Academic literature on the topic 'CNRN'

ABSTRACT An interesting but largely unanswered biological question is how eukaryotic organisms regulate the size of multicellular tissues. During development, a lawn of Dictyostelium cells breaks up into territories, and within the territories the cells aggregate in dendritic streams to form groups of ∼20,000 cells. Using random insertional mutagenesis to search for genes involved in group size regulation, we found that an insertion in the cnrN gene affects group size. Cells lacking CnrN (cnrN −) form abnormally small groups, which can be rescued by the expression of exogenous CnrN. Relayed pulses of extracellular cyclic AMP (cAMP) direct cells to aggregate by chemotaxis to form aggregation territories and streams. cnrN − cells overaccumulate cAMP during development and form small territories. Decreasing the cAMP pulse size by treating cnrN − cells with cAMP phosphodiesterase or starving cnrN − cells at a low density rescues the small-territory phenotype. The predicted CnrN sequence has similarity to phosphatase and tensin homolog (PTEN), which in Dictyostelium inhibits cAMP-stimulated phosphatidylinositol 3-kinase signaling pathways. CnrN inhibits cAMP-stimulated phosphatidylinositol 3,4,5-trisphosphate accumulation, Akt activation, actin polymerization, and cAMP production. Our results suggest that CnrN is a protein with some similarities to PTEN and that it regulates cAMP signal transduction to regulate territory size.

Abstract BACKGROUND: Identifying the extent of involvement of the vessel and nerve, particularly in regard to preoperative evaluation and precise localization of the tumor and its relation to the structures of the extremities, has important applications for advancing the treatment of lower extremity diseases. OBJECTIVE: To review the technical feasibility of simultaneous visualization of nerves and vessels of the lower extremities by using magnetization-prepared susceptibility-weighted magnetic resonance (MR) imaging (MP-SWI) at 3.0T. METHODS: Ten healthy volunteers and 10 patients were studied. Optimized MP-SWI, MR neurography (MRN) based on 3D diffusion-weighted steady-state free precession imaging and contrast-enhanced MR angiography (CE-MRA) sequences were performed for each subject. The means of signal-to-noise ratio (SNR)n, SNRv, SNRm, contrast-to-noise ratio (CNR)n,m and CNRv,m were calculated and the certainty of identifying nerves and vessels was determined. CNRn,m between MP-SWI and MRN, and CNRv,m between MP-SWI and CE-MRA were compared. RESULTS: MP-SWI provides slightly poorer CNRv,m than CE-MRA, whereas MP-SWI provides a better CNRn,m than MRN. In thin-slice-thickness maximum-intensity projection arbitrary planes, the sciatic nerve and its branches were clearly identified (score 1 or 2 of 2) in 17 subjects (85%); the femoral artery and the main branches were identified (score 1 or 2 of 2) in all 20 subjects (100%). The nerves are isointense to slightly hypointense to muscle, and the vessels show a more obvious hyperintense signal than muscle in MP-SWI. CONCLUSION: The proposed MP-SWI demonstrates the feasibility of simultaneously visualizing nerves and vessels of the lower extremities without using an exogenous contrast agent. It may enable straightforward localization of a disease process to a specific nerve and vessel.

SUMMARYA new CNR (caudatum non-reversal) mutant of Paramecium caudatum was isolated after gamma ray mutagenesis. This CNR lacks not only the transient inward Ca2+ current but also the sustained Ca2+ current. It was shown to complement the three known CNR mutants of P. caudatum (cnrA, cnrB and cnrC) by crossbreeding analyses. Thus, this new mutant belongs to a 4th CNR locus, designated cnrD. The defect of cnrD can be partially rescued by microinjection of cytoplasm from any of the three CNR mutants or the three Pawns (pwA, pwB and pwC) in P. tetraurelia. Since the three CNR genes have been shown to be different from the three Pawn genes by cytoplasmic complementation test (Haga et al. 1983), this result suggests that cnrD is the 7th non-excitable mutant in Paramecium. Thus, there are at least seven genes controlling Ca2+ channel function in Paramecium.

ABSTRACT Ralstonia sp. strain CH34 is resistant to nickel and cobalt cations. Resistance is mediated by the cnrdeterminant located on plasmid pMOL28. The cnr genes are organized in two clusters, cnrYXH and cnrCBA. As revealed by reverse transcriptase PCR and primer extension, transcription from these operons is initiated from promoters located upstream of the cnrY and cnrC genes. These two promoters exhibit conserved sequences at the −10 (CCGTATA) and −35 (CRAGGGGRAG) regions. The CnrH gene product, which is required for expression of both operons, is a sigma factor belonging to the sigma L family, whose activity seems to be governed by the membrane-bound CnrY and CnrX gene products in response to Ni2+. Half-maximal activation from the cnrCBAoperon was determined by using appropriate lacZ gene fusions and was shown to occur at an Ni2+ concentration of about 50 μM.

