The photosynthetic bacterial reaction center in native and artificial envirnoments: effects on light-induced electron transfer

In this thesis we focussed on the characterization of the reaction center (RC) protein purified from the photosynthetic bacterium Rhodobacter sphaeroides. In particular, we discussed the effects of native and artificial environment on the light-induced electron transfer processes. The native environment consist of the inner antenna LH1 complex that copurifies with the RC forming the so called core complex, and the lipid phase tightly associated with it. In parallel, we analyzed the role of saccharidic glassy matrices on the interplay between electron transfer processes and internal protein dynamics. As a different artificial matrix, we incorporated the RC protein in a layer-by-layer structure with a twofold aim: to check the behaviour of the protein in such an unusual environment and to test the response of the system to herbicides. By examining the RC in its native environment, we found that the light-induced charge separated state P+QB - is markedly stabilized (by about 40 meV) in the core complex as compared to the RC-only system over a physiological pH range. We also verified that, as compared to the average composition of the membrane, the core complex copurifies with a tightly bound lipid complement of about 90 phospholipid molecules per RC, which is strongly enriched in cardiolipin. In parallel, a large ubiquinone pool was found in association with the core complex, giving rise to a quinone concentration about ten times larger than the average one in the membrane. Moreover, this quinone pool is fully functional, i.e. it is promptly available at the QB site during multiple turnover excitation of the RC. The latter two observations suggest important heterogeneities and anisotropies in the native membranes which can in principle account for the stabilization of the charge separated state in the core complex. The thermodynamic and kinetic parameters obtained in the RC-LH1 complex are very close to those measured in intact membranes, indicating that the electron transfer properties of the RC in vivo are essentially determined by its local environment. The studies performed by incorporating the RC into saccharidic matrices evidenced the relevance of solvent-protein interactions and dynamical coupling in determining the kinetics of electron transfer processes. The usual approach when studying the interplay between internal motions and protein function consists in freezing the degrees of freedom of the protein at cryogenic temperature. We proved that the “trehalose approach” offers distinct advantages with respect to this traditional methodology. We showed, in fact, that the RC conformational dynamics, coupled to specific electron transfer processes, can be modulated by varying the hydration level of the trehalose matrix at room temperature, thus allowing to disentangle solvent from temperature effects. The comparison between different saccharidic matrices has revealed that the structural and dynamical protein-matrix coupling depends strongly upon the sugar. The analyses performed in RCs embedded in polyelectrolyte multilayers (PEM) structures have shown that the electron transfer from QA - to QB, a conformationally gated process extremely sensitive to the RC environment, can be strongly modulated by the hydration level of the matrix, confirming analogous results obtained for this electron transfer reaction in sugar matrices. We found that PEM-RCs are a very stable system, particularly suitable to study the thermodynamics and kinetics of herbicide binding to the QB site. These features make PEM-RC structures quite promising in the development of herbicide biosensors. The studies discussed in the present thesis have shown that, although the effects on electron transfer induced by the native and artificial environments tested are markedly different, they can be described on the basis of a common kinetic model which takes into account the static conformational heterogeneity of the RC and the interconversion between conformational substates. Interestingly, the same distribution of rate constants (i.e. a Gamma distribution function) can describe charge recombination processes in solutions of purified RC, in RC-LH1 complexes, in wet and dry RC-PEM structures and in glassy saccharidic matrices over a wide range of hydration levels. In conclusion, the results obtained for RCs in different physico-chemical environments emphasize the relevance of the structure/dynamics solvent/protein coupling in determining the energetics and the kinetics of electron transfer processes in a membrane protein complex.

