Sapienza University of Rome

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    Analisi degli impianti di digestione anaerobica alimentati a biomasse ed effetti dell’ozono sulla digestione anaerobica di fanghi e reflui zootecnici

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    La ricerca, oltre ad effettuare una dettagliata analisi del potenziale energetico delle biomasse vuole individuare e studiare alcune migliorie nei pretrattamenti di digestione anaerobica che possano aumentare sia la quantità che la “qualità energetica” della miscela di gas prodotti dalla digestione anaerobica. Tra i vari pretrattamenti possibili, l’attenzione è stata poi concentrata sull’ozonolisi. Le sperimentazioni sulla DA di fanghi di depurazione, effettuate nel laboratorio attrezzato per l’occasione, hanno evidenziato che l’ozono ossidando alcune molecole complesse rende digeribile frazione maggiore del substrato; l’ossidazione di alcune tipologie di molecole riduce i tempi di idrolisi; l’ozono ha un effetto depressivo su alcuni ceppi batterici antagonisti e determina una riduzione dei tempi di acclimatazione di quelli metanigeni. Questi fattori hanno portato ad un evidente aumento della velocità di produzione del metano (mediamente del 55% nei campioni di laboratorio). In tutti i campioni di fanghi analizzati si è inoltre riscontrato un aumento di produzione di metano superiore al 50%

    Il contratto e le sue categorie ordinanti tra codice civile e codice del consumo

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    Analisi comparatistica di alcune categorie contrattuali, quali la nullità, tra Codice civile e Codice del consumo

    Del peccato alessandrino: realtà e limiti della maestrìa di un autore e di un personaggio (Libro de Alexandre)

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    La tesi si presenta come una monografia sul poema castigliano duecentesco Libro de Alexandre, incentrata sul serrato confronto con la produzione romanzesca francese del secolo precedente, in particolare con il genere particolare dei romanzi di antichità; è anche l'occasione per rivedere criticamente le due principali linee interpretative del Libro: quella cioè che lo lega a ambiente di corte, con una spiccata caratterizzazione nel senso di speculum principis; e quella che invece lo connette con il mondo universitario

    Enhanced SPH modeling of free-surface flows with large deformations

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    The subject of the present thesis is the development of a numerical solver to study the violent interaction of marine flows with rigid structures. Among the many numerical models available, the Smoothed Particle Hydrodynamics (SPH) has been chosen as it proved appropriate in dealing with violent free-surface flows. Due to its Lagrangian and meshless character it can naturally handle breaking waves and fragmentation that generally are not easily treated by standard methods. On the other hand, some consolidated features of mesh-based methods, such as the solid boundary treatment, still remain unsolved issues in the SPH context. In the present work a great part of the research activity has been devoted to tackle some of the bottlenecks of the method. Firstly, an enhanced SPH model, called delta-SPH, has been proposed. In this model, a proper numerical diffusive term has been added in the continuity equation in order to remove the spurious numerical noise in the pressure field which typically affects the weakly-compressible SPH models. Then, particular attention has been paid to the development of suitable techniques for the enforcement of the boundary conditions. As for the free-surface, a specific algorithm has been designed to detect free-surface particles and to define a related level-set function with two main targets: to allow the imposition of peculiar conditions on the free-surface and to analyse and visualize more easily the simulation outcome (especially in 3D cases). Concerning the solid boundary treatment, much effort has been spent to devise new techniques for handling generic body geometries with an adequate accuracy in both 2D and 3D problems. Two different techniques have been described: in the first one the standard ghost fluid method has been extended in order to treat complex solid geometries. Both free-slip and no-slip boundary conditions have been implemented, the latter being a quite complex matter in the SPH context. The proposed boundary treatment proved to be robust and accurate in evaluating local and global loads, though it is not easy to extend to generic 3D surfaces. The second technique has been adopted for these cases. Such a technique has been developed in the context of Riemann-SPH methods and in the present work is reformulated in the context of the standard SPH scheme. The method proved to be robust in treating complex 3D solid surfaces though less accurate than the former. Finally, an algorithm to correctly initialize the SPH simulation in the case of generic geometries has been described. It forces a resettlement of the fluid particles to achieve a regular and uniform spacing even in complex configurations. This pre-processing procedure avoids the generation of spurious currents due to local defects in the particle distribution at the beginning of the simulation. The delta-SPH model has been validated against several problems concerning fluid-structure interactions. Firstly, the capability of the solver in dealing with water impacts has been tested by simulating a jet impinging on a flat plate and a dam-break flow against a vertical wall. In this cases, the accuracy in the prediction of local loads and of the pressure field have been the main focus. Then, the viscous flow around a cylinder, in both steady and unsteady conditions, has been simulated comparing the results with reference solutions. Finally, the generation and propagation of 2D gravity waves has been simulated. Several regimes of propagation have been tested and the results compared against a potential flow solver. The developed numerical solver has been applied to several cases of free-surface flows striking rigid structures and to the problem of the generation and evolution of ship generated waves. In the former case, the robustness of the solver has been challenged by simulating 2D and 3D water impacts against complex solid surfaces. The numerical outcome have been compared with analytical solutions, experimental data and other numerical results and the limits of the model have been discussed. As for the ship generated waves, the problem has been firstly studied within the 2D+t approximation, focusing on the occurrence and features of the breaking bow waves. Then, a dedicated 3D SPH parallel solver has been developed to tackle the simulation of the entire ship in constant forward motion. This simulation is quite demanding in terms of complexities of the boundary geometry and computational resources required. The wave pattern obtained has been compared against experimental data and results from other numerical methods, showing in both the cases a fair and promising agreement.CNR-INSEA

