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Optimisation of the bolometric performances of the CUORE-0/CUORE and LUCIFER detectors for the neutrinoless double beta decay search.
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CDKL5 e sindrome di Rett: un approccio molecolare per la definizione di una correlazione genotipo/fenotipo.
No full textLa sindrome di Rett è una grave malattia del neurosviluppo legata al cromosoma X che colpisce principalmente individui di sesso femminile. Le bambine affette da sindrome di Rett subiscono uno sviluppo postnatale apparentemente normale fino all'età di 6-18 mesi, per poi manifestare un marcato declino neurologico con decorso molto variabile. Circa il 25% delle pazienti sono affette da forme atipiche che si discostano dalla forma classica o per il fatto di essere più blande con un iter meno devastante o per un fenotipo più “aggressivo” con insorgenza precoce che può portare anche a crisi epilettiche non trattabili farmacologicamente.
La maggior parte dei casi di forma classica di Rett è causata da mutazioni nel gene MECP2, un repressore trascrizionale espresso maggiormente nel cervello che lega il DNA metilato e che causa la formazione di una struttura cromatinica compatta e trascrizionalmente inerte. Circa solo il 50% delle pazienti con varianti della sindrome di Rett però sono portatrici di mutazioni in questo gene. Per questa classe di fenotipi sono state descritte nel 2004 mutazioni a carico del gene CDKL5 codificante per una serin-treonina chinasi e nel 2008 altre a carico del gene FOXG1, un fattore trascrizionale. La ricerca scientifica ha quindi ampliato i propri obbiettivi al fine di comprendere se questi tre geni, apparentemente diversi fra loro, potessero essere accomunati da uno stesso pathway molecolare. A tutt'oggi però i risultati sono ancora scarsi e, a volte, contraddittori. Per quanto riguarda gli studi su CDKL5, un aspetto generalmente accettato risiede nel fatto che in tutti i casi l'attività catalitica di CDKL5 appare di estrema importanza. Con questa premessa, sarebbe quindi interessante osservare con quale modalità le mutazioni a carico di CDKL5 possano influire sulla sua funzione enzimatica.
L'obbiettivo della mia ricerca è stato quello di analizzare otto mutazioni puntiformi (A40V, N71D, V132G, R178W, W195R, E203D, L220P e T288I) giacenti sul dominio catalitico di CDKL5. Queste mutazioni sono state riscontrate in pazienti con la variante Hanefeld. Per ogni mutazione è stata valutata la localizzazione cellulare e l'attività chinasica sul motivo TEY. Inoltre, grazie all'ausilio di strumenti bioinformatici, è stato creato un modello tridimensionale del dominio chinasico di CDKL5 ed è stato possibile predire l'influenza che ogni mutazione ha sulla struttura della proteina.
L'analisi di localizzazione subcellulare ci ha permesso di concludere che in generale le mutazioni a carico del dominio catalitico non influenzano in maniera significativa la distribuzione di CDKL5 all'interno della cellula, a differenza delle mutazioni troncanti sulla coda carbossiterminale, precedentemente analizzate nel nostro laboratorio. Ciononostante per le mutazioni W195R e E203D si è osservato un accumulo della proteina nel compartimento citoplasmatico. E' stata inoltre osservata la perdita della tipica organizzazione in dots di CDKL5. Le analisi bioinformatiche collocano questi due residui nell' α-elica F del sottodominio IX del dominio chinasico della proteina. A quest'elica, comune alle MAP chinasi, era già stata precedentemente attribuita una cruciale importanza nell'orchestrazione dell'attività chinasica. E' quindi possibile che una sua precisa conformazione spaziale sia necessaria per una corretta interazione con le altre proteine e per una altrettanto corretta distribuzione della proteina all'interno della cellula.
L'analisi dell'attività catalitica invece ha permesso di evidenziare che le mutazioni in esame possono portare a perdita totale di fosforilazione (A40V), a una sua diminuzione (V132G, R178W, W195R, E203D, L220P e T288I) oppure a nessun effetto evidente (N71D). Per questa mutazione perciò è stato proposto un saggio di stabilità che ha evidenziato un'emivita minore rispetto alla forma canonica, dando un'ulteriore prova di come i livelli di CDKL5 probabilmente debbano essere finemente regolati per una sua corretta funzionalità neuronale.