Wordline approach to higher spin fields

The main object of this thesis is the analysis and the quantization of spinning particle models which employ extended ”one dimensional supergravity” on the worldline, and their relation to the theory of higher spin fields (HS). In the first part of this work we have described the classical theory of massless spinning particles with an SO(N) extended supergravity multiplet on the worldline, in flat and more generally in maximally symmetric backgrounds. These (non)linear sigma models describe, upon quantization, the dynamics of particles with spin N/2. Then we have analyzed carefully the quantization of spinning particles with SO(N) extended supergravity on the worldline, for every N and in every dimension D. The physical sector of the Hilbert space reveals an interesting geometrical structure: the generalized higher spin curvature (HSC). We have shown, in particular, that these models of spinning particles describe a subclass of HS fields whose equations of motions are conformally invariant at the free level; in D = 4 this subclass describes all massless representations of the Poincar´e group. In the third part of this work we have considered the one-loop quantization of SO(N) spinning particle models by studying the corresponding partition function on the circle. After the gauge fixing of the supergravity multiplet, the partition function reduces to an integral over the corresponding moduli space which have been computed by using orthogonal polynomial techniques. Finally we have extend our canonical analysis, described previously for flat space, to maximally symmetric target spaces (i.e. (A)dS background). The quantization of these models produce (A)dS HSC as the physical states of the Hilbert space; we have used an iterative procedure and Pochhammer functions to solve the differential Bianchi identity in maximally symmetric spaces. Motivated by the correspondence between SO(N) spinning particle models and HS gauge theory, and by the notorious difficulty one finds in constructing an interacting theory for fields with spin greater than two, we have used these one dimensional supergravity models to study and extract informations on HS. In the last part of this work we have constructed spinning particle models with sp(2) R symmetry, coupled to Hyper K¨ahler and Quaternionic-K¨ahler (QK) backgrounds.

A new approach for the dynamic modelling of the human knee

Mathematical models of the knee joint are important tools which have both theoretical and practical applications. They are used by researchers to fully understand the stabilizing role of the components of the joint, by engineers as an aid for prosthetic design, by surgeons during the planning of an operation or during the operation itself, and by orthopedists for diagnosis and rehabilitation purposes. The principal aims of knee models are to reproduce the restraining function of each structure of the joint and to replicate the relative motion of the bones which constitute the joint itself. It is clear that the first point is functional to the second one. However, the standard procedures for the dynamic modelling of the knee tend to be more focused on the second aspect: the motion of the joint is correctly replicated, but the stabilizing role of the articular components is somehow lost. A first contribution of this dissertation is the definition of a novel approach — called sequential approach — for the dynamic modelling of the knee. The procedure makes it possible to develop more and more sophisticated models of the joint by a succession of steps, starting from a first simple model of its passive motion. The fundamental characteristic of the proposed procedure is that the results obtained at each step do not worsen those already obtained at previous steps, thus preserving the restraining function of the knee structures. The models which stem from the first two steps of the sequential approach are then presented. The result of the first step is a model of the passive motion of the knee, comprehensive of the patello-femoral joint. Kinematical and anatomical considerations lead to define a one degree of freedom rigid link mechanism, whose members represent determinate components of the joint. The result of the second step is a stiffness model of the knee. This model is obtained from the first one, by following the rules of the proposed procedure. Both models have been identified from experimental data by means of an optimization procedure. The simulated motions of the models then have been compared to the experimental ones. Both models accurately reproduce the motion of the joint under the corresponding loading conditions. Moreover, the sequential approach makes sure the results obtained at the first step are not worsened at the second step: the stiffness model can also reproduce the passive motion of the knee with the same accuracy than the previous simpler model. The procedure proved to be successful and thus promising for the definition of more complex models which could also involve the effect of muscular forces.

Path planning for image based visual servoing

This thesis deals with Visual Servoing and its strictly connected disciplines like projective geometry, image processing, robotics and non-linear control. More specifically the work addresses the problem to control a robotic manipulator through one of the largely used Visual Servoing techniques: the Image Based Visual Servoing (IBVS). In Image Based Visual Servoing the robot is driven by on-line performing a feedback control loop that is closed directly in the 2D space of the camera sensor. The work considers the case of a monocular system with the only camera mounted on the robot end effector (eye in hand configuration). Through IBVS the system can be positioned with respect to a 3D fixed target by minimizing the differences between its initial view and its goal view, corresponding respectively to the initial and the goal system configurations: the robot Cartesian Motion is thus generated only by means of visual informations. However, the execution of a positioning control task by IBVS is not straightforward because singularity problems may occur and local minima may be reached where the reached image is very close to the target one but the 3D positioning task is far from being fulfilled: this happens in particular for large camera displacements, when the the initial and the goal target views are noticeably different. To overcame singularity and local minima drawbacks, maintaining the good properties of IBVS robustness with respect to modeling and camera calibration errors, an opportune image path planning can be exploited. This work deals with the problem of generating opportune image plane trajectories for tracked points of the servoing control scheme (a trajectory is made of a path plus a time law). The generated image plane paths must be feasible i.e. they must be compliant with rigid body motion of the camera with respect to the object so as to avoid image jacobian singularities and local minima problems. In addition, the image planned trajectories must generate camera velocity screws which are smooth and within the allowed bounds of the robot. We will show that a scaled 3D motion planning algorithm can be devised in order to generate feasible image plane trajectories. Since the paths in the image are off-line generated it is also possible to tune the planning parameters so as to maintain the target inside the camera field of view even if, in some unfortunate cases, the feature target points would leave the camera images due to 3D robot motions. To test the validity of the proposed approach some both experiments and simulations results have been reported taking also into account the influence of noise in the path planning strategy. The experiments have been realized with a 6DOF anthropomorphic manipulator with a fire-wire camera installed on its end effector: the results demonstrate the good performances and the feasibility of the proposed approach.