    YEAST AS A MODEL FOR THE STUDY OF HUMAN p53

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    The p53 tumor suppressor gene is a major barrier against cancer, preventing tumor development and promotes apoptosis induced by chemotherapy. P53 is able to regulate apoptosis both through its transcriptional activity and by the induction of the outer mitochondrial membrane (OMM) permeabilization promoting the release of cytochrome c. In the yeast S. cerevisiae, the machinery of the basic apoptotic process seems to be conserved as it presents many of the cytological markers of apoptosis such as chromatin condensation, DNA fragmentation and the release of cytochrome c from mitochondria to the cytoplasm. It was recently reported that the expression of p53 in S. cerevisiae is able to activate the apoptotic processes, making this system a good model to analyze the basic mechanisms of apoptosis induced by p53. It was recently identified a novel mutation in p53, in which lysine 351 is replaced by an asparagine (K351N) in a cisplatin-resistant ovarian carcinoma cell line (A2780 CIS). The K351N mutation is associated with the acquisition of resistance to apoptosis induced by cis-platinum in this cell line. The K351N mutation significantly reduces the thermodynamic stability of p53 tetramers, the transcriptional activity of p53 and affects the export from the nucleus to the cytosol induced by cisplatinum treatment. The characterization of this mutant could thus help to envisage the development of new cancer drugs that can suppress this phenotype in tumors. We cloned the two human genes, p53 and its mutated form p53K351N, under the control of Gal1-Gal10 vector and we transformed them in both wild type and S. cerevisiae strains mutated in genes involved in the apoptotic response. We then analyzed the effect of the p53 expression during an apoptotic stimulus (H2O2) and during aging

    quale destino senza trattamento?

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    La patologia nodulare tiroidea è molto frequente (prevalenza nella popolazione generale 50% circa), ma spesso asintomatica. In letteratura, molti studi sono volti a valutare quale sia la terapia più adeguata per la gestione dei noduli stessi. Nel nostro studio abbiamo valutato se realmente ci sia la necessità di effettuare una terapia in caso di noduli tiroidei. Pertanto, abbiamo valutato la storia naturale dei noduli tiroidei citologicamente benigni (con particolare riguardo alla evoluzione volumetrica, mediante studio ecografico della morfologia tiroidea), e abbiamo verificato l’influenza sulla crescita dei noduli tiroidei da parte di fattori esogeni ed endogeni, nell’arco di 5 anni di follow-upTale studio è volto a valutare la storia naturale dei noduli tiroidei citologicamente benigni (con particolare riguardo alla evoluzione volumetrica, mediante studio ecografico della morfologia tiroidea), e a verificare l’influenza sulla crescita dei noduli tiroidei da parte di fattori esogeni ed endogeni, nell’arco di 5 anni di follow-upRicerca indipendent

    High frequency GPS as a potential contribution for monitoring a seismogenic structure

