Sapienza University of Rome

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    The electron spectrometer of the PlasmonX experiment: from the design to the operation

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    The PlasmonX project at the Laboratori Nazionali di Frascati was proposed in 2008. Concerning the plasma acceleration, the main purpose of the project consists in R&D activity aimed at demonstrate the high-gradient acceleration technique by the use FLAME, an ultra-short, high power laser system. The central topic of this thesis is the design, construction and commissioning of the device we use to characterize the accelerated electrons. As expected from simulation codes that investigates the interaction of a laser pulse with a preformed plasma, the accelerated electron bunch has peculiar characteristics and it is extremely challenging to realize a device capable to fit all of them. We expect energy spread over three order of magnitude (from few MeV to the GeV region), a significant angular divergence at low energy (10 mrad) and a huge number of particles (10^9) to detect at the same time. Considering these aspects we have designed, realized and operate an electron spectrometer that is largely described in this work

    N-linked peptidoresorc[4]arene-based receptors designed for protein surface recognition. NMR analysis of Italian virgin olive oils and structural analysis of polysaccharides.

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    The first part of this work concerned the synthesis of N-linked peptideresorcarenes and the study of their surface interaction with enzymes. As known, an important class of protein surface receptors based on the attachment of four cyclic peptides to a calix[4]arene scaffold was developed by Hamilton and targeted to the serine protease α-chymotrypsin (ChT). Moving from Hamilton’s results and from some preliminary molecular modeling studies, valyl-leucine, leucyl-valine and valyl-aspartic peptidoresorc[4]arenes have been designed with the aim to target the predominantly cationic region surrounding the active site of ChT. By varying sequence, nature, and stereochemistry of the side chains, we prepared anionically functionalized N-linked peptidoresorc[4]arenes by hydrogenation of their precursor benzyl esters. From this family of receptors we have identified noncompetitive inhibitors of ChT, which function by binding to the surface of the enzyme in the neighborhood of the active site cleft (Ki values ranging from 13 to 0.8 µM). The second topic of the work was the NMR characterization of the Italian virgin olive oils from the harvesting seasons 2009/10, 2010/11. Following the experimental protocol established in the Annalaura Segre NMR Laboratory (CMI, CNR in Montelibretti, Rome), based on 1H-NMR and statistical multivariate analysis of the data (ANOVA, PCA and LDA), nearly 300 Italian virgin olive oil samples, produced in two harvesting years, 2009/10 and 2010/11, by certified chains in different italian regions have been studied. The NMR results confirm that the chemical composition of olive oils, with regards to minor components, is influenced by geographical, ecological and genetic factors and depends also on the harvesting year. We could also identify some oil components that remain stable in different harvesting years, representing seasonal-independent characteristics of the oil produced in each region. A contemporary investigation, carried out at CNR, was focused on structural analysis of polysaccharides. Specificaly, we performed NMR characterization of a carboxy-methyl derivative of scleroglucan, a polysaccharide produced by fungi of the Sclerotium genus, to identify the position involved in the carboxymethylation; furthermore, a preliminary structural study has been performed on a set of polysaccharides obtained from the cultures of Hericium erinaceus, with the aim of identifying the configuration and the connections between the monosaccharidic units

    Bayesian Modeling of Presence-only Data

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    This thesis develops models and methods for statistical analysis of presence-only data. Besides constructing new models, the emphasis is on the theoretical characteristics of new models and on Bayesian prediction. Monte Carlo Markov chains algorithms are developed for the new presence-only data models in order to be able to simulate the posterior distribution of the unknowns and the predictive distribution of variable of interest. The new methods are applied to simulated data. One application in ecologic science have been a driving force behind the work