Sulla progettazione in zona sismica di strutture dotate di dissipatori fluido-viscosi: proposta di una metodologia

CHAPTER 1:FLUID-VISCOUS DAMPERS In this chapter the fluid-viscous dampers are introduced. The first section is focused on the technical characteristics of these devices, their mechanical behavior and the latest evolution of the technology whose they are equipped. In the second section we report the definitions and the guide lines about the design of these devices included in some international codes. In the third section the results of some experimental tests carried out by some authors on the response of these devices to external forces are discussed. On this purpose we report some technical schedules that are usually enclosed to the devices now available on the international market. In the third section we show also some analytic models proposed by various authors, which are able to describe efficiently the physical behavior of the fluid-viscous dampers. In the last section we propose some cases of application of these devices on existing structures and on new-construction structures. We show also some cases in which these devices have been revealed good for aims that lies outside the reduction of seismic actions on the structures. CHAPTER 2:DESIGN METHODS PROPOSED IN LITERATURE In this chapter the more widespread design methods proposed in literature for structures equipped by fluid-viscous dampers are introduced. In the first part the response of sdf systems in the case of harmonic external force is studied, in the last part the response in the case of random external force is discussed. In the first section the equations of motion in the case of an elastic-linear sdf system equipped with a non-linear fluid-viscous damper undergoing a harmonic force are introduced. This differential problem is analytically quite complex and it’s not possible to be solved in a closed form. Therefore some authors have proposed approximate solution methods. The more widespread methods are based on equivalence principles between a non-linear device and an equivalent linear one. Operating in this way it is possible to define an equivalent damping ratio and the problem becomes linear; the solution of the equivalent problem is well-known. In the following section two techniques of linearization, proposed by some authors in literature, are described: the first technique is based on the equivalence of the energy dissipated by the two devices and the second one is based on the equivalence of power consumption. After that we compare these two techniques by studying the response of a sdf system undergoing a harmonic force. By introducing the equivalent damping ratio we can write the equation of motion of the non-linear differential problem in an implicit form, by dividing, as usual, for the mass of the system. In this way, we get a reduction of the number of variables, by introducing the natural frequency of the system. The equation of motion written in this form has two important properties: the response is linear dependent on the amplitude of the external force and the response is dependent on the ratio of the frequency of the external harmonic force and the natural frequency of the system only, and not on their single values. All these considerations, in the last section, are extended to the case of a random external force. CHAPTER 3: DESIGN METHOD PROPOSED In this chapter the theoretical basis of the design method proposed are introduced. The need to propose a new design method for structures equipped with fluid-viscous dampers arises from the observation that the methods reported in literature are always iterative, because the response affects some parameters included in the equation of motion (such as the equivalent damping ratio). In the first section the dimensionless parameterε is introduced. This parameter has been obtained from the definition of equivalent damping ratio. The implicit form of the equation of motion is written by introducing the parameter ε, instead of the equivalent damping ratio. This new implicit equation of motions has not any terms affected by the response, so that once ε is known the response can be evaluated directly. In the second section it is discussed how the parameter ε affects some characteristics of the response: drift, velocity and base shear. All the results described till this point have been obtained by keeping the non-linearity of the behavior of the dampers. In order to get a linear formulation of the problem, that is possible to solve by using the well-known methods of the dynamics of structures, as we did before for the iterative methods by introducing the equivalent damping ratio, it is shown how the equivalent damping ratio can be evaluated from knowing the value of ε. Operating in this way, once the parameter ε is known, it is quite easy to estimate the equivalent damping ratio and to proceed with a classic linear analysis. In the last section it is shown how the parameter ε could be taken as reference for the evaluation of the convenience of using non-linear dampers instead of linear ones on the basis of the type of external force and the characteristics of the system. CHAPTER 4: MULTI-DEGREE OF FREEDOM SYSTEMS In this chapter the design methods of a elastic-linear mdf system equipped with non-linear fluidviscous dampers are introduced. It has already been shown that, in the sdf systems, the response of the structure can be evaluated through the estimation of the equivalent damping ratio (ξsd) assuming the behavior of the structure elastic-linear. We would to mention that some adjusting coefficients, to be applied to the equivalent damping ratio in order to consider the actual behavior of the structure (that is non-linear), have already been proposed in literature; such coefficients are usually expressed in terms of ductility, but their treatment is over the aims of this thesis and we does not go into further. The method usually proposed in literature is based on energy equivalence: even though this procedure has solid theoretical basis, it must necessary include some iterative process, because the expression of the equivalent damping ratio contains a term of the response. This procedure has been introduced primarily by Ramirez, Constantinou et al. in 2000. This procedure is reported in the first section and it is defined “Iterative Method”. Following the guide lines about sdf systems reported in the previous chapters, it is introduced a procedure for the assessment of the parameter ε in the case of mdf systems. Operating in this way the evaluation of the equivalent damping ratio (ξsd) can be done directly without implementing iterative processes. This procedure is defined “Direct Method” and it is reported in the second section. In the third section the two methods are analyzed by studying 4 cases of two moment-resisting steel frames undergoing real accelerogramms: the response of the system calculated by using the two methods is compared with the numerical response obtained from the software called SAP2000-NL, CSI product. In the last section a procedure to create spectra of the equivalent damping ratio, affected by the parameter ε and the natural period of the system for a fixed value of exponent α, starting from the elasticresponse spectra provided by any international code, is introduced.