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    The Global Positioning System (GPS) has become an essential complement to seismic instruments for seismological studies because of its high precision, its easy of deployment and its ability to make measurements of displacement that are local to global in scale. Although several studies have demonstrated the fundamental rule of GPS in monitoring deformation associated with earthquakes [Larson et al.,2003; Bock et al.,2004; Larson, 2009; Yokota et al., 2009], its potential use for Seismology has not been fully investigated. This dissertation addresses the use of GPS for earthquake studies from two different directions - understanding and taking advantages of the increasing sample rate of GPS data - understanding and taking advantages of the availability of low-latency ancillary products (orbit and clock estimates) provided by different public organizations. The access to GPS data with increasing sample rate represents an important source because data at high frequencies allow to detect more details about the kinematic processes. In this area, we considered 10 Hz GPS data acquired from two sites located just on the activated fault ("near-source"), during the Mw 6.3 L'Aquila earthquake. The comparison between GPS and strong motion time series along with their frequency contents, con firms, on the one hand, the GPS capability to detect the rst seismic arrivals (P waves) and, on the other hand, the need of GPS sampling rates greater than 2.5 Hz (i.e. 5 or 10Hz) in the near eld of moderate-magnitude events to provide "alias-free" solutions of coseismic dynamic displacements. These displacements are very useful to constrain the kinematic rupture history of the main shock[Avallone et al., 2011]. Besides high-rate data, we used also lower frequency data of both L'Aquila and 2010 Chile event, to exploit the potential use of publicly available products for the estimation of mean coseismic displacements in the shortest time following an earthquake. By using JPL Ultra-Rapid orbits and clocks, a static coseismic displacement (5 minute solution) can be retrieved within about few hours after an earthquake. Instead, JPL Rapid products which also include high-rate 30-second clock estimates (starting from August 2011) make possible the detection of dynamic coseismic displacements (30 s and lower solution) within about 1 day after an earthquake

    LA CONCORRENZA FISCALE DANNOSA

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    Neuropathic pain in neuropathy:A combined clinical, neurophysiological and morphological study

