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Manifold learning techniques and statistical approaches applied to the disruption prediction in tokamaks
Get PDFThe nuclear fusion arises as the unique clean energy source capable to meet the energy needs of the entire world in the future. On present days, several experimental fusion devices are operating to optimize the fusion process, confining the plasma by means of magnetic fields. The goal of plasma confined in a magnetic field can be achieved by linear cylindrical configurations or toroidal configurations, e.g., stellarator, reverse field pinch, or tokamak. Among the explored magnetic confinement techniques, the tokamak configuration is to date considered the most reliable. Unfortunately, the tokamak is vulnerable to instabilities that, in the most severe cases, can lead to lose the magnetic confinement; this phenomenon is called disruption. Disruptions are dangerous and irreversible events for the device during which the plasma energy is suddenly released on the first wall components and vacuum vessel causing runaway electrons, large mechanical forces and intense thermal loads, which may cause severe damage to the vessel wall and the plasma face components. Present devices are designed to resist the disruptive events; for this reason, today, the disruptions are generally tolerable. Furthermore, one of their aims is the investigation of disruptive boundaries in the operational space. However, on future devices, such as ITER, which must operate at high density and at high plasma current, only a limited number of disruptions will be tolerable. For these reasons, disruptions in tokamaks must be avoided, but, when a disruption is unavoidable, minimizing its severity is mandatory. Therefore, finding appropriate mitigating actions to reduce the damage of the reactor components is accepted as fundamental objective in the fusion community. The physical phenomena that lead plasma to disrupt are non-linear and very complex. The present understanding of disruption physics has not gone so far as to provide an analytical model describing the onset of these instabilities and the main effort has been devoted to develop data-based methods. In the present thesis the development of a reliable disruption prediction system has been investigated using several data-based approaches, starting from the strengths and the drawbacks of the methods proposed in the literature. In fact, literature reports numerous studies for disruption prediction using data-based models, such as neural networks. Even if the results are encouraging, they are not sufficient to explain the intrinsic structure of the data used to describe the complex behavior of the plasma. Recent studies demonstrated the urgency of developing sophisticated control schemes that allow exploring the operating limits of tokamak in order to increase the reactor performance.
For this reason, one of the goal of the present thesis is to identify and to develop tools for visualization and analysis of multidimensional data from numerous plasma diagnostics available in
the database of the machine. The identification of the boundaries of the disruption free plasma parameter space would lead to an increase in the knowledge of disruptions. A viable approach to understand disruptive events consists of identifying the intrinsic structure of the data used to describe the plasma operational space. Manifold learning algorithms attempt to identify these structures in order to find a low-dimensional representation of the data. Data for this thesis comes from ASDEX Upgrade (AUG). ASDEX Upgrade is a medium size tokamak experiment located at IPP Max-Planck-Institut für Plasmaphysik, Garching bei München (Germany). At present it is the largest tokamak in Germany. Among the available methods the attention has been mainly devoted to data clustering techniques. Data clustering consists on grouping a set of data in such a way that data in the same group (cluster) are more similar to each other than those in other groups. Due to the inherent predisposition for visualization, the most popular and widely used clustering technique, the Self-Organizing Map (SOM), has been firstly investigated. The SOM allows to extract information from the multidimensional operational space of AUG using 7 plasma parameters coming from successfully terminated (safe) and disruption terminated (disrupted) pulses. Data to train and test the SOM have been extracted from AUG experiments performed between July 2002 and November 2009. The SOM allowed to display the AUG operational space and to identify regions with high risk of disruption (disruptive regions) and those with low risk of disruption (safe regions). In addition to space visualization purposes, the SOM can be used also to monitor the time evolution of the discharges during an experiment. Thus, the SOM has been used as disruption predictor by introducing a suitable criterion, based on the trend of the trajectories on the map throughout the different regions. When a plasma configuration with a high risk of disruption is recognized, a disruption alarm is triggered allowing to perform disruption avoidance or mitigation actions. The data-based models, such as the SOM, are affected by the so-called "ageing effect". The ageing effect consists in the degradation of the predictor performance during the time. It is due to the fact that, during the operation of the predictor, new data may come from experiments different from those used for the training. In order to reduce such effect, a retraining of the predictor has been proposed. The retraining procedure consists of a new training procedure performed adding to the training set the new plasma configurations coming from more recent experimental campaigns. This aims to supply the novel information to the model to increase the prediction performances of the predictor.
Another drawback of the SOM, common to all the proposed data-based models in literature, is the need of a dedicated set of experiments terminated with a disruption to implement the predictive
model. Indeed, future fusion devices, like ITER, will tolerate only a limited number of disruptive events and hence the disruption database won't be available.
