New Synthetic Polyamines as Multi-Target-Directed Ligands for the Treatment of Alzheimer's Disease and Cancer: Design, Synthesis and Biological Evaluation

Alzheimer's disease (AD) and cancer represent two of the main causes of death worldwide. They are complex multifactorial diseases and several biochemical targets have been recognized to play a fundamental role in their development. Basing on their complex nature, a promising therapeutical approach could be represented by the so-called "Multi-Target-Directed Ligand" approach. This new strategy is based on the assumption that a single molecule could hit several targets responsible for the onset and/or progression of the pathology. In particular in AD, most currently prescribed drugs aim to increase the level of acetylcholine in the brain by inhibiting the enzyme acetylcholinesterase (AChE). However, clinical experience shows that AChE inhibition is a palliative treatment, and the simple modulation of a single target does not address AD aetiology. Research into newer and more potent anti-AD agents is thus focused on compounds whose properties go beyond AChE inhibition (such as inhibition of the enzyme β-secretase and inhibition of the aggregation of beta-amyloid). Therefore, the MTDL strategy seems a more appropriate approach for addressing the complexity of AD and may provide new drugs for tackling its multifactorial nature. In this thesis, it is described the design of new MTDLs able to tackle the multifactorial nature of AD. Such new MTDLs designed are less flexible analogues of Caproctamine, one of the first MTDL owing biological properties useful for the AD treatment. These new compounds are able to inhibit the enzymes AChE, beta-secretase and to inhibit both AChE-induced and self-induced beta-amyloid aggregation. In particular, the most potent compound of the series is able to inhibit AChE in subnanomolar range, to inhibit β-secretase in micromolar concentration and to inhibit both AChE-induced and self-induced beta-amyloid aggregation in micromolar concentration. Cancer, as AD, is a very complex pathology and many different therapeutical approaches are currently use for the treatment of such pathology. However, due to its multifactorial nature the MTDL approach could be, in principle, apply also to this pathology. Aim of this thesis has been the development of new molecules owing different structural motifs able to simultaneously interact with some of the multitude of targets responsible for the pathology. The designed compounds displayed cytotoxic activity in different cancer cell lines. In particular, the most potent compounds of the series have been further evaluated and they were able to bind DNA resulting 100-fold more potent than the reference compound Mitonafide. Furthermore, these compounds were able to trigger apoptosis through caspases activation and to inhibit PIN1 (preliminary result). This last protein is a very promising target because it is overexpressed in many human cancers, it functions as critical catalyst for multiple oncogenic pathways and in several cancer cell lines depletion of PIN1 determines arrest of mitosis followed by apoptosis induction. In conclusion, this study may represent a promising starting pint for the development of new MTDLs hopefully useful for cancer and AD treatment.

