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Knowledge management: the issue of multimedia contents
Get PDFKnowledge Management is a very important topic in business and in academy research. There are many fields of applications for knowledge management, including cognitive science, sociology, management science, information science,
knowledge engineering, artificial intelligence, and economics. Many studies on different aspects of Knowledge Management have been published, becoming common in the early 1990s. In this work, we want to represent Knowledge through a mixed-iterative approach, where top-down and bottom-up analyses of the knowledge domain
which has to be represented are applied: these are typical approaches for this kind of problems. In this case, they are applied following an iterative approach
which allows, through further refinements, for the efficient formalization able to represent the domain's knowledge of interest. We start from the concept of the “domain knowledge base”. The fundamental
body of knowledge available on a domain is the knowledge valuable for the knowledge users. We need to represent and manage this knowledge, to define a formalization and codification of the knowledge in the domain. After this
formalization we can manage this knowledge using knowledge repositories. In this thesis, we present four different formalization and management of knowledge for multimedia contents, using our proposed approach:
1. User Generated Contents from famous platform (Flickr, YouTube, etc.);
2. audio recordings regarding linguistic corpus and information added to that
corpus with annotations;
3. knowledge associated with construction processes;
4. descriptions and reviews of Italian wines.
The most important result we achieved with this thesis was the opportunity to make this disparaged knowledge available and manageable. In the current market, exploiting existing knowledge is a mainstream business, but in order to
exploit it, one must be able to manage it first. As a token of this importance, not only about ten scientific publications, but most of all a number of industrial
research projects, in partnership with ICT companies – one of which with a total value above one million Euros – stemmed from the studies discussed in this thesis
Remote sensing and GIS-based mapping on landslide phenomena and landslide susceptibility evaluation of Debresina Area (Ethiopia) and Rio San Girolamo basin (Sardinia)
Get PDFThe thesis presents GIS based spatial data analysis for landslide phenomena and susceptibility mapping which
is carried out in Debresina area of the Afar rift margin (in Ethiopia) and in Rio San Girolamo basin at the
margin of Campidano graben (in Sardinia, Italy). Both of these distant study areas are prone to various types
of landslide and landslide-generated hazards with tremendous damages such as loss of human lives, failure of
infrastructures, and damage on agricultural fields and on the natural environment. Landslides and related
hazards have no geographic boundaries. They occur in both developed countries (like Italy) and in developing
countries (like Ethiopia) causing a continuous threat to human beings all over the world.
The objectives of this study in both project areas were therefore: (1) to generate maps of landslide inventory
and various landslide causative factors, and evaluate their contribution to the occurrences of landslide and its
frequency in the respective study areas, (2) to evaluate the landslide susceptibility and prepare maps of both
study areas using various GIS based methods and compare their results, (3) to recommend landslide hazard
mitigation strategies based on the final findings of the study for both respective project areas.
The study accomplished:(1) characterization of 160 and 108 landslide occurrences in Debresina and
R.S.Girolamo areas respectively (2) remote sensing and field investigations of the landslide causative factors
(3) laboratory investigations of some physical, mineralogical and geotechnical properties of rocks and soils, and (4) GIS-based data analysis and landslide susceptibility evaluation using Overlay Mapping (OM),
Frequency Ratio (FR), Analytical Hierarchal Process (AHP) and Global Limit Equilibrium (GLE) methods.
Besides, methods like the Kinematic Analysis and Melton Ratio are also applied to further appraise the effect
of geological structures in the Debresina area and to identify the type of debris flow, debris flood and normal
flood in the R.S.Girolamo respectively.
Though the utilized landslide causative factors vary depending on the applied methods and the specific
condition of the study areas, a total of seven landslide causative factors such as lithology, proximity to faults
and to drainages, land use, slope, aspect and elevation were selected and prepared in GIS for landslide
susceptibility mapping in the Debresina area. Six similar causative factors are also used at the R.S.Girolamo
area excluding proximity to fault.