Algorithms for on-line image registration from multiple views

Images of a scene, static or dynamic, are generally acquired at different epochs from different viewpoints. They potentially gather information about the whole scene and its relative motion with respect to the acquisition device. Data from different (in the spatial or temporal domain) visual sources can be fused together to provide a unique consistent representation of the whole scene, even recovering the third dimension, permitting a more complete understanding of the scene content. Moreover, the pose of the acquisition device can be achieved by estimating the relative motion parameters linking different views, thus providing localization information for automatic guidance purposes. Image registration is based on the use of pattern recognition techniques to match among corresponding parts of different views of the acquired scene. Depending on hypotheses or prior information about the sensor model, the motion model and/or the scene model, this information can be used to estimate global or local geometrical mapping functions between different images or different parts of them. These mapping functions contain relative motion parameters between the scene and the sensor(s) and can be used to integrate accordingly informations coming from the different sources to build a wider or even augmented representation of the scene. Accordingly, for their scene reconstruction and pose estimation capabilities, nowadays image registration techniques from multiple views are increasingly stirring up the interest of the scientific and industrial community. Depending on the applicative domain, accuracy, robustness, and computational payload of the algorithms represent important issues to be addressed and generally a trade-off among them has to be reached. Moreover, on-line performance is desirable in order to guarantee the direct interaction of the vision device with human actors or control systems. This thesis follows a general research approach to cope with these issues, almost independently from the scene content, under the constraint of rigid motions. This approach has been motivated by the portability to very different domains as a very desirable property to achieve. A general image registration approach suitable for on-line applications has been devised and assessed through two challenging case studies in different applicative domains. The first case study regards scene reconstruction through on-line mosaicing of optical microscopy cell images acquired with non automated equipment, while moving manually the microscope holder. By registering the images the field of view of the microscope can be widened, preserving the resolution while reconstructing the whole cell culture and permitting the microscopist to interactively explore the cell culture. In the second case study, the registration of terrestrial satellite images acquired by a camera integral with the satellite is utilized to estimate its three-dimensional orientation from visual data, for automatic guidance purposes. Critical aspects of these applications are emphasized and the choices adopted are motivated accordingly. Results are discussed in view of promising future developments.