In order to overcome this shortcoming, a disruption prediction system for AUG built using only input signals from safe pulses has been implemented. The predictor model is based on a Fault Detection and Isolation (FDI) approach. FDI is an important and active research field which allows to monitor a system and to determine when a fault happens. The majority of model-based FDI procedures are based on a statistical analysis of residuals. Given an empirical model identified on a reference dataset, obtained under Normal Operating Conditions (NOC), the discrepancies between the new observations and those estimated by the NOCs (residuals) are calculated. The residuals are considered as a random process with known statistical properties. If a fault happens, a change of these properties is detected. In this thesis, the safe pulses are assumed as the normal operation conditions of the process and the disruptions are assumed as status of fault. Thus, only safe pulses are used to train the NOC model. In order to have a graphical representation of the trajectory of the pulses, only three plasma parameters have been used to build the NOC model. Monitoring the time evolution of the residuals by introducing an alarm criterion based on a suitable threshold on the residual values, the NOC model properly identifies an incoming disruption. Data for the training and the tests of the NOC model have been extracted from AUG experiments executed between July 2002 and November 2009. The assessment of a specific disruptive phase for each disruptive discharge represents a relevant issue in understanding the disruptive events. Up to now at AUG disruption precursors have been assumed appearing into a prefixed time window, the last 45ms for all disrupted discharges. The choice of such a fixed temporal window could limit the prediction performance. In fact, it generates ambiguous information in cases of disruptions with disruptive phase different from 45ms. In this thesis, the Mahalanobis distance is applied to define a specific disruptive phase for each disruption. In particular, a different length of the disruptive phase has been selected for each disrupted pulse in the training set by labeling each sample as safe or disruptive depending on its own Mahalanobis distance from the set of the safe discharges.
Then, with this new training set, the operational space of AUG has been mapped using the Generative Topography Mapping (GTM). The GTM is inspired by the SOM algorithm, with the aim to overcome its limitations.
The GTM has been investigated in order to identify regions with high risk of disruption and those with low risk of disruption. For comparison purposes a second SOM has been built. Hence, GTM and SOM have been tested as disruption predictors. Data for the training and the tests of the SOM
and the GTM have been extracted from AUG experiments executed from May 2007 to November 2012.
The last method studied and applied in this thesis has been the Logistic regression model (Logit). The logistic regression is a well-known statistic method to analyze problems with dichotomous dependent variables. In this study the Logit models the probability that a generic sample belongs to the non-disruptive or the disruptive phase. The time evolution of the Logit Model output (LMO) has been used as disruption proximity index by introducing a suitable threshold. Data for the training and the tests of the Logit models have been extracted from AUG experiments executed from May 2007 to November 2012. Disruptive samples have been selected through the Mahalanobis distance criterion.
Finally, in order to interpret the behavior of data-based predictors, a manual classification of disruptions has been performed for experiments occurred from May 2007 to November 2012. The manual classification has been performed by means of a visual analysis of several plasma parameters for each disruption. Moreover, the specific chains of events have been detected and used to classify disruptions and when possible, the same classes introduced for JET are adopte
A new class of auxetic lattices
Get PDFIn this work we have studied the mechanical and thermal behavior of a new class of auxetic
lattices. We have started introducing a novel two-dimensional lattice family with three
different realizations that leads to a Poisson's ratio arbitrarily close to the thermodynamic
limit corresponding to ν = -1. The effect is achieved by the superposition of clockwise and
anti-clockwise internal rotations leading to a macroscopic non-chiral effect. We have detailed
the kinematic of the mechanical system for three types of periodic lattices and we have
determined analytically the macroscopic constitutive properties of these structures. The
dependence of the effective properties on the constitutive and geometrical parameters of
the micro-structure is given and a comparative analysis with hexagonal, triangular and
square honeycombs is also performed. We have present also experimental evidence that
the new lattices can achieve a negative Poisson's ratio ν=-0.9931± 0.0025.
Later we have extended our study to a three-dimensional model that can reproduce the
same particular auxetic behavior. The system, we have introduced, has an elementary cell
with cubic shape. We have proposed two different versions, these two different systems are
generally anisotropic, or more precisely cubic according to symmetry consideration, but one
of them can be modified in its structural properties so that the macroscopic behavior
becomes isotropic. The anisotropic elastic character of the material is obviously reflected on
the effective Young's modulus E and on the effective Poisson's ratio ν, which are therefore
a function of the direction in the solid. We have given a complete numerical study of these
two elastic constants in particular focusing on the Poisson's ratio ν. The maximum and
minimum global Poisson's ratio ν obtained, for the anisotropic tridimensional lattice, are -1 and 1. In the case of the isotropic tridimensional lattice, Poisson's ratio ν ranges from -0.58 to 0.14.
