rate of about 31.2 μmole/h. This rate is higher than that of CR doped and pure TiO2. A constant H2 generation rate is obtained for long periods of time by all the investigated TiO2 films because of the separate evolution of H2 and O2 gas, thus eliminating the back-reaction effect. Even Ar+ or N+ ion implantation of energy 30 keV was adopted to vary the energy band gap of TiO2 film in order to absorb visible light.The original anatase phase was not changed by implantation. Increase in full visible absorption range was observed for both kinds of ion implanted-TiO2 films which further increases with the ion fluencies, while N+ ion implantation also causes the shift of the absorption edge from UV to visible light range. N+ implanted TiO2 showed narrowing of band gap from 3.2 eV for untreated anatase TiO2 to 2.78 eV for maximum implantation dose. The Ar+ and N+ implantation creates oxygen vacancies related defect energy level in the band gap. In case of N+ implantation, nitrogen also substitutionally replaces the oxygen atoms thus forming an energy level just above the valence band which further interacts with O 2p states resulting in the narrowing of band gap. The black solar absorber material develop over the copper target to absorb concentrated solar radiation and supply heat to the surrounding water. A black copper oxide layer was synthesized over copper substrate by using chemical oxidation treatment. We varied several treatment parameters and optimized the best condition to obtain a black textured layer which has the properties to absorb total solar radiation. The untreated polished copper showed 50 to 60 % reflectance (R) (incidence angle of 15o) and this value decreases to almost zero for whole wavelength range after formation of black copper oxide. The percentage absorption decreases by negligible amount as the angle of incidence increases. The SEM images of the copper oxide layer at high magnification showed a nano-petal like structure which causes the surface texture effect for higher absorption where surface irregularities such as grooves and pores with dimensions similar to the wavelength of the incident radiation simply increase the solar absorptance by multiple reflections. Long time thermal stability and corrosion resistance in hot water was also studied for the copper oxide film. The results revealed that the copper oxide was very stable and showed no changes in optical properties after the test. For the same water heating system a quartz window is used through which the solar radiation is transmitted on the copper target. Thus to acquire high power conversion efficiency it is necessary for quartz window to transmit the entire solar radiation incident on it without much lost due to the reflection on the surface. In general quartz window is able to transmit 90-91 % of the solar radiation while 1-2 % is absorbed and 7-8 % is reflected from the surface. Thus to have nearly complete transmittance it is necessary to cover the surface of quartz window with anti-reflecting (AR) coating: this was the part of my work. We developed single-layer and multi-layer AR coating for single specific wavelength and broad-band wavelength range respectively. Low reflective index material like MgF2 is deposited by e-beam technique to obtain single-layer AR coating. While Al2O3 and ZrO2 layers deposited, by RF-magnetron sputtering, on top of MgF2 forms multi-layer AR coating. The combination of MgF2/ZrO2/Al2O3/MgF2 deposited on both side of quartz showed excellent results with reflectance value of around 0.8% in broad spectral range. The heat exchanger efficiency obtained after using these developed black copper oxide absorber material and AR coating is around 83 % which seems to be significantly higher than the other commercially available water heating system. Concentrating solar power (CSP) systems are utilized to convert sunlight to thermal electric power by using solar absorber. However, the solar absorber are operated at elevated temperature (700-800 oC) and should be spectrally selective to act as perfect absorbers over the solar spectrum (high solar absorptance (α)) and perfect reflectors in the thermal infrared (IR) (low thermal emittance (ε)). Cermet composite solar absorber shows such selective properties at high temperatures. In the present work, we developed Al-AlN based multilayer cermet films by RF magnetron sputtering. We choose combination of Ni/AlxN(1-x)/AlN layers as a solar absorber due to its stability at elevated temperature and high corrosion resistance. In this combination, Ni layer, deposited near to substrate, act as the IR light reflector to provide high thermal emittance. While AlxN(1-x) layer act as an absorber layer for UV-Vis spectrum of solar radiation and transparent AlN layer on top functions as AR coating. To improve absorptance, 3 or 4 layers of AlxN(1-x) film with grading of metal content was synthesized by varying N2 flow during deposition. The optical measurement for these multilayer selective absorber films showed high solar absorptance of 0.92-0.96 and low thermal emittance of around 0.1-0.07. To test the stability of our multilayer coating at high temperature, we annealed these samples at 700 oC with holding time of 2 hrs in air, low vacuum and high vacuum. We observed a slight decrease in solar absorptance value (0.90) for the annealed samples but the results showed that overall performance was not hindered by heat treatment thus proving the thermal stability of our multilayer cermet coating.

In the present thesis two main results are presented. The first is a study of the statistical properties of the finite-time maximum Lyapunov exponent determined out of a time series by using the divergent rate method. To reach this goal, we developed a new, completely automatic algorithm based on the method developed by Gao and Zheng. A main achievement of this part of the work is the interpretation of the uncertainty in the light of the work by Grassberger, Badii e Politi of 1988 on the theoretical distribution of maximum Lyapunov exponents. We showed that the analysis and identification of clusters in diagrams representing uncertainty vs. maximum Lyapunov exponent can provide useful information about the optimal choice of the embedding parameters. In addition, our results allow us to identify systems that can provide suitable benchmarks for the comparison and ranking of different embedding methods. The second main result concerns the development of a new method for the assessment of the optimal embedding parameters. Our method is based on two assumptions: a potential-like quantity is defined on the lattice of points that characterize the embedding; the optimal embedding choice coincides with local extrema (maxima or minima) of this potential. Throughout the work, we used "synthetic" time series generated by numerically integrating the difference and differential equations that describe the following dynamical systems: the Hénon map, the Lorenz attractor, the Rössler attractor and the Mackey-Glass attractor. These four systems are widely used as references in the scientific literature. In the last part of the work, we have started to examine EEG recordings by using the techniques developed in the main part of the work. The EEG recordings are sampled on healthy subjects in resting-state. These investigations are still at a starting phase.

Simulating rare structural rearrangements of macromolecules with classical computational methods, such as Molecular Dynamics (MD), is an outstanding challenge. A multitude of technological advancements, from development of petaFLOPS supercomputers to advent of various enhance sampling methods, has granted access to time intervals of microseconds and even milliseconds in recent years. Yet, many key events occur on exponentially longer timescales. Here, path sampling techniques have the advantage of focusing the computational power on barrier-crossing trajectories, but generating uncorrelated transition paths that explore significantly different conformational regions remains a problem. To address this issue, we devised a hybrid path-sampling scheme, graph-Transition Path Sampling (gTPS), that generates the trial transition pathways using a quantum annealer. We first employ a classical computer to perform an uncharted exploration of the conformational space using a data-driven MD method. The dataset is then post-processed using a path-integral-based method to obtain a coarse-grained network representation of reactive pathways. By resorting to quantum annealing, the entire ensemble of these pathways can be encoded into a superposition in the initial quantum state of the annealer. Finally, by performing the quantum adiabatic transition on the state of the annealer, one can potentially generate/sample uncorrelated paths while they retain a high statistical probability (follow low free energy regions). We have first validated this scheme on a prototypically simple transition (α_R↔C_5 of alanine dipeptide) which could be extensively characterized on a desktop computer. Subsequently, we scaled up in complexity by generating a protein conformational transition (Bovine Pancreatic Trypsin Inhibitor - BPTI) that occurs on the millisecond timescale, obtaining results that match those of the Anton special-purpose supercomputer. Finally, we dicuss our current investigations on the application of gTPS to the unfolding process of headpiece subdomain of Villin and BPTI. Despite limitations due to the available quantum hardware, our study highlights how realistic biomolecular simulations provide a potentially impactful new ground for applying, testing, and advancing quantum technologies.

Thesis (Ph. D.)--University of Washington, 2002. / Includes bibliographical references (leaves 240-251).