Nell'ultimo periodo del mio dottorato ho avuto inoltre la possibilità di valutare un ipotetico ruolo di CDKL5 nella maturazione neuronale, in quanto è stata osservata la sua presenza a livello dei centrosomi in cellule proliferanti fissate in metafase.
E' ormai assodato il ruolo del centrosoma nelle tre fasi della maturazione neuronale e perciò ho approfondito questo aspetto verificando la colocalizzazione di CDKL5 nel centrosoma anche in colture di neuroni corticali in via di maturazione. Questa scoperta non chiarisce con certezza quale sia lo specifico ruolo di CDKL5 in questo fenomeno ma offre sicuramente una nuova chiave di lettura per stabilire quale meccanismo neuronale venga a mancare nelle pazienti portatrici di difetti in questo gene
Fine-roots dynamics, anatomy and carbon-nitrogen concentrations in relation to forest management and soil water content. Case studies in beech(Fagus sylvatica L.) and Turkey-oak (Quercus cerris L.) forests.
No full textUncertainties in estimates of fine root dynamics prevent a proper quantification of net primary productivity and belowground C allocation. Moreover, model studies for estimating carbon budgets are biased by the lack of fine roots datasets at forest stand level. This study shed some lights on fine root dynamics in two different Italian forests. In particular fine-root systems was investigated: 1) in three beech forest stands (Fagus sylvatica L.) located in Southern-Alps in relation to different forest management practices and age 2) in a mature Turkey-oak stand (Quercus cerris L.) located in the Southern Apennines in relation to soil moisture seasonal changes.
Data from beech forests showed that conversion from coppice to high forest practice induced considerable variations in fine-root traits. Reduction of stand tree density induced a reduction of total fine-root mass and an increase of both production and turnover rate. Both fine-root production and turnover rate increased in converted stands. When fine-roots Carbon and Nitrogen contents were analyzed, their ratio was significantly lower in converted stands, supporting the finding of a higher turnover rate. A histological study was carried to assess if also anatomical changes occurred due to conversion practices. Anatomy on fine roots showed a higher percentage of xylem cells in conversion stands explaining the lowest carbon concentration.
Turkey-oak fine-root biomass and length showed a bimodal pattern with a peak in summer and a peak in autumn. SRL had only one peak in summer. All fine root traits increased during the transition from the wet to dry season. These results indicate a pulse in root growth in order to increase the soil exploitation when soil water content is low. Moreover, during the summer period, Q. cerris change fine-root morphology leading an increase of fine root length per unit mass
Host immune suppression by toxoneuron nigriceps polidnavirus: use of Drtosophila melanogaster as an experimental model system.
No full textHost regulation strategies adopted by parasitic Hymenoptera are increasingly attracting the scientific interest, since several data support the idea that these strategies include targeting of evolutionarily conserved pathways.
This is in particular emerging from molecular and functional analyses of several parasitoid-associated polydnaviruses (PDVs), whose gene products, expressed in the tissues of parasitized hosts, interact with key signaling molecules (Pennacchio and Strand. 2006; Espagne et al. 2004; Falabella et al. 2003; Falabella et al. 2007; Provost et al. 2004; Thoetkiattikul et al. 2005).
T. nigriceps bracovirus (TnBV) is the PDV associated with Toxoneuron nigriceps (Hymenoptera, Braconidae), the endophagous larval parasitoid of the tobacco budworm Heliotis virescens (Lepidoptera, Noctuide).
We recently identified a host gene, named 102, which is targeted by a small TnBV transcript. Several data indicate that this gene is involved in the immune response, but its mode of action is still unclear.
Since the 102 gene is highly conserved throughout evolution, to investigate the function of the protein encoded by the 102 gene, we decided to use Drosophila melanogaster as a model system, since it offers a wide range of molecular genetic tools not available in other systems: its genome is fully sequenced; detailed knowledge about the molecular pathways regulating cellular immune responses is available; several sophisticated genetic and molecular genetic techniques have been developed and can be used as powerful tools to dissect the functional mechanisms underlying a wide range of biological processes.