After having considered the mechanical behavior of the lattices we have studied their thermal behavior. The particular geometry of the micro-structures makes possible to have dissimilar expansions of the elements within the lattice, leading to an effective coefficient of thermal expansion different from that of the constituent elements. It is possible to reach strongly negative, null, or positive coefficient of thermal expansion using conventional constituent materials with positive thermal expansion. A theoretical expression of the macroscopic coefficient of thermal expansion of the lattices has been provided in full analytical form as a function of the coefficients of thermal expansion of the constituent materials and of the geometrical configuration of the lattices. We have tested experimentally a typology of lattice to prove that achieves a negative coefficient of thermal expansion.
The novel systems are constructible at any length-scale, including the micro-scale, from conventional components with different mechanical and thermal properties, which may be combined to ensure the required macroscopic behavior. For this reason they can be used in several engineering fields: bio-medic, structural, aeronautics, civil, etc.
An interesting aspect, that concerns the thermal behavior, is that the macroscopic thermal expansion is not anymore an intrinsic property of the material but it is correlated to the micro-structure and to the ratio between the coefficients of thermal expansion of the constituent materials. This allow for example to realize structure insensitive to temperature changes or with a specific coefficient of thermal expansion depending on the application, without no need to use special materials generally very expensive
Produzione di H2 e CH4 da frazioni biodegradabili di rifiuti urbani e da siero lattiero-caseario
Get PDFNowadays one of the main technical tasks is finding clean and renewable energy sources in order to overtake the dependence from fossil fuels. Bio-hydrogen and bio-methane production are considered interesting energetic alternatives, especially if the biological processes are applied to low cost and widely available substrates such as biodegradable wastes.
Anaerobic digestion (AD) is a well-known technology to manage organic waste in an environmentally sustainable way, since it allows to achieve a certain level of stabilization of the organic matter and to exploit the energetic potential of the substrate; AD of biodegradable organic residues has therefore received renewed attention by the scientific and technical community over the last decades (Mata-Alvarez et al., 2000; Mata-Alvarez, 2002; De Baere, 2003; Bolzonella et al., 2006; Karagiannidis and Perkoulidis, 2009).
If degradation of biodegradable organic substrates is appropriately operated in a two-staged mode (see e.g., Han and Shin, 2004a; Liu et al., 2006; Gómez et al., 2006, 2009; Ueno et al., 2007; Chu et al., 2008; Wang and Zhao, 2009; Lee et al., 2010b; Dong et al., 2011), separation of the acidogenic phase (producing through dark fermentation (DF) hydrogen and carbon dioxide as the gaseous products while releasing volatile fatty acids into the liquid solution) from the methanogenic stage (in which the residual and dissolved biodegradable organic matter from the first stage is finally converted into methane and carbon dioxide) can be accomplished.
By means of the separation of the two biological phases, it is possible to obtain hydrogen besides methane gas, both to be exploited with various techniques. Considering the energetic aspect, combined H2 + CH4 production is, from a theoretical point of view, more favourable than conventional anaerobic digestion (Dong et al., 2011).
Hydrogen gas, in particular, is considered a clean energy carrier characterized by the highest energy content per unit weight of any known fuel (142 kJ/g), and positive environmental implications from H2 utilization can be obtained from production through biological processes and from renewable sources.
Various potentially biodegradable organic residues have been tested for fermentative H2 production, including food waste (FW), the organic fraction of municipal solid waste (OFMWS), and various agro-industrial residues, mainly due to their high carbohydrate content and wide availability (see e.g. Okamoto et al., 2000; Lay et al., 2003; Kim et al., 2004a; Liu et al., 2006; Alibardi et al., 2010, 2011; Kim et al., 2011a; Nazlina et al., 2011; De Gioannis et al., 2013).
Whatever the substrate under concern, full-scale implementation of fermentative H2 production requires significant and stable generation rates. Since H2 is an intermediate by-product of anaerobic digestion and some fermentation reactions have low or null H2 production, identification of suitable conditions to harvest specific fermentative bacteria and/or inhibit the H2-consuming biomass is mandatory. Achieving optimal and stable H2 generation while keeping treatment costs low and producing an effluent suitable for further treatment, is probably the main technical issue to be addressed. To this regard, operational parameters including temperature, pH, presence of inoculum and its eventual pre-treatment, substrate to inoculum ratio (F/M), reactor configuration, substrate concentration, hydraulic retention time (HRT) and organic loading rate should be the subject for optimization of process efficiency.