Welfare provision in Sweden and the dominant position of the Sap

There have been almost fifty years since Harry Eckstein' s classic monograph, A Theory of Stable Democracy (Princeton, 1961), where he sketched out the basic tenets of the “congruence theory”, which was to become one of the most important and innovative contributions to understanding democratic rule. His next work, Division and Cohesion in Democracy, (Princeton University Press: 1966) is designed to serve as a plausibility probe for this 'theory' (ftn.) and is a case study of a Northern democratic system, Norway. What is more, this line of his work best exemplifies the contribution Eckstein brought to the methodology of comparative politics through his seminal article, “ “Case Study and Theory in Political Science” ” (in Greenstein and Polsby, eds., Handbook of Political Science, 1975), on the importance of the case study as an approach to empirical theory. This article demonstrates the special utility of “crucial case studies” in testing theory, thereby undermining the accepted wisdom in comparative research that the larger the number of cases the better. Although not along the same lines, but shifting the case study unit of research, I intend to take up here the challenge and build upon an equally unique political system, the Swedish one. Bearing in mind the peculiarities of the Swedish political system, my unit of analysis is going to be further restricted to the Swedish Social Democratic Party, the Svenska Arbetare Partiet. However, my research stays within the methodological framework of the case study theory inasmuch as it focuses on a single political system and party. The Swedish SAP endurance in government office and its electoral success throughout half a century (ftn. As of the 1991 election, there were about 56 years - more than half century - of interrupted social democratic "reign" in Sweden.) are undeniably a performance no other Social Democrat party has yet achieved in democratic conditions. Therefore, it is legitimate to inquire about the exceptionality of this unique political power combination. Which were the different components of this dominance power position, which made possible for SAP's governmental office stamina? I will argue here that it was the end-product of a combination of multifarious factors such as a key position in the party system, strong party leadership and organization, a carefully designed strategy regarding class politics and welfare policy. My research is divided into three main parts, the historical incursion, the 'welfare' part and the 'environment' part. The first part is a historical account of the main political events and issues, which are relevant for my case study. Chapter 2 is devoted to the historical events unfolding in the 1920-1960 period: the Saltsjoebaden Agreement, the series of workers' strikes in the 1920s and SAP's inception. It exposes SAP's ascent to power in the mid 1930s and the party's ensuing strategies for winning and keeping political office, that is its economic program and key economic goals. The following chapter - chapter 3 - explores the next period, i.e. the period from 1960s to 1990s and covers the party's troubled political times, its peak and the beginnings of the decline. The 1960s are relevant for SAP's planning of a long term economic strategy - the Rehn Meidner model, a new way of macroeconomic steering, based on the Keynesian model, but adapted to the new economic realities of welfare capitalist societies. The second and third parts of this study develop several hypotheses related to SAP's 'dominant position' (endurance in politics and in office) and test them afterwards. Mainly, the twin issues of economics and environment are raised and their political relevance for the party analyzed. On one hand, globalization and its spillover effects over the Swedish welfare system are important causal factors in explaining the transformative social-economic challenges the party had to put up with. On the other hand, Europeanization and environmental change influenced to a great deal SAP's foreign policy choices and its domestic electoral strategies. The implications of globalization on the Swedish welfare system will make the subject of two chapters - chapters four and five, respectively, whereupon the Europeanization consequences will be treated at length in the third part of this work - chapters six and seven, respectively. Apparently, at first sight, the link between foreign policy and electoral strategy is difficult to prove and uncanny, in the least. However, in the SAP's case there is a bulk of literature and public opinion statistical data able to show that governmental domestic policy and party politics are in a tight dependence to foreign policy decisions and sovereignty issues. Again, these country characteristics and peculiar causal relationships are outlined in the first chapters and explained in the second and third parts. The sixth chapter explores the presupposed relationship between Europeanization and environmental policy, on one hand, and SAP's environmental policy formulation and simultaneous agenda-setting at the international level, on the other hand. This chapter describes Swedish leadership in environmental policy formulation on two simultaneous fronts and across two different time spans. The last chapter, chapter eight - while trying to develop a conclusion, explores the alternative theories plausible in explaining the outlined hypotheses and points out the reasons why these theories do not fit as valid alternative explanation to my systemic corporatism thesis as the main causal factor determining SAP's 'dominant position'. Among the alternative theories, I would consider Traedgaardh L. and Bo Rothstein's historical exceptionalism thesis and the public opinion thesis, which alone are not able to explain the half century social democratic endurance in government in the Swedish case.

Contribution of Non-Covalent Interactions and Electronic Effects on the Conformational Landscape and Tautomeric Equilibria of Molecules and Molecular Complexes: Structural and Dynamical Data from Rotational Spectroscopy

This thesis concerns the study of complex conformational surfaces and tautomeric equilibria of molecules and molecular complexes by quantum chemical methods and rotational spectroscopy techniques. In particular, the focus of this research is on the effects of substitution and noncovalent interactions in determining the energies and geometries of different conformers, tautomers or molecular complexes. The Free-Jet Absorption Millimeter Wave spectroscopy and the Pulsed-Jet Fourier Transform Microwave spectroscopy have been applied to perform these studies and the obtained results showcase the suitability of these techniques for the study of conformational surfaces and intermolecular interactions. The series of investigations of selected medium-size molecules and complexes have shown how different instrumental setups can be used to obtain a variety of results on molecular properties. The systems studied, include molecules of biological interest such as anethole and molecules of astrophysical interest such as N-methylaminoethanol. Moreover halogenation effects have been investigated on halogen substituted tautomeric systems (5-chlorohydroxypyridine and 6-chlorohydroxypyridine), where it has shown that the position of the inserted halogen atom affects the prototropic equilibrium. As for fluorination effects, interesting results have been achieved investigating some small complexes where a molecule of water is used as a probe to reveal the changes on the electrostatic potential of different fluorinated compounds: 2-fluoropyridine, 3-fluoropyridine and penta-fluoropyridine. While in the case of the molecular complex between water and 2-fluoropyridine and 3-fluoropyridine the geometry of the complex with one water molecule is analogous to that of pyridine with the water molecule linked to the pyridine nitrogen, the case of pentafluoropyridine reveals the effect of perfluorination and the water oxygen points towards the positive center of the pyridine ring. Additional molecular adducts with a molecule of water have been analyzed (benzylamine-water and acrylic acid-water) in order to reveal the stabilizing driving forces that characterize these complexes.