Functional photoactive and electroactive nanodevices

Most of current ultra-miniaturized devices are obtained by the top-down approach, in which nanoscale components are fabricated by cutting down larger precursors. Since this physical-engineering method is reaching its limits, especially for components below 30 nm in size, alternative strategies are necessary. Of particular appeal to chemists is the supramolecular bottom-up approach to nanotechnology, a methodology that utilizes the principles of molecular recognition to build materials and devices from molecular components. The subject of this thesis is the photophysical and electrochemical investigation of nanodevices obtained harnessing the principles of supramolecular chemistry. These systems operate in solution-based environments and are investigated at the ensemble level. The majority of the chemical systems discussed here are based on pseudorotaxanes and catenanes. Such supramolecular systems represent prototypes of molecular machines since they are capable of performing simple controlled mechanical movements. Their properties and operation are strictly related to the supramolecular interactions between molecular components (generally photoactive or electroactive molecules) and to the possibility of modulating such interactions by means of external stimuli. The main issues addressed throughout the thesis are: (i) the analysis of the factors that can affect the architecture and perturb the stability of supramolecular systems; (ii) the possibility of controlling the direction of supramolecular motions exploiting the molecular information content; (iii) the development of switchable supramolecular polymers starting from simple host-guest complexes; (iv) the capability of some molecular machines to process information at molecular level, thus behaving as logic devices; (v) the behaviour of molecular machine components in a biological-type environment; (vi) the study of chemically functionalized metal nanoparticles by second harmonic generation spectroscopy.

New mechanisms for modelling the motion of the human ankle complex

The relevance of human joint models was shown in the literature. In particular, the great importance of models for the joint passive motion simulation (i.e. motion under virtually unloaded conditions) was outlined. They clarify the role played by the principal anatomical structures of the articulation, enhancing the comprehension of surgical treatments, and in particular the design of total ankle replacement and ligament reconstruction. Equivalent rigid link mechanisms proved to be an efficient tool for an accurate simulation of the joint passive motion. This thesis focuses on the ankle complex (i.e. the anatomical structure composed of the tibiotalar and the subtalar joints), which has a considerable role in human locomotion. The lack of interpreting models of this articulation and the poor results of total ankle replacement arthroplasty have strongly suggested devising new mathematical models capable of reproducing the restraining function of each structure of the joint and of replicating the relative motion of the bones which constitute the joint itself. In this contest, novel equivalent mechanisms are proposed for modelling the ankle passive motion. Their geometry is based on the joint’s anatomical structures. In particular, the role of the main ligaments of the articulation is investigated under passive conditions by means of nine 5-5 fully parallel mechanisms. Based on this investigation, a one-DOF spatial mechanism is developed for modelling the passive motion of the lower leg. The model considers many passive structures constituting the articulation, overcoming the limitations of previous models which took into account few anatomical elements of the ankle complex. All the models have been identified from experimental data by means of optimization procedure. Then, the simulated motions have been compared to the experimental one, in order to show the efficiency of the approach and thus to deduce the role of each anatomical structure in the ankle kinematic behavior.

Studies of pure rotational spectra of isolated molecules and molecular adducts using pulsed jet Fourier transform microwave (PJ-FTM) spectroscopy

This thesis focuses on studying molecular structure and internal dynamics by using pulsed jet Fourier transform microwave (PJ-FTMW) spectroscopy combined with theoretical calculations. Several kinds of interesting chemical problems are investigated by analyzing the MW spectra of the corresponding molecular systems. First, the general aspects of rotational spectroscopy are summarized, and then the basic theory on molecular rotation and experimental method are described briefly. ab initio and density function theory (DFT) calculations that used in this thesis to assist the assignment of rotational spectrum are also included. From chapter 3 to chapter 8, several molecular systems concerning different kind of general chemical problems are presented. In chapter 3, the conformation and internal motions of dimethyl sulfate are reported. The internal rotations of the two methyl groups split each rotational transition into several components line, allowing for the determination of accurate values of the V3 barrier height to internal rotation and of the orientation of the methyl groups with respect to the principal axis system. In chapter 4 and 5, the results concerning two kinds of carboxylic acid bi-molecules, formed via two strong hydrogen bonds, are presented. This kind of adduct is interesting also because a double proton transfer can easily take place, connecting either two equivalent or two non-equivalent molecular conformations. Chapter 6 concerns a medium strong hydrogen bonded molecular complex of alcohol with ether. The dimer of ethanol-dimethylether was chosen as the model system for this purpose. Chapter 7 focuses on weak halogen…H hydrogen bond interaction. The nature of O-H…F and C-H…Cl interaction has been discussed through analyzing the rotational spectra of CH3CHClF/H2O. In chapter 8, two molecular complexes concerning the halogen bond interaction are presented.