In particular, the influence of pH on fermentative H2 production is quite controversial in the literature. Generally, pH is a key parameter in fermentation that affects the degree of substrate hydrolysis, the activity of hydrogenase, as well as the metabolic pathways (Kim et al., 2011b). Changes in pH are thus reflected by variations in substrate and energy utilization, synthesis of proteins and various storage products, and metabolites production (Mu et al., 2006). In mixed anaerobic cultures, the operating pH also affects the relative proportions of microbial species (Fang and Liu, 2002; Shin and Youn, 2005; Mu et al., 2006; Nazlina et al., 2011). Highly acidic or basic pH values can negatively affect the activity of hydrogen-producing bacteria, since ATP is used to ensure cell neutrality rather than to produce H2 (Nazlina et al., 2011); low pHs can also result in inhibition of the hydrogenase activity (Khanal et al., 2004; Nazlina et al., 2011). Literature studies (see e.g., Yu et al., 2002; Khanal et al., 2004; Rechtenbach et al., 2008; Rechtenbach and Stegmann, 2009; Guo et al., 2010) generally agree upon the fact that H2-producing pathways involving acetate and butyrate production are favoured at pHs of approximately 4.5-6.0, while neutral or higher pHs promote ethanol and propionate production (associated to either H2-neutral or H2-consuming pathways). The effects of pH on the metabolic pathways and the associated fermentation yield have also been reported to depend on the specific characteristics of the inoculum and substrate (Nazlina et al., 2011), in particular for complex substrate compositions. The results of studies on the effect of pH on H2 production often show inconsistencies due to the different experimental conditions (substrate/inoculum type, amount and pre-treatment method, pH control strategy), so that systematic investigations on this specific issue are still missing.
Also, the effects of the ratio between substrate and inoculum also indicated as F/M (food to microorganism ratio), S/I or S/X (substrate to inoculum ratio), I/S and ISR (inoculum to substrate ratio) are poorly documented for anaerobic digestion of FW (Boulanger et al., 2012) and only few works are conducted specifically on dark fermentation of FW. Pan et al. (2008) has reported the effect of F/M (food to microorganism ratio) on hydrogen production of mixed food waste, finding that the optimal F/M ratio in mesophilic conditions was 6, with an H2 production of 39 ml/g VS. Further increase of the F/M resulted in diminished H2 production.
During the present research activity, combined H2 and CH4 production from two residues having different characteristics, cheese whey (CW) and municipal solid waste organic fraction (OFMSW), was studied. Various factors (in particular pH and F/M ratios) were studied in order to enhance H2 and CH4 yields, in particular to assess the optimal operating conditions for fermentative hydrogen production from the two substrates considered. As far as OFMSW was concerned, also the possibility of producing a compost of good quality from the solid phase of the anaerobic digestate was assessed.
In the first part of the research, the activity focused on CW treatment. Cheese whey is a by-product of cheese manufacturing and its main components are lactose (45-50 g/l), proteins (6-8 g/l), lipids (4-5 g/l) and mineral salts (8-10% dried extract). The CW treated in this study, is the effluent from cheese production using a mixture of sheep and cow milk.
Preliminary dark fermentation batch tests confirmed that hydrogen production from CW is possible even without any specific inoculum and strongly affected by multiple factors including substrate characteristics, as well as pH. Afterwards, semi-continuous anaerobic digestion tests were performed obtaining a stable hydrogen and methane production. For the first stage, three test were conducted, under mesophilic conditions with an HRT of 2 days, at the following pHs (7.5; 6.5; 5.5). The test operated with pH continuously controlled at 5.5 reached the maximum average yield of 80.8 Nl H2/kg TOC (38.4 Nl H2/kg VS) while in the second stage, operating under mesophilic conditions without pH control and adopting a HRT of 10 days, the average yield was 660.7 Nl CH4/kg TOC (383.6 Nl CH4/kg VS).
The second part of the research activity was devoted to the OFMSW treatment. OFMSW may represent a relatively inexpensive and suitable source of biodegradable organic matter mainly due to its high carbohydrate content and wide availability (Okamoto et al., 2000; Lay et al., 2003; Kim et al., 2004; Liu et al., 2006; Li et al., 2008a; Li et al., 2008b; Zhu et al., 2008; Wang and Zhao, 2009; Kim et al., 2011a; Nazlina et al., 2011).
