Toll-like receptor 2/MyD88 signaling mediates zymosan-induced joint hypernociception in mice: Participation of TNF-alpha, IL-1 beta and CXCL1/KC

Arthritic pain is a serious health problem that affects a large number of patients. Toll-like receptors (TLRs) activation within the joints has been implicated in pathophysiology of arthritis. However, their role in the genesis of arthritic pain needs to be demonstrated. In the present study, it was addressed the participation of TLR2 and TLR4 and their adaptor molecule MyD88 in the genesis of joint hypernociception (a decrease in the nociceptive threshold) during zymosan-induced arthritis. Zymosan injected in the tibio-tarsal joint induced mechanical hypernociception in C57BL/6 wild type mice that was reduced in TLR2 and MyD88 null mice. On the other hand, zymosan-induced hypernociception was similar in C3H/HePas and C3H/Hej mice (TLR4 mutant mice). Zymosan-induced joint hypernociception was also reduced in TNFR1 null mice and in mice treated with IL-1 receptor antagonist or with an antagonist of CXCR1/2. Moreover, the joint production of TNF-alpha, IL-1 beta and CXCL1/KC by zymosan was dependent on TLR2/MyD88 signaling. Investigating the mechanisms by which TNF-alpha, IL-1 beta and CXCL1/KC mediate joint hypernociception, joint administration of these cytokines produced mechanical hypernociception, and they act in an interdependent manner. In last instance, their hypernociceptive effects were dependent on the production of hypernociceptive mediators, prostaglandins and sympathetic amines. These results indicate that in zymosan-induced experimental arthritis, TLR2/MyD88 is involved in the cascade of events of joint hypernociception through a mechanism dependent on cytokines and chemokines production. Thus, TLR2/MyD88 signaling might be a target for the development of novel drugs to control pain in arthritis. (C) 2011 Elsevier B.V. All rights reserved.

Multivariate gene expression analysis reveals functional connectivity changes between normal/tumoral prostates

Abstract Background Prostate cancer is a leading cause of death in the male population, therefore, a comprehensive study about the genes and the molecular networks involved in the tumoral prostate process becomes necessary. In order to understand the biological process behind potential biomarkers, we have analyzed a set of 57 cDNA microarrays containing ~25,000 genes. Results Principal Component Analysis (PCA) combined with the Maximum-entropy Linear Discriminant Analysis (MLDA) were applied in order to identify genes with the most discriminative information between normal and tumoral prostatic tissues. Data analysis was carried out using three different approaches, namely: (i) differences in gene expression levels between normal and tumoral conditions from an univariate point of view; (ii) in a multivariate fashion using MLDA; and (iii) with a dependence network approach. Our results show that malignant transformation in the prostatic tissue is more related to functional connectivity changes in their dependence networks than to differential gene expression. The MYLK, KLK2, KLK3, HAN11, LTF, CSRP1 and TGM4 genes presented significant changes in their functional connectivity between normal and tumoral conditions and were also classified as the top seven most informative genes for the prostate cancer genesis process by our discriminant analysis. Moreover, among the identified genes we found classically known biomarkers and genes which are closely related to tumoral prostate, such as KLK3 and KLK2 and several other potential ones. Conclusion We have demonstrated that changes in functional connectivity may be implicit in the biological process which renders some genes more informative to discriminate between normal and tumoral conditions. Using the proposed method, namely, MLDA, in order to analyze the multivariate characteristic of genes, it was possible to capture the changes in dependence networks which are related to cell transformation.

Cloning and characterization of a novel alternatively spliced transcript of the human CHD7 putative helicase

Abstract Background The CHD7 (Chromodomain Helicase DNA binding protein 7) gene encodes a member of the chromodomain family of ATP-dependent chromatin remodeling enzymes. Mutations in the CHD7 gene are found in individuals with CHARGE, a syndrome characterized by multiple birth malformations in several tissues. CHD7 was identified as a binding partner of PBAF complex (Polybromo and BRG Associated Factor containing complex) playing a central role in the transcriptional reprogramming process associated to the formation of multipotent migratory neural crest, a transient cell population associated with the genesis of various tissues. CHD7 is a large gene containing 38 annotated exons and spanning 200 kb of genomic sequence. Although genes containing such number of exons are expected to have several alternative transcripts, there are very few evidences of alternative transcripts associated to CHD7 to date indicating that alternative splicing associated to this gene is poorly characterized. Findings Here, we report the cloning and characterization by experimental and computational studies of a novel alternative transcript of the human CHD7 (named CHD7 CRA_e), which lacks most of its coding exons. We confirmed by overexpression of CHD7 CRA_e alternative transcript that it is translated into a protein isoform lacking most of the domains displayed by the canonical isoform. Expression of the CHD7 CRA_e transcript was detected in normal liver, in addition to the DU145 human prostate carcinoma cell line from which it was originally isolated. Conclusions Our findings indicate that the splicing event associated to the CHD7 CRA_e alternative transcript is functional. The characterization of the CHD7 CRA_e novel isoform presented here not only sets the basis for more detailed functional studies of this isoform, but, also, contributes to the alternative splicing annotation of the CHD7 gene and the design of future functional studies aimed at the elucidation of the molecular functions of its gene products.

Carcinoma de células escamosas em glândula mamária de gata doméstica

Background: In the feline species, 80% to 93% of neoplasias in the mammary gland are malignant, being the majority carcinomas. Among them, there is the mammary squamous cell carcinoma, which amounts to a very rare neoplasm in the domestic cat, with considerable potential for malignancy. This study aimed to report a case of squamous cell mammary carcinoma in the feline species. Case: A female cat, mixed breed, ten years old, presented history of skin lesion. The cat had been spayed two years before, but with previous administration of contraceptives. At the physical examination, it was observed ulcer between the caudal abdominal mammary glands. The occurrence of skin or mammary neoplasia was conceived. The following complementary tests were requested: complete blood count, serum biochemical profi le (renal and hepatic), chest radiographs, abdominal ultrasound, and incisional biopsy of the ulcerated region periphery, followed by classic histopathology. The lesion histopathology was compatible with squamous cell carcinoma of the mammary gland. Due to such a diagnosis, bilateral mastectomy was recommended. The material obtained during the surgical procedure was sent for anatomopathological analysis. Microscopically, surgical margins infi ltration and a regional lymph node were verifi ed. The owner was advised of the need for complementary therapies and medical monitoring of the cat. However, there was no return. It is noteworthy that the animal’s physical and laboratory examinations showed no neoplasia in other regions, being the squamous cell carcinoma of the mammary gland considered primary. Discussion: The malignant mammary neoplasia genesis in feline species, in general, seems to be related to steroid hormones. The ovariectomized females are less likely to develop the disease when compared to intact cats, but there is no protective effect of surgery on those spayed after two years of age regarding the appearance of the neoplasia. Thus, at the time the reported patient was ovariectomized, this effect no longer occurred. The synthetic progestins regularly used to prevent estrus increase by three times the risk of breast carcinomas onset. In humans, there is no clear defi nition of the etiology and pathogenesis of mammary squamous cell carcinoma. However, it has been suggested its association with extreme forms of squamous metaplasia present in pre-existing mammary adenocarcinoma, besides cysts, chronic infl ammations, abscesses and mammary gland adenofi bromas. In a hypothetical way, this etiology could also be related to the feline mammary carcinoma, although, for the case at issue, the exogenous and endogenous hormonal infl uence should not be excluded. It has been reported that mammary squamous cell carcinomas in cats are classifi ed in grades II and III (ie, moderately and poorly differentiated, respectively). Thus, they are considered tumors with more unfavorable prognosis. However, the monitoring of the clinical course, in order to evaluate possible recurrence of the neoplasia and metastases to distant sites, was not possible as the animal under discussion did not return. The squamous cell carcinoma is the most common skin tumor in feline species, despite the primary location in the mammary gland. It is, therefore, important to differentiate squamous cell carcinoma originated in the breast from histological types derived from skin. The description of this special and rare feline mammary carcinoma is important due to its particular characteristics and potential for malignancy.

Estudo cinético de um episódio agudo de translocação bacteriana e de suas repercussões imunológicas e microcirculatórias em ratos

Introdução: Muitos pacientes ainda morrem devido a infecções. Crescentes relatos da literatura atual têm atribuído ao intestino o papel de agravamento de doenças graves, e/ou a sua participação na gênese da sepse por mecanismo de translocação bacteriana (TB). Objetivo: Avaliar de forma cinética a TB e suas repercussões microcirculatórias e imunológicas. Método: Ratos Wistar-EPM (n=162) foram aleatoriamente distribuídos em grupo Sham (n=72) e grupo TB (n=90), e avaliados nos períodos de 2h, 6h, 24h, 72h, 7 e 14 dias, em relação a índice de translocação bacteriana; microscopia intravital; perfusão tecidual; e componentes celulares e humorais da linfa mesentérica por linfograma, citometria de fluxo e CBA-Flex. Resultado: A TB ocorreu somente no grupo TB e foi expressiva nas primeiras 24 horas tornando-se negativa somente com 7 dias. A conseqüência de um episódio de TB repercutiu na celularidade e citocinas pró e antiinflamatórias da linfa mesentérica associado a lesões da microcirculação e hipoperfusão tecidual de forma local e sistêmica. A citometria de fluxo mostrou que a linfa mesentérica eferente pós TB difere significativamente do grupo Sham quanto a número e subpopulação de linfócitos. Conclusão: Um episódio agudo de TB determinou uma recuperação máxima bacteriana com 6 horas e sua completa depuração entre 3 e 7 dias, além de provocar alterações da microcirculação intestinal e sistêmica associadas à ativação do GALT, principalmente no período de permanência das bactérias translocadas no hospedeiro, sendo a via linfática mesenterial uma importante rota na intercomunicação imunológica entre o ambiente intestinal e sistêmico.

Efeitos da Prostaglandina E1 na gênese de capilares sanguíneos em músculo esquelético isquêmico de ratos: estudo histológico e ultra-estrutural

Objetivo: o objetivo deste trabalho foi estudar os aspectos morfológicos e ultra-estruturais na gênese de capilares sanguíneos em músculo esquelético do membro caudal de ratos submetidos à isquemia sob a ação da Prostaglandina E1 (PGE1), administrada por via intramuscular ou endovenosa. Métodos: foram utilizados 60 ratos (Rattus norvegicus albinus), linhagem Wistar-UEM, distribuídos aleatoriamente em três grupos de 20, redistribuídos igualmente em dois subgrupos, observados no 7o e 14o dias, sendo um grupo controle onde apenas foi provocada a isquemia no membro, outro com a isquemia e a injeção da PGE1 via intramuscular (IM), e outro com a isquemia e a injeção da PGE1 endovenosa (EV). Para análise dos resultados, foram realizadas a coloração com hematoxilina & eosina (HE), a imuno-histoquímica e a microscopia eletrônica de transmissão (MET). Resultados: constatou-se um aumento estatisticamente significante no número de capilares nos subgrupos com o uso da PGE1 IM e EV, através da contagem nos cortes corados com HE. Houve marcação de capilares e vasos de maior calibre nestes mesmos subgrupos, porém, esta reação não foi eficiente para a quantificação dos capilares. Na MET encontraram-se evidências de formação de novos capilares. Conclusões: a PGE1, administrada por via IM ou EV, promoveu, após 14 dias de observação, um aumento no número de capilares no músculo esquelético de ratos submetido à isquemia, identificáveis histologicamente com a coloração em HE. Na análise ultra-estrutural encontraram-se alterações que sugerem, nos animais sob a ação da PGE1, que a neoformação vascular possa ter ocorrido por angiogênese e vasculogênese. A imuno-coloração, apesar da marcação de capilares e vasos maiores, não permitiu estabelecer uma correlação com o aumento de vasos encontrados na coloração com HE.

Transcriptional regulation of human mu-opioid receptor gene: functional characterization of activating and inhibitory transcription factors

The organization of the nervous and immune systems is characterized by obvious differences and striking parallels. Both systems need to relay information across very short and very long distances. The nervous system communicates over both long and short ranges primarily by means of more or less hardwired intercellular connections, consisting of axons, dendrites, and synapses. Longrange communication in the immune system occurs mainly via the ordered and guided migration of immune cells and systemically acting soluble factors such as antibodies, cytokines, and chemokines. Its short-range communication either is mediated by locally acting soluble factors or transpires during direct cell–cell contact across specialized areas called “immunological synapses” (Kirschensteiner et al., 2003). These parallels in intercellular communication are complemented by a complex array of factors that induce cell growth and differentiation: these factors in the immune system are called cytokines; in the nervous system, they are called neurotrophic factors. Neither the cytokines nor the neurotrophic factors appear to be completely exclusive to either system (Neumann et al., 2002). In particular, mounting evidence indicates that some of the most potent members of the neurotrophin family, for example, nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF), act on or are produced by immune cells (Kerschensteiner et al., 1999) There are, however, other neurotrophic factors, for example the insulin-like growth factor-1 (IGF-1), that can behave similarly (Kermer et al., 2000). These factors may allow the two systems to “cross-talk” and eventually may provide a molecular explanation for the reports that inflammation after central nervous system (CNS) injury has beneficial effects (Moalem et al., 1999). In order to shed some more light on such a cross-talk, therefore, transcription factors modulating mu-opioid receptor (MOPr) expression in neurons and immune cells are here investigated. More precisely, I focused my attention on IGF-I modulation of MOPr in neurons and T-cell receptor induction of MOPr expression in T-lymphocytes. Three different opioid receptors [mu (MOPr), delta (DOPr), and kappa (KOPr)] belonging to the G-protein coupled receptor super-family have been cloned. They are activated by structurallyrelated exogenous opioids or endogenous opioid peptides, and contribute to the regulation of several functions including pain transmission, respiration, cardiac and gastrointestinal functions, and immune response (Zollner and Stein 2007). MOPr is expressed mainly in the central nervous system where it regulates morphine-induced analgesia, tolerance and dependence (Mayer and Hollt 2006). Recently, induction of MOPr expression in different immune cells induced by cytokines has been reported (Kraus et al., 2001; Kraus et al., 2003). The human mu-opioid receptor gene (OPRM1) promoter is of the TATA-less type and has clusters of potential binding sites for different transcription factors (Law et al. 2004). Several studies, primarily focused on the upstream region of the OPRM1 promoter, have investigated transcriptional regulation of MOPr expression. Presently, however, it is still not completely clear how positive and negative transcription regulators cooperatively coordinate cellor tissue-specific transcription of the OPRM1 gene, and how specific growth factors influence its expression. IGF-I and its receptors are widely distributed throughout the nervous system during development, and their involvement in neurogenesis has been extensively investigated (Arsenijevic et al. 1998; van Golen and Feldman 2000). As previously mentioned, such neurotrophic factors can be also produced and/or act on immune cells (Kerschenseteiner et al., 2003). Most of the physiologic effects of IGF-I are mediated by the type I IGF surface receptor which, after ligand binding-induced autophosphorylation, associates with specific adaptor proteins and activates different second messengers (Bondy and Cheng 2004). These include: phosphatidylinositol 3-kinase, mitogen-activated protein kinase (Vincent and Feldman 2002; Di Toro et al. 2005) and members of the Janus kinase (JAK)/STAT3 signalling pathway (Zong et al. 2000; Yadav et al. 2005). REST plays a complex role in neuronal cells by differentially repressing target gene expression (Lunyak et al. 2004; Coulson 2005; Ballas and Mandel 2005). REST expression decreases during neurogenesis, but has been detected in the adult rat brain (Palm et al. 1998) and is up-regulated in response to global ischemia (Calderone et al. 2003) and induction of epilepsy (Spencer et al. 2006). Thus, the REST concentration seems to influence its function and the expression of neuronal genes, and may have different effects in embryonic and differentiated neurons (Su et al. 2004; Sun et al. 2005). In a previous study, REST was elevated during the early stages of neural induction by IGF-I in neuroblastoma cells. REST may contribute to the down-regulation of genes not yet required by the differentiation program, but its expression decreases after five days of treatment to allow for the acquisition of neural phenotypes. Di Toro et al. proposed a model in which the extent of neurite outgrowth in differentiating neuroblastoma cells was affected by the disappearance of REST (Di Toro et al. 2005). The human mu-opioid receptor gene (OPRM1) promoter contains a DNA sequence binding the repressor element 1 silencing transcription factor (REST) that is implicated in transcriptional repression. Therefore, in the fist part of this thesis, I investigated whether insulin-like growth factor I (IGF-I), which affects various aspects of neuronal induction and maturation, regulates OPRM1 transcription in neuronal cells in the context of the potential influence of REST. A series of OPRM1-luciferase promoter/reporter constructs were transfected into two neuronal cell models, neuroblastoma-derived SH-SY5Y cells and PC12 cells. In the former, endogenous levels of human mu-opioid receptor (hMOPr) mRNA were evaluated by real-time PCR. IGF-I upregulated OPRM1 transcription in: PC12 cells lacking REST, in SH-SY5Y cells transfected with constructs deficient in the REST DNA binding element, or when REST was down-regulated in retinoic acid-differentiated cells. IGF-I activates the signal transducer and activator of transcription-3 (STAT3) signaling pathway and this transcription factor, binding to the STAT1/3 DNA element located in the promoter, increases OPRM1 transcription. T-cell receptor (TCR) recognizes peptide antigens displayed in the context of the major histocompatibility complex (MHC) and gives rise to a potent as well as branched intracellular signalling that convert naïve T-cells in mature effectors, thus significantly contributing to the genesis of a specific immune response. In the second part of my work I exposed wild type Jurkat CD4+ T-cells to a mixture of CD3 and CD28 antigens in order to fully activate TCR and study whether its signalling influence OPRM1 expression. Results were that TCR engagement determined a significant induction of OPRM1 expression through the activation of transcription factors AP-1, NF-kB and NFAT. Eventually, I investigated MOPr turnover once it has been expressed on T-cells outer membrane. It turned out that DAMGO induced MOPr internalisation and recycling, whereas morphine did not. Overall, from the data collected in this thesis we can conclude that that a reduction in REST is a critical switch enabling IGF-I to up-regulate human MOPr, helping these findings clarify how human MOPr expression is regulated in neuronal cells, and that TCR engagement up-regulates OPRM1 transcription in T-cells. My results that neurotrophic factors a and TCR engagement, as well as it is reported for cytokines, seem to up-regulate OPRM1 in both neurons and immune cells suggest an important role for MOPr as a molecular bridge between neurons and immune cells; therefore, MOPr could play a key role in the cross-talk between immune system and nervous system and in particular in the balance between pro-inflammatory and pro-nociceptive stimuli and analgesic and neuroprotective effects.

