University of Cagliari

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    Valutazione della vulnerabilità delle coste della Sardegna a fenomeni di erosione ed inondazione dovuti all'impatto degli eventi estremi meteo-marini

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    The main goal of this work is to provide a regional assessment of the coastal vulnerability of Sardinian sandy beaches to storm impacts. To do this we have assessed the geomorphic coastal vulnerability taking into account the intensity of storm induced hazards and the adaptation capacity of the system. The methodology aplied allows to calculate quantitatively -in a separate manner- the erosion and inundation hazards induced by the storms associated to a given probability of occurrence. The practical application of this method is to provide information that allows stakeholders to manage resource allocation and mitigate consequences. This framework has been developed by covering the following steps:(i). Define forcing conditions for the Sardinian coast using a storm classification method; to obtain this we have divided the Sardinian coast in 4 different sectors. For each sector storm events have been defined from hindcast wave data obtained for the period between 1979-2012. (ii) Find out the induced beach response to each storm class measured by the quantification of the flooding and erosion hazards. In each sector sandy beaches have been characterized in terms of their slope, height, widht and grain size. (iii) Estimation of a coastal vulnerability index formulated in terms of these two intermediate variables by means of a linear function that ranges from a minimum value of 0 (optimum state) to a maximum of 1 (failure state), defining 5 qualitative categories (Very Low, Low,. Medium, High, Very High). (iv) Assessment and mapping of the coastal vulnerability index along different sectors of the island. In terms of prospective analysis we have built a projected timeline of beach hazard based on existing storm data fitted into an extreme probability function. Once the probability of occurrence of the flooding and erosion hazards has been assessed and a risk level defined by the stakeholders, the spatial distribution of vulnerabilities associated to selected probability level will permit to "robustly" compare areas along the coast to identify the most endangered zones

    Ruolo della TDP-43 nella formazione dei granuli da stress nella Sclerosi Laterale Amiotrofica

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    Amyotrophic Lateral Sclerosis (ALS) is a late-onset neurodegenerative disease characterized by the selective loss of upper and lower motor neurons; most ALS cases are sporadic, and only 5-10% are familial. About 4% of familial cases, are due to mutations in TARDBP, the gene encoding TDP-43, that is an ubiquitous nuclear protein that regulates mRNA functions and metabolism. Recent studies suggest that TDP-43 may regulates stress granules dynamics that are cytoplasmic structures composed of non-translating messenger ribonucleoproteins (mRNPs) that rapidly aggregate in cells exposed to adverse environmental conditions. Stress granules function in part to triage RNA and sequester transcripts not needed for coping with the stress. We evaluated stress granule dynamics in primary fibroblast cultures from skin of ALS patients carriying TARDBPA382T mutation, ALS patients without any TARDBP mutation and healthy controls. After treatment with sodium arsenite (0,5 mM), for 30 and 60 minutes, we observed a significantly higher number of cells exhibiting stress granules, identified by immunostaining for specific markers (TIA-1 and HuR), in fibroblasts from healthy controls compare with those from ALS patients carriying TARDBPA382T mutation. Moreover, fibroblasts from healthy controls showed more stress granules per cell compare with those from ALS patients, while no differences were observed in stress granule size between groups. Fibroblasts from ALS patients without any TARDBP mutation, showed the same ability to form stress granules as cells from healthy controls, confirming that the decrease was associated to TARDBPA382T mutation rather than other factors attributable to ALS. In all samples analyzed TDP-43 immunostaining was always observed into the nucleus of all the cells and even after sodium arsenite treatment TDP-43 was never localized in stress granules. The involvement of TDP-43 in stress granule assembly was confirmed by silencing TARDBP gene in fibroblasts from healthy controls. After sodium arsenite treatment, fibroblasts in wich TARDBP gene was silenced, showed a significantly lower number of cells exhibiting stress granules compare with unsilenced controls. Following stress stimuli, we observed, using MTT assay, a significant higher cytotoxicity in fibroblasts from patients carriying TARDBPA382T mutation compare with healthy controls. Expression of G3BP, a core stress granule component, was significantly lower after sodium arsenite treatment in fibroblasts from patients carriying TARDBPA382T mutation compare with healthy controls. We can conclude that TARDBPA382T mutation caused a reduction in the ability of human fibroblasts to respond to stress through loss of TDP-43 function in stress granule nucleation. The pathogenetic action revealed in our study model does not seem to be mediated by changes in the localization of the TDP-43 protein, but we found that this protein contributes to stress granule formation through a regulatory effect on the G3BP core protein. These data demonstrate that TDP-43 may modulate stress granule formation contributing to the cellular response to acute stress and suggest that TARDBPA382T mutation may compromise the cellular stress response, contributing to neuronal vulnerability in ALS