Cadherins are cell adhesion molecules that are critical for tissue development. In this report, we identified members of the cadherin family cadherin-related neuronal receptors (CNRs) 1 and 5 expressed in rat incisors by the differential display method. Quantitative RT-PCR revealed that CNR1 mRNA is expressed in the secretory stage but reduced in the early-maturation stage, while CNR5 mRNA is expressed in both these stages. In situ hybridization showed that strong expression of CNR1 is strong in the secretory stage, but reduced in the early phase and diminished in the late phase of the early-maturation stage. CNR5 mRNA is expressed almost at the same levels in the secretory and in the early phase of the early-maturation stages but is absent in the late phase of the early-maturation stage. Both CNR1 and 5 mRNA are continuously expressed in odontoblasts. Immunohistology showed that CNR proteins are expressed in the secretory and early-maturation stages of ameloblasts, but no protein expression at the late-maturation stage was observed. CNR proteins were continuously expressed in odontoblasts. We found that recombinant CNR1 binds dental epithelial and mesenchymal cells through N-terminal domain EC1 in vitro. These results suggest that CNR1 and CNR5 may play an important role in enamel and dentin formation, probably through cell-cell and/or cell-matrix interactions.

ABSTRACT The linked resistance to nickel and cobalt of Ralstonia eutropha-like strain CH34 (Alcaligenes eutrophusCH34) is encoded by the cnr operon, which is localized on the megaplasmid pMOL28. The regulatory genes cnrYXH have been cloned, overexpressed, and purified in Escherichia coli. CnrY fractionated as a 10.7-kDa protein in in vitro translation assays. CnrX, a periplasmic protein of 16.5 kDa, was overproduced and purified as a histidine-tagged fusion protein inE. coli. His-CnrX was found to posses a secondary structure content rich in alpha-helical and beta-sheet structures. CnrH, a sigma factor of the extracytoplasmic function family, was purified as an N-terminally histidine-tagged fusion. In gel shift mobility assays, His-CnrH, in the presence of E. coli core RNA polymerase enzyme, could retard at least two different promoter DNA targets,cnrYp and cnrHp, localized within thecnrYXH locus. These promoters and their transcription start sites were confirmed by primer extension. Purified His-CnrX did not inhibit the DNA-binding activity of His-CnrH and is therefore unlikely to be an anti-sigma factor, as previously hypothesized (EMBL M91650 description entry). To study the transcriptional response of the regulatory locus to metals and to probe promoter regions, transcriptional fusions were constructed between fragments ofcnrYXH and the luxCDABE, luciferase reporter genes. Nickel and cobalt specifically induced thecnrYXH-luxCDABE fusion at optimal concentrations of 0.3 mM Ni2+ and 2.0 mM Co2+ in a noncomplexing medium for metals. The two promoter regions PY (upstreamcnrY) and PH (upstream cnrH) were probed and characterized using this vector and were found to control the nickel-inducible regulatory response of the cnr operon. The cnrHp promoter was responsible for full transcription of the cnrCBA structural resistance genes, while thecnrYp promoter was necessary to obtain metal-inducible transcription from the cnrHp promoter. The zinc resistance phenotype (ZinB) of a spontaneous cnr mutant strain, AE963, was investigated and could be attributed to an insertion of IS1087, a member of the IS2 family of insertion elements, within the cnrY gene.

Abstract Introduction: Endocannabinoid signaling (ECS), mediated primarily by cannabinoid receptors (CNR) 1 and 2, is implicated in embryo implantation, decidualization, and placentation, but less is known about its role in late pregnancy or labour. Reports of elevated serum endocannabinoid concentrations during labour suggest that ECS may modulate uterine function leading up to and during parturition. Effects on uterine function likely vary depending on: the type of cannabinoid present, the intrauterine tissue, and CNR1/2 expression. Study of ECS gene expression in late pregnancy is therefore important to determine the contribution of this pathway to the normal and pathologic physiology of labour, for instance in preterm labour. Examining ECS gene expression in pregnancy may also contribute insight into the effects of exogenous cannabinoid consumption (reported in ~5% of pregnancies) on the late-pregnant uterus. To understand when and where cannabinoid signaling may impact uterine functions, we conducted an observational study on pregnant human and mouse intrauterine tissues. Methods: Human amnion, chorion, decidua, placenta, and upper/lower myometrium (n=6 participants) were biopsied at cesarean delivery (term, non-labour) to determine CNR expression by qPCR. Additional decidua (n=80) and upper/lower myometrium (n=82) samples were similarly obtained with and without labour, at term and preterm, for CNR expression analysis by qPCR. Mouse uteri for CNR expression analysis by qPCR were obtained from timed-mated C57BL6 mice at days 15-20 of pregnancy, in active labour, or post-partum. Human and mouse expression data were analyzed by Student’s t-test, one-way ANOVA (Bonferroni post-hoc), and Pearson’s correlation, as appropriate. Results: Term non-labour chorion, placenta, myometrium and decidua express CNRs, with 2-fold higher expression of CNR1 versus CNR2. In myometrium and decidua, neither CNR1 or CNR2 expression differed with labour status. CNR1 expression correlated positively with gestational age in decidua (r=0.346, p=0.0266) and lower segment myometrium (r=0.3667, p=0.0270) with labour. In mouse uteri, Cnr1 and Cnr2 expression significantly increased post-partum compared to mid/late pregnancy (vs day 19, p<0.0001 Cnr1; vs days 15-18, p<0.05 Cnr2). Conclusion: ECS may occur in the human decidua and myometrium throughout pregnancy and labour as CNR1 and CNR2 expression is maintained throughout. In our mouse model, higher Cnr1 and Cnr2 expression post-partum suggests that ECS may play a role in uterine resolution following delivery. Additional RNAseq analysis of the mouse tissues studied is underway to address whether expression of genes involved in production, transport or metabolism of cannabinoids are altered in late pregnancy or with the initiation of parturition.