Indagine sulla nozione di fatto urbano ne L'architettura della città di Aldo Rossi

Questa tesi di dottorato di ricerca ha come oggetto la nozione di fatto urbano elaborata e presentata da Aldo Rossi nel libro L’architettura della città edito nel 1966. Ne L’architettura della città sono molteplici le definizioni e le forme con cui è enunciata la nozione di fatto urbano. Nel corso della tesi si è indagato come la costruzione nel tempo di questo concetto è stata preceduta da diversi studi giovanili intrapresi dal 1953, poi riorganizzati e sintetizzati a partire dal 1963 in un quaderno manoscritto dal titolo “Manuale di urbanistica”, in diversi appunti e in due quaderni manoscritti. Il lavoro di ricerca ha ricostruito la formulazione della nozione di fatto urbano attraverso gli scritti di Rossi. In questa direzione la rilevazione della partecipazione di Rossi a dibattiti, seminari, riviste, corsi universitari o ricerche accademiche è apparsa di fondamentale importanza, per comprendere la complessità di un lavoro non riconducibile a dei concetti disciplinari, ma alla formazione di una teoria trasmissibile. Il tentativo di comprendere e spiegare la nozione di fatto urbano ha condotto ad esaminare l’accezione con cui Rossi compone L’architettura della città, che egli stesso assimila ad un trattato. L’analisi ha identificato come la composizione del libro non è direttamente riferibile ad un uso classico della stesura editoriale del trattato, la quale ha tra i riferimenti più noti nel passato la promozione di una pratica corretta come nel caso vitruviano o un’impalcatura instauratrice di una nuova categoria come nel caso dell’Alberti. La mancanza di un sistema globale e prescrittivo a differenza dei due libri fondativi e il rimando non immediato alla stesura di un trattato classico è evidente ne L’architettura della città. Tuttavia la possibilità di condurre la ricerca su una serie di documenti inediti ha permesso di rilevare come negli scritti a partire dal 1953, sia maturata una trattazione delle questioni centrali alla nozione di fatto urbano ricca di intuizioni, che aspirano ad un’autonomia, sintetizzate, seppure in modo non sistematico, nella stesura del celebre libro. Si è così cercato di mettere in luce la precisazione nel tempo della nozione di fatto urbano e della sua elaborazione nei molteplici scritti antecedenti la pubblicazione de L’architettura della città, precisando come Rossi, pur costruendo su basi teoriche la nozione di fatto urbano, ne indichi una visione progressiva, ossia un uso operativo sulla città. La ricerca si è proposta come obiettivo di comprendere le radici culturali della nozione di fatto urbano sia tramite un’esplorazione degli interessi di Rossi nel suo percorso formativo sia rispetto alla definizione della struttura materiale del fatto urbano che Rossi individua nelle permanenze e che alimenta nella sua definizione con differenti apporti derivanti da altre discipline. Compito di questa ricerca è stato rileggere criticamente il percorso formativo compiuto da Rossi, a partire dal 1953, sottolinearne gli ambiti innovativi e precisarne i limiti descrittivi che non vedranno mai la determinazione di una nozione esatta, ma piuttosto la strutturazione di una sintesi complessa e ricca di riferimenti ad altri studi. In sintesi la tesi si compone di tre parti: 1. la prima parte, dal titolo “La teoria dei fatti urbani ne L’architettura della città”, analizza il concetto di fatto urbano inserendolo all’interno del più generale contesto teorico contenuto nel libro L’architettura della città. Questo avviene tramite la scomposizione del libro, la concatenazione delle sue argomentazioni e la molteplicità delle fonti esplicitamente citate da Rossi. In questo ambito si precisa la struttura del libro attraverso la rilettura dei riferimenti serviti a Rossi per comporre il suo progetto teorico. Inoltre si ripercorre la sua vita attraverso le varie edizioni, le ristampe, le introduzioni e le illustrazioni. Infine si analizza il ruolo del concetto di fatto urbano nel libro rilevando come sia posto in un rapporto paritetico con il titolo del libro, conseguendone un’accezione di «fatto da osservare» assimilabile all’uso proposto dalla geografia urbana francese dei primi del Novecento. 2. la seconda parte, dal titolo “La formazione della nozione di fatto urbano 1953-66”, è dedicata alla presentazione dell’elaborazione teorica negli scritti di Rossi prima de L’architettura della città, ossia dal 1953 al 1966. Questa parte cerca di descrivere le radici culturali di Rossi, le sue collaborazioni e i suoi interessi ripercorrendo la progressiva definizione della concezione di città nel tempo. Si è analizzato il percorso maturato da Rossi e i documenti scritti fin dagli anni in cui era studente alla Facoltà di Architettura Politecnico di Milano. Emerge un quadro complesso in cui i primi saggi, gli articoli e gli appunti testimoniano una ricerca intellettuale tesa alla costruzione di un sapere sullo sfondo del realismo degli anni Cinquanta. Rossi matura infatti un impegno culturale che lo porta dopo la laurea ad affrontare discorsi più generali sulla città. In particolare la sua importante collaborazione con la rivista Casabella-continuità, con il suo direttore Ernesto Nathan Rogers e tutto il gruppo redazionale segnano il periodo successivo in cui compare l’interesse per la letteratura urbanistica, l’arte, la sociologia, la geografia, l’economia e la filosofia. Seguono poi dal 1963 gli anni di lavoro insieme al gruppo diretto da Carlo Aymonino all’Istituto Universitario di Architettura di Venezia, e in particolare le ricerche sulla tipologia edilizia e la morfologia urbana, che portano Rossi a compiere una sintesi analitica per la fondazione di una teoria della città. Dall’indagine si rileva infatti come gli scritti antecedenti L’architettura della città sviluppano lo studio dei fatti urbani fino ad andare a costituire il nucleo teorico di diversi capitoli del libro. Si racconta così la genesi del libro, la cui scrittura si è svolta nell’arco di due anni, e le aspirazioni che hanno portato quello che era stato concepito come un “manuale d’urbanistica” a divenire quello che Rossi definirà “l’abbozzo di un trattato” per la formulazione di una scienza urbana. 3. la terza parte, dal titolo “La struttura materiale dei fatti urbani: la teoria della permanenza”, indaga monograficamente lo studio della città come un fatto materiale, un manufatto, la cui costruzione è avvenuta nel tempo e del tempo mantiene le tracce. Sul tema della teoria della permanenza è stato importante impostare un confronto con il dibattito vivo negli anni della ricostruzione dopo la guerra intorno ai temi delle preesistenze ambientali nella ricostruzione negli ambienti storici. Sono emersi fin da subito importanti la relazione con Ernesto Nathan Rogers, le discussioni sulle pagine di Casabella-Continuità, la partecipazione ad alcuni dibatti e ricerche. Si è inoltre Rilevato l’uso di diversi termini mutuati dalle tesi filosofiche di alcune personalità come Antonio Banfi e Enzo Paci, poi elaborati dal nucleo redazionale di Casabella-Continuità, di cui faceva parte anche Rossi. Sono così emersi alcuni spostamenti di senso e la formulazione di un vocabolario di termini all’interno della complessa vicenda della cultura architettonica degli anni Cinquanta e Sessanta. 1. Si è poi affrontato questo tema analizzando le forme con cui Rossi presenta la definizione della teoria della permanenza e i contributi desunti da alcuni autori per la costruzione scientifica di una teoria dell’architettura, il cui fine è quello di essere trasmissibile e di offrire strumenti di indagine concreti. Questa ricerca ha permesso di ipotizzare come il lavoro dei geografi francesi della prima metà del XX secolo, e in particolare il contributo più rilevante di Marcel Poëte e di Pierre Lavedan, costituiscono le fonti principali e il campo d’indagine maggiormente esplorato da Rossi per definire la teoria della permanenza e i monumenti. Le permanenze non sono dunque presentate ne L’architettura della città come il “tutto”, ma emergono da un metodo che sceglie di isolare i fatti urbani permanenti, consentendo così di compiere un’ipotesi su “ciò che resta” dopo le trasformazioni continue che operano nella città. Le fonti su cui ho lavorato sono state quelle annunciate da Rossi ne L’architettura della città, e più precisamente i testi nelle edizioni da lui consultate. Anche questo lavoro ha permesso un confronto dei testi che ha fatto emergere ne L’architettura della città l’uso di termini mutuati da linguaggi appartenenti ad altre discipline e quale sia l’uso di concetti estrapolati nella loro interezza. Presupposti metodologici Della formulazione della nozione di fatto urbano si sono indagate l’originalità dell’espressione, le connessioni presunte o contenute negli studi di Rossi sulla città attraverso la raccolta di fonti dirette e indirette che sono andate a formare un notevole corpus di scritti. Le fonti dirette più rilevanti sono state trovare nelle collezioni speciali del Getty Research Institute di Los Angeles in cui sono conservati gli Aldo Rossi Papers, questo archivio comprende materiali inediti dal 1954 al 1988. La natura dei materiali si presenta sotto forma di manoscritti, dattiloscritti, quaderni, documenti ciclostilati, appunti sparsi e una notevole quantità di corrispondenza. Negli Aldo Rossi Papers si trovano anche 32 dei 47 Quaderni Azzurri, le bozze de L’architettura della città e dell’ Autobiografia Scientifica. Per quanto riguarda in particolare L’architettura della città negli Aldo Rossi Papers sono conservati: un quaderno con il titolo “Manuale d’urbanistica, giugno 1963”, chiara prima bozza del libro, degli “Appunti per libro urbanistica estate/inverno 1963”, un quaderno con la copertina rossa datato 20 settembre 1964-8 agosto 1965 e un quaderno con la copertina blu datato 30 agosto 1965-15 dicembre 1965. La possibilità di accedere a questo archivio ha permesso di incrementare la bibliografia relativa agli studi giovanili consentendo di rileggere il percorso culturale in cui Rossi si è formato. E’ così apparsa fondamentale la rivalutazione di alcune questioni relative al realismo socialista che hanno portato a formare un più preciso quadro dei primi scritti di Rossi sullo sfondo di un complesso scenario intellettuale. A questi testi si è affiancata la raccolta delle ricerche universitarie, degli articoli pubblicati su riviste specializzate e degli interventi a dibattiti e seminari. A proposito de L’architettura della città si è raccolta un’ampia letteratura critica riferita sia al testo in specifico che ad una sua collocazione nella storia dell’architettura, mettendo in discussione alcune osservazioni che pongono L’architettura della città come un libro risolutivo e definitivo. Per quanto riguarda il capitolo sulla teoria della permanenza l’analisi è stata svolta a partire dai testi che Rossi stesso indicava ne L’architettura della città rivelando i diversi apporti della letteratura urbanistica francese, e permettendo alla ricerca di precisare le relazioni con alcuni scritti centrali e al contempo colti da Rossi come opportunità per intraprendere l’elaborazione dell’idea di tipo. Per quest’ultima parte si può precisare come Rossi formuli la sua idea di tipo in un contesto culturale dove l’interesse per questo tema era fondamentale. Dunque le fonti che hanno assunto maggior rilievo in quest’ultima fase emergono da un ricco panorama in cui Rossi compie diverse ricerche sia con il gruppo redazionale di Casabella-continuità, sia all’interno della scuola veneziana negli anni Sessanta, ma anche negli studi per l’ILSES e per l’Istituto Nazionale d’Urbanistica. RESEARCH ON THE NOTION OF URBAN ARTIFACT IN THE ARCHITECTURE OF THE CITY BY ALDO ROSSI. Doctoral candidate: Letizia Biondi Tutor: Valter Balducci The present doctoral dissertation deals with the notion of urban artifact that was formulated and presented by Aldo Rossi in his book The Architecture of the City, published in 1966. In The Architecture of the City, the notion of urban artifact is enunciated through a wide range of definitions and forms. In this thesis, a research was done on how the construction of this concept over time was preceded by various studies started in 1953 during the author’s youth, then re-organized and synthesized since 1963 in a manuscript titled “Manual of urban planning” and in two more manuscripts later on. The work of research re-constructed the formulation of the notion of urban artifact through Rossi’s writings. In this sense, the examination of Rossi’s participation in debates, seminars, reviews, university courses or academic researches was of fundamental importance to understand the complexity of a work which is not to be attributed to disciplinary concepts, but to the formulation of a communicable theory. The effort to understand and to explain the notion of urban artifact led to an examination of the meaning used by Rossi to compose The Architecture of the City, which he defines as similar to a treatise. Through this analysis, it emerged that the composition of the book is not directly ascribable to the classical use of editorial writing of a treatise, whose most famous references in the past are the promotion of a correct practice as in the case of Vitruvio’s treatise, or the use of a structure that introduces a new category as in the Alberti case. Contrary to the two founding books, the lack of a global and prescriptive system and the not immediate reference to the writing of a classical treatise are evident in The Architecture of the City. However, the possibility of researching on some unpublished documents allowed to discover that in the writings starting from 1953 the analysis of the questions that are at the core of the notion of urban artifact is rich of intuitions, that aim to autonomy and that would be synthesized, even though not in a systematic way, in his famous book. The attempt was that of highlighting the specification over time of the notion of urban artifact and its elaboration in the various writings preceding the publication of The Architecture of the City. It was also specified that, despite building on theoretical grounds, Rossi indicates a progressive version of the notion of urban artifact, that is a performing use in the city. The present research aims to understand the cultural roots of the notion of urban artifact in two main directions: analyzing, firstly, Rossi’s interests along his formation path and, secondly, the definition of material structure of an urban artifact identified by Rossi in the permanences and enriched by various contributions from other disciplines. The purpose of the present research is to revise the formation path made by Rossi in a critical way, starting by 1953, underlining its innovative aspects and identifying its describing limits, which will never lead to the formulation of an exact notion, but rather to the elaboration of a complex synthesis, enriched by references to other studies. In brief, the thesis is composed of three parts: 1. The first part, titled “The Theory of urban artifacts in The Architecture of the City”, analyzes the concept of urban artifact in the more general theoretical context of the book The Architecture of the City. Such analysis is done by “disassembling” the book, and by linking together the argumentations and the multiplicity of the sources which are explicitly quoted by Rossi. In this context, the book’s structure is defined more precisely through the revision of the references used by Rossi to compose his theoretical project. Moreover, the author’s life is traced back through the various editions, re-printings, introductions and illustrations. Finally, it is specified which role the concept of urban artifact has in the book, pointing out that it is placed in an equal relation with the book’s title; by so doing, the concept of urban artifact gets the new meaning of “fact to be observed”, similar to the use that was suggested by the French urban geography at the beginning of the 20th century. 2. The second part, titled “The formation of the notion of urban artifact 1953-66”, introduces the theoretical elaboration in Rossi’s writings before The Architecture of the City, that is from 1953 to 1966. This part tries to describe Rossi’s cultural roots, his collaborations and his interests, tracing back the progressive definition of his conception of city over time. The analysis focuses on the path followed by Rossi and on the documents that he wrote since the years as a student at the Department of Architecture at the Politecnico in Milan. This leads to a complex scenario of first essays, articles and notes that bear witness to the intellectual research aiming to the construction of a knowledge on the background of the Realism of the 1950s. Rossi develops, in fact, a cultural engagement that leads him after his studies to deal with more general issues about the city. In particular, his important collaboration with the architecture magazine “Casabella-continuità”, with the director Ernesto Nathan Rogers and with the whole redaction staff mark the following period when he starts getting interested in city planning literature, art, sociology, geography, economics and philosophy. Since 1963, Rossi has worked with the group directed by Carlo Aymonino at the “Istituto Universitario di Architettura” (University Institute of Architecture) in Venice, especially researching on building typologies and urban morphology. During these years, Rossi elaborates an analytical synthesis for the formulation of a theory about the city. From the present research, it is evident that the writings preceding The Architecture of the City develop the studies on urban artifacts, which will become theoretical core of different chapters of the book. In conclusion, the genesis of the book is described; written in two years, what was conceived to be an “urban planning manual” became a “treatise draft” for the formulation of an urban science, as Rossi defines it. 3. The third part is titled “The material structure of urban artifacts: the theory of permanence”. This research is made on the study of the city as a material fact, a manufacture, whose construction was made over time, bearing the traces of time. As far as the topic of permanence is concerned, it was also important to draw a comparison with the debate about the issues of environmental pre-existence of re-construction in historical areas, which was very lively during the years of the Reconstruction. Right from the beginning, of fundamental importance were the relationship with Ernesto Nathan Rogers, the discussions on the pages of Casabella-Continuità and the participation to some debates and researches. It is to note that various terms were taken by the philosophical thesis by some personalities such as Antonio Banfi and Enzo Paci, and then re-elaborated by the redaction staff at Casabella-Continuità, which Rossi took part in as well. Through this analysis, it emerged that there were some shifts in meaning and the formulation of a vocabulary of terms within the complex area of the architectonic culture in the 1950s and 1960s. Then, I examined the shapes in which Rossi introduces the definition of the theory of permanence and the references by some authors for the scientific construction of an architecture theory whose aim is being communicable and offering concrete research tools. Such analysis allowed making a hypothesis about the significance for Rossi of the French geographers of the first half of the 20th century: in particular, the work by Marcel Poëte and by Pierre Lavedan is the main source and the research area which Rossi mostly explored to define the theory of permanence and monuments. Therefore, in The Architecture of the City, permanencies are not presented as the “whole”, but they emerge from a method which isolates permanent urban artifacts, in this way allowing making a hypothesis on “what remains” after the continuous transformations made in the city. The sources examined were quoted by Rossi in The Architecture of the City; in particular I analyzed them in the same edition which Rossi referred to. Through such an analysis, it was possible to make a comparison of the texts with one another, which let emerge the use of terms taken by languages belonging to other disciplines in The Architecture of the City and which the use of wholly extrapolated concepts is. Methodological premises As far as the formulation of the notion of urban artifact is concerned, the analysis focuses on the originality of the expression, the connections that are assumed or contained in Rossi’s writings about the city, by collecting direct and indirect sources which formed a significant corpus of writings. The most relevant direct sources were found in the special collections of the Getty Research Institute in Los Angeles, where the “Aldo Rossi Papers” are conserved. This archive contains unpublished material from 1954 to 1988, such as manuscripts, typescripts, notebooks, cyclostyled documents, scraps and notes, and several letters. In the Aldo Rossi Papers there are also 32 out of the 47 Light Blue Notebooks (Quaderni Azzurri), the rough drafts of The Architecture of the City and of the “A Scientific Autobiography”. As regards The Architecture of the City in particular, the Aldo Rossi Papers preserve: a notebook by the title of “Urban planning manual, June, 1963”, which is an explicit first draft of the book; “Notes for urban planning book summer/winter 1963”; a notebook with a red cover dated September 20th, 1964 – August 8th, 1965; and a notebook with a blue cover dated August 30th, 1965 – December 15th, 1965. The possibility of accessing this archive allowed to increase the bibliography related to the youth studies, enabling a revision of the cultural path followed by Rossi’s education. To that end, it was fundamental to re-evaluate some issues linked to the socialist realism which led to a more precise picture of the first writings by Rossi against the background of the intellectual scenario where he formed. In addition to these texts, the collection of university researches, the articles published on specialized reviews and the speeches at debates and seminars were also examined. About The Architecture of the City, a wide-ranging critical literature was collected, related both to the text specifics and to its collocation in the story of architecture, questioning some observations which define The Architecture of the City as a conclusive and definite book. As far as the chapter on the permanence theory is concerned, the analysis started by the texts that Rossi indicated in The Architecture of the City, revealing the different contributions from the French literature on urban planning. This allowed to the present research a more specific definition of the connections to some central writings which, at the same time, were seen by Rossi as an opportunity to start up the elaboration of the idea of type. For this last part, it can be specified that Rossi formulates his idea of type in a cultural context where the interest in this topic was fundamental. Therefore, the sources which played a central role in this final phase emerge from an extensive panorama in which Rossi researched not only with the redaction staff at Casablanca-continuità and within the School of Venice in the 1960s, but also in his studies for the ILSES (Institute of the Region Lombardia for Economics and Social Studies) and for the National Institute of Urban Planning.

Emotional engagement and orienting: the effects of picture size on affective response

For their survival, humans and animals can rely on motivational systems which are specialized in assessing the valence and imminence of dangers and appetitive cues. The Orienting Response (OR) is a fundamental response pattern that an organism executes whenever a novel or significant stimulus is detected, and has been shown to be consistently modulated by the affective value of a stimulus. However, detecting threatening stimuli and appetitive affordances while they are far away compared to when they are within reach constitutes an obvious evolutionary advantage. Building on the linear relationship between stimulus distance and retinal size, the present research was aimed at investigating the extent to which emotional modulation of distinct processes (action preparation, attentional capture, and subjective emotional state) is affected when reducing the retinal size of a picture. Studies 1-3 examined the effects of picture size on emotional response. Subjective feeling of engagement, as well as sympathetic activation, were modulated by picture size, suggesting that action preparation and subjective experience reflect the combined effects of detecting an arousing stimulus and assessing its imminence. On the other hand, physiological responses which are thought to reflect the amount of attentional resources invested in stimulus processing did not vary with picture size. Studies 4-6 were conducted to substantiate and extend the results of studies 1-3. In particular, it was noted that a decrease in picture size is associated with a loss in the low spatial frequencies of a picture, which might confound the interpretation of the results of studies 1-3. Therefore, emotional and neutral images which were either low-pass filtered or reduced in size were presented, and affective responses were measured. Most effects which were observed when manipulating image size were replicated by blurring pictures. However, pictures depicting highly arousing unpleasant contents were associated with a more pronounced decrease in affective modulation when pictures were reduced in size compared to when they were blurred. The present results provide important information for the study of processes involved in picture perception and in the genesis and expression of an emotional response. In particular, the availability of high spatial frequencies might affect the degree of activation of an internal representation of an affectively charged scene, and might modulate subjective emotional state and preparation for action. Moreover, the manipulation of stimulus imminence revealed important effects of stimulus engagement on specific components of the emotional response, and the implications of the present data for some models of emotions have been discussed. In particular, within the framework of a staged model of emotional response, the tactic and strategic role of response preparation and attention allocation to stimuli varying in engaging power has been discussed, considering the adaptive advantages that each might represent in an evolutionary view. Finally, the identification of perceptual parameters that allow affective processing to be carried out has important methodological applications in future studies examining emotional response in basic research or clinical contexts.

Rafael Moneo: la complessità del vuoto. Dalle matrici formali dell'opera di Oteiza e Chillida

The experience of void, essential to the production of forms and to make use them, can be considered as the base of the activities that attend to the formative processes. If void and matter constitutes the basic substances of architecture. Their role in the definition of form, the symbolic value and the constructive methods of it defines the quality of the space. This job inquires the character of space in the architecture of Moneo interpreting the meaning of the void in the Basque culture through the reading of the form matrices in the work of Jorge Oteiza and Eduardo Chillida. In the tie with the Basque culture a reading key is characterized by concurring to put in relation some of the theoretical principles expressed by Moneo on the relationship between place and time, in an unique and specific vision of the space. In the analysis of the process that determines the genesis of the architecture of Moneo emerges a trajectory whose direction is constructed on two pivos: on the one hand architecture like instrument of appropriation of the place, gushed from an acquaintance process who leans itself to the reading of the relations that define the place and of the resonances through which measuring it, on the other hand the architecture whose character is able to represent and to extend the time in which he is conceived, through the autonomy that is conferred to them from values. Following the trace characterized from this hypothesis, that is supported on the theories elaborated from Moneo, surveying deepens the reading of the principles that construct the sculptural work of Oteiza and Chillida, features from a search around the topic of the void and to its expression through the form. It is instrumental to the definition of a specific area that concurs to interpret the character of the space subtended to a vision of the place and the time, affine to the sensibility of Moneo and in some way not stranger to its cultural formation. The years of the academic formation, during which Moneo enters in contact with the Basque artistic culture, seem to be an important period in the birth of that knowledge that will leads him to the formulation of theories tied to the relationship between time, place and architecture. The values expressed through the experimental work of Oteiza and Chillida during years '50 are valid bases to the understanding of such relationships. In tracing a profile of the figures of Oteiza and Chillida, without the pretension that it is exhaustive for the reading of the complex historical period in which they are placed, but with the needs to put the work in a context, I want to be evidenced the important role carried out from the two artists from the Basque cultural area within which Moneo moves its first steps. The tie that approaches Moneo to the Basque culture following the personal trajectory of the formative experience interlaces to that one of important figures of the art and the Spanish architecture. One of the more meaningful relationships is born just during the years of his academic formation, from 1958 to the 1961, when he works like student in the professional office of the architect Francisco Sáenz de Oiza, who was teaching architectural design at the ETSAM. In these years many figures of Basque artists alternated at the professional office of Oiza that enjoys the important support of the manufacturer and maecenas Juan Huarte Beaumont, introduced to he from Oteiza. The tie between Huarte and Oteiza is solid and continuous in the years and it realizes in a contribution to many of the initiatives that makes of Oteiza a forwarder of the Basque culture. In the four years of collaboration with Oiza, Moneo has the opportunity to keep in contact with an atmosphere permeated by a constant search in the field of the plastic art and with figures directly connected to such atmosphere. It’s of a period of great intensity as in the production like in the promotion of the Basque art. The collective “Blanco y Negro”, than is held in 1959 at the Galería Darro to Madrid, is only one of the many times of an exhibition of the work of Oteiza and Chillida. The end of the Fifties is a period of international acknowledgment for Chillida that for Oteiza. The decade of the Fifties consecrates the hypotheses of a mythical past of the Basque people through the spread of the studies carried out in the antecedent years. The archaeological discoveries that join to a context already rich of signs of the prehistoric era, consolidate the knowledge of a strong cultural identity. Oteiza, like Chillida and other contemporary artists, believe in a cosmogonist conception belonging to the Basques, connected to their matriarchal mythological past. The void in its meaning of absence, in the Basque culture, thus as in various archaic and oriental religions, is equivalent to the spiritual fullness as essential condition to the revealing of essence. Retracing the archaic origins of the Basque culture emerges the deep meaning that the void assumes as key element in the religious interpretation of the passage from the life to the death. The symbology becomes rich of meaningful characters who derive from the fact that it is a chthonic cult. A representation of earth like place in which divine manifest itself but also like connection between divine and human, and this manipulation of the matter of which the earth it is composed is the tangible projection of the continuous search of the man towards God. The search of equilibrium between empty and full, that characterizes also the development of the form in architecture, in the Basque culture assumes therefore a peculiar value that returns like constant in great part of the plastic expressions, than in this context seem to be privileged regarding the other expressive forms. Oteiza and Chillida develop two original points of view in the representation of the void through the form. Both use of rigorous systems of rules sensitive to the physics principles and the characters of the matter. The last aim of the Oteiza’s construction is the void like limit of the knowledge, like border between known and unknown. It doesn’t means to reduce the sculptural object to an only allusive dimension because the void as physical and spiritual power is an active void, that possesses that value able to reveal the being through the trace of un-being. The void in its transcendental manifestation acts at the same time from universal and from particular, like in the atomic structure of the matter, in which on one side it constitutes the inner structure of every atom and on the other one it is necessary condition to the interaction between all the atoms. The void can be seen therefore as the action field that concurs the relations between the forms but is also the necessary condition to the same existence of the form. In the construction of Chillida the void represents that counterpart structuring the matter, inborn in it, the element in absence of which wouldn’t be variations neither distinctive characters to define the phenomenal variety of the world. The physics laws become the subject of the sculptural representation, the void are the instrument that concurs to catch up the equilibrium. Chillida dedicate himself to experience the space through the senses, to perceive of the qualities, to tell the physics laws which forge the matter in the form and the form arranges the places. From the artistic experience of the two sculptors they can be transposed, to the architectonic work of Moneo, those matrices on which they have constructed their original lyric expressions, where the void is absolute protagonist. An ambit is defined thus within which the matrices form them drafts from the work of Oteiza and Chillida can be traced in the definition of the process of birth and construction of the architecture of Moneo, but also in the relation that the architecture establishes with the place and in the time. The void becomes instrument to read the space constructed in its relationships that determine the proportions, rhythms, and relations. In this way the void concurs to interpret the architectonic space and to read the value of it, the quality of the spaces constructing it. This because it’s like an instrument of the composition, whose role is to maintain to the separation between the elements putting in evidence the field of relations. The void is that instrument that serves to characterize the elements that are with in the composition, related between each other, but distinguished. The meaning of the void therefore pushes the interpretation of the architectonic composition on the game of the relations between the elements that, independent and distinguished, strengthen themselves in their identity. On the one hand if void, as measurable reality, concurs all the dimensional changes quantifying the relationships between the parts, on the other hand its dialectic connotation concurs to search the equilibrium that regulated such variations. Equilibrium that therefore does not represent an obtained state applying criteria setting up from arbitrary rules but that depends from the intimate nature of the matter and its embodiment in the form. The production of a form, or a formal system that can be finalized to the construction of a building, is indissolubly tied to the technique that is based on the acquaintance of the formal vocation of the matter, and what it also can representing, meaning, expresses itself in characterizing the site. For Moneo, in fact, the space defined from the architecture is above all a site, because the essence of the site is based on the construction. When Moneo speaks about “birth of the idea of plan” like essential moment in the construction process of the architecture, it refers to a process whose complexity cannot be born other than from a deepened acquaintance of the site that leads to the comprehension of its specificity. Specificity arise from the infinite sum of relations, than for Moneo is the story of the oneness of a site, of its history, of the cultural identity and of the dimensional characters that that they are tied to it beyond that to the physical characteristics of the site. This vision is leaned to a solid made physical structure of perceptions, of distances, guideline and references that then make that the process is first of all acquaintance, appropriation. Appropriation that however does not happen for directed consequence because does not exist a relationship of cause and effect between place and architecture, thus as an univocal and exclusive way does not exist to arrive to a representation of an idea. An approach that, through the construction of the place where the architecture acquires its being, searches an expression of its sense of the truth. The proposal of a distinction for areas like space, matter, spirit and time, answering to the issues that scan the topics of the planning search of Moneo, concurs a more immediate reading of the systems subtended to the composition principles, through which is related the recurrent architectonic elements in its planning dictionary. From the dialectic between the opposites that is expressed in the duality of the form, through the definition of a complex element that can mediate between inside and outside as a real system of exchange, Moneo experiences the form development of the building deepening the relations that the volume establishes in the site. From time to time the invention of a system used to answer to the needs of the program and to resolve the dual character of the construction in an only gesture, involves a deep acquaintance of the professional practice. The technical aspect is the essential support to which the construction of the system is indissolubly tied. What therefore arouses interest is the search of the criteria and the way to construct that can reveal essential aspects of the being of the things. The constructive process demands, in fact, the acquaintance of the formative properties of the matter. Property from which the reflections gush on the relations that can be born around the architecture through the resonance produced from the forms. The void, in fact, through the form is in a position to constructing the site establishing a reciprocity relation. A reciprocity that is determined in the game between empty and full and of the forms between each other, regarding around, but also with regard to the subjective experience. The construction of a background used to amplify what is arranged on it and to clearly show the relations between the parts and at the same time able to tie itself with around opening the space of the vision, is a system that in the architecture of Moneo has one of its more effective applications in the use of the platform used like architectonic element. The spiritual force of this architectonic gesture is in the ability to define a place whose projecting intention is perceived and shared with who experience and has lived like some instrument to contact the cosmic forces, in a delicate process that lead to the equilibrium with them, but in completely physical way. The principles subtended to the construction of the form taken from the study of the void and the relations that it concurs, lead to express human values in the construction of the site. The validity of these principles however is tested from the time. The time is what Moneo considers as filter that every architecture is subordinate to and the survival of architecture, or any of its formal characters, reveals them the validity of the principles that have determined it. It manifests thus, in the tie between the spatial and spiritual dimension, between the material and the worldly dimension, the state of necessity that leads, in the construction of the architecture, to establish a contact with the forces of the universe and the intimate world, through a process that translate that necessity in elaboration of a formal system.

Aspetti di vita quotidiana, religiosa, militare e civile in Britannia e lungo il Vallo di Adriano

The dissertation aims to provide an overview of some aspects of everyday life in Roman Britain in general and in the area of Hadrian’s Wall in particular. In a preliminary description, the writer addresses the complex topic related to the genesis of borders as the fulfillment of the expansionist parable of Rome, and as the space manifestation of the sunset of the idea of an imperium sine fine. Then the thesis passes to examine, in subsequent chapters, first the religious theme in its peculiar indigenous component and in the cultural practices triggered by the process of Romanization, secondly the question whether is possible to study everyday life in the northernmost province of the Empire through a discussion of the civilian settlements in proximity to military sites. This issue is drawn especially thanks to the analysis of the so-called Vindolanda tablets, which constitute a valuable evidence of a lively environment both under human and social respect. Before giving an indication of the specific bibliography, the work offers a number of appendices which elaborate part of the information which has been supplied in the previous sections. Mention of the epigraphic repertoires and literary and antiquarian sources is finally made.

Chortheater. Genesi di un modello Tipologie corali nel Novecento

In the Nineties year in the German Studies’ area appears a new reflection around the theatrical chorus thank to the activity of theatrical personalities as Heiner Müller, Einar Schleef, Elfriede Jelinek or Christoph Marthaler. So Hans Thies Lehmann, in his compendium about the Postdramatic Theater (Hans-Thies Lehmann, Postdramatisches Theater, Verlag der Autoren, Frankfurt am Main 1999) advances the new category of the Chortheater (Chor Theatre) to explain e new form of drama and performative event; again in 1999 appear the important essay of Detlev Baur (Detlev Baur, Der Chor im Theater des 20. Jahrhunderts. Typologie des theatralen Mittels Chor, Niemeyer, Tübingen 1999), that gives an important device about this instrument but without giving the reasons of the its modifications in such different historical times. Then in 2004, Erika Fischer-Lichte, (Theatre, Sacrifice, Ritual. Exploring Forms of Political Theatre, Routledge, London-New York 2005), reflects about the connection between ritual and theatre in the 20th Century. Thank to this studies the search aim was to give a new story of the chorus as theatrical and performative tool, in his liminal essence in creating immersive or alienating theatrical relation with the audience and to give specific features to distinguish it from general categories such as choral theatre o ensemble theatre.

The role of interleuchin 6 (IL-6) in the promotion of an aggressive and stem cell-like phenotype in human breast cancer cells and in stem/progenitor cells expanded in vitro as mammospheres

High serum levels of Interleukin-6 (IL-6) correlate with poor outcome in breast cancer patients. However no data are available on the relationship between IL-6 and stem/progenitor cells which may fuel the genesis of breast cancer in vivo. Herein, we address this issue in mammospheres (MS), multi-cellular structures enriched in stem/progenitor cells of the mammary gland, and also in MCF-7 breast cancer cells. We show that MS from node invasive breast carcinoma tissues express IL-6 mRNA at higher levels than MS from matched non-neoplastic mammary glands. We find that IL-6 mRNA is detectable only in basal-like breast carcinoma tissues, an aggressive variant showing stem cell features. Our results reveal that IL-6 triggers a Notch-3-dependent up-regulation of the Notch ligand Jagged-1, whose interaction with Notch-3 promotes the growth of MS and MCF-7 derived spheroids. Moreover, IL-6 induces a Notch-3-dependent up-regulation of the carbonic anhydrase IX gene, which promotes a hypoxia-resistant/invasive phenotype in MCF-7 cells and MS. Finally, an autocrine IL-6 loop relies upon Notch-3 activity to sustain the aggressive features of MCF-7-derived hypoxia-selected cells. In conclusion, our data support the hypothesis that IL-6 induces malignant features in Notch-3 expressing, stem/progenitor cells from human ductal breast carcinoma and normal mammary gland.

Studio di fenomeni d'instabilità gravitativa sui fondali marini, con particolare riferimento all'isola di Stromboli

In the last decade the interest for submarine instability grew up, driven by the increasing exploitation of natural resources (primary hydrocarbons), the emplacement of bottom-lying structures (cables and pipelines) and by the development of coastal areas, whose infrastructures increasingly protrude to the sea. The great interest for this topic promoted a number of international projects such as: STEAM (Sediment Transport on European Atlantic Margins, 93-96), ENAM II (European North Atlantic Margin, 96-99), GITEC (Genesis and Impact of Tsunamis on the European Coast 92-95), STRATAFORM (STRATA FORmation on Margins, 95-01), Seabed Slope Process in Deep Water Continental Margin (Northwest Gulf of Mexico, 96-04), COSTA (Continental slope Stability, 00-05), EUROMARGINS (Slope Stability on Europe’s Passive Continental Margin), SPACOMA (04-07), EUROSTRATAFORM (European Margin Strata Formation), NGI's internal project SIP-8 (Offshore Geohazards), IGCP-511: Submarine Mass Movements and Their Consequences (05-09) and projects indirectly related to instability processes, such as TRANSFER (Tsunami Risk ANd Strategies For the European region, 06-09) or NEAREST (integrated observations from NEAR shore sourcES of Tsunamis: towards an early warning system, 06-09). In Italy, apart from a national project realized within the activities of the National Group of Volcanology during the framework 2000-2003 “Conoscenza delle parti sommerse dei vulcani italiani e valutazione del potenziale rischio vulcanico”, the study of submarine mass-movement has been underestimated until the occurrence of the landslide-tsunami events that affected Stromboli on December 30, 2002. This event made the Italian Institutions and the scientific community more aware of the hazard related to submarine landslides, mainly in light of the growing anthropization of coastal sectors, that increases the vulnerability of these areas to the consequences of such processes. In this regard, two important national projects have been recently funded in order to study coastal instabilities (PRIN 24, 06-08) and to map the main submarine hazard features on continental shelves and upper slopes around the most part of Italian coast (MaGIC Project). The study realized in this Thesis is addressed to the understanding of these processes, with particular reference to Stromboli submerged flanks. These latter represent a natural laboratory in this regard, as several kind of instability phenomena are present on the submerged flanks, affecting about 90% of the entire submerged areal and often (strongly) influencing the morphological evolution of subaerial slopes, as witnessed by the event occurred on 30 December 2002. Furthermore, each phenomenon is characterized by different pre-failure, failure and post-failure mechanisms, ranging from rock-falls, to turbidity currents up to catastrophic sector collapses. The Thesis is divided into three introductive chapters, regarding a brief review of submarine instability phenomena and related hazard (cap. 1), a “bird’s-eye” view on methodologies and available dataset (cap. 2) and a short introduction on the evolution and the morpho-structural setting of the Stromboli edifice (cap. 3). This latter seems to play a major role in the development of largescale sector collapses at Stromboli, as they occurred perpendicular to the orientation of the main volcanic rift axis (oriented in NE-SW direction). The characterization of these events and their relationships with successive erosive-depositional processes represents the main focus of cap.4 (Offshore evidence of large-scale lateral collapses on the eastern flank of Stromboli, Italy, due to structurally-controlled, bilateral flank instability) and cap. 5 (Lateral collapses and active sedimentary processes on the North-western flank of Stromboli Volcano), represented by articles accepted for publication on international papers (Marine Geology). Moreover, these studies highlight the hazard related to these catastrophic events; several calamities (with more than 40000 casualties only in the last two century) have been, in fact, the direct or indirect result of landslides affecting volcanic flanks, as observed at Oshima-Oshima (1741) and Unzen Volcano (1792) in Japan (Satake&Kato, 2001; Brantley&Scott, 1993), Krakatau (1883) in Indonesia (Self&Rampino, 1981), Ritter Island (1888), Sissano in Papua New Guinea (Ward& Day, 2003; Johnson, 1987; Tappin et al., 2001) and Mt St. Augustine (1883) in Alaska (Beget& Kienle, 1992). Flank landslide are also recognized as the most important and efficient mass-wasting process on volcanoes, contributing to the development of the edifices by widening their base and to the growth of a volcaniclastic apron at the foot of a volcano; a number of small and medium-scale erosive processes are also responsible for the carving of Stromboli submarine flanks and the transport of debris towards the deeper areas. The characterization of features associated to these processes is the main focus of cap. 6; it is also important to highlight that some small-scale events are able to create damage to coastal areas, as also witnessed by recent events of Gioia Tauro 1978, Nizza, 1979 and Stromboli 2002. The hazard potential related to these phenomena is, in fact, very high, as they commonly occur at higher frequency with respect to large-scale collapses, therefore being more significant in terms of human timescales. In the last chapter (cap. 7), a brief review and discussion of instability processes identified on Stromboli submerged flanks is presented; they are also compared with respect to analogous processes recognized in other submerged areas in order to shed lights on the main factors involved in their development. Finally, some applications of multibeam data to assess the hazard related to these phenomena are also discussed.

L'invention de l'Orthodoxie. Religion et Modernité dans le discours nationaliste roumain du XIX-ème et du XX-ème siècles

Our thesis entitled The Invention of Orthodoxy. Religion and Modernity in Romanian nationalist discourse from the XIXth to the XXth century is intended to be a history of the idea of “Romanianess” which brings together, in a structural as well as in a conceptual dimension, three major themes: Romanian Orthodoxy, Modernity and the Political. Having as premise for the study of the Romanian case the simultaneous genesis of the religious and political communities, from the Middle Ages to Modernity, the purpose of our inquiry is to formulate a theologico-political definition of ‘’Romanian Orthodoxy’’. Thus, within a main theoretical framework that values the contributions of Carl Schmitt, Michel Foucault and Reinhart Koselleck, our analysis of selected texts that go from the 1860’s to the 1940’s tries to answer the question regarding the relationship between Romanian Orthodoxy and Modernity, as well as its reflection upon the political identity and organisation of the Romanian society. Considering the political context of the events that underline our conceptual focus, we consider that the proper answer to our investigation lies within the logic of multiplicity; namely, we refer to a plural Romania which is divided, at the beginning of the XXth century, between Traditionalism and Modernity, between a massive rural, agrarian society and an urban minority elite, striving to single out, in an phenomenological approach, the “Romanian way”. Secondly, we refer to a plural Modernity, which is at the same time social, cultural, religious and political. Thirdly, the logic of multiplicity applies as well in the interpretation of the fractures present within the religious nationalist discourse; namely, the rejection of Orthodoxy during the XIXth century, as it was considered an impediment in Romania’s path to adopting western modernity and later on, starting with the 1930, the restoration of the “Orthodox ethos” as a source of cultural and political values of the Romanian nation.