    Top-Down Attention Modelling in a Cocktail Party Scenario

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    Computational auditory scene analysis (CASA) focuses on the problem of building machines able to understand and interpret complex acoustic scenarios and react, after a brief period, in an opportune way. A complex acoustic scenario can be characterized by several sounds of various origin and nature coming from different sources. Consequently, one of the main challenges is the simultaneous elaboration of all this information with limited computational resources. Colin Cherry, in1953, investigated human behavior in the same circumstances, (which he called “cocktail party problem”). He performed several experiments proving that people are very efficient cocktail party solvers, making use of attentive mechanisms. Attentive mechanisms, in fact, allow the brain to focus on what it is necessary to follow and ignore what it is possible to discard. This selection procedure is driven by many factors; depending on the nature of these factors, it is possible to distinguish between a bottom-up and top-down perspective. In the first case, sounds of interest are those which stand out from the scene, without involving a real attentive processing, but just the pre-attentive one. In the second case, the goal, a particular task, the previous decisions and the acquired models guide the subjects' attention. The fusion of these two modalities suggests to the brain what is salient and what can be attenuated or deleted. In this thesis, we propose a top-down attention model and we carry out behavioral experiments –inspired by the Cherry’s ones- to investigate the role of top-down attention in the cocktail party. In particular, we model top-down attention as a sequential decision making process driven by a task – modeled as a classification problem - in an environment with random subsets of features missing, but where we have the possibility to gather additional features among the ones that are missing. Thus, the top-down attention problem is reduced to finding the answer to the question what to measure next? Attention is based on the top-down saliency of the missing features given as the estimated difference in classification confusion (entropy) with and without the given feature. The difference in confusion is computed conditioned on the available set of features. We also investigated missing data problem, comparing the efficiency of some missing data techniques and used the results to make our attention model more realistic by also allowing the initial training phase to take place with incomplete data. Moreover, we simulate the cocktail party problem in the model and make predictions about sensitivity to confounders under different levels of attention. We finally examine the role of temporal and spectral overlaps for human speech intelligibility, and how the presence of a task influences it. We also investigated multi-modal human-robot interaction and proposed a multimodal speaker identification system, combining acoustic and visual features to identify and track people taking part in a conversation.This thesis is the result of an informal joint Ph.D. between Sapienza, University of Rome and DTU, Technical University of Denmark. I spent the first half of my Ph.D. period in Italy, working under the supervision of Prof. Fiora Pirri and the other half in Denmark, working under the supervision of Prof. Lars Kai Hansen. Unfortunately, because of Danish legislation at the time I started, it was not possible to have the formal agreement between the two universities

    Investigation of cartlilage aging by means of MRI, DTI and DS techniques

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    Articular cartilage (AC) is an aneural and avascular tissue that covers the ends of articulating bones in diarthrodial joints, and its main functions are to distribute joint loading and to provide nearly frictionless movement of the articulating bones. The mechanical properties of AC can be attribute to the complex structure of its extracellular matrix (ECM), mainly composed by collagen fibres, proteoglycan (PG) aggregates and interstitial water [1, 2]. Nowadays, the progression of mean expectation of life has highlighted the importance of a correct diagnosis for many age-related diseases. In AC, aging process occur in older age with cellular senescence [3, 4] and ECM modifications [5, 6], frequently involving in Osteoarthritic diseases [7–9]. Osteoarthritis (OA) is the most common degenerative joint disease and represent one of the most common disabilities cause (6,6% of Italian population, actually), posing a high economical burden to society. OA is characterized by the proceeding destruction of AC by uncontrolled proteolysis of ECM and typically leads to a remodeling of affected joints. No treatment neither early diagnosis method currently exist for OA pathologies, and the detection of differences and relations between early OA and aging is still an open field in clinical research [3, 8, 10]. To understand the progression of the disease, the comprehension of mechanisms involving on to ECM components during AC degradation is essential. The reduction of PGs concentration is recognized as the first symptom of degeneration in OA [11–14], while collagen fibers result more resistant from degradation. Using different experimental techniques, it is possible to observe the contribution of degradation of a specific macromolecule to the AC disease progression. Dielectric Spectroscopy (DS) resulted as an indirect indicator of collagen fibrils integrity through observation of intermolecular hydrogen bounds formation between water molecules [15]. Moreover, some water molecules result oriented along collagen fibers and that orientation is well recognized by Magnetic Resonance T2 -weighted imaging (T2w-MRI) contrast variations through intra-molecular dipole interactions of water hydrogen nuclei[16-18]. The study of the dynamic of water molecules in cartilage resulted to provide information on cartilage structure [19-21]. Diffusion Tensor Imaging (DTI) [22-26] is a widely used Magnetic Resonance technique to investigate fiber microstructures in human brain, like in skeletal muscle tissue [27]. Moreover, some authors [20, 28, 29] have demonstrated that DTI technique can recognise collagen fibril orientation and other authors [20, 30, 31] have shown how the reduction of proteoglycan content in cartilage affect water Apparent Diffusion Coefficient (ADC). For all the cartilage futures listed so far, and taking into account the potentiality provided by DTI investigations, here we monitored cartilage aging by means of DTI and T2 -weighted imaging techniques. Specifically, starting to the observation that in cartilage is generally observed a reduction in water content during aging [32], we investigate in vitro cartilage samples during natural dehydration process. Moreover, we combined NMR with DS measurements to deeply investigate structural variation in cartilage matrix. [1] Zernia, G. 2006. Collagen dynamics in articular cartilage under osmotic pressure. NMR Biomed. 19:1010-1019. [2] Newman, A.P. 1998. Articular cartilage repair. Am. J. Sports. Med. 26:309-324. [3] R. F. Loeser. Aging and osteoarthritis. Curr. Op. Rheum.,(23), 492 (2011). [4] H. Muir. The chondrocyte, architect of cartilage. biomechanics,structure, function and molecular biology of cartilage matrix macromolecules. Bioessays, (17), 1039 (1995). [5] E. Wachtel, A. Maroudas and R. Schneiderman. Age-related changes in collagen packing of human articular cartilage. Bioch. Bioph. Acta, (1243), 239 (1995). [6] J. Dudhia. Aggrecan, aging and assembly in articular cartilage.Cellular and Molecular Life Sciences, (62), 2241 (2005). [7] M. B. Goldring and S. R. Goldring. Osteoarthritis. J. Cell. Physiol., (213), 626 (2007). [8] D. Umlauf, S. Frank, T. Pap and J. Bertrand. Cartilage biology, pathology, and repair. Cellular and Molecular Life Sciences,(67), 41974211 (2010). [9] F. Eckstein, M. Kunzy, M. Schutzery, M. Hudelmaier, R. D.Jackson, J. Yu, C. B. Eaton and E. Schneider. Two year longitudinal change and teste-retest-precision of knee cartilage morphology in a pilot study for the osteoarthritis initiative. OsteoArthritis and Cartilage, (15), 1326 (2007). [10] M. Beekhuizen, Y. M. Bastiaansen-Jenniskens, W. Koevoet,D. B. F. Saris, W. J. A. Dhert, L. B. Creemers and G. J. V. M.van Osch. Osteoarthritic synovial tissue inhibition of proteoglycan production in human osteoarthritic knee cartilage. Arth.& Rheum., (63), 1918 (2011). [11] H. J. Mankin, H. Dorfman, L. Lippiello and L. Zarins. Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hips. ii: Correlation of morphology with biochemical and metabolic data. J. Bone Joint. Surg. Am., (53), 523 (1971). [12] A. A. V. de Loo, O. Arntz, I. Otterness and W. V. den Berg. Proteoglycan loss and subsequent replenishment in articularcartilage after a mild arthritic insult by il-1 in mice: impaired proteoglycan turnover in the recovery phase. Ag. Act., (41), 200 (1994). [13] G. Grushko, R. Schneiderman and A. Maroudas. Some bichemical and biophysical parameters for the study of the pathogenesis of osteoarthritis: comparison between the processes of aging and degeneration in human hip cartilage. Conn. Tiss. Res., (19), 149 (1989). [14] J. Degroot, N. Verzijl, R. Bank, F. P. J. Lafeber, J. W. J. Bijlsma and J. Tekoppele. Age-related decrease in proteoglycan syntesis of human articular chondrocytes. Arth. Reum., (42), 1003 (1999). [15] J. R. Grigera, F. Vericat, K. Hallenga and H. Berendsen. Dielectric properties of hydrated collagen. Biopol., (18), 35 (1979). [16] Akella, S.V.S., R.R. Regatte, A.J. Wheaton, A. Borthakur, and R. Reddy. 2004. Reduction of Residual Dipolar Interaction in Cartilage by Spin-Lock Technique. Magn. Res. Med. 52:1103-1109. [17] Migchelsen, C. and H.J.C. Berendsen. 1973. Proton exchange and molecular orientation of water in hydrated collagen fibers. J.Chem.Phys. 59(1):296-305. [18] Shinar, H., and G. Navon. 2006. Multinuclear NMR and Microscopic MRI studies of articular cartilage nanostructure. NMR Biomed.19:877-893. [19] Filidoro, L., O. Dietrich, J. Weber, E. Rauch, T. Oerther, M. Wick, M.F. Reiser, and C. Glaser. 2005. High-Resolution DTI of human patellar cartilage: feasibility and preliminary findings. Magn. Res. Med. 53:993-998. [20] Raya, J.G., Melkus, G., Adam-Neumair, S., Dietrich, O., Mutzel, E., Kahr, B., Reiser, M.F., Jakob, P.M., Putz, R. and C. Glaser. 2011. Change of diffusion tensor imaging parameters in articular cartilage with progressive proteoglycan extraction. Invest. Radiol. 46:401-409. [21] Azuma, T., Nakai, R., Takizawa O. and S. Tsutsumi. 2009. In vivo structural analysis of articular cartilage using diffusion tensor magnetic resonance imaging. Magn. Res. Im. 27:1242-1248. [22] Basser, P.J., and C. Pierpaoli. 1996. Microstructural and Physiological Features of Tissues elucidated by Quantitative-Diffusion-Tensor MRI. J.Magn.Res. 111:209-219. [23] Pierpaoli, C., P. Jezzard, P.J. Basser, J. Barnett , and G. Di Chiro. 1996. Diffusion tensor MR imaging of the human brain. Radiol. 201:637-648. [24] Basser, P.J., J. Mattiello, and D. LeBihan. 1994. MR Diffusion Tensor Spectroscopy and Imaging. Bioph. J. 66:259-267. [25] Le Bihan, D. 1991. Molecular diffusion nuclear magnetic resonance imaging. Magn. Res. Quart. 7:1-30. [26] Basser, P.J., and D.K. Jones. 2002. Diffusion-Tensor MRI. NMR Biomed. 15:456 -467. [27] Napadow, V.J., V. Q. Chen, V. Mai, P.T.C. So, and R. J. Gilbert. 2001. Quantitative Analysis of Three-Dimensional-Resolved Fiber Architecture in Heterogeneous Skeletal Muscle Tissue Using NMR and Optical Imaging Methods. Bioph. J. 80:2968-2975. [28] De Visser, S.K., J. C. Bowden, E. Wentrup-Byrne, L. Rintoul, T. Bostrom, J. M. Pope D and K. I. Momot. 2008. Anisotropy of collagen fibre alignment in bovine cartilage: comparison of polarised light microscopy and spatially resolved diffusion-tensor measurements. Ost. and Cart.16: 689-697. [29] Pierce, D.M., Trobin W., Raya J.G., Trattnig S., Bishof H., Glaser C. and G.A. Holzapfeli. 2010. DT-MRI based computation of collagen fiber deformation in human articular cartilage: a feasibility study. Ann. Biom. Eng. 38:2447–2463. [30] Meder, R., S. K. de Visser, J. C. Bowden, T. Bostrom, and J. M. Pope. 2006. Diffusion tensor imaging of articular cartilage as a measure of tissue microstructure Ost. and Cart. 14, 875-881. [31] Othman, S.F., Williams, J.M., Sumner, D.R. and R.L. Magin. 2004. MRI heterogeneity of articular cartilage in strong magnetic field: dependence on proteoglycan content. Magn. Res. Eng. 23B(1):33-43. [32] Venn, M. F. 1978. Variation of chemical composition with age in human femoral head cartilage. Ann. Rheum. Dis. 37:168-174