Synthetic OFMSW was produced in laboratory, in order to make easier the comparison between the results of different tests, according to the following recipe: 8% of meat, 72% of fruit and vegetables, 8% of bread and 12% of cooked pasta (on a wet weight basis). Batch dark fermentation tests using untreated activated sludge as source of inoculum (T= 39°C; pH = 6.5) were performed at four F/M ratios (4; 7; 12 and 18) in order to assess the optimal one. The optimal F/M ratio resulted to be 7, corresponding to the maximum H2 yield of 89.9 Nl H2/ kg VS. Then, the effluent of the first stage (operated with the optimal F/M) was fed, mixed with methanogenic inoculum (F/M ratio = 0.5), to the second stage reactor to investigate methane production. The attained H2 and CH4 production was compared to the CH4 production achieved with a conventional single-stage batch reactor. The results confirm an higher CH4 yield for the second stage, 354 Nl CH4/kg VS versus 271 Nl CH4/kg VS for the single-stage.
After a detailed analysis of the informations obtained from the batch tests, a double stage system was operated under semi-continuous conditions in order to better approximate the full scale operation. In the first semi-continuous stage, (T = 39°C; HRT = 2 days; pH = 6.5; F/M = 18), the average yield was 31,8 Nl H2/kg VS while in the second one a stable methane production of 432 Nl CH4/kg VS was obtained at HRT = 25 days (T = 39°C; pH not set).
Finally, the solid phase of the digestate coming out form the double stage operated under semi-continuous conditions was composted after dewatering and mixing with a bulking agent. The final product was analysed for the main compost properties. The obtained compost reached a good stability (BOD4= 2 mg O2/l) and did not showed problems of phytotoxicity (germination index = 50%)
Diabetes-related ultrastructural and immunohistochemical changes in human salivary gland parenchyma and a study on a native scaffold obtained from salivary gland stroma
Get PDFSystemic pathologies such as diabetes and Sjögren’s syndrome, medications, and radiation therapy often affect salivary gland morphology and functionality, giving rise to changes in quantity and composition of saliva and to numerous oral complications that severely compromise the patient’s life quality. The aim of this thesis, articulated into two sections, was to evaluate:
1) if salivary gland morphology and functionality are affected by type 2 diabetes mellitus even when there are not evident signs of oral injuries;
2) the possibility to use a native scaffold derived from human salivary glands as a substrate in which salivary cells can be host to restore damaged salivary glands.
The first part of the investigations was carried out with surgical samples of salivary glands obtained from subjects, half diabetics and half non-diabetics, all without evident oral diseases. The samples were processed for light and electron microscopy and random images were subjected to morphometrical evaluation. The calculations revealed diabetes-related alterations such as acinar swelling and remarkable changes in serous cells, where secretory granules appeared enlarged but reduced in their total number. On the other hand, an increased number of granules anchored to the apical membrane was found, as well as an altered number of apical vesicles and microvilli (both involved in the mechanisms of membrane recycle). Taken together these findings suggest the occurrence of difficulties in the last step of exocytosis, and demonstrate that the structures involved in the secretory process are altered by diabetes per se. Other samples were analyzed by means of immunogold staining method to reveal the ultrastructural localization of melatonin and its receptors MT1 and MT2, until now never reported. Both melatonin and receptors were reactive in the secretory granules, in cytoplasmic vesicles and on cell surfaces, suggesting that their interaction could allow melatonin storage within specific cell compartments. Melatonin staining when performed on diabetic major salivary glands highlighted changes in the labeling intensity related with the diabetic condition.
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The second part is focused on the characterization of a native salivary gland scaffold in view of its use in gland reconstruction. As well as diabetes, radiation therapy, Sjögren’s syndrome, and several medications also give rise to salivary gland degeneration and xerostomia, but the therapies commonly used are not satisfactory so far. An emerging alternative approach to ameliorate the life quality of xerostomic patients is the regeneration of salivary parenchyma. A “Native Human Submandibular Gland Scaffold” (nHSMGS) was isolated from healthy submandibular glands, and was analyzed by light and electron microscopy and by histochemistry. Morphological examinations showed a fiber arrangement similar to that of the intact glands, while histochemistry revealed the presence of collagen type I, III, and IV. Then, a human salivary gland cell line and human fibroblasts were seeded and cultured on the scaffold in order to verify its reliability as autologous substrate for cells expansion. Results showed that a high cell percentage was proliferating after 4 days of culture, and that most cells were still alive after 8 days. All these data encourage the use of the nHSMGS as autologous scaffold in which expand salivary cells for the restoring of damaged salivary glands
Exploitation of new pharmacological targets for neuropathic pain reliefe
Get PDFNeuropathic pain is a complex chronic condition which affects the somatosensory system, poorly managed with the conventional treatments despite the immense advances in pain treatment strategies. Damage of peripheral nervous system, due to injury or disease, leads to abnormal responses to painful and not-painful stimuli; conventional analgesics can only alleviate pain in acute situation, and finding an effective treatment which can relief chronic neuropathic pain remains still challenging.
Mammalian STOML3, a MEC-2 homologue, is a member of a large family of stomatin proteins characterized by a common stomatin domain, expressed by DRG sensory neurons involved in regulation of mechanosensation, which is required for normal mechanoreceptor function. Previous data revealed that in STOML3 null mice 30-40% of Aδ and Aβ fibers lacked all mechanosensitivity; in addition, tactile behaviors are impaired and symptoms of neuropathic pain in CCI mice are also largely attenuated (Wetzel et al, 2007).
Here I investigated the mechanisms by which STOML3 acts as an important contributor in the neuropathic pain symptoms and I demonstrate that small molecule modulation that both reversibly silence mechanoreceptors in vivo and attenuate touch perception in mice can reverse established neuropathic pain symptoms, making STOML3 a promising novel peripheral target for the treatment of sensory disorders
Modulation of Hyperpolarization-Activated Cation Currents (Ih) by Ethanol in Rat Hippocampal CA3 Pyramidal Neurons
Get PDFIt is well established that ethanol (EtOH), through the interaction with several
membrane proteins, as well as intracellular pathways, is capable to modulate many
neuronal function. Recent reports show that EtOH increases the firing rate of
hippocampal GABAergic interneurons through the positive modulation of the
hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels. This effect
might be consistent with the increase of GABA release from presynaptic terminals
observed in both CA1 and CA3 inhibitory synapses that leads the enhancement of the
GABAergic system induced by EtOH. The activation of HCN produced an inward
currents that are commonly called Ih. Ih play an important role for generating specific
neuronal activities in different brain regions, including specific sub-regions of the
hippocampal formation, such as CA1 and CA3 pyramidal neurons and hippocampal
GABAergic interneurons. The main physiologic effect mediated by HCN-induced Ih is
directed to the control of the neuronal resting membrane potential and action
potential (AP) discharge as well as dampen synaptic integration. Since robust Ih are
also present in CA3 glutamatergic neurons, I here investigated whether the action of
EtOH in the control of CA3 excitability can be correlated with its possible direct
interaction with these cation channels. For this purpose, patch-clamp experiments
were performed in CA3 pyramidal neurons from hippocampal coronal slices obtained
from male Sprague-Dawley rats. The data obtained demonstrated that EtOH is able to
modulate Ih in biphasic manner depending on the concentrations used. Low EtOH
concentrations enhanced Ih amplitude, while high reversibly reduced them. This
biphasic action induced by EtOH reflects on firing rate and synaptic integration. In
addition, in this reports it has been shown that EtOH modulates the function of HCN
channels through interfering with the cAMP/AC/PKA intracellular pathways, an effect
that is mimicked also by other endogenous compounds such as dopamine through D1
receptors activation. These data suggest that the HCN-mediated Ih currents in CA3
pyramidal neurons are sensitive to EtOH action, which at low or relevant
concentrations is able to increase or reduce their function respectively. Altogether
these data suggest a potential new mechanism of EtOH actions on hippocampal
formation and may help to better understand the depressant central activity showed
by this drug of abus
L'azione economica tra etica e neurobiologia
Get PDFThe heated debate over the conflict between ethics and economics is often described
as an epochal issue, an expression of present-day fragility, resulting from the
implosion of the development model, which has characterised western society.
The debate, however, exposes a paradox. Whilst, on the one hand, the neoclassical
economic theory is radically criticized, on the other such criticism does not appear to
delineate any solid, practicable alternative. Thus, the mainstream economic theory is
still taught, practised by individuals as well as institutions, and further developed by
the prevailing academic research.
For this reason, a viable alternative needs to be sought, along with a new research
methodology, which would allow to apply novel and more coherent theoretical
assumptions into effective research and real cases.
The theoretical instruments by which to create the models for human behaviour
need to take into account the biological foundation of behaviour, expressed in
evolutionary genetics terms.
The aim of this paper is to establish whether our moral knowledge of economics
may claim any scientific objectivity in light of advances in subject areas that differ in
their scope and methods: moral philosophy, economics, cognitive neuroscience and
artificial intelligence, each of which makes a specific contribution to understanding
the operation of the human mind and towards forming the moral values onto which
economic choice and action are founded.
Given that the object of the study of economic science is the analysis of complex
systems, nowadays the most efficient method seems to be artificial life simulation
Il Libano politico tra partiti, famiglie e religione nella situazione contemporanea
Get PDFThis thesis covers a survey about the political life in my home country Lebanon where I
have approached the different political parties and the political families that were involved in the
social and political life dating back to the Lebanese independence, in addition to the tight relation
between politics and religions, which constitutes the pillars of our political regime.
Before getting core of my thesis, I highlighte
and the scientific approach among which I tackled the history of the political parties and families
My thesis is divided into 3 chapters:
Chapter 1: In the first section, I defined the concept of a party and its creation in the
western side of the globe and the Arabic East in addition to the ideological transfer from West to
East. I tackled as well the adaptation of the East to this eastern understanding of political parties
within its environment and society. The second section tackles the creation of the civil society in
the West and its adoption in the eastern region especially in Lebanon, which allows the
development of the social life by authorizing the creation of political parties and communities. I
discussed as well the creation of the political parties in the West and its impact on the East and
the role of freedom and democracy in allowing the creation of civil and non-political
communities.
Regarding Chapter 2, I tackled the history of the communities and the political parties in
Lebanon stressing on those who had high impact on the national and regional political situation
dating back to World War I and passing through the French mandate period and the Lebanese
independence until the civil war. I have shown the situation of the Lebanese parties and their
division nowadays into 2 blocs inside the community, each founding its principles based on the
18 religions recognized in Lebanon. In this Chapter, there is a clear picture about the tight
relation between religion and politics, the latter based on religion instead of citizenship and civil
secularism.
In the last Chapter, I approached the concept of the Lebanese political families involved
in politics and public affairs acquiring official positions in the government but on the other hand
offering social, cultural and educational services to their communities. In my country, those
services are called clientele services where the family offers its help to the citizens in exchange
of their vote during the elections. In this regard, I have mentioned 3 standards political families,
their foundation and most important personalities in addition to their roles in politics.
I have also tackled the role of the Lebanese political families in the political life and their
contribution in reaching our independence in addition to their perseverance in protection our
liberty until nowadays despite the hard phases my country have gone through.
In the second section from this chapter, I have landed into the history of the foundation of
the Lebanese Parliament and its principles, the electoral voting operation of its members upon
religious law instead of civil and the development of the electoral law that have differed from a
round to another.
At the end of the chapter, I have focused on the political families that have founded
political parties in order to organize their political activities attracting supporters that follow the
same ideas and political ideology. I have also focused on the historical and current role of these
parties on the Lebanese scene and their impact on the Lebanese community who majorly belong
to the families of those parties.
In the conclusion of my thesis, I have recapitulated the 3 chapters with my personal opinion to
constitute a Lebanese state based on secularism instead of religion despite the diversified
religions inside the Lebanese society
Characterization of ftsA conditional lethal mutants shows that FtsA is required at early and late stages of cell division in Streptococcus pneumoniae
Get PDFFtsA is an essential cell division protein fairly conserved among Eubacteria. It is an actin-like protein that structurally differs from actin because it lacks one of the four subdomains that is replaced by an additional one located elsewhere in the structure. FtsA localizes early at the cell division site, together or immediately after FtsZ, where it is needed both to tether FtsZ to the membrane and also to recruit to midcell the other cell division proteins. In agreement with this, FtsA interacts, at least, with itself, FtsZ, ZapA and the septal PBP, FtsI.
Despite the advances in understanding cell division in Streptococcus pneumoniae, little is known about the early stages of the process. Here I present the characterization of S. pneumoniae ftsA thermosensitive (Ts) mutants, obtained by error-prone random PCR, allelic replacement and subsequent screening for ability to grow at 28°C (permissive temperature) but not at 40°C (non permissive temperature). Out of 8000 transformants screened, three, named A19TS, A20TS and A21TS, were identified and shown to carry mutated ftsA alleles and express the corresponding mutated protein. The mutations mapped in different domains of the FtsA structure, thought to be involved in FtsA polymerization, interactions with FtsZ and/or with other cell division proteins. Temperature shifting experiments, carried out in rich medium, showed that in contrast to the Rx1 wild type, that grew well at both 28°C and 40°C, the FtsA Ts mutants stopped growing and started lysing about 60 to 90 minutes after shifting to the non permissive temperature, in a mutation specific manner. The lysis was greatly reduced when the shift to 40°C was performed in a chemically-defined medium or in a lytA- background. Detection of FtsAwt and FtsATS, in crude extracts, derived from cultures after shifting at 28°C and 40°C, revealed that all the FtsA Ts proteins are stable at both temperatures, indicating that protein degradation is not the cause of the Ts phenotype.