Caratterizzazione del legame di molecole di interesse farmaceutico alla sieroalbumina umana mediante biocromatografia e dicroismo circolare

Negli ultimi anni, un crescente numero di studiosi ha focalizzato la propria attenzione sullo sviluppo di strategie che permettessero di caratterizzare le proprietà ADMET dei farmaci in via di sviluppo, il più rapidamente possibile. Questa tendenza origina dalla consapevolezza che circa la metà dei farmaci in via di sviluppo non viene commercializzato perché ha carenze nelle caratteristiche ADME, e che almeno la metà delle molecole che riescono ad essere commercializzate, hanno comunque qualche problema tossicologico o ADME [1]. Infatti, poco importa quanto una molecola possa essere attiva o specifica: perché possa diventare farmaco è necessario che venga ben assorbita, distribuita nell’organismo, metabolizzata non troppo rapidamente, ne troppo lentamente e completamente eliminata. Inoltre la molecola e i suoi metaboliti non dovrebbero essere tossici per l’organismo. Quindi è chiaro come una rapida determinazione dei parametri ADMET in fasi precoci dello sviluppo del farmaco, consenta di risparmiare tempo e denaro, permettendo di selezionare da subito i composti più promettenti e di lasciar perdere quelli con caratteristiche negative. Questa tesi si colloca in questo contesto, e mostra l’applicazione di una tecnica semplice, la biocromatografia, per caratterizzare rapidamente il legame di librerie di composti alla sieroalbumina umana (HSA). Inoltre mostra l’utilizzo di un’altra tecnica indipendente, il dicroismo circolare, che permette di studiare gli stessi sistemi farmaco-proteina, in soluzione, dando informazioni supplementari riguardo alla stereochimica del processo di legame. La HSA è la proteina più abbondante presente nel sangue. Questa proteina funziona da carrier per un gran numero di molecole, sia endogene, come ad esempio bilirubina, tiroxina, ormoni steroidei, acidi grassi, che xenobiotici. Inoltre aumenta la solubilità di molecole lipofile poco solubili in ambiente acquoso, come ad esempio i tassani. Il legame alla HSA è generalmente stereoselettivo e ad avviene a livello di siti di legame ad alta affinità. Inoltre è ben noto che la competizione tra farmaci o tra un farmaco e metaboliti endogeni, possa variare in maniera significativa la loro frazione libera, modificandone l’attività e la tossicità. Per queste sue proprietà la HSA può influenzare sia le proprietà farmacocinetiche che farmacodinamiche dei farmaci. Non è inusuale che un intero progetto di sviluppo di un farmaco possa venire abbandonato a causa di un’affinità troppo elevata alla HSA, o a un tempo di emivita troppo corto, o a una scarsa distribuzione dovuta ad un debole legame alla HSA. Dal punto di vista farmacocinetico, quindi, la HSA è la proteina di trasporto del plasma più importante. Un gran numero di pubblicazioni dimostra l’affidabilità della tecnica biocromatografica nello studio dei fenomeni di bioriconoscimento tra proteine e piccole molecole [2-6]. Il mio lavoro si è focalizzato principalmente sull’uso della biocromatografia come metodo per valutare le caratteristiche di legame di alcune serie di composti di interesse farmaceutico alla HSA, e sul miglioramento di tale tecnica. Per ottenere una miglior comprensione dei meccanismi di legame delle molecole studiate, gli stessi sistemi farmaco-HSA sono stati studiati anche con il dicroismo circolare (CD). Inizialmente, la HSA è stata immobilizzata su una colonna di silice epossidica impaccata 50 x 4.6 mm di diametro interno, utilizzando una procedura precedentemente riportata in letteratura [7], con alcune piccole modifiche. In breve, l’immobilizzazione è stata effettuata ponendo a ricircolo, attraverso una colonna precedentemente impaccata, una soluzione di HSA in determinate condizioni di pH e forza ionica. La colonna è stata quindi caratterizzata per quanto riguarda la quantità di proteina correttamente immobilizzata, attraverso l’analisi frontale di L-triptofano [8]. Di seguito, sono stati iniettati in colonna alcune soluzioni raceme di molecole note legare la HSA in maniera enantioselettiva, per controllare che la procedura di immobilizzazione non avesse modificato le proprietà di legame della proteina. Dopo essere stata caratterizzata, la colonna è stata utilizzata per determinare la percentuale di legame di una piccola serie di inibitori della proteasi HIV (IPs), e per individuarne il sito(i) di legame. La percentuale di legame è stata calcolata attraverso il fattore di capacità (k) dei campioni. Questo parametro in fase acquosa è stato estrapolato linearmente dal grafico log k contro la percentuale (v/v) di 1-propanolo presente nella fase mobile. Solamente per due dei cinque composti analizzati è stato possibile misurare direttamente il valore di k in assenza di solvente organico. Tutti gli IPs analizzati hanno mostrato un’elevata percentuale di legame alla HSA: in particolare, il valore per ritonavir, lopinavir e saquinavir è risultato maggiore del 95%. Questi risultati sono in accordo con dati presenti in letteratura, ottenuti attraverso il biosensore ottico [9]. Inoltre, questi risultati sono coerenti con la significativa riduzione di attività inibitoria di questi composti osservata in presenza di HSA. Questa riduzione sembra essere maggiore per i composti che legano maggiormente la proteina [10]. Successivamente sono stati eseguiti degli studi di competizione tramite cromatografia zonale. Questo metodo prevede di utilizzare una soluzione a concentrazione nota di un competitore come fase mobile, mentre piccole quantità di analita vengono iniettate nella colonna funzionalizzata con HSA. I competitori sono stati selezionati in base al loro legame selettivo ad uno dei principali siti di legame sulla proteina. In particolare, sono stati utilizzati salicilato di sodio, ibuprofene e valproato di sodio come marker dei siti I, II e sito della bilirubina, rispettivamente. Questi studi hanno mostrato un legame indipendente dei PIs ai siti I e II, mentre è stata osservata una debole anticooperatività per il sito della bilirubina. Lo stesso sistema farmaco-proteina è stato infine investigato in soluzione attraverso l’uso del dicroismo circolare. In particolare, è stato monitorata la variazione del segnale CD indotto di un complesso equimolare [HSA]/[bilirubina], a seguito dell’aggiunta di aliquote di ritonavir, scelto come rappresentante della serie. I risultati confermano la lieve anticooperatività per il sito della bilirubina osservato precedentemente negli studi biocromatografici. Successivamente, lo stesso protocollo descritto precedentemente è stato applicato a una colonna di silice epossidica monolitica 50 x 4.6 mm, per valutare l’affidabilità del supporto monolitico per applicazioni biocromatografiche. Il supporto monolitico monolitico ha mostrato buone caratteristiche cromatografiche in termini di contropressione, efficienza e stabilità, oltre che affidabilità nella determinazione dei parametri di legame alla HSA. Questa colonna è stata utilizzata per la determinazione della percentuale di legame alla HSA di una serie di poliamminochinoni sviluppati nell’ambito di una ricerca sulla malattia di Alzheimer. Tutti i composti hanno mostrato una percentuale di legame superiore al 95%. Inoltre, è stata osservata una correlazione tra percentuale di legame è caratteristiche della catena laterale (lunghezza e numero di gruppi amminici). Successivamente sono stati effettuati studi di competizione dei composti in esame tramite il dicroismo circolare in cui è stato evidenziato un effetto anticooperativo dei poliamminochinoni ai siti I e II, mentre rispetto al sito della bilirubina il legame si è dimostrato indipendente. Le conoscenze acquisite con il supporto monolitico precedentemente descritto, sono state applicate a una colonna di silice epossidica più corta (10 x 4.6 mm). Il metodo di determinazione della percentuale di legame utilizzato negli studi precedenti si basa su dati ottenuti con più esperimenti, quindi è necessario molto tempo prima di ottenere il dato finale. L’uso di una colonna più corta permette di ridurre i tempi di ritenzione degli analiti, per cui la determinazione della percentuale di legame alla HSA diventa molto più rapida. Si passa quindi da una analisi a medio rendimento a una analisi di screening ad alto rendimento (highthroughput- screening, HTS). Inoltre, la riduzione dei tempi di analisi, permette di evitare l’uso di soventi organici nella fase mobile. Dopo aver caratterizzato la colonna da 10 mm con lo stesso metodo precedentemente descritto per le altre colonne, sono stati iniettati una serie di standard variando il flusso della fase mobile, per valutare la possibilità di utilizzare flussi elevati. La colonna è stata quindi impiegata per stimare la percentuale di legame di una serie di molecole con differenti caratteristiche chimiche. Successivamente è stata valutata la possibilità di utilizzare una colonna così corta, anche per studi di competizione, ed è stata indagato il legame di una serie di composti al sito I. Infine è stata effettuata una valutazione della stabilità della colonna in seguito ad un uso estensivo. L’uso di supporti cromatografici funzionalizzati con albumine di diversa origine (ratto, cane, guinea pig, hamster, topo, coniglio), può essere proposto come applicazione futura di queste colonne HTS. Infatti, la possibilità di ottenere informazioni del legame dei farmaci in via di sviluppo alle diverse albumine, permetterebbe un migliore paragone tra i dati ottenuti tramite esperimenti in vitro e i dati ottenuti con esperimenti sull’animale, facilitando la successiva estrapolazione all’uomo, con la velocità di un metodo HTS. Inoltre, verrebbe ridotto anche il numero di animali utilizzati nelle sperimentazioni. Alcuni lavori presenti in letteratura dimostrano l’affidabilita di colonne funzionalizzate con albumine di diversa origine [11-13]: l’utilizzo di colonne più corte potrebbe aumentarne le applicazioni.