    Nuove osservazioni sulla biomeccanica dell’uretere umano

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    The function of ureter is to transport the urine from the kidney to the urinary bladder. Ureteral peristalsis, the principal motor event that propels urine along the ureter, is the result of coordinated contractions of longitudinal and circular smooth muscle inside the organ wall. Alterations of static and dynamic biomechanical properties of the ureteral wall lead to pathological states compromising regular urine transportation to bladder. Although knowledge on ureteral motility has advanced considerably, the molecular contractile mechanism of ureteral smooth muscle cells is not fully understood. This study provides information about baseline mechanical properties of the entire muscle and the molecular contractile mechanism in human ureter smooth muscle and proposed to investigate if changes in mechanical motor performance in different regions of isolated human ureter are attributable to differences in myosin crossbridge interactions. Classic mechanical, kinetic and energetic parameters derived from the tension-velocity relationship were studied in ureteral smooth muscle strips oriented longitudinally and circularly from abdominal and pelvic human ureter parts. By applying of Huxley’s mathematical model we calculated the total working crossbridge number per mm2 (Ψ), elementary force per single crossbridge (Π0), duration of maximum rate constant of crossbridge attachment 1/f1 and detachment 1/g2 and peak mechanical efficiency (Eff.max). Although no substantial differences exist in structural, biochemical and histological characteristics along the human ureter, abdominal longitudinal smooth muscle strips showed a higher maximum isometric tension, greater shortening, faster shortening velocity and higher maximum peak of work and power output than pelvic ones. Contractile differences were associated with significantly higher crossbridge number per mm2. Abdominal longitudinal muscle strips showed a lower duration of maximum rate constant of crossbridge attachment and detachment and higher peak mechanical efficiency than pelvic ones. Such data suggest that the abdominal human ureter exhibited better mechanical motor performance than pelvic ureter, mainly related to a higher crossbridge number and crossbridge kinetics differences. We believe that our results will be useful to understand better the physiology and physiopathology of ureteral smooth muscle, as well as improving the evaluation of pharmacological and surgical therapies in particular clinical cases

    I negozi collegati nel diritto societario

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    The aim of the research is to analyse the connections between agreements under Company law and the study of legal consequences of such bonds. The research is organized in three main sections. The first part is dedicated to reconstruct the theories of linked contracts and economic operations. It emerges the tendency of the legislator to legislate hypothesis of linked contracts in Business Law in order to achieve more certainty in business transactions. The second section is concentrated over hypothesis of linked contracts in Company Law provided by the legislature. It is therefore analysed the relationship between Company’s Agreements and Shareholders' Agreements, the relationship between Cooperative’s Agreement and Agreements with its own shareholders, the leveraged buy-out operations, the regulation of funding in relation to a specific transaction and the payment for share capital secured in Limited Liability Partnerships (In Italian Company's Law defined as «società a responsabilità limitata»). The third part concentrates on the analysis of a series of court judgements regarding hypothesis of linked contracts created pursuant to the power of autonomy of the parties: the connection between a Company’s Agreement and the agreement to sell a property to the same company; the connection between a Company’s Agreement and a contract between the company and his own shareholder; the connection between a Company’s Agreement and the stipulation of a shared property agreement with a shareholder. The analysis proceeds by focusing on three situations in which the connection is set up in a way to circumvent the law: in the first it is violated the rule to protect the integrity of the share capital, in the second the proper fulfilment of taxes and in the third one the pre-emption clause. The conclusions point out the characteristics of linked contracts in Company Law