A diferencia de la importancia de las investigaciones que, tradicionalmente, han dado protagonismo al mundo andino, son muy pocos los estudios que, desde el ámbito disciplinario de la historia, han abordado los territorios y las sociedades de las denominadas tierras bajas. En Bolivia, esto significa referirse, fundamentalmente, a la Amazonía que era percibida como “tierras baldías”, sin dueño, al margen de la civilización y susceptibles de ser ocupadas. En este sentido, desde mediados del siglo XIX, la amazonía boliviana pasó a ser administrada por el recién creado departamento del Beni, cuya historia sólo ha sido abordada recientemente y focalizada en acontecimientos del siglo XX. No obstante, se desconocen los aspectos más significativos de la historia socioeconómica y política del Beni durante la etapa de construcción de Bolivia como estado-nación siendo el estudio de este proceso el objetivo general de la tesis. Entendiendo que la conformación y consolidación del estado boliviano pasaba por el control de la amazonía, este trabajo aborda los avances y retrocesos producidos en el proceso de construcción del departamento del Beni, a través de las distintas políticas desarrolladas por el Estado. Ello ha permitido comprender los aspectos más importantes de la región beniana desde 1842, año de la creación del departamento, hasta el establecimiento definitivo de sus límites interestatales e interdepartamentales, en 1938. Así, se han analizado los programas y disposiciones estatales que pretendían nacionalizar la amazonía, siendo de especial interés aquellas que perseguían la exploración y colonización del territorio, la organización político-administrativa del departamento y su definición jurisdiccional; se han considerado también las relaciones, actitudes y prácticas desarrolladas por los grupos dirigentes, los grupos de poder local y regional y las poblaciones indígenas en el ejercicio de sus derechos y el acceso a las cotas de poder político y económico, que permitieron la construcción de la sociedad regional; y, finalmente, se han identificado las principales transformaciones de carácter socioeconómico de la región y, por ende, en la gestión de los recursos naturales y la tierra. Los principales aportes de esta investigación radican en la disección de las políticas estatales relativas hacia el Beni, y el uso y apropiación de éstas por parte de la sociedad local (blanco-mestiza e indígena) en el contexto de construcción del estado-nación boliviano. De ello se desprende que la construcción del departamento y de la sociedad beniana fue posible, fundamentalmente, por el control privado de los recursos naturales y económicos -tierras, ganadería, bosques- existentes en la región por parte de los actores locales y regionales en detrimento, en la mayor parte de las ocasiones, del Estado y también de las poblaciones indígenas. En fin, consideramos que la investigación realizada muestra la incapacidad de todos los gobiernos bolivianos para desarrollar sus políticas orientalistas –defensa de la soberanía, colonización del territorio, etc.- siendo lo acontecido en el Beni, buen indicador de la debilidad e incapacidad de los dirigentes bolivianos para incorporar la amazonía a la república a lo largo del siglo XIX e inicios del siglo XX. / “For a history of Beni. A socioeconomic, political and ideological study of the Bolivian Amazon, centuries XIX-XX.” SUMMARY: There are very few studies that approach, from the discipline of history, to the territories and the societies of the lowlands. In Bolivia, refers principally to the Amazon, perceived as "the uncultivated lands" that must be occupied. From the middle of 19th century, the Bolivian Amazon was administrated by the department of Beni, whose history in the republican era has been poorly approached. Thus, the general aim of this thesis is the study of the most significant political and socioeconomic aspects of the history of Beni during the construction of Bolivia as nation-state. The control of the Amazon was basic for the consolidation of the Bolivian nation-state. Through diverse policies developed by the State, this thesis examines the progress and setbacks in the construction of the department of Beni, since 1842, the year of the department’s creation, until the final demarcation of their borders in 1938. It analyzes the government programs and regulations that wanted to nationalize the Amazon through the exploration and colonization of the territory, political and administrative organization of the department of Beni and its jurisdiction. Also considers the relationships, attitudes and practices developed by the local and regional groups and indigenous peoples in the exercise of their rights and access to political positions and economic power. And finally, identifies the main socioeconomic transformations in the region and in the management of natural resources and land. The main contributions of this research are in the dissection of state policies concerning the Beni, and the use and the appropriation of them by local society (white-mestizo and indigenous) in the context of construction of the Bolivian nation-state. Thus, the construction the department of Beni and their society was possible mainly by the private control of natural and economic resources of the region -land, livestock and forests- by local and regional groups against, in occasions, the State and indigenous populations. In short, the history of Beni shows the weakness and inability of Bolivian leaders to incorporate the Amazon to the republic during the 19th and early 20th century.