ABSTRACT At the beginning of the industrial atomic age, launched by President Dwight Eisenhower's speech on the peaceful uses of nuclear energy (“Atoms for Peace”, addressed to the United Nations General Assembly, New York, 8 December 1953), and after the birth of the first atomic agencies in France (Commissariat a l'Énergie Atomique, 1945) and the United States (the U.S. Atomic Energy Commission, 1946), the Comitato Nazionale per le Ricerche Nucleari (National Committee for Nuclear Research–CNRN) was also established in Italy (1952). The new institution, in 1960 became a self-governing organization with a modified name, Comitato Nazionale per l'Energia Nucleare (National Committee for Nuclear Energy–CNEN). Its mission was to promote and develop Italian research in nuclear science and technology. Mining and mineral exploration were among the early activities that the National Committee undertook beginning in 1954, when the Divisione Geomineraria (Geology and Mining Division) was established. A regional-scale geochemical and geophysical prospecting survey for U-Th bearing ores involved different Italian regions both in northern and in southern Italy. Geological surveys, for instance, were systematically carried out in the Alps beginning in 1954. They were run by three main teams of geologists. The paper aims to analyze the key factors that contributed to fostering the emergence of a new field of research about uranium and nuclear geology in Italy during the years immediately after WWII.

The structures and NMR fluxionality of a wide variety of organometallic complexes (including tetrahedral cluster cations and systems of the type (CnRn)ML3, where R = Et, Ph) are discussed. Barriers to tripodal and peripheral substituent rotations are reported, and the relevance of correlated rotations to molecular machines is outlined. Haptotropic shifts in (cyclopenta[def]phenanthrenyl)MLn and (cyclopenta[l]phenanthrenyl)MLn complexes are rationalized in terms of the aromatic character of the transition states. Likewise, the barriers to silatropic shifts in polyindenylsilanes can be correlated with the aromaticity of the intermediate isoindenes. Finally, the use of cobalt clusters to control cyclohexane ring conformations is described.Key words: NMR ring currents, fluxionality, correlated rotations, molecular rearrangements, haptotropic shifts.

2011/2012
Lo studio della fisica nucleare in Italia ebbe il suo mito fondativo nelle vicende dei “ragazzi di via Panisperna”, dal nome della via romana in cui sorgevano i laboratori diretti da Enrico Fermi. Dopo aver raggiunto la fama mondiale (in particolare con il Nobel per la fisica di Fermi nel 1938), il gruppo fu disperso a causa della politica (sia razziale che scientifica) del regime fascista. Mentre Fermi ed altri, espatriati in America, davano il proprio determinante contributo alla realizzazione della bomba atomica, in Italia rimase il solo Edoardo Amaldi che, nel dopoguerra, si trovò ad essere, nel Paese e fuori, un fondamentale punto di riferimento per la fisica italiana. Nell’immediato dopoguerra, a fronte di un sostanziale disinteresse del Governo italiano in materia di ricerca, furono le industrie elettriche private a muovere i primi passi verso la ricerca e lo sviluppo della tecnologia nucleare, concedendo il proprio appoggio ad alcuni giovani ricercatori del Politecnico di Milano che diedero vita al CISE (Centro Informazioni Studi Esperienze). Parallelamente, la “comunità dei fisici” iniziava a ritagliarsi un proprio spazio autonomo di manovra. Nel 1951 i gruppi universitari che si occupavano di fisica fondamentale diedero vita all’Istituto Nazionale di Fisica Nucleare (INFN) mentre l'anno successivