11 resultados para Cathepsin L-like

em AMS Tesi di Dottorato - Alm@DL - Università di Bologna


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The cathepsin enzymes represent an important family of lysosomal proteinases with a broad spectrum of functions in many, if not in all, tissues and cell types. In addition to their primary role during the normal protein turnover, they possess highly specific proteolytic activities, including antigen processing in the immune response and a direct role in the development of obesity and tumours. In pigs, the involvement of cathepsin enzymes in proteolytic processes have important effects during the conversion of muscle to meat, due to their influence on meat texture and sensory characteristics, mainly in seasoned products. Their contribution is fundamental in flavour development of dry-curing hams. However, several authors have demonstrated that high cathepsin activity, in particular of cathepsin B, is correlated to defects of these products, such as an excessive meat softness together with abnormal free tyrosine content, astringent or metallic aftertastes and formation of a white film on the cut surface. Thus, investigation of their genetic variability could be useful to identify DNA markers associated with these dry cured hams parameters, but also with meat quality, production and carcass traits in Italian heavy pigs. Unfortunately, no association has been found between cathepsin markers and meat quality traits so far, in particular with cathepsin B activity, suggesting that other genes, besides these, affect meat quality parameters. Nevertheless, significant associations were observed with several carcass and production traits in pigs. A recent study has demonstrated that different single nucleotide polymorphisms (SNPs) localized in cathepsin D (CTSD), F (CTSF), H and Z genes were highly associated with growth, fat deposition and production traits in an Italian Large White pig population. The aim of this thesis was to confirm some of these results in other pig populations and identify new cathepsin markers in order to evaluate their effects on cathepsin activity and other production traits. Furthermore, starting from the data obtained in previous studies on CTSD gene, we also analyzed the known polymorphism located in the insulin-like growth factor 2 gene (IGF2 intron3-g.3072G>A). This marker is considered the causative mutation for the quantitative trait loci (QTL) affecting muscle mass and fat deposition in pigs. Since IGF2 maps very close to CTSD on porcine chromosome (SSC) 2, we wanted to clarify if the effects of the CTSD marker were due to linkage disequilibrium with the IGF2 intron3-g.3072G>A mutation or not. In the first chapter, we reported the results from these two SSC2 gene markers. First of all, we evaluated the effects of the IGF2 intron3-g.3072G>A polymorphism in the Italian Large White breed, for which no previous studies have analysed this marker. Highly significant associations were identified with all estimated breeding values for production and carcass traits (P<0.00001), while no effects were observed for meat quality traits. Instead, the IGF2 intron3-g.3072G>A mutation did not show any associations with the analyzed traits in the Italian Duroc pigs, probably due to the low level of variability at this polymorphic site for this breed. In the same Duroc pig population, significant associations were obtained for the CTSD marker for all production and carcass traits (P < 0.001), after excluding possible confounding effects of the IGF2 mutation. The effects of the CTSD g.70G>A polymorphism were also confirmed in a group of Italian Large White pigs homozygous for the IGF2 intron3-g.3072G allele G (IGF2 intron3-g.3072GG) and by haplotype analysis between the markers of the two considered genes. Taken together, all these data indicated that the IGF2 intron3-g.3072G>A mutation is not the only polymorphism affecting fatness and muscle deposition in pigs. In the second chapter, we reported the analysis of two new SNPs identified in cathepsin L (CTSL) and cathepsin S (CTSS) genes and the association results with meat quality parameters (including cathepsin B activity) and several production traits in an Italian Large White pig population. Allele frequencies of these two markers were evaluated in 7 different pig breeds. Furthermore, we mapped using a radiation hybrid panel the CTSS gene on SSC4. Association studies with several production traits, carried out in 268 Italian Large White pigs, indicated positive effects of the CTSL polymorphism on average daily gain, weight of lean cuts and backfat thickness (P<0.05). The results for these latter traits were also confirmed using a selective genotype approach in other Italian Large White pigs (P<0.01). In the 268 pig group, the CTSS polymorphism was associated with feed:gain ratio and average daily gain (P<0.05). Instead, no association was observed between the analysed markers and meat quality parameters. Finally, we wanted to verify if the positive results obtained for the cathepsin L and S markers and for other previous identified SNPs (cathepsin F, cathepsin Z and their inhibitor cystatin B) were confirmed in the Italian Duroc pig breed (third chapter). We analysed them in two groups of Duroc pigs: the first group was made of 218 performance-tested pigs not selected by any phenotypic criteria, the second group was made of 100 Italian Duroc pigs extreme and divergent for visible intermuscular fat trait. In the first group, the CTSL polymorphism was associated with weight of lean cuts (P<0.05), while suggestive associations were obtained for average daily gain and backfat thickness (P<0.10). Allele frequencies of the CTSL gene marker also differed positively among the visible intermuscular extreme tails. Instead, no positive effects were observed for the other DNA markers on the analysed traits. In conclusion, in agreement with the present data and for the biological role of these enzymes, the porcine CTSD and CTSL markers: a) may have a direct effect in the biological mechanisms involved in determining fat and lean meat content in pigs, or b) these markers could be very close to the putative functional mutation(s) present in other genes. These findings have important practical applications, in particular the CTSD and CTSL mutations could be applied in a marker assisted selection (MAS) both in the Italian Large White and Italian Duroc breeds. Marker assisted selection could also increase in efficiency by adding information from the cathepsin S genotype, but only in the Italian Large White breed.

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Reconstruction of bone is needed for high bone loss due to congenital deformities, trauma or neoplastic diseases. Commonly, orthopaedic surgical treatments are autologus or allogenic bone implant or prosthetic implant. A choice to the traditional approaches could be represented by tissue engineering that use cells (and/or their products) and innovative biomaterials to perform bone substitutes biologically active as an alternative to artificial devices. In the last years, there was a wide improvement in biology on stem cells potential research and in biomedical engineering through development of new biomaterials designed to resemble the physiological tissues. Tissue engineering strategies and smart materials aim together to stimulate in vivo bone regeneration. This approaches drive at restore not only structure integrity and/or function of the original tissue, but also to induce new tissue deposition in situ. An intelligent bone substitute is now designed like not only a scaffold but also as carrier of regeneration biomolecular signals. Biomimetics has helped to project new tissue engineered devices to simulate the physiological substrates architecture, such extracellular matrix (ECM), and molecular signals that drive the integration at the interface between pre-existing tissue and scaffold. Biomimetic strategies want to increase the material surface biological activity with physical modifications (topography) o chemical ones (adhesive peptides), to improve cell adhesion to material surface and possibly scaffold colonization. This study evaluated the effects of biomimetic modifications of surgical materials surface, as poly-caprolattone (PCL) and titanium on bone stem cells behaviour in a marrow experimental model in vitro. Two biomimetic strategies were analyzed; ione beam irradiation, that changes the surface roughness at the nanoscale, and surface functionalization with specific adhesive peptides or Self Assembled Monolayers (SAMs). These new concept could be a mean to improve the early (cell adhesion, spreading..) and late phases (osteoblast differentiation) of cell/substrate interactions.

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This study aims at analysing Brian O'Nolans literary production in the light of a reconsideration of the role played by his two most famous pseudonyms ,Flann Brien and Myles na Gopaleen, behind which he was active both as a novelist and as a journalist. We tried to establish a new kind of relationship between them and their empirical author following recent cultural and scientific surveys in the field of Humour Studies, Psychology, and Sociology: taking as a starting point the appreciation of the comic attitude in nature and in cultural history, we progressed through a short history of laughter and derision, followed by an overview on humour theories. After having established such a frame, we considered an integration of scientific studies in the field of laughter and humour as a base for our study scheme, in order to come to a definition of the comic author as a recognised, powerful and authoritative social figure who acts as a critic of conventions. The history of laughter and comic we briefly summarized, based on the one related by the French scholar Georges Minois in his work (Minois 2004), has been taken into account in the view that humorous attitude is one of man’s characteristic traits always present and witnessed throughout the ages, though subject in most cases to repression by cultural and political conservative power. This sort of Super-Ego notwithstanding, or perhaps because of that, comic impulse proved irreducible exactly in its influence on the current cultural debates. Basing mainly on Robert R. Provine’s (Provine 2001), Fabio Ceccarelli’s (Ceccarelli 1988), Arthur Koestler’s (Koestler 1975) and Peter L. Berger’s (Berger 1995) scientific essays on the actual occurrence of laughter and smile in complex social situations, we underlined the many evidences for how the use of comic, humour and wit (in a Freudian sense) could be best comprehended if seen as a common mind process designed for the improvement of knowledge, in which we traced a strict relation with the play-element the Dutch historian Huizinga highlighted in his famous essay, Homo Ludens (Huizinga 1955). We considered comic and humour/wit as different sides of the same coin, and showed how the demonstrations scientists provided on this particular subject are not conclusive, given that the mental processes could not still be irrefutably shown to be separated as regards graduations in comic expression and reception: in fact, different outputs in expressions might lead back to one and the same production process, following the general ‘Economy Rule’ of evolution; man is the only animal who lies, meaning with this that one feeling is not necessarily biuniquely associated with one and the same outward display, so human expressions are not validation proofs for feelings. Considering societies, we found that in nature they are all organized in more or less the same way, that is, in élites who govern over a community who, in turn, recognizes them as legitimate delegates for that task; we inferred from this the epistemological possibility for the existence of an added ruling figure alongside those political and religious: this figure being the comic, who is the person in charge of expressing true feelings towards given subjects of contention. Any community owns one, and his very peculiar status is validated by the fact that his place is within the community, living in it and speaking to it, but at the same time is outside it in the sense that his action focuses mainly on shedding light on ideas and objects placed out-side the boundaries of social convention: taboos, fears, sacred objects and finally culture are the favourite targets of the comic person’s arrow. This is the reason for the word a(rche)typical as applied to the comic figure in society: atypical in a sense, because unconventional and disrespectful of traditions, critical and never at ease with unblinkered respect of canons; archetypical, because the “village fool”, buffoon, jester or anyone in any kind of society who plays such roles, is an archetype in the Jungian sense, i.e. a personification of an irreducible side of human nature that everybody instinctively knows: a beginner of a tradition, the perfect type, what is most conventional of all and therefore the exact opposite of an atypical. There is an intrinsic necessity, we think, of such figures in societies, just like politicians and priests, who should play an elitist role in order to guide and rule not for their own benefit but for the good of the community. We are not naïve and do know that actual owners of power always tend to keep it indefinitely: the ‘social comic’ as a role of power has nonetheless the distinctive feature of being the only job whose tension is not towards stability. It has got in itself the rewarding permission of contradiction, for the very reason we exposed before that the comic must cast an eye both inside and outside society and his vision may be perforce not consistent, then it is satisfactory for the popularity that gives amongst readers and audience. Finally, the difference between governors, priests and comic figures is the seriousness of the first two (fundamentally monologic) and the merry contradiction of the third (essentially dialogic). MPs, mayors, bishops and pastors should always console, comfort and soothe popular mood in respect of the public convention; the comic has the opposite task of provoking, urging and irritating, accomplishing at the same time a sort of control of the soothing powers of society, keepers of the righteousness. In this view, the comic person assumes a paramount importance in the counterbalancing of power administration, whether in form of acting in public places or in written pieces which could circulate for private reading. At this point comes into question our Irish writer Brian O'Nolan(1911-1966), real name that stood behind the more famous masks of Flann O'Brien, novelist, author of At Swim-Two-Birds (1939), The Hard Life (1961), The Dalkey Archive (1964) and, posthumously, The Third Policeman (1967); and of Myles na Gopaleen, journalist, keeper for more than 25 years of the Cruiskeen Lawn column on The Irish Times (1940-1966), and author of the famous book-parody in Irish An Béal Bocht (1941), later translated in English as The Poor Mouth (1973). Brian O'Nolan, professional senior civil servant of the Republic, has never seen recognized his authorship in literary studies, since all of them concentrated on his alter egos Flann, Myles and some others he used for minor contributions. So far as we are concerned, we think this is the first study which places the real name in the title, this way acknowledging him an unity of intents that no-one before did. And this choice in titling is not a mere mark of distinction for the sake of it, but also a wilful sign of how his opus should now be reconsidered. In effect, the aim of this study is exactly that of demonstrating how the empirical author Brian O'Nolan was the real Deus in machina, the master of puppets who skilfully directed all of his identities in planned directions, so as to completely fulfil the role of the comic figure we explained before. Flann O'Brien and Myles na Gopaleen were personae and not persons, but the impression one gets from the critical studies on them is the exact opposite. Literary consideration, that came only after O'Nolans death, began with Anne Clissmann’s work, Flann O'Brien: A Critical Introduction to His Writings (Clissmann 1975), while the most recent book is Keith Donohue’s The Irish Anatomist: A Study of Flann O'Brien (Donohue 2002); passing through M.Keith Booker’s Flann O'Brien, Bakhtin and Menippean Satire (Booker 1995), Keith Hopper’s Flann O'Brien: A Portrait of the Artist as a Young Post-Modernist (Hopper 1995) and Monique Gallagher’s Flann O'Brien, Myles et les autres (Gallagher 1998). There have also been a couple of biographies, which incidentally somehow try to explain critical points his literary production, while many critical studies do the same on the opposite side, trying to found critical points of view on the author’s restless life and habits. At this stage, we attempted to merge into O'Nolan's corpus the journalistic articles he wrote, more than 4,200, for roughly two million words in the 26-year-old running of the column. To justify this, we appealed to several considerations about the figure O'Nolan used as writer: Myles na Gopaleen (later simplified in na Gopaleen), who was the equivalent of the street artist or storyteller, speaking to his imaginary public and trying to involve it in his stories, quarrels and debates of all kinds. First of all, he relied much on language for the reactions he would obtain, playing on, and with, words so as to ironically unmask untrue relationships between words and things. Secondly, he pushed to the limit the convention of addressing to spectators and listeners usually employed in live performing, stretching its role in the written discourse to come to a greater effect of involvement of readers. Lastly, he profited much from what we labelled his “specific weight”, i.e. the potential influence in society given by his recognised authority in determined matters, a position from which he could launch deeper attacks on conventional beliefs, so complying with the duty of a comic we hypothesised before: that of criticising society even in threat of losing the benefits the post guarantees. That seemingly masochistic tendency has its rationale. Every representative has many privileges on the assumption that he, or she, has great responsibilities in administrating. The higher those responsibilities are, the higher is the reward but also the severer is the punishment for the misfits done while in charge. But we all know that not everybody accepts the rules and many try to use their power for their personal benefit and do not want to undergo law’s penalties. The comic, showing in this case more civic sense than others, helped very much in this by the non-accessibility to the use of public force, finds in the role of the scapegoat the right accomplishment of his task, accepting the punishment when his breaking of the conventions is too stark to be forgiven. As Ceccarelli demonstrated, the role of the object of laughter (comic, ridicule) has its very own positive side: there is freedom of expression for the person, and at the same time integration in the society, even though at low levels. Then the banishment of a ‘social’ comic can never get to total extirpation from society, revealing how the scope of the comic lies on an entirely fictional layer, bearing no relation with facts, nor real consequences in terms of physical health. Myles na Gopaleen, mastering these three characteristics we postulated in the highest way, can be considered an author worth noting; and the oeuvre he wrote, the whole collection of Cruiskeen Lawn articles, is rightfully a novel because respects the canons of it especially regarding the authorial figure and his relationship with the readers. In addition, his work can be studied even if we cannot conduct our research on the whole of it, this proceeding being justified exactly because of the resemblances to the real figure of the storyteller: its ‘chapters’ —the daily articles— had a format that even the distracted reader could follow, even one who did not read each and every article before. So we can critically consider also a good part of them, as collected in the seven volumes published so far, with the addition of some others outside the collections, because completeness in this case is not at all a guarantee of a better precision in the assessment; on the contrary: examination of the totality of articles might let us consider him as a person and not a persona. Once cleared these points, we proceeded further in considering tout court the works of Brian O'Nolan as the works of a unique author, rather than complicating the references with many names which are none other than well-wrought sides of the same personality. By putting O'Nolan as the correct object of our research, empirical author of the works of the personae Flann O'Brien and Myles na Gopaleen, there comes out a clearer literary landscape: the comic author Brian O'Nolan, self-conscious of his paramount role in society as both a guide and a scourge, in a word as an a(rche)typical, intentionally chose to differentiate his personalities so as to create different perspectives in different fields of knowledge by using, in addition, different means of communication: novels and journalism. We finally compared the newly assessed author Brian O'Nolan with other great Irish comic writers in English, such as James Joyce (the one everybody named as the master in the field), Samuel Beckett, and Jonathan Swift. This comparison showed once more how O'Nolan is in no way inferior to these authors who, greatly celebrated by critics, have nonetheless failed to achieve that great public recognition O’Nolan received alias Myles, awarded by the daily audience he reached and influenced with his Cruiskeen Lawn column. For this reason, we believe him to be representative of the comic figure’s function as a social regulator and as a builder of solidarity, such as that Raymond Williams spoke of in his work (Williams 1982), with in mind the aim of building a ‘culture in common’. There is no way for a ‘culture in common’ to be acquired if we do not accept the fact that even the most functional society rests on conventions, and in a world more and more ‘connected’ we need someone to help everybody negotiate with different cultures and persons. The comic gives us a worldly perspective which is at the same time comfortable and distressing but in the end not harmful as the one furnished by politicians could be: he lets us peep into parallel worlds without moving too far from our armchair and, as a consequence, is the one who does his best for the improvement of our understanding of things.

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The sexual attraction is a complex emotional event, with somatic modifications, that like all the emotions, belongs to the psychic dimension and that, too much simply, can be led back, from a explicative point of view, to biological and psychical causes. The sexual attraction represents a personal experience, that is difficult to record, but of which every adult is able to delineate a correspondence with own “lived”. In the within of biological sciences, many experimental studies were been conducted with the aim to know which chemistries substances and cerebral zones are involved in front of a stimulus assessed like sexually attractive. Contrarily, there are little researches conducted in psychological field, aimed to the understanding the psychical factors, often unconscious, tinged to the subjective processes of sexual attraction: the sexual attraction remains an unexplored psychological event and unprovided of adapted instruments of assessment. The present thesis is oriented in primis to examine the existing scientific literature, in order to provide an exhaustive picture of the sexual attraction and to analyze the instruments of survey available for the empirical assessment of it. Secondly, the thesis is oriented to introduce two studies: the first study is aimed to adapt the Cuestionario de Atracción Sexual - CAS (Fernández ET to, 2006a; 2006b; 2006c) to the Italian language; the second study is aimed to assess the attitudes towards the sexual attraction in a sample of university students, in order to establish if some differences or association with some psychological dimensions (attachment stiles and alexithymia) exist.

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The effector function of natural killer (NK) cells is regulated by activating and inhibitory receptors, termed killer immunoglobulin-like receptors (KIRs). In haploidentical T-cell depleted transplantation the donor/recipient KIR mismatch significantly impacts on NK-mediated tumor cell killing, particularly in acute myeloid leukaemia (AML). Thirty-four high risk AML patients entered a phase I-II study of adoptive NK-cell based immunotherapy and were screened for the availability of one haploidentical KIR ligand mismatched donor. Thirteen of them resulted as having one suitable donor. NK cells were enriched from steady-state leukaphereses by using a double-step immunomagnetic separation system, consisting in depletion of CD3+ T cells followed by positive selection of CD56+ NK cells. CD56+ cells were enriched from 7,70% (1,26-11,70) to 93,50% (66,41-99,20) (median recovery 53,05% (30,97-72,85), median T-depletion 3,03 log (2,15-4,52) viability >92%) and their citotoxic activity was inalterate. All patients (4 progressions, 1 partial remission and 8 complete remissions) received NK cell infusion which was preceeded by immunosuppressive chemotherapy (fludarabine and cyclophosphamide) and followed by interleukin 2 injections. The median number of reinfused NK cells was 2,74x10(e)6/kg(1,11-5,00) and contamining CD3+ T cells were always less than 1x10(e)5/kg. The procedure was well-tolerated and no significant toxicity, including GvHD, related to NK cell infusion was observed. The donor NK cells were demonstrated in 5/10 patients. Among the 8 patients in complete remission 5 patients are stable after 18, 15, 4, 2 months of follow-up. Three other patients relapsed after 2 and 7 months. The patient in partial remission obtained a complete remission, which lasted for 6 months. The 4 patients with active/progressive disease showed the persistence of disease. This clinical observation may be correlated with in vitro studies, indicating that AML cells are capable to induce NK cell apoptosis in a dose-depend manner. In summery, a two-step enrichment of CD56+ NK cells allows the collection of a suitable number of target cells to be used as adoptive immunotherapy in AML patients. Infusion of NK cells is feasible and safe and adoptively transferred NK cells can be detected after infusion.

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The olive oil extraction industry is responsible for the production of high quantities of vegetation waters, represented by the constitutive water of the olive fruit and by the water used during the process. This by-product represent an environmental problem in the olive’s cultivation areas because of its high content of organic matter, with high value of BOD5 and COD. For that reason the disposal of the vegetation water is very difficult and needs a previous depollution. The organic matter of vegetation water mainly consists of polysaccharides, sugars, proteins, organic acids, oil and polyphenols. This last compounds are the principal responsible for the pollution problems, due to their antimicrobial activity, but, at the same time they are well known for their antioxidant properties. The most concentrate phenolic compounds in waters and also in virgin olive oils are secoiridoids like oleuropein, demethyloleuropein and ligstroside derivatives (the dialdehydic form of elenolic acid linked to 3,4-DHPEA, or p-HPEA (3,4-DHPEA-EDA or p-HPEA-EDA) and an isomer of the oleuropein aglycon (3,4-DHPEA-EA). The management of the olive oil vegetation water has been extensively investigated and several different valorisation methods have been proposed, such as the direct use as fertilizer or the transformation by physico-chemical or biological treatments. During the last years researchers focused their interest on the recovery of the phenolic fraction from this waste looking for its exploitation as a natural antioxidant source. At the present only few contributes have been aimed to the utilization for a large scale phenols recovery and further investigations are required for the evaluation of feasibility and costs of the proposed processes. The present PhD thesis reports a preliminary description of a new industrial scale process for the recovery of the phenolic fraction from olive oil vegetation water treated with enzymes, by direct membrane filtration (microfiltration/ultrafiltration with a cut-off of 250 KDa, ultrafiltration with a cut-off of 7 KDa/10 KDa and nanofiltration/reverse osmosis), partial purification by the use of a purification system based on SPE analysis and by a liquid-liquid extraction system (LLE) with contemporary reduction of the pollution related problems. The phenolic fractions of all the samples obtained were qualitatively and quantitatively by HPLC analysis. The work efficiency in terms of flows and in terms of phenolic recovery gave good results. The final phenolic recovery is about 60% respect the initial content in the vegetation waters. The final concentrate has shown a high content of phenols that allow to hypothesize a possible use as zootechnic nutritional supplements. The purification of the final concentrate have garanteed an high purity level of the phenolic extract especially in SPE analysis by the use of XAD-16 (73% of the total phenolic content of the concentrate). This purity level could permit a future food industry employment such as food additive, or, thanks to the strong antioxidant activity, it would be also use in pharmaceutical or cosmetic industry. The vegetation water depollutant activity has brought good results, as a matter of fact the final reverse osmosis permeate has a low pollutant rate in terms of COD and BOD5 values (2% of the initial vegetation water), that could determinate a recycling use in the virgin olive oil mechanical extraction system producing a water saving and reducing thus the oil industry disposal costs .

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The wheel - rail contact analysis plays a fundamental role in the multibody modeling of railway vehicles. A good contact model must provide an accurate description of the global contact phenomena (contact forces and torques, number and position of the contact points) and of the local contact phenomena (position and shape of the contact patch, stresses and displacements). The model has also to assure high numerical efficiency (in order to be implemented directly online within multibody models) and a good compatibility with commercial multibody software (Simpack Rail, Adams Rail). The wheel - rail contact problem has been discussed by several authors and many models can be found in the literature. The contact models can be subdivided into two different categories: the global models and the local (or differential) models. Currently, as regards the global models, the main approaches to the problem are the so - called rigid contact formulation and the semi – elastic contact description. The rigid approach considers the wheel and the rail as rigid bodies. The contact is imposed by means of constraint equations and the contact points are detected during the dynamic simulation by solving the nonlinear algebraic differential equations associated to the constrained multibody system. Indentation between the bodies is not permitted and the normal contact forces are calculated through the Lagrange multipliers. Finally the Hertz’s and the Kalker’s theories allow to evaluate the shape of the contact patch and the tangential forces respectively. Also the semi - elastic approach considers the wheel and the rail as rigid bodies. However in this case no kinematic constraints are imposed and the indentation between the bodies is permitted. The contact points are detected by means of approximated procedures (based on look - up tables and simplifying hypotheses on the problem geometry). The normal contact forces are calculated as a function of the indentation while, as in the rigid approach, the Hertz’s and the Kalker’s theories allow to evaluate the shape of the contact patch and the tangential forces. Both the described multibody approaches are computationally very efficient but their generality and accuracy turn out to be often insufficient because the physical hypotheses behind these theories are too restrictive and, in many circumstances, unverified. In order to obtain a complete description of the contact phenomena, local (or differential) contact models are needed. In other words wheel and rail have to be considered elastic bodies governed by the Navier’s equations and the contact has to be described by suitable analytical contact conditions. The contact between elastic bodies has been widely studied in literature both in the general case and in the rolling case. Many procedures based on variational inequalities, FEM techniques and convex optimization have been developed. This kind of approach assures high generality and accuracy but still needs very large computational costs and memory consumption. Due to the high computational load and memory consumption, referring to the current state of the art, the integration between multibody and differential modeling is almost absent in literature especially in the railway field. However this integration is very important because only the differential modeling allows an accurate analysis of the contact problem (in terms of contact forces and torques, position and shape of the contact patch, stresses and displacements) while the multibody modeling is the standard in the study of the railway dynamics. In this thesis some innovative wheel – rail contact models developed during the Ph. D. activity will be described. Concerning the global models, two new models belonging to the semi – elastic approach will be presented; the models satisfy the following specifics: 1) the models have to be 3D and to consider all the six relative degrees of freedom between wheel and rail 2) the models have to consider generic railway tracks and generic wheel and rail profiles 3) the models have to assure a general and accurate handling of the multiple contact without simplifying hypotheses on the problem geometry; in particular the models have to evaluate the number and the position of the contact points and, for each point, the contact forces and torques 4) the models have to be implementable directly online within the multibody models without look - up tables 5) the models have to assure computation times comparable with those of commercial multibody software (Simpack Rail, Adams Rail) and compatible with RT and HIL applications 6) the models have to be compatible with commercial multibody software (Simpack Rail, Adams Rail). The most innovative aspect of the new global contact models regards the detection of the contact points. In particular both the models aim to reduce the algebraic problem dimension by means of suitable analytical techniques. This kind of reduction allows to obtain an high numerical efficiency that makes possible the online implementation of the new procedure and the achievement of performance comparable with those of commercial multibody software. At the same time the analytical approach assures high accuracy and generality. Concerning the local (or differential) contact models, one new model satisfying the following specifics will be presented: 1) the model has to be 3D and to consider all the six relative degrees of freedom between wheel and rail 2) the model has to consider generic railway tracks and generic wheel and rail profiles 3) the model has to assure a general and accurate handling of the multiple contact without simplifying hypotheses on the problem geometry; in particular the model has to able to calculate both the global contact variables (contact forces and torques) and the local contact variables (position and shape of the contact patch, stresses and displacements) 4) the model has to be implementable directly online within the multibody models 5) the model has to assure high numerical efficiency and a reduced memory consumption in order to achieve a good integration between multibody and differential modeling (the base for the local contact models) 6) the model has to be compatible with commercial multibody software (Simpack Rail, Adams Rail). In this case the most innovative aspects of the new local contact model regard the contact modeling (by means of suitable analytical conditions) and the implementation of the numerical algorithms needed to solve the discrete problem arising from the discretization of the original continuum problem. Moreover, during the development of the local model, the achievement of a good compromise between accuracy and efficiency turned out to be very important to obtain a good integration between multibody and differential modeling. At this point the contact models has been inserted within a 3D multibody model of a railway vehicle to obtain a complete model of the wagon. The railway vehicle chosen as benchmark is the Manchester Wagon the physical and geometrical characteristics of which are easily available in the literature. The model of the whole railway vehicle (multibody model and contact model) has been implemented in the Matlab/Simulink environment. The multibody model has been implemented in SimMechanics, a Matlab toolbox specifically designed for multibody dynamics, while, as regards the contact models, the CS – functions have been used; this particular Matlab architecture allows to efficiently connect the Matlab/Simulink and the C/C++ environment. The 3D multibody model of the same vehicle (this time equipped with a standard contact model based on the semi - elastic approach) has been then implemented also in Simpack Rail, a commercial multibody software for railway vehicles widely tested and validated. Finally numerical simulations of the vehicle dynamics have been carried out on many different railway tracks with the aim of evaluating the performances of the whole model. The comparison between the results obtained by the Matlab/ Simulink model and those obtained by the Simpack Rail model has allowed an accurate and reliable validation of the new contact models. In conclusion to this brief introduction to my Ph. D. thesis, we would like to thank Trenitalia and the Regione Toscana for the support provided during all the Ph. D. activity. Moreover we would also like to thank the INTEC GmbH, the society the develops the software Simpack Rail, with which we are currently working together to develop innovative toolboxes specifically designed for the wheel rail contact analysis.

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The aim of this proposal is to explain the paradigm of the American foreign policy during the Johnson Administration, especially toward Europe, within the NATO framework, and toward URSS, in the context of the détente, just emerged during the decade of the sixties. During that period, after the passing of the J. F. Kennedy, President L. B. Johnson inherited a complex and very high-powered world politics, which wanted to get a new phase off the ground in the transatlantic relations and share the burden of the Cold war with a refractory Europe. Known as the grand design, it was a policy that needed the support of the allies and a clear purpose which appealed to the Europeans. At first, President Johnson detected in the problem of the nuclear sharing the good deal to make with the NATO allies. At the same time, he understood that the United States needed to reassert their leadeship within the new stage of relations with the Soviet Union. Soon, the “transatlantic bargain” became something not so easy to dealt with. The Federal Germany wanted to say a word in the nuclear affairs and, why not, put the finger on the trigger of the atlantic nuclear weapons. URSS, on the other hand, wanted to keep Germany down. The other allies did not want to share the onus of the defense of Europe, at most the responsability for the use of the weapons and, at least, to participate in the decision-making process. France, which wanted to detach herself from the policy of the United States and regained a world role, added difficulties to the manage of this course of action. Through the years of the Johnson’s office, the divergences of the policies placed by his advisers to gain the goal put the American foreign policy in deep water. The withdrawal of France from the organization but not from the Alliance, give Washington a chance to carry out his goal. The development of a clear-cut disarm policy leaded the Johnson’s administration to the core of the matter. The Non-proliferation Treaty signed in 1968, solved in a business-like fashion the problem with the allies. The question of nuclear sharing faded away with the acceptance of more deep consultative role in the nuclear affairs by the allies, the burden for the defense of Europe became more bearable through the offset agreement with the FRG and a new doctrine, the flexible response, put an end, at least formally, to the taboo of the nuclear age. The Johnson’s grand design proved to be different from the Kennedy’s one, but all things considered, it was more workable. The unpredictable result was a real détente with the Soviet Union, which, we can say, was a merit of President Johnson.