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    Neuropathic pain (NP) is a major symptom which may be intractable in common neurological disorders such as neuropathy, spinal cord injury, multiple sclerosis and stroke. Pain is a complex sensation strongly modulated by cognitive influences, and understanding the underlying pathophysiological mechanisms in patients remains a challenge for pain specialists. The aim of my Phd-research was to show in according with present evidence-based studies the correlation between clinical manifestations of neuropathic pain and the underlying alteration of the different groups of fibers (Aβ, Aδ or C). In the second chapter I revised the previous guidelines about neuropathic pain assessment. History and clinical examination are a requirement to confirm the presence of a NP, and also an important step in reaching an aetiological diagnosis for NP. History and bedside examination are still fundamental to a correct diagnosis, while screening tools and questionnaires are useful in indicating probable NP. I argued in particular a recent technique, skin biopsy; I approached it at the beginning of my Phd during my stage at the I.R.C.S.S. C. Besta in Milan; then, I imported this procedure in our laboratory (Department of Pathological Anatomy, Sapienza University). We are now able to process skin biopsies and immunoassayed them with polyclonal anti-protein-gene-product 9.5 antibodies (specific for nerve fibers) using immunohistochemistry or immunofluorescence, which allowed demonstrating the extensive innervations of the epidermidis. In the following chapters I approached some common conditions of neuropathic pain. The third chapter is dedicated to the post-herpetic neuralgia, an exceptionally drug-resistant neuropathic pain. To investigate the pathophysiological mechanisms underlying postherpetic neuralgia we clinically investigated sensory disturbances, pains and itching, with an 11-point numerical rating scale in 41 patients with ophthalmic postherpetic neuralgia. In all the patients we recorded the blink reflex, mediated by non-nociceptive myelinated Aβ-fibers, and trigeminal laser evoked potentials (LEPs) related to nociceptive myelinated Aδ- and unmyelinated C-fiber activation. We also sought possible correlations between clinical sensory disturbances and neurophysiological data. Neurophysiological testing yielded significantly abnormal responses on the affected side compared with the normal side. The blink reflex delay correlated with the intensity of paroxysmal pain, whereas the Aδ- and C-LEP amplitude reduction correlated with the intensity of constant pain . Allodynia correlated with none of the neurophysiological data. Our study shows that postherpetic neuralgia impairs all sensory fiber groups. The neurophysiological-clinical correlations suggest that constant pain arises from a marked loss of nociceptive afferents, whereas paroxysmal pain is related to Aβ-fiber demyelination. These findings might be useful for a better understanding of pain mechanisms in postherpetic neuralgia. In the fourth chapter I treated the differential involvement of Aδ and Aβ fibers in neuropathic pain related to carpal tunnel syndrome (CTS). We studied 70 patients with a diagnosis of CTS (117 CTS hands). We used the DN4 questionnaire to select patients with neuropathic pain, and the Neuropathic Pain Symptom Inventory (NPSI) to assess the intensity of the various qualities of neuropathic pain. All patients underwent a standard nerve conduction study (NCS) to assess the function of non-nociceptive Aβ-fibres, and the cutaneous silent period (CSP) after stimulation of the IIIrd and Vth digits, to assess the function of nociceptive Aδ-fibres. In 40 patients (75 CTS hands) we also recorded LEPs in response to stimuli delivered to the median nerve territory and mediated by nociceptive Aδ-fibres. We sought possible correlations between neurophysiological data and the various qualities of neuropathic pain as assessed by the NPSI. We found that the median nerve sensory conduction velocity correlated with paroxysmal pain and abnormal sensations, whereas LEP amplitude correlated with spontaneous constant pain. Our findings suggest that whereas paroxysmal pain and abnormal sensations reflect demyelination of non-nociceptive Aβ-fibres, spontaneous constant pain arises from damage to nociceptive Aδ-fibres. In the fifth chapter I treated the mechanisms of pain in multiple sclerosis. In this clinical and neurophysiological study we sought information on the clinical characteristics and underlying mechanisms of neuropathic pain related to the disease. A total of 302 consecutive patients with multiple sclerosis were screened for neuropathic pain by clinical examination and the DN4 tool. In patients selected for having ongoing extremity pain or Lhermitte’s phenomenon, we recorded somatosensory evoked potentials, mediated by Aβ non-nociceptive fibres, and LEP, mediated by Aδ nociceptive fibres. Of the 302 patients, 92 had pain (30%), and 42 (14%) neuropathic pain. Patients with neuropathic pain had more severe multiple sclerosis, as assessed by the expanded disability severity score, than those without pain. Whereas in patients with ongoing neuropathic pain laser evoked potentials were more frequently abnormal than somatosensory evoked potentials we found the opposite in patients with Lhermitte’s phenomenon. Our data underline the clinical importance of pain in multiple sclerosis and indicate that a more severe disease is associated with a higher risk of developing neuropathic pain. The prevalence of pain we found, lower than that reported in previous studies, may reflect the lower disease severity in our patients. Neurophysiological data show that whereas ongoing extremity pain is associated with spinothalamic pathway damage, Lhermitte’s phenomenon is related to damage of non-nociceptive pathways. These findings may be useful in designing a new therapeutic approach to neuropathic pain related to multiple sclerosis. The sixth chapter is dedicated to the mechanisms of pain in distal symmetric neuropathy. I and my colleagues performed a clinical, neurophysiological and histomorphological study on patients with neuropathic pain in distal symmetric neuropathy. In patients with distal symmetric polyneuropathy we assessed non-nociceptive Aβ- and nociceptive Aδ- and C-afferents to investigate their role in the development of neuropathic pain. We screened 2240 consecutive patients with sensory disturbances and collected 269 