Correlazioni tra proprietá reologiche, struttura e processabilitá di blend di LLDPE/LDPE

Polymer blends constitute a valuable way to produce relatively low cost new materials. A still open question concerns the miscibility of polyethylene blends. Deviations from the log-additivity rule of the newtonian viscosity are often taken as a signature of immiscibility of the two components. The aim of this thesis is to characterize the rheological behavior in shear and elongation of five series of LLDPE/LDPE blends whose parent polymers have been chosen with different viscosity and SCB content and length. Synergistic effects have been measured for both zero shear viscosity and melt strength. Both SCB length and viscosity ratio between the components have been found to be key parameters for the miscibility of the pure polymers. In particular the miscibility increases with increasing SCB length and with decreasing the LDPE molecular weight and viscosity. This rheological behavior has significant effects on the processability window of these blends when the uni or biaxial elongational flows are involved. The film blowing is one of the processes for which the synergistic effects above mentioned can be crucial. Small scale experiments of film blowing performed for one of the series of blends has demonstrated that the positive deviation of the melt strength enlarges the processability window. In particular, the bubble stability was found to improve or disappear when the melt strength of the samples increased. The blending of LDPE and LLDPE can even reduce undesired melt flow instability phenomena widening, as a consequence, the processability window in extrusion. One of the series of blends has been characterized by means of capillary rheometry in order to allow a careful morphological analysis of the surface of the extruded polymer jets by means of Scanning Electron Microscopy (SEM) with the aim to detect the very early stages of the small scale melt instabilty at low shear rates (sharksin) and to follow its subsequent evolution as long as the shear rate was increased. With this experimental procedure it was possible to evaluate the shear rate ranges corresponding to different flow regions: smooth extrudate surface (absence of instability), sharkskin (small scale instability produced at the capillary exit), stick-slip transition (instability involving the whole capillary wall) and gross melt fracture (i.e. a large scale "upstream" instability originating from the entrance region of the capillary). A quantitative map was finally worked out using which an assessment of the flow type for a given shear rate and blend composition can be predicted.