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It is believed that the way of being and the communicative-relational skills of every individual have multifactorial origins, including the quality of primary relationships with caregivers. For some time, the need for health care professionals to possess specific communicative and interpersonal skills has been highlighted. To the degree course in Nursing, like to all other degree programs related to health, access is granted to students who have large individual differences, both in terms of personality, and in terms of relational skills. Each academic year, therefore, the people responsible for the didactic organization of every course, are faced with having to prepare a training plan capable of addressing communicative-relational aspects and, at the same time, of being adequate to the real attitudes of incoming students. Thus, the need for appropriate tools for measuring the personological and vocational traits considered specific to health professions was born. This study has a twofold objective. On one hand, it aims at selecting a battery of psychological tests to detect psychological and attitudinal patterns, to facilitate the coordinators of graduate courses in their didactic organization and planning of educational training; on the other hand, it seeks to assess the correlations between communicative-relational skills (Relational-Communicative style, according to the model of patient-centered medicine-TRS) (Mucchielli’s Test of Spontaneous Attitudes – usual kind of attitude in dual relationships), personality traits (Alexithymia), styles of attachment to parental figures (PBI), and the capability of recognizing facial emotions, in a sample of students enrolled in the first year of a degree in Nursing.

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La ricerca ha ad oggetto l’analisi di clausole, contenute nei contratti del commercio internazionale, che sembrano finalizzate a fornire in anticipo una metodologia dell’interpretazione del contratto. L’elaborato pertanto analizza i profili di validità ed efficacia di singole e specifiche clausole, come le “clausole d’intero accordo”, le “clausole di non modificazione orale”, le clausole contenenti definizioni, e simili, alla luce delle regole giudiriche di derivazione eteronoma applicabili al contratto, siano esse rappresentate da una legge nazionale, da una convenzione internazionale di diritto materiale uniforme, o da fonti ulteriori c.d. di soft law, come i Principi Unidroit sui contratti del commercio internazionale. La ricerca ha pertanto rivelato che, diversamente da quanto possa apparire a prima vista, svariate tipologie di clausole analizzate non coinvolgono profili legati all'’nterpretazione del contratto, quanto piuttosto di documentazione e forma dello stesso. L’elaborato contiene infine alcune considerazioni di teoria generale del diritto.

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L’attuale rilevanza rappresentata dalla stretta relazione tra cambiamenti climatici e influenza antropogenica ha da tempo posto l’attenzione sull’effetto serra e sul surriscaldamento planetario così come sull’aumento delle concentrazioni atmosferiche dei gas climaticamente attivi, in primo luogo la CO2. Il radiocarbonio è attualmente il tracciante ambientale per eccellenza in grado di fornire mediante un approccio “top-down” un valido strumento di controllo per discriminare e quantificare il diossido di carbonio presente in atmosfera di provenienza fossile o biogenica. Ecco allora che ai settori applicativi tradizionali del 14C, quali le datazioni archeometriche, si affiancano nuovi ambiti legati da un lato al settore energetico per quanto riguarda le problematiche associate alle emissioni di impianti, ai combustibili, allo stoccaggio geologico della CO2, dall’altro al mercato in forte crescita dei cosiddetti prodotti biobased costituiti da materie prime rinnovabili. Nell’ambito del presente lavoro di tesi è stato quindi esplorato il mondo del radiocarbonio sia dal punto di vista strettamente tecnico e metodologico che dal punto di vista applicativo relativamente ai molteplici e diversificati campi d’indagine. E’ stato realizzato e validato un impianto di analisi basato sul metodo radiometrico mediante assorbimento diretto della CO2 ed analisi in scintillazione liquida apportando miglioramenti tecnologici ed accorgimenti procedurali volti a migliorare le performance del metodo in termini di semplicità, sensibilità e riproducibilità. Il metodo, pur rappresentando generalmente un buon compromesso rispetto alle metodologie tradizionalmente usate per l’analisi del 14C, risulta allo stato attuale ancora inadeguato a quei settori applicativi laddove è richiesta una precisione molto puntuale, ma competitivo per l’analisi di campioni moderni ad elevata concentrazione di 14C. La sperimentazione condotta su alcuni liquidi ionici, seppur preliminare e non conclusiva, apre infine nuove linee di ricerca sulla possibilità di utilizzare questa nuova classe di composti come mezzi per la cattura della CO2 e l’analisi del 14C in LSC.