    Valutazione della funzione cardiaca nei pazienti affetti da Atassia di Friedreich: studio con Tissue Doppler Imaging e Speckle Tracking Echocardiography

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    Background. Friedreich ataxia (FRDA) is an autosomal recessive degenerative disease characterized by progressive gait and limb ataxia, hypertrophic cardiomyopathy, diabetes and sensory neuropathy. Large GAA repeat expansions in the first intron of the frataxin gene are the most common mutation underlying FRDA. This mutation results in intramitochondrial iron accumulation and oxidative stress increase. FRDA is associated with progressive cardiac hypertrophy; however, subclinical left ventricular (LV) dysfunction may occur in FRDA patients in spite of normal LV ejection fraction (LVEF) and mass. Moreover cardiac sudden death is the most common cause of exitus in these patients. Methods. We enrolled 5 FRDA patients (age: 39.8 ± 19.05 years; 2F and 3M) free of cardiovascular risk factors and 5 sex- and age-matched healthy subjects (age 32.75 ± 6.22 years); they underwent to clinical evaluation, standard echocardiography with Tissue Doppler, 2D and 3D Speckle Tracking. Results. No significant differences were identified in terms of anthropometric characteristics and cardiovascular risk profile between the two groups. All echocardiographic standard parameters, including LV dimensions, LV mass, LVEF and E/E’ ratio resulted in the normal range, in absence of significant differences between patients and healthy subjects. On the other hand, we found a reduction in Global Longitudinal Strain (GLS; 10.93 ± 1.72 % vs 15.92 ± 1.17%, p= 0.003), as already reported in literature. Moreover we compared values of longitudinal strain of LV basal and apical segments between the two groups, thus identifying a significant impairment of apical regions in FRDA patients (10.12 ± 3.48 % vs 18.7 ± 2.57, p =0.02). Conclusions. Our data seem to suggest that the observed reduction in GLS could be due to a segmental impairment of systolic function at apical level. This finding could be explained by the sympathetic denervation reported in other forms of neurodegenerative disorders, such Parkinson’s disease and Multiple sclerosis

    Use of local available material for inverted pavement technique

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    This research has the purpose to build infrastructures by using new techniques, new materials and to start a sustainable design with the utilization of local resources. The project also aims to minimize the use of non-renewable sources as hot mix asphalt. Concerning the materials, it is particularly highlighted the use of stone materials available in the Region of Sardinia, currently extracted to create infrastructures and bitumen layers. New techniques have been studied to build up infrastructures such as the Inverted Pavement Technique used in South Africa for more than 30 years. In particular we focused on the realization of the G1 Layer for this paving. Through this work, we are willing to determine the possible use of the materials present in Sardinia to build Inverted Pavement infrastructure. The target is to better use the local obtainable resources in terms of aggregates, trying to make the most of their mechanical and physical features. During the research, a great attention was focused on the illustration of different typologies of paving currently used in Europe and in South Africa, specially those realized through base layers with granular material, examining in depth the anisotropic property of granular bases too. A panoramic of the property of road construction material used in South Africa is presented, by analyzing the issues linked to the type of minerals that are in the rocks and the way through which they affect the resistance and durability of one layer of the paving. In the first phase of the study, we concentrated on the specification of the kinds of materials mined in Sardinia and their location. Then, we chose to investigate about the following materials: andesite, basalt, quartzite, trachite, dolomite and ignimbrite. All these are materials with good features such as mechanical endurance and durability. An in-depth bibliographic research was done about the 'Inverted Pavement’ technique for understanding the behavior of this type of paving during the useful life, compared to a traditional paving. The building technique of the G1 layer was mainly examined, because some phases, such as that called "slushing", are considered complex and the main point for the good result of layer and the whole superstructure. To make sure the material is suitable, we referred to South-African regulations and we carried all the mechanical tests foreseen to categorize it as G1. Chemical analyses and thin sections were analyzed, because they are considered preliminary characterizations on the study of materials. Some triaxial tests were performed with several confining pressures to define the elastic modulus and other strength parameters.Anyway it is not enough to comparison chemistry and petrography to establish that a material is suitable. For this reason, were done other physical-mechanical laboratory tests. Two test sections of Inverted Pavements realized in Atlanta, using granite, were examined and were done some laboratory tests on material. From the monitoring of these two test sections and from the result of tests, it emerged that Inverted pavement has performances greater than conventional paving and that other kinds of materials can be used for realization

    Segni e colori nel telaio del tempo: tracce, luce e materia nella policromia della Sardegna. Contributo alla conoscenza e conservazione di dipinti murali romani e medievali

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    This research project, starting from the lack of information of the wall paintings technique in Sardinia, has reconstructed the pictorial palette and the artistic techniques used in the late Roman and medieval times. An integrated analytical protocol (XRD, μATR-FTIR, SEM-EDS) was carried out in order to characterize pigments, binders, degradation and restoration products. The roman wall paintings technique in hypogeum environments in Cagliari widely used a proteinaceous material as additive, so that they cannot be considered made with a fresco technique. Egyptian Blue, red, yellow and green earths have been detected. The stratigraphic observation has revealed the presence of a tonal foundation for the drafting of Egyptian Blue, red and yellow earths. Undocumented restorations have been discovered. It is conceivable that in medieval wall painting technique in Sardinia lime and an organic material as binder were employed. The hypothesis that a proteinaceous material, such as casein, now totally mineralized, would have given origin to a widespread presence of calcium oxalate in the pictorial stratigraphy has been advanced. Lapis, red, yellow and green earths have been detected. It is not excluded that the investigated wall paintings lost the finishing layers because of detachments or excessive cleanings in restorations. A tonal foundation for Lapis and green earth has been detected as well as the presence of restoration products; compatibly with the restoration reports acrylic resins could have been used. The research project also investigated the colour system as a potential strain of a new discipline, the "symbolic History", in order to investigate how the perception of colours in a given historical period has been reflected in pictorial techniques, in the choice of the colours and pigments influencing the material consistency of the wall paintings. As a final point, the thesis deepened the mechanisms and tools of the collaborative knowledge as opportunity to review the polychrome apparatuses according to this new perspective. This research project is therefore designed as an analytical investigation on polychromy and wall painting techniques used in Roman and medieval times in Sardinia, in a vision that transcends the purely analytical methodology in order share and expand the knowledge to the general public and in the scientific community

    Design, synthesis and SAR of small molecules acting on pain pathways

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    Pain is a pathological disease that constitutes one of the most important problems of public health. Epidemiological studies showed that about 20% of the Europe population is affected by moderate or chronic pain. This data highlighted the gigantic impact of this problem not only in the suffering people but also in term of costs for public health. The classes of drugs most used today in the treatment of pain are NSAIDs and opioids. Unfortunately, both have important side effects specially when used in chronic treatment. Therefore, the research of new drugs which exploiting new targets that have an analgesic effect without the side effects is important. This thesis describes the design, synthesis and biological activity of compounds which have potential analgesic activity by their action on three different pathways involved in pain information transmission. 1. The first class of compounds, are amide derivatives of the principal NSAIDs or correlated molecules, they are designed to be able to interact with the endocannabinoid system. In particular, described compounds were designed and tested as inhibitors of FAAH, the principal enzyme involved on the metabolization of endocannabinoids. The aim was to cause an increase of the endocannabinoids concentration which leads to analgesic effect by the potentiation of the endocannabinoid tone. Some of the studied compounds showed inhibitory activity against FAAH at micromolar to nanomolar concentrations. 2. The second class of compounds were designed to interact with prokineticin system. Numerous studies highlighted the involvement of this system in different physiological processes including nociception. Activation of these receptors on the neurons on the pain pathways produces hyperalgesic effects. Therefore, the development of prokineticin receptor antagonists could be a new strategy for pain therapy. Compounds described in this thesis are endowed with triazinedione structure. A new synthetic procedure was set up allowing yields up to 50% higher than reported for analogue compounds. The triazinediones showed in vivo Design, synthesis and SAR of small molecules acting on pain pathways analgesic activity at picomolar concentrations and demonstrated antagonistic activity on prokineticin receptors. 3. The third target on which the compounds reported in this thesis act is the channel-receptor TRPV1, which is an important component of pain information transmission pathways. TRPV1 opening causes an influx of positive ions inside the cell that lead to its depolarization and consequent propagation of the information on the upper levels. In this case then the block of this channel with antagonist or molecules that cause receptor desensitization could result in an analgesic effect. The above mentioned triazinediones demonstrated a modulatory activity component against TRPV1 receptor, which may explain at least in part their in vivo analgesic activity

    L’immigrazione meridionale a Torino nell’Italia del miracolo economico. Il caso della Sardegna durante la stagione della Rinascita

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    Southern immigration in Turin in Italy in the economic miracle. The case of Sardinia during the season of Rinascita. The aims of this work to analyze the Italian migration phenomenon during the 1950s and 1960s of the twentieth century. Italian emigration was a social phenomenon of great importance in the Italian society and the analysis of the history of migration in its various economic, social and political, he joined the Italian national history. It is a known fact that Italy was a nation of great emigration from the nineteenth century to the present day and therefore in the following work I have tried to reconstruct the history of Italian emigration during the second world war. This topic is devoted the first chapter of this work. At the end of World War II, Italy was a poor and agricultural nation and the lack of jobs pushed the Italians to emigrate to Europe and northern Italy to obtain better living conditions. The emigration of Italian workers was at the base of Italian foreign policy and the President of the Italian Government Alcide De Gasperi, who shook economic agreements with European countries to encourage the emigration of the Italian workforce. After the catastrophe of Marcinelle the emigration to northern Italy (more precisely to the city of Turin) represented an important alternative to emigration to Europe. Immigration to the city of Turin is dedicated the second chapter of this work. The city of Turin during the fifties and sixties of the twentieth century was hit by a large flow of migrants coming from southern Italy. Italians from southern Italy went to Turin to look for a job, a home and a better future. With immigration in Turin were born numerous problems: immigrants were living in old houses in the historic center of Turin, were heavy jobs that did not guarantee good living conditions, also the relationship between Italians from southern Italy and the Turin population were very difficult. After analyzing the Southern Italian Immigration in Turin, in the third chapter of this work, I have tried to describe the events and stories of the many Sardinian arrived in Turin during the fifties and sixties of the twentieth century to look for a job and better living conditions. The Sardinians in Turin managed to integrate into the city and were praised for their qualities of honesty, hard work, seriousness and for their intellectual abilities

    Morpho-colorimetric and non-parametric analysis in statistical classification of vascular flora

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    This dissertation concerns the task of classifying objects by methods of morpho-colorimetric and non-parametric statistical analysis. The study can be applied in botany where manual classification of seeds is still a common practice. It is labor-intensive, subjective, and suffers from contradiction, as well as it is a time-consuming task even for highly specialized botanists. Starting from this problem, automated, consistent, and efficient algorithms of classification of seeds have been developed allowing the researcher to have a valid support for reducing drastically time for classification and, at the same time, an exploratory tool that detects latent patterns in data that human eye cannot identify. Firstly an approach called Background Subtraction, that enhances the quality of segmentation process output of an image, has been proposed. From RGB images it allows to get more precise binary images which need of a reduced intervention of manual correction. Then for each object data concern size, texture, color and shape have been extracted. These have been used as input for classification process, in which four classifiers have been performed: Linear Discriminant Analysis (LDA), Classification And Regression Trees (CART), Support Vector Machines (SVM) and Naïve Bayes (NB). In order to enhance the classification accuracy an approach of classifier combination, indicated as CA, has been developed. It consists in spliting the complex problem of classifying among D classes into D−1 sub problems less complex than the original one, each of them classifying between only two classes. Combining the four classifiers considered, CA allowed to reduce of 25% the misclassification error obtained by the best of the four classifiers. Finally, approach aimed at evaluating the reliability of a classification rule has been proposed. The algorithms proposed are developed and optimized for botanical seeds, but they are suitable to a larger class of morphological classification problems. In order to make these algorithms usable and executable, functions have been created in R language and published

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