Analisi dell’influenza dei moti rigidi di una trattrice agricola sulle vibrazioni a corpo intero trasmesse all’operatore

L’esposizione degli operatori in campo agricolo alle vibrazioni trasmesse al corpo intero, produce effetti dannosi alla salute nel breve e nel lungo termine. Le vibrazioni che si generano sulle trattrici agricole hanno una elevata intensità e una bassa frequenza. Le componenti orizzontali, amplificate dalla posizione elevata della postazione di guida dall’asse di rollio, presentano maggiori criticità per quanto riguarda i sistemi di smorzamento rispetto alle componenti verticali. Queste caratteristiche rendono difficoltosa la progettazione dei sistemi dedicati alla riduzione del livello vibrazionale per questa categoria di macchine agricole. Nonostante l’installazione di diversi sistemi di smorzamento, il livello di vibrazioni a cui è sottoposto l’operatore può superare, in diverse condizioni di impiego, i livelli massimi imposti dalla legge per la salvaguardia della salute. L’obiettivo di questo lavoro è quello di valutare l’influenza dei moti rigidi di una trattrice (beccheggio, rollio e saltellamento) dotata di sospensione assale anteriore, sospensione cabina e sospensione sedile, sul livello vibrazionale trasmesso all’operatore.E’ stata pertanto strumenta una trattrice con accelerometri e inclinometri installati su telaio, cabina e sedile e utilizzata in diverse condizioni di lavoro in campo e di trasporto su strada. Dall’analisi delle prove effettuate emerge che durante il trasporto su strada è predominante l’accelerazione longitudinale, a causa dell’elevata influenza del beccheggio. La sospensione riduce notevolmente il moto rigido di beccheggio mentre l’effetto della sospensione della cabina è quello di incrementare, in ogni condizione di lavoro, il livello di accelerazione trasmesso dal telaio della macchina.

Inverse Static Analysis of Massive Parallel Arrays of Three-State Actuators via Artificial Intelligence

Massive parallel robots (MPRs) driven by discrete actuators are force regulated robots that undergo continuous motions despite being commanded through a finite number of states only. Designing a real-time control of such systems requires fast and efficient methods for solving their inverse static analysis (ISA), which is a challenging problem and the subject of this thesis. In particular, five Artificial intelligence methods are proposed to investigate the on-line computation and the generalization error of ISA problem of a class of MPRs featuring three-state force actuators and one degree of revolute motion.

Hydrodynamical simulations of early-type galaxies: effects of galaxy shape and stellar dynamics on hot coronae

Early-Type galaxies (ETGs) are embedded in hot (10^6-10^7 K), X-ray emitting gaseous haloes, produced mainly by stellar winds and heated by Type Ia supernovae explosions, by the thermalization of stellar motions and occasionally by the central super-massive black hole (SMBH). In particular, the thermalization of the stellar motions is due to the interaction between the stellar and the SNIa ejecta and the hot interstellar medium (ISM) already residing in the ETG. A number of different astrophysical phenomena determine the X-ray properties of the hot ISM, such as stellar population formation and evolution, galaxy structure and internal kinematics, Active Galactic Nuclei (AGN) presence, and environmental effects. With the aid of high-resolution hydrodynamical simulations performed on state-of-the-art galaxy models, in this Thesis we focus on the effects of galaxy shape, stellar kinematics and star formation on the evolution of the X-ray coronae of ETGs. Numerical simulations show that the relative importance of flattening and rotation are functions of the galaxy mass: at low galaxy masses, adding flattening and rotation induces a galactic wind, thus lowering the X-ray luminosity; at high galaxy masses the angular momentum conservation keeps the central regions of rotating galaxies at low density, whereas in non-rotating models a denser and brighter atmosphere is formed. The same dependence from the galaxy mass is present in the effects of star formation (SF): in light galaxies SF contributes to increase the spread in Lx, while at high galaxy masses the halo X-ray properties are marginally sensitive to SF effects. In every case, the star formation rate at the present epoch quite agrees with observations, and the massive, cold gaseous discs are partially or completely consumed by SF on a time-scale of few Gyr, excluding the presence of young stellar discs at the present epoch.