Protein-protein interaction assays showed that all three FtsATS proteins lost their ability to self-interact but retained their ability to interact with the FtsAWT protein and FtsZ. Consistently, GFP-FtsAWT, expressed under the control of the PZn inducible promoter at the ectopic bga locus of the S. pneumoniae chromosome, fully complemented the Ts phenotype of two, A20TS and A21TS, mutants. Interestingly, the Ts phenotype of the A19TS mutant was only partially complemented by GFP-FtsAWT, which localized as multiple rings in the partially complemented elongated A19TS+PZn-GFP-FtsAWT cells, suggesting the FtsA19TS may be dominant over FtsAWT.
Localization studies, using fluorescence microscopy, showed that CFP-FtsZ, DivIVA-GFP, GFP-StkP, GFP-GpsB and GFP-PBP2x exhibited proper localization in the Rx1WT at 28°C and 40°C, while in the FtsA Ts mutants these cell division markers were localized properly at 28°C but retained or lost their localization upon shifting to 40°C depending on the specific mutant. Notably, in all FtsA Ts mutants, FtsZ lost its septal localization after shifting to 40°C. The results are consistent with what was observed in a zinc dependent ftsA conditional lethal S. pneumoniae mutant, where the only source of FtsA was GFP-FtsA expressed under the control of the PZn inducible promoter, indicating that S. pneumoniae FtsA is required for efficient midcell localization of FtsZ and supporting the notion that in Gram-positives, which lack ZipA, FtsA may be absolutely necessary for anchoring FtsZ to the membrane.
Together these results confirm that FtsA is essential in S. pneumoniae and further validate it as a target to develop novel inhibitors active on septation. Moreover, the data suggest that an early block in cell division in S. pneumoniae impairs both growth and division, supporting a model in which a single machinery, containing both complexes, one for peripheral elongation and one for septum formation, directed by FtsZ, and likely by FtsA, is present at the midcell of oval-shaped cocci
Progettare con l'energia. Il Mediterraneo fra tradizione e innovazione
Get PDFStarting from the premise that the contemporary transformations in the Mediterranean
landscape have produced non places and architectures that are not recognisable by the
collectivity, the research considers the environmental issue as the key to critically review
the architectural solutions accrued during the man’s history in which the technique,
becoming a prerequisite for progress, has taken over the nature. The sustainability, as it
has been investigated in this thesis, is not only a value in time and space, but it is the way
for the reform of the project of Mediterranean architecture that is ecologically sound and
culturally recognisable.
The key used in order to investigate the sense of Mediterranean architecture and to
understand its evolution and the possible future developments in respect of sustainability
is the tradition. The concept of tradition is understood as selection of the repertoire of
knowledge inherited from the past through which the material culture is actualised in
compliance with the invariants that constitute its identity in respect with the continuity with
the present.
The goal is the definition of the principles that allow to an architecture to act sustainably to
the habitat, that changes the environment respecting its balance and its resources and the
needs of man. In this sense in this thesis is marked the importance of the minor
architectures, that result from a spontaneous process of adaptation, repetition and
assimilation of models in which are tested the principles of natural ventilation, the selection
of sunlight, the use of water in order to optimise the environmental comfort.
The intent is to build a reflection about the architecture of today, linking it with terms such
as "sustainability", "tradition" and "climate" and inserting these arguments within a
geographical and cultural context, at the same time relevant but also complex, that is the
Mediterranean area. It is described not only as an expression of a condition of
geographical location, but also through the translation of this condition in an architectural
language, which consciously prefers some principles in respect to others. Idea of
architecture, with precise formal features and space, recognisable only if fully associated
to its own context and cultural climate.
Through the description of several design experiences located in the Mediterranean basin
the thesis highlights some cases in which the project, the climate and the tradition closely
coexist.
The projects presented describes the compositional and formal quality, simplicity and
rigour, the research for a balance between tradition and innovation. This research, in fact,
while dealing with the bioclimatic architecture, explores one of the unresolved issues of the
sustainable architecture, which is the difficult conciliation of the eco-compatibility
requirements with the needs of the architectural composition and with the construction of
the form. On the one hand the scientific horizon, on the other the figurative one, are trying
to find a balance through the definition of their components: climate, architecture and man