Indicatori di correlazione e di disordine basati sul concetto di entropia

The aim of this work is to carry out an applicative, comparative and exhaustive study between several entropy based indicators of independence and correlation. We considered some indicators characterized by a wide and consolidate literature, like mutual information, joint entropy, relative entropy or Kullback Leibler distance, and others, more recently introduced, like Granger, Maasoumi and racine entropy, also called Sρ, or utilized in more restricted domains, like Pincus approximate entropy or ApEn. We studied the behaviour of such indicators applying them to binary series. The series was designed to simulate a wide range of situations in order to characterize indicators limit and capability and to identify, case by case, the more useful and trustworthy ones. Our target was not only to study if such indicators were able to discriminate between dependence and independence because, especially for mutual information and Granger, Maasoumi and Racine, that was already demonstrated and reported in literature, but also to verify if and how they were able to provide information about structure, complexity and disorder of the series they were applied to. Special attention was paid on Pincus approximate entropy, that is said by the author to be able to provide information regarding the level of randomness, regularity and complexity of a series. By means of a focused and extensive research, we furthermore tried to clear the meaning of ApEn applied to a couple of different series. In such situation the indicator is named in literature as cross-ApEn. The cross-ApEn meaning and the interpretation of its results is often not simple nor univocal and the matter is scarcely delved into by literature, thereby users can easily leaded up to a misleading conclusion, especially if the indicator is employed, as often unfortunately it happens, in uncritical manner. In order to plug some cross-ApEn gaps and limits clearly brought out during the experimentation, we developed and applied to the already considered cases a further indicator we called “correspondence index”. The correspondence index is perfectly integrated into the cross-ApEn computational algorithm and it is able to provide, at least for binary data, accurate information about the intensity and the direction of an eventual correlation, even not linear, existing between two different series allowing, in the meanwhile, to detect an eventual condition of independence between the series themselves.

Fabrication, Electrical Characterization and Simulation of Thin Film Solar Cells: CdTe and CIGS Materials

CdTe and Cu(In,Ga)Se2 (CIGS) thin film solar cells are fabricated, electrically characterized and modelled in this thesis. We start from the fabrication of CdTe thin film devices where the R.F. magnetron sputtering system is used to deposit the CdS/CdTe based solar cells. The chlorine post-growth treatment is modified in order to uniformly cover the cell surface and reduce the probability of pinholes and shunting pathways creation which, in turn, reduces the series resistance. The deionized water etching is proposed, for the first time, as the simplest solution to optimize the effect of shunt resistance, stability and metal-semiconductor inter-diffusion at the back contact. In continue, oxygen incorporation is proposed while CdTe layer deposition. This technique has been rarely examined through R.F sputtering deposition of such devices. The above experiments are characterized electrically and optically by current-voltage characterization, scanning electron microscopy, x-ray diffraction and optical spectroscopy. Furthermore, for the first time, the degradation rate of CdTe devices over time is numerically simulated through AMPS and SCAPS simulators. It is proposed that the instability of electrical parameters is coupled with the material properties and external stresses (bias, temperature and illumination). Then, CIGS materials are simulated and characterized by several techniques such as surface photovoltage spectroscopy is used (as a novel idea) to extract the band gap of graded band gap CIGS layers, surface or bulk defect states. The surface roughness is scanned by atomic force microscopy on nanometre scale to obtain the surface topography of the film. The modified equivalent circuits are proposed and the band gap graded profiles are simulated by AMPS simulator and several graded profiles are examined in order to optimize their thickness, grading strength and electrical parameters. Furthermore, the transport mechanisms and Auger generation phenomenon are modelled in CIGS devices.

La resistenza dei legami. Narrazioni e rappresentazioni della famiglia nella trilogia di romanzi “Past Imperfect” (2004-2011) di Nuruddin Farah

Il presente progetto di ricerca riguarda la terza trilogia di romanzi di Nuruddin Farah, “Past Imperfect” (2004-2011). L’analisi dei tre testi che compongono la trilogia – “Links” (2004), “Knots” (2007) e “Crossbones” (2011) – evidenzia la persistente rilevanza delle narrazioni e delle rappresentazioni della famiglia all’interno di tutta la produzione letteraria dell’autore. Questa prospettiva critica richiede l’impiego di una metodologia che riunisce vari aspetti della critica letteraria di matrice post-strutturalista e, per altri versi, di stampo materialista, assecondando così le due principali tendenze critiche presenti all’interno degli studi postcoloniali. Lo stesso approccio teorico-metodologico può essere applicato anche in altri due ambiti critici chiamati in causa dalla trilogia di Nuruddin Farah: la cosiddetta “world literature” e la cosiddetta “failed-state fiction”. L’analisi delle narrazioni e delle rappresentazioni della famiglia richiede, inoltre, un approccio interdisciplinare molto esteso, stimolando ricerche negli ambiti della semiotica, dell’antropologia, della psicanalisi, dei Gender Studies e dei Trauma Studies.