Computational strategies to include protein flexibility in Ligand Docking and Virtual Screening

The dynamic character of proteins strongly influences biomolecular recognition mechanisms. With the development of the main models of ligand recognition (lock-and-key, induced fit, conformational selection theories), the role of protein plasticity has become increasingly relevant. In particular, major structural changes concerning large deviations of protein backbones, and slight movements such as side chain rotations are now carefully considered in drug discovery and development. It is of great interest to identify multiple protein conformations as preliminary step in a screening campaign. Protein flexibility has been widely investigated, in terms of both local and global motions, in two diverse biological systems. On one side, Replica Exchange Molecular Dynamics has been exploited as enhanced sampling method to collect multiple conformations of Lactate Dehydrogenase A (LDHA), an emerging anticancer target. The aim of this project was the development of an Ensemble-based Virtual Screening protocol, in order to find novel potent inhibitors. On the other side, a preliminary study concerning the local flexibility of Opioid Receptors has been carried out through ALiBERO approach, an iterative method based on Elastic Network-Normal Mode Analysis and Monte Carlo sampling. Comparison of the Virtual Screening performances by using single or multiple conformations confirmed that the inclusion of protein flexibility in screening protocols has a positive effect on the probability to early recognize novel or known active compounds.

Techniques for Lagrangian modelling of dispersion in geophysical flows

Basic concepts and definitions relative to Lagrangian Particle Dispersion Models (LPDMs)for the description of turbulent dispersion are introduced. The study focusses on LPDMs that use as input, for the large scale motion, fields produced by Eulerian models, with the small scale motions described by Lagrangian Stochastic Models (LSMs). The data of two different dynamical model have been used: a Large Eddy Simulation (LES) and a General Circulation Model (GCM). After reviewing the small scale closure adopted by the Eulerian model, the development and implementation of appropriate LSMs is outlined. The basic requirement of every LPDM used in this work is its fullfillment of the Well Mixed Condition (WMC). For the dispersion description in the GCM domain, a stochastic model of Markov order 0, consistent with the eddy-viscosity closure of the dynamical model, is implemented. A LSM of Markov order 1, more suitable for shorter timescales, has been implemented for the description of the unresolved motion of the LES fields. Different assumptions on the small scale correlation time are made. Tests of the LSM on GCM fields suggest that the use of an interpolation algorithm able to maintain an analytical consistency between the diffusion coefficient and its derivative is mandatory if the model has to satisfy the WMC. Also a dynamical time step selection scheme based on the diffusion coefficient shape is introduced, and the criteria for the integration step selection are discussed. Absolute and relative dispersion experiments are made with various unresolved motion settings for the LSM on LES data, and the results are compared with laboratory data. The study shows that the unresolved turbulence parameterization has a negligible influence on the absolute dispersion, while it affects the contribution of the relative dispersion and meandering to absolute dispersion, as well as the Lagrangian correlation.

Non-Covalent Interaction: Revealed by Rotational Spectroscopy

The pulsed jet Fourier transform microwave spectroscopy have been applied to several molecular complexes involving H2O, freons, methane, carboxylic acids, and rare gas. The obtained results showcase the suitability of this technique for studying the intermolecular interactions. The rotational spectra of three water adducts of halogenated organic molecules, i.e. chlorotrifluoroethylene, isoflurane and alfa,alfa,alfa,-trifluoroanisole, have been investigated. It has been found that, the halogenation of the partner molecules definitely changes the way in which water will link to the partner molecule. Quadrupole hyperfine structures and/or the tunneling splittings have been observed in the rotational spectra of difluoromethane-dichloromethane, chlorotrifluorometane-fluoromethane, difluoromethane-formaldehyde and trifluoromethane-benzene. These features have been useful to describe their intermolecular interactions (weak hydrogen bonds or halogen bonds), and to size the potential energy surfaces of their internal motions. The rotational spectrum of pyridine-methane pointed out that methane prefers to locate above the ring and link to pyridine through a C-H•••π weak hydrogen bond, rather than the C-H•••n interaction. This behavior, typical of complexes of pyridine with rare gases, suggests classifying CH4, in relation to its ability to form molecular complexes with aromatic molecules, as a pseudo rare gas. The conformational equilibria of three bi-molecules of carboxylic acids, acrylic acid-trifluoroacetic acid, difluoroacetic acid-formic acid and acrylic acid-fluoroacetic acid have been studied. The increase of the hydrogen bond length upon H→D isotopic substitution (Ubbelohde effect) has been deduced from the elongation of the carboxylic carbons C•••C distance. The van der Waals complex tetrahydrofuran-krypton shows that the systematic doubling of the rotational lines has been attributed to the residual pseudo-rotation of tetrahydrofuran in the complex, based on the values of the Coriolis coupling constants, and on the type (mu_b) of the interstate transitions.