    Test and Thermo-optical Analysis for Qualification of LARES Satellite Cube Corner Reflectors

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    In this document will be shown and explained all the experiences and the activities executed during the Ph.D. studies, from November 2009 up to November 2011. The whole work has been developed in La Sapienza - Universita di Roma", in a special facility for simulated space environment settled up in 2010. To re fine some part of this work a stage in GFZ - GeoForschungsZentrum " has been attended, thanks to the collaboration of Dr. Reinhart Neubert. The aim of this work was been to qualify the CCRs of the LARES satellite. The last developments of the project LARES have led to some results that have called for these kind of tests: thermal simulations have shown an operative temperature of the satellite in orbit in a range from 80C up to 150C, higher than the values expected. According to these last results, to ensure the good working of CCRs and of their mounting systems, a procedure of painting of the surface of the satellites has been proposed. Anyway, even if these proposal would assure the drop in temperature, there were some risks about the fragmentation and detachment of the paint during in-orbit phases, after some years of exposition to the space environment. Because LARES satellite aims to measure Lense-Thirring with a very high precision these e ects could introduce some errors. So the proposal of validation of the CCRs in simulated space environment in the range calculated by the simulation has been performed to ensure the good working of the optics of LARES satellite, avoiding the painting procedure in case of successful results. All the tests realized on CCRs have shown a good working capacity of the systems even at high temperature, with just some negligible e ffects of energy loss because of mechanical deformations caused by the severe thermal condition imposed to the system.La Sapienza - Università di Roma, Università del Salento, GFZ, CG

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    Pubblicazioni Aperte Digitali Interateneo Sapienza
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