patients with distal symmetric polyneuropathy (57% with pain and 43% without). All patients underwent the Neuropathic Pain Symptom Inventory to rate ongoing, paroxysmal and provoked pains, a standard NCS to assess Aβ-fibre function, LEPs to assess Aδ-fibre function, and skin biopsy to assess the unmyelinated innervations of the epidermidis. Patients with pain had the same age, but a longer delay since symptom onset than those without . Loss of intraepidermal innervation did not correlate with the presence of neuropathic pain. Whereas the LEP amplitude was significantly lower in patients with pain than in those without , NCS and intraepidermal fibre nerves data did not differ between groups. LEPs were more severely affected in patients with ongoing pain than in those with provoked pain. Our findings indicate that the impairment of Aβ-fibres has no role in the development of ongoing or provoked pain. In patients with ongoing pain the severe LEP suppression and the correlation between pain intensity and LEP attenuation may indicate that this type of pain reflects damage to nociceptive axons. The partially preserved LEPs in patients with provoked pain suggest that thistype of pain is related to the abnormal activity arising from partially spared and sensitised nociceptive terminals. Because clinical and neurophysiological abnormalities followed similar patterns regardless of aetiology, pain should be classified and treated on mechanism-based grounds. In the seventh chapter I treated the mechanisms of allodynia in distal symmetric polyneuropathy allodynia. Patients with painful neuropathy frequently complain of allodynia, i.e. pain in response to a normally non-painful stimulus. Many authors consider allodynia to be generated by sensitization of the second-order nociceptive neurons to Aβ-fibre input (central sensitization). With the hypothesis that patients suffering from this type of pain probably have a relative sparing of Aβ-fibres in comparison with patients with ongoing pain only, we sought aimed at seeking information on mechanisms underlying allodynia. In 200 patients with distal symmetric polyneuropathy (114 with pain, 86 without) we assessed non-nociceptive Aβ- and nociceptive Aδ-afferents to investigate their role in the development of allodynia. After a detailed clinical examination and pain questionnaires patients underwent a standard nerve conduction study (NCS) to assess Aβ-fibre function, and LEPs to assess Aδ-fibre function. Forthy-four out of 114 patients with painful neuropathy suffered from allodynia. While NCS data did not differ between patients with and without allodynia, LEP amplitude was higher in patients with allodynia than in those without. Our data argue against a role of Aβ-fibres and central sensitization as the main mechanism for the development of allodynia in distal symmetric polyneuropathy. The partially preserved LEPs in patients with allodynia suggests that this type of pain might be related to the abnormal reduction of mechanical threshold of nociceptive terminals (peripheral sensitization). In the eighth chapter I treated neuropathic pain in patient with crioglobulinemia. The study aimed at gaining information on peripheral neuropathy and neuropathic pain in patients with cryoglobulinaemia. We collected 48 consecutive patients with cryoglobulinaemia. All patients underwent a standard NCS to assess A-fibre function, LEPs to assess A-fibre function, and skin biopsy to assess C-fibre terminals. We used DN4 questionnaire to diagnose neuropathic pain, and the Neuropathic Pain Symptom Inventory to rate the intensity of the different qualities of neuropathic pain. Thirty patients had a peripheral neuropathy. Twenty-three had neuropathic pain as assessed by the DN4 questionnaire. NPSI questionnaire showed that the most frequent type of pain was the burning pain. Patients with peripheral neuropathy had an older age than those without . The duration of the disease correlated with the density of epidermal innervation as assessed by skin biopsy. The severity of the ongoing burning pain correlated with the amplitude of LEPs, but not with the density of epidermal innervation . Our findings showed that an older age is associated with the development of peripheral neuropathy, and a longer duration of disease with a more severe peripheral nerve damage, as assessed by skin biopsy. The correlation between the intensity of ongoing pain and LEP attenuation indicate that neuropathic pain reflects damage to nociceptive axons. In the ninth chapter I discussed the research on a peptide, the kiss-peptine, whose antagonist could be a new analgesic drug. More studies should be perform in the next future about it . Kisspeptin is a neuropeptide known for its role in the hypothalamic regulation of the reproductive axis. Following the recent description of kisspeptin and its 7-TM receptor, GPR54, in the dorsal root ganglia and dorsal horns of the spinal cord, we examined the role of kisspeptin in the regulation of pain sensitivity in mice. Immunofluorescent staining in the mouse skin showed the presence of GPR54 receptors in PGP9.5-positive sensory fibers. Intraplantar injection of kisspeptin (1 or 3 nmol/5 μl) induced a small nocifensive response in naive mice, and lowered thermal pain threshold in the hot plate test. Both intraplantar and intrathecal (0.5 or 1 nmol/3 μl) injection of kisspeptin caused hyperalgesia in the first and second phases of the formalin test, whereas the GPR54 antagonist, p234 (0.1 or 1 nmol), caused a robust analgesia. Intraplantar injection of kisspeptin combined with formalin enhanced TRPV1 phosphorylation at Ser800 at the injection site, and increased ERK1/2 phosphorylation in the ipsilateral dorsal horn as compared to naive mice and mice treated with formalin alone. These data demonstrate for the first time that kisspeptin regulates pain sensitivity in rodents and suggest that peripheral GPR54 receptors could be targeted by novel drugs in the treatment of inflammatory pain. In the tenth last chapter I gathered all the conclusion of the single studies. Here I tried to associate each quality of pain to an underling pathophysiological alteration, since the aim of y studies was to show the correlation between clinical manifestations of neuropathic pain and the underlying alteration of the different groups of fibers (A-β, A-δ or C)

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    Pubblicazioni Aperte Digitali Interateneo Sapienza
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