Results of the study revealed that: (I) the major final triggering factor for the September 2005 landslide event
of Debresina area is most probably earthquake besides to the saturation and active gully erosion while in
R.S.Girolamo are rainfall and active gully erosion (II) More than 77% of the landslide occurrence in Debresina
area is contributed by complex/composite slide and debris/earth slide while about 75% landslide occurrences
in R.S.Girolamo is covered by debris flow (III) all the methods (OM, FR and AHP) more or less give similar
V Remote Sensing & GIS-based Mapping on Landslide Phenomena & Landslide Susceptibility Evaluation of Debresina
area (Ethiopia) & R.S. Girolamo basin (Sardinia)
indication that an area is susceptible to slope failure in Debresina area if it is covered by lithology of
colluvium-eluvium, debris deposits, various tuffs and clay soils, have slope range of 10°-40°, land use of river
course, arable and bare rock, have proximity to fault of 0-600m and to drainage 0-300m, have elevation of
2000-2500m and with an aspect to East and Southeast. Whereas the R.S. Girolamo area is prone to landslide if
it has a lithology of alluvium, talus, granite and colluvium; have a slope class >260, have land use of river
coarse, forest and bare rock, have proximity to drainage of 0-100m, with elevation of 450-600m and having an
aspect of facing North, Northwest, Northeast and Southward (IV) the top landslide causative factors in
Debresina area are lithology (34.2%), proximity to fault (24.5%), proximity to drainage (16.2%) while in the
R.S. Girolamo the main landslide influencing factors are proximity to drainage (41%), lithology (24%) and
land use (13%), (V) the prediction accuracy of the OM, FR and AHP methods in both study areas is compared
based on Area under the Curve (AUC) method and results verified that the percentage of prediction accuracy
of the methods in general is higher at the Debresina area than in R.S.Girolamo. This could be mainly attributed
to the prevalent landslide types in each study areas. Hence, it can be suggested that the applicability of these
methods for the susceptibility analysis flow-like landslides (e.g. debris flow) and rock falls/topples are
relatively lower than in the other types of landslide types (VI) in the GLE method of circular failure surface,
the reduction of the SF from the dry slope to the saturated slope condition for the Debresina area is 43-45%,
but in the case of R.S.Girolamo the reduction of SF reaches up to 64-71%. This evidenced that the triggering
impact of water for slope failure is greater in R.S.Girolamo than in Debresina area (VII) the overall study
results of the various methods presented in this thesis have shown the great potential of GIS-based landslide
predictions and can therefore be used as a basic data for preliminary slope management and land-use planning
of the respective study areas.
The state of prevention towards the hazards is quite different in both areas, owing to the developmental
difference of the two countries, Ethiopia and Italia. Thus, in R.S.Girolamo landslide and related hazard
prevention measures are better institutionalized and, hence, with better territorial management and public
awareness of the hazard. Whereas in Debresina area, no responsible institution exists to date and the territorial
management is poor, and people have no idea how to prevent landslide hazards. Based on the obtained
susceptibility maps and considering the economic, cultural and technological differences of the two study
areas, landslide hazard mitigation strategies and remedial measure options are recommended
Il muro. Concetti e tecniche
Get PDFThe aim of this research is to investigate the role of the wall in the mediterranean architecture. In this geographical and cultural area, the wall gains qualities which go beyond the strictly structural and constructive function, becoming a structuring and qualifying element for settlements and living spaces and also the expression of local identity. The research, by “interpreting” the wall as a conceptual category, wants to give an answer to the deep need of improvement of the urban habitat architectural quality within a more proper relationship between identity characters and contemporary project.