In Drosophila melanogaster two putative protein sequences, showing 38% and 34% identity, respectively, with the translation product of the 102 gene, were found by Blast analyses. One of these is highly expressed in larval hemocytes, like its Heliotis virescence counterpart. Moreover, as reported in the Flyatlas database (http://www.flyatlas.org/), the gene is strongly expressed also in the fat body.
I took advantage of the well-established RNAi strategies based on the GAL4/UAS binary system to interfere with the expression of this gene in immuno-competent tissues (i.e. hemocytes and fat body) of Drosophila melanogaster. First of all, I evaluated the potential impact of this tissue-specific RNA interference on viability and found a dramatic lethal effect approaching 100%. Lethal phase measurements indicated that mortality was prominent in larval and pupal stages. Morphological analyses of the larvae in which the 102 gene had been targeted by RNA interference showed the presence of huge melanotic masses freely floating in the hemocoel. This tumorous-like phenotype is usually associated with altered and/or excessive performance of the immune system. Accordingly, hemocyte counts indicated that hemocyte overproliferation occurred in larvae, and increased numbers of both plasmatocytes and lamellocytes were found in their hemolymph. Furthermore, in these larvae, the sessile hemocyte population, was also affected.
Finally, morphological analyses of melanotic masses clearly identified their association with hemocytes, forming a cellular capsule around them
Il capello come matrice per il monitoraggio della esposizione ad antiparassitari.
No full textThis Thesis is based mainly on the results of the timing analysis applied to the gamma-ray pulsars observed principally by the AGILE satellite and also extended, in some cases, to observations with the Fermi-LAT satellite and the MAGIC Cherenkov telescope. Aim of this extended study of pulsars at the high energies was to characterize their properties based, now, on a more statistically relevant sample, and be able to disentangle useful informations that can be key to explain the emission mechanisms in pulsars.
THE SCIENTIFIC CONTEXT Pulsars are highly-magnetized, rapidly-rotating neutron stars. As explained in Chapter 1, they have been observed in the radio band over the past forty years, due to their highly anisotropic emission, which, when combined with the misalignment between the rotation and the magnetic axis, produces the pulsed emission we observed, also called the ”lighthouse effect”. Pulsars have been observed as gamma-ray emitters as well, but it is only in the past three years that their number hit the double digits and they started to yield their potential as keys to explain the neutron stars mechanisms.
In Chapter 1, the basics of pulsar theory are given. While the phenomenological aspects have been widely studied thanks to extensive radio observations through the years, their electrodynamics represents an articulated field that is difficult to probe. The ”classical” models of magnetosphere predict the presence of regions of particles’ under-density (a ”gap”), inside an overall force-free magnetized area that surrounds the pulsar, where the particles can be accelerated and can produce the observed radiation, after a number of cascade processes. More ”modern” models of magnetosphere, with their roots in old predictions, discuss the hypothesis of a totally force-free magnetosphere. The discussed theories search for a confirmation in our gamma-ray observations, as the gamma-rays are the ones carrying away a good fraction of the rotational energy loss.
THE NEW PERSPECTIVES OPENED BY THE MULTI-BAND OBSERVATIONS
In April 2007 the Italian Space Agency launched the AGILE satellite for gamma-ray astronomy. About one year later, AGILE was joined in the observation of gammarays by the 16 times bigger Fermi-LAT satellite launched by NASA. AGILE and Fermi-LAT, with their wide field of view and large collective area, are particularly suited for the study of pulsars at high energies. Most recently, the window of veryhigh energy observations has opened up to pulsar studies and, in particular, by the MAGIC telescope, with the lowest up to now threshold for ground-based telescopes, at 25 GeV. Its observations are briefly described, together with AGILE and Fermi-LAT’s, in Chapter 2.
The techniques for studying pulsars in the gamma-rays are also explained in Chapter 2, with the fundamental premise about the radio observations which were part of my analysis work, as they constitute the primary basis for the gammaray observations. The advances with respect to the observations of the previous generation gamma-ray instruments are highlighted. In particular, AGILE was able to take into account, for the first time in gamma-ray observations, the timing noise that affects young pulsars. In this way, the observations can be carried out for longer time spans without being affected by sensible light curve smearing. Thus, we could take advantage of the long time span, up to now the longest for gamma-ray observations, to increase the resolution of our light curves and see structures at the sub-millisecond level.
GAMMA-RAY PULSARS AGILE and Fermi-LAT pulsar observations first concentrated on the known gamma-ray pulsars. As shown in Chapter 3, the apparently ”familiar” pulsars actually hid thriving new prospects for pulsar studies, as well as the new pulsars subsequently detected, described in Chapter 4.
In these two Chapters, the properties of the gamma-ray emission ars analyzed for a number of pulsars, mainly using AGILE data, but also with Fermi-LAT and MAGIC observations. The light curves are investigated with increased resolution from previous observations and the spectral properties are addressed. The availability of a statistically significant sample of gamma-ray pulsars led us to draw some lines on the models. The classical polar cap model seems to be failing the test of gamma-ray observations for most of the present sample, and a simple explanation of which can be found in conservation laws arguments discussed in Chapter 4. At the same time it starts getting clear that a model that contemplates a single gap zone does not seem to be feasible to explain the observed pulse profiles. And, possibly, the entire gap theory should be combined with the more physical force-free models.
Episodes of variability in pulsars have been observed and studied in this context. The Vela glitch of August 2007 was observed by AGILE in search for gamma-ray emission. The Crab pulsar could have a contribution to the emission from a newly observed third pulsar peak, that is less significant and much weaker than the canonical two, and could be due to giant pulses. AGILE observed the first gamma-ray millisecond pulsar but its emission only appeared in a restricted time interval, leading to the interesting possibility that pulsar emission might have some intrinsic variability.
HIGH MAGNETIC FIELD PULSARS After the advent of Fermi-LAT, AGILE found its collocation in the gamma-ray astronomy in the characterization of the low-energy gamma-rays (from 30 to 100 MeV), where the collective areas of the two instruments is equivalent, but AGILE deals with much lower background. For this reason, we concentrated on those pulsars that show a low-energy cutoff, which were theorized to emit gamma-ray radiation through the exotic QED process of photon splitting.
A detailed analysis of the two most significant cases is given in Chapter 5. We have found that the concurrence of a high magnetic field and an aligned geometry, could overcome the objections from Chapter 4 against inner magnetosphere emission and be, indeed, dominated by polar cap emission. Interestingly, this phenomenology, that is observed in pulsars that are similar to magnetars, may be observed in objects that are transitioning from pulsar to magnetar.
THE ENVIRONMENT OF PULSARS Young pulsars are known to power a relativistic wind of particles that surrounds the pulsar and is best known as its Pulsar Wind Nebula (PWN). Important phenomena take place in the PWN and they are powered by the pulsar inside it. As discussed in Chapter 6, very high energy emission was already observed from PWN, but high energy emission was missing, in a spectral region where important constraints on the emission processes could be given.
AGILE was the first satellite to detect GeV emission from a PWN apart from Crab, Vela X, and it was also the first to claim the unexpected flux variation in the Crab Nebula which underwent two intense flares in 2010 and 2011. In Chapter 6 we give a description of the events and a possible trail for an interpretation, although no clear picture can yet emerge from the observed events.
CONCLUSIONS AND FUTURE PROSPECTS The multi-band approach that has been used for the observations described in this Thesis has proven valid for the exploitation of new science and the most useful approach for the comprehensive analysis of pulsar phenomena across the electromagnetic spectrum. As a completion to this work, the more comprehensive AGILE Pulsar Catalog is in preparation. It will comprise all the pulsars observed by AGILE and particularly focus on the low-energy tail of them, which present interesting properties that bridge pulsars and magnetars
Prevalenza della sintomatologia neuropsichiatrica e suo trattamento farmacologico in una popolazione di anziani istituzionalizzati attraverso l’uso della Neuropsychiatric Inventory-Nursing Home version (NPI-NH).
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Effective interactions and phase behavior of colloidal dispersions.
No full textThe thesis deals with a number topics concerning the equilibrium properties and the phase behavior of colloidal suspensions, a class of physical systems that have attracted a broad interest during the last few decades, serving both as a valuable test bench for ideas in condensed matter physics and as building blocks for novel materials. An emphasis is placed on the notion of effective interaction, which enables the construction of simple models that are studied by use of theory and computer simulation. The questions addressed include the thermodynamics of particles interacting through a short-ranged attraction, fluctuation-induced (critical Casimir) forces, and the effect of polydispersity on the freezing transition of charged colloids
Multiloop amplitudes in superstring theory.
No full textString theory is a candidate for a unified theory of all forces in nature.
String theory is a quantum theory, and, because it includes a state that can be identified with the graviton, it is a quantum theory of gravity. So it could be a framework for describing the four fundamental interactions. The main idea is to replace the description of particles as zero dimensional object with one dimensional object, a string. Mimicking the procedure followed in QFT one can formulate the theory using the Feynmann path integral. In this context one would be able to compute the amplitudes for a process of string scattering, as, for example, in QED. It was shown that correct definition of the amplitudes is strictly connected with the construction of a suitable measure on the moduli space of certain Riemann surfaces of genus g. Thus an essential element in the computation of string amplitudes is the definition of this chiral measure.
During the last fifteen years the correct expression for the superstring measure was found just up to genus two. In this thesis I will present a general method to compute the measure up to five loop which as a byproduct also improves the known results for genus two and shows that the previous formulated ansatze for the genus three amplitude was wrong. In the first part I present the well known construction of the partition function in the bosonic theory. Actually, this is the starting point for the the generalization to the supersymmetric case. Then, I introduce the mathematical background we need to obtain the superstring measure. Finally, I discuss in great details the construction of the measure up to genus five and some open problems are emphasized. Moreover, I will also point out that the path integral procedure leads to some ambiguities related to the infinite dimension of the functional measure appearing in the path integral and I will explain the main difficulties related to its mathematically rigorous definition
La Bisanzio dei lumi. L'impero romano d'oriente nella storiografia e nella cultura.
No full textIn the 17th and 18th centuries, especially (but not exclusively) starting from the reign of Louis XIV, the interest in Byzantine Empire has seen in France – and also in Italy although in a more marginal way – a new flowering.
In this period of time, almost a century and a half, going from the reign of the Sun King (1638-1715) until the French Revolution (1789), the revival of Byzantine studies is determined from different factors – religious, political, emotional, philosophical – which cannot be reduced only to the discreditable image provided by the Enlightenment (however, not by “all” Enlightenment).
The Byzantine Empire with its Greek orthodox faith becomes from a catholic point of view the emblem of the betrayal of the “true” Roman Catholic faith and, for this reason, connected with the more recent Protestant Reformation. From another one, Byzantium is meant to glorify Louis XIV, whose lineage went back to the Latin emperors of Constantinople (1204-1261), as well as to support his pretensions to the Constantinopolitan throne against Habsburg’s one. At the same time, if from one side Byzantine history is aimed at the celebration of French monarchy, on the other one, with the rise of the Ottoman Empire threatening Europe, the Byzantine Empire conquered by the Turks in 1453 is raised as a negative model to avoid. In the end, with the rise of Enlightenment thought in the 18th century, Byzantium is taken as example of the despotism and the violence of despotic power against an absolutism more “enlightened”.
However, contemporary, a positive, although not predominant, view of the Byzantine Empire can be found. In particular that is concerning the crusades involving the Byzantine Empire between the 11th and 13th centuries, seen and condemned as an attack of the Latins against the Byzantines.
The aim of this work is hence to shed light on the complexity of the “Byzantium problem” in the 17th-18th centuries, showing how the history of Byzantine Empire has been subject to a different and sometimes controversial, interpretations which it is not possible to ascribe to a coherent and uniform thought