If we observe villages and rural settlements in the Mediterranean basin, we will inevitably identify some primitive elements which characterize, build, structure and distinguish public from private spaces. Courtyard, wall, basic elements (the cell) and road are “particles”. When they combine organically, they model settlement patterns and determine spatial perception, both partial and global. Through its mass and continuity, the wall contains all these basic elements of the Mediterranean architecture and it does not have merely a building function. It is structuring rather than only structural, it defines architectural space, it is a border and a continuum in stereotomy. As a conceptual category, it acquires complex meanings and conveys ideas like a precise living culture, to stay and relate to other people. Actually, the wall is the concrete expression of introversion, it is a border, an enclosure, it defines and creates spatial hierarchies, it protects and gives an order, it is a presence/absence, permeability, gravity, light and dark. Thus exploration, that is the theoretical and practical study of its meanings as a conceptual category, as well as the study of spatial phenomena and spatial organization, is aimed at finding a new interpretation and giving a new impulse to wall construction in these places. In the course of the last century, the cultural impoverishment has threatened these areas and it has undermined the basis of their identity. This is leading to the loss of their original peculiarities
Studio dei tratti immunofenotipici e valutazione del loro contributo nell'insorgenza di patologie
Get PDFThe regulation of the immune response has been intensively
studied for decades, however, the effect of the genetic factors affecting the immune cell levels is largely unknown. In order to better understand the immune system regulation and its involvement in diseases, we evaluated the quantitative variation of several leuckocyte populations in peripheral blood including monocytes, granulocytes, circulating dendritic cells and lymphocytes
divided in NK, B and T cell subsets. Immunophenotypes, assessed by flow cytometry, were initially measured in 1,629 volunteers,belonging to the SardiNIA project, who have been genotipically characterized with the MetaboChip and ImmuoChip arrays. For each of the 272 assessed traits, we performed a sequenced-based GWAS approach with 8.2 million genotyped and imputed variants derived from the gene arrays and from a reference panel of 1,146 low pass whole-genome sequenced Sardinians. Our results showed
that, on the average, the genetic component accounts for 40% (min 3% max 87%) of the phenotypic variation of the immune traits analyzed. Furthermore, we identified, and confirmed in a total of 2,870 volunteers, comprising 1,241 additional individuals, 23 independent signals at 13 loci (p-value<5.26x10-10). Among the associated loci, four of them (HLA, IL2RA, CIITA, ATXN2/SH2B3) are known to be associated with immune and non-immune diseases, indicating the relevance of this approach for identification of immune-related genetic factors in health and disease
Neonatal exposure to estradiol in female rats influences neuroactive steroid concentrations and behaviour in the adult rat
Get PDFThe gonadal steroids, in particular estradiol, exert an important action during perinatal period in the regulation of sexual dimorphism and neuronal plasticity, and in the growth and development of nervous system. Exposure of the developing female to estrogens during perinatal period may have long-lasting effects that are now regarded as “programming” the female neuroendocrine axis to malfunction in adulthood. The purpose of this study was to describe the effect of a single administration of a low dose (10 μg) of β-estradiol 3-benzoate (EB) to female rats on the day of birth on brain and plasma concentrations of the neuroactive steroid allopregnanolone, general behaviours and behavioral sensitivity to benzodiazepines. Neonatal administration of EB induces a dramatic reduction in the cerebrocortical and plasma levels of allopregnanolone and progesterone that were apparent in both juvenile (21 days) and adult (60 days). In contrast, this treatment did not affect 17β-estradiol levels. Female rats treated with β-estradiol 3-benzoate showed a delay in vaginal opening, aciclicity characterized by prolonged estrus, and ovarian failure. Given that allopregnanolone elicits anxiolytic, antidepressive, anticonvulsant, sedative-hypnotic effects and facilitates social behaviour, we assessed whether this treatment might modify different emotional, cognitive and social behaviours. This treatment did not affect locomotor activity, anxiety- and mood-related behaviours, seizures sensitivity and spatial memory. In contrast, neonatal β-estradiol 3-benzoate-treated rats showed a dominant, but not aggressive, behaviour and an increase in body investigation, especially anogenital investigation, characteristic of male appetitive behaviour. On the contrary, neonatal administration of β-estradiol 3-benzoate to female rats increases sensitivity to the anxiolytic, sedative, and amnesic effects of diazepam in adulthood.
These results indicate that the marked and persistent reduction in the cerebrocortical and peripheral concentration of the neuroactive steroid allopregnanolone induced by neonatal treatment with β-estradiol 3-benzoate does not change baseline behaviours in adult rats. On the contrary, the low levels of allopregnanolone seems to be associated to changes in the behavioural sensitivity to the positive allosteric modulator of the GABAA receptor, diazepam. These effects of estradiol suggest that it plays a major role in pharmacological regulation both of GABAergic transmission and of the abundance of endogenous modulators of such transmission during development of the central nervous system
On the feasibility of the communications in the TVWS spectrum analysis and coexistence issue
Get PDFIn the last decade, the enormous growth in the wireless industry has come from using only a small part of the wireless spectrum, nominally less than 10% under 3 GHz. Nowadays, the vast majority of the available spectral resources have already been licensed. Measurements made by
the Federal Communication Commission (FCC) have shown that a great part of the spectrum, although allocated, is virtually unused. For all this reasons, in the last years, several countries have already (USA) or are in the process (EU, China, Japan, South Korea) of switching off
analog TV broadcasting in favor of Digital Terrestrial Television (DTT) broadcasting systems and digital switchover plans have driven a thorough review of TV spectrum exploitation. The resulting unused channels within this band are called “TV white spaces” (TVWS).
Even after the redistribution of the digital TV channels, the problem of an efficient utilization of the allocated frequencies is still far from being solved. For example, there are still large territorial areas on which, although allocated, the TV channels result unused, due to coverage
problems. New spectrum allocation approaches such as the dynamic spectrum access method have been studied. This new concept implies that the radio terminals have the capacity to monitor their own radio environment and consequently adapt to the transmission conditions on whatever frequency
band are available (adaptive radio). If this concept is supplemented with the capacity of analyzing the surrounding radio environment in search of white spaces, the term adaptive radio is extended to Cognitive Radio (CR). The spectrum management rule of CR is that all new users
for the spectrum are secondary (cognitive) users (SU) and requires that they must detect and avoid the primary (licensed) users (PU) in terms of used frequencies, transmission power and modulation scheme. In the TV bands specifically, the presence of PUs (e.g. TV broadcasters) can
be revealed both performing a spectrum sensing operation and considering the information provided by the external databases called “geo-location databases” (GL-DB). The database provides, for a certain location, the list of the free TV channels and the allowable maximum
effective isotropic radiated power (EIRP) for transmitting without harmful interference to incumbent users. Decision thresholds are still a critical parameter for protecting services in a scenario where cognitive devices would be operating. There are cases where the approach based on GL
Spectrum Occupancy DB might not be available, either because the database does not exist for
that area (for example in non densely populated areas) or in the case that access to the database is not possible (deep indoor operation, low populated areas etc.). Several studies have suggested that radio noise has increased significantly over the last decades and consequently the
assumptions about decision thresholds and interference protection ratios might be outdated. The
Hidden Node Margin (HNM) is a parameter that quantifies the difference between the potential interfered signal values at the location where it is measured or estimated by the cognitive device, and the actual value at the location where the receiving antenna for this signal is located. HNM is a key parameter to define the protection requirements that cognitive devices must comply in order not to create any harmful interference to broadcast receiving systems. In this context, this thesis goes in a precise direction, with four main topics related to the feasibility of communication cognitive systems operating in the TVWS, considering coexistence as the main operational issue.
The first topic studies new spectrum sensing approaches in order to improve the more critical functionality of CRs. In the second topic an unlicensed indoor short-range distribution system for the wireless retransmission in the DTT band of High definition TV (HDTV) contents with
immediate implementations as home entertainment systems has been carried out. The third topic of this thesis is about a particular database developed in order to provide information to easily calculate HNM values and associated statistics, TV Channel Occupancy and Man Made Noise
Upper Limits. The empirical data for this work has been recorded in different locations of Spain and Italy during 2011 and 2012 thanks to the partnership between the Department of Electrical and Electronic Engineering (D.I.E.E.) of the University of Cagliari and the Department of Electronics and Telecommunications of the University of Bilbao (UPV/EHU). Finally in the last topic we focus on the IEEE 802.22 WRAN standard evaluating, thanks to extended
measurements, the performance of an 802.22 system operating into the same coverage range of a DTT receiver
La dimensione intermedia.Gli spazi transitivi, i limiti dell’uso, i confini dialettici
Get PDFRational thought interpreted architecture simply as a container for activities, a machine that absorbed energy from within, different separated pieces of a single mechanism. Rational urban planning is thus rooted in Elementarism and the separation of functions.
Modern architecture dismantles the rigid relationship between interior space and walls, modern urban planning considered the urban space, releasing it from the ties of dependency that governed the relationship between roads, streets and the constructed block.
(…)the traditional compact city, where every part assumed a form in relation to its neighbour, creating squares and urban fabrics, went on dangerously subdividing and breaking up on account of an over simplistic application if the principles of modern urban planning. (cit. Josep Maria Montaner, Sistemas arquitectònicos contemporaneous, Editorial Gustavo Gili, SL, Barcellona, 2008).
The additive approach had served to dissolve, or separate the urban space, raising planning to an abstract state which distanced the architect’s attention from the authentic, and conceiving of the city as a mere composition of volumes within the space according to the territorial scale, where the space of the lived-in area was an almost discounted consequence, perhaps substituting the notion of neutral space to that of place.
The heated argument since the post-World War II period, which resulted in an affirmation of the crisis at the CIAM 9, refocuses attention on the idea of habitat as a system of spaces, an articulation of the private, the public and the semi-public; connected to spaces by the limits created by flexibility of use, by unclear borders, by complex extensions. The habitat is a system only inasmuch as it is a union of heterogeneous elements on a different scale which are inter-related according to an internal organization which results in the strategic adaptation to the complexity of the context and which creates, or builds a whole which can’t be explained by the sum of its parts. There are no isolated objects within, but all the elements are assimilated and melt into the fabric; every part is present and acts according to a role and in continuity with the others.
The house is a “half-open, half-closed ” being, a continuous threshold, a space that is in transition in which exchanges take place and a labyrinthine style complexity appears. A topological labyrinth, the place for living is thus an individual organization wherein the dweller appropriates the space.
The logical progression of this phenomenological concept of the house leads us to the relationship between public and private where we find a scaled reproduction mechanism which from the microcosm of the variety of the house
Abstract
recalls genuine and authentic planning models. This is what the architects at CIAM at Dubrovnik (’56) meant when they sparked polemics by comparing the vitality of the Kasbah with its labyrinthine spatial organization to the purity of modern prismically-limited visions.
The Kasbah, its traditional fabric, the rural villages of the Mediterranean demonstrate the imprecision and mingling of limits and functions, the compact nature and continuity of the mass of blocks of houses that surrounds and combines spaces of different types and creates relationships of osmotic permeability, density and porosity in complicated ways.
In Modern architecture, the urban matrix experiments with a radical transformation in which one passes from a constructed fabric which functions as a continuous solid, in which open spaces appear as sculpted figures extracted from a mouldable mass, to a creation based on isolated convex, which generate a continuous void, in which the open space ceases to have a precise form and which instead becomes a background, while the role of the figure or shape is taken over by buildings that appear as isolated fragments. Therefore we are faced with a radical topological transformation of the urban space.
The lesson of the traditional fabrics and their systematic clarity, their irrational components that are in a certain way spontaneous in defining dimensions, proportions and filters, is revealed as a determining factor in offering consolidated solutions entirely appropriate to everyday needs and functions. From a rationalistic approach which breaks down into clearly defined and juxtaposed sections and elements, one passes towards a more intuitive approach (phenomenological) which interprets and reads in the mixture of the system (that is, within the compact and solid system of the settlement) those elements that go to make it up and which express it even though there is no sense or solution of continuity.
The Kasbah - whose continuous evolution derives from no rational control or logic in any way - is a compact system, a porous mass, an organism made up of penetrating micro-systems, transits and stasis. It is an authentic machine for living, where the term machine is meant in its widest sense as an organized and perfectly functioning unit. If within the Athens Charter a clear call was made for the definition of clearly defined spaces in terms of limits and functions, the position of Team 10 underlines imprecision as the added value of space and place.
A concept of new and radical space is thus defined, the threshold, a spatiality of intermediate scale which becomes enriched through the possibility of usage, of personalization and colonization by virtue of its “middle space” nature, its functional vagueness, its measured yet informal character, by its encircling and deceiving urban dimension. Thresholds are the spaces that regulate the permeability of compact and dense fabrics, they are identifiable where urban solidity opens itself up to possibilities of penetration, where the pores of the building become shadowy places favourable to the dialectic stasis between individual and collective; where the characteristics of the semi-closed, half-closed and filtered spaces create relational balances, dynamics of controlled sharing, discreet dialogues with that which is outside the private family microcosm.
The threshold is the structure of space that regulates the dialogue with the rest (the complex) and itself becomes a place for living, a spatial device at the centre of the family background and a hinge between individual and collective. An intermediate space, a void for transition and meeting. The threshold is an imprecise limit, it is a space marked out for use, from the private fixtures, an expressed yet empty area; it is a third party that is neither private nor public, it has an in-between nature. Once again the Smithsons state that architectural reflection should start from the smallest scale, which means starting from the relationship between house and street, home and road, and thus this research is aimed at reflecting on the architectural and urban devices which make up the basis of this relationship. With the intervention of Team X it is now clear that living is not a fact confined to an apartment or dwelling, a private and individual space, but that it is exactly that by virtue of its extension and presence within the urban context, its links with public spaces. A reading of urban fabrics, and the Kasbahs in particular as organized systems reveals them as design tools in the conception of places for living not as individual architectural facts, building events in which the exclusive nature of the house and its external projections are detailed, but as systems for and of places, environments, objects that on different scales articulate the context of the habitat
Regional policy and energy efficiency: a computable general equilibrium approach
Get PDFThe Computable General Equilibrium (CGE) modelling frameworks used in this thesis are single-Country dynamic models with myopic or forward looking expectation. The latter can be seen as an applied and more extensive version of the skeletal model presented in Abel and Blanchard (1983). Investment decisions follow a Tobin’s q adjustment process, and are separated from savings decisions. The former reflect the intertemporal optimization of firms and the latter are the outcome of intertemporal optimization by households.
First essay. After European Structural Funds reform in 1988, the European Union (EU) stressed the importance to evaluate the effectiveness of the Cohesion Policy that aims to promote the development and structural adjustment of lagging regions. For regions under Objective 1, structural funds represent the most important EU tool to generate an increase in productivity and competitiveness over the long term of less developed regions by financing investments on tangible, intangible and human capital. Thus, in our analysis, we focus on the regional Research and Development (R&D) policy implemented to increase the stock of knowledge capital (intangible capital). In particular, we analyze two Operational Programs financed by SF that the Sardinia Regional Government made operational from 1994 to 2006: Programma Operativo Plurifondo (POP) 1994-1999 and Programma Operativo Regionale (POR) 2000-2006.
Second Essay. We investigate a particular issue related with energy efficiency improvements. The International Energy Agency (IEA, 2009) suggests the importance of efficiency improvement to reduce energy use and, within the European Union, one of the targets for member states is to reduce energy consumption by 20% through increased energy efficiency (European Commission, 2009). Energy efficiency improvement has the unquestionable benefits to reduce the price of energy services. However, it is still debatable the extent to which, improvement in the productivity of energy, is effective in terms of reducing the consumption of energy and thus the associated negative externalities (e.g., carbon dioxide emissions, CO2). Thus policy makers are particularly interested to determine the size of the energy rebound effect. We attempt to quantify the magnitude of the system-wide rebound effects from an increase in energy efficiency in the industrial use of energy in Italy. To this end, we use a large scale numerical dynamic general equilibrium model calibrated using the Italian Social Accounting Matrix for the year 2006. A number of authors have examined the impacts of increased energy efficiency within the demand and the production side of the economy using CGE models (Semboja, 1994; Grepperud and Rasmussen, 2004; Glomsrød and Taojuan, 2005; Hanley et al, 2006 and 2009; Allan et al, 2007; Turner, 2009). For instance, the works of Allan et al, (2007) and Turner (2009) for the UK, and Anson and Turner (2009) and Hanley et al, (2006; 2009) for Scotland evaluate the impact of an increase in energy efficiency in the industrial use of energy. From this literature, rebound effects are the more common finding.
While there is an increasing interest in US and UK to identify and quantify the rebound effects, it seems there is still a little interest in the rest of Europe and especially in Italy. To the best of our knowledge, do not exist in the energy economic literature estimations of energy rebound related to Italy. We then propose to fill the gap and take Italy as a case study. We believe it would be useful to compare rebound estimates with those of the existing literature, furthermore the estimation of the rebound would eventually provide a useful indicator to policymakers that are compelled to reduce carbon emission and transform the Country in a highly energy-efficient, low-carbon economy through policy aimed to increase energy efficiency (European Commission, 200
Studio delle modificazioni post-traduzionali della proteina AIRE e dell’effetto sulla sua attività trascrizionale, stabilità e localizzazione cellulare
Get PDFThe AIRE protein plays a remarkable role as a regulator of central tolerance by controlling the promiscuous expression of tissue-specific antigens in thymic medullary epithelial cells. Defects in the AIRE gene cause the autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy, a rare disease frequent in Iranian Jews, Finns, and Sardinian population.
AIRE protein has functional domains shared by others transcriptional factors thus suggesting that AIRE plays an important role in the regulation of the transcriptional process. AIRE protein is primarily known as a transcriptional regulator which functions as activator or repressor, depending on the cellular context in which the protein is functionally active. However, the exact mechanism has not yet completely clarified. It is widely accepted that its proper functioning is critical for the organization and maintenance of immunological tolerance.
AIRE is capable of interacting with numerous proteins. The first characterized partner of AIRE is the ubiquitous transcription factor CREB-binding protein (CBP), which regulates DNA transcription through the acetylation and deacetylation of histones. Several evidences have shown that AIRE-CBP interaction occurs in nuclear bodies and increases the expression of its target genes (Akiyoshi H et al 2004), (Pitkänen J. et al 2005), (Ferguson BJ et al 2008). More recently, the role of p300 in AIRE acetylation, which could influence the selection of AIRE activated genes (Saare et al 2012) has been described.
In the acetylation process, the lysines are the residues target and their position in the side chain is very important for protein function.
In this study, we have precisely mapped, by mass spectrometry experiments, the sites of protein acetylation and, by mutagenesis assays, we have described a set of acetylated lysines as being crucial in influencing the subcellular localization of AIRE.
On the basis of our results and those reported in literature, we propose a model in which lysines acetylation increases the stability of AIRE in the nucleus, where it assembles in aggregates called Nuclear Bodies.
We have explored the role of acetyltransferase enzymes, beside p300, involved in the lysine acetylation of AIRE.
Furthermore, since acetylation is a reversible process, once assessed that AIRE is deacetylated, we have also explored the possible role of the deacetylase complex in the biological function of AIRE protein
The elastic behavior of polymer chains: theory and simulations
Get PDFThis thesis provides a picture on the thermo-elastic behavior of polymer molecules with biological relevance. In particular, this essay deals with the thermo-elasticity of single polymer molecules subjected to uniform stretching (generated by an applied force) or non-uniform stretching (generated by an external field). Analytical
expressions and molecular dynamics simulations are elaborated considering some generalizations of the freely-jointed chain (FJC) and the worm-like chain (WLC) models. The analytical theory, based on classical statistical mechanics, allows a rigorous mathematical treatment, while the study of complex systems is covered by means of Monte Carlo simulations. On the one hand, the uniform stretching of a single polymer, imposed by an external pulling force, is pursued for studying the statistical mechanics of small molecules. When the thermodynamic limit is not satisfied, different boundary conditions (either Helmholtz or Gibbs ensemble) yield different elastic behavior,
showing the fascinating intrication native to the thermodynamics of small systems. This complexity is shown to be even more suggestive when investigating bistable molecules of which domains exhibit transitions between two stable states. This scenario leads from cooperative to non-cooperative response of each domain to the external force, depending on the specific statistical ensemble
considered. Universal scaling laws are provided, governing the overall elasticity of the polymer systems.
On the other hand, the non-uniform stretching of a single
molecule, imposed by an external field, is studied to analyze the average configurational properties of polymers and leads to another very intricating scenario concerning the behavior of the variances describing the fluctuations of the system. Furthermore, for the WLC model our attention fall in the investigation of the forceextension curve, for which we derive new approximated expressions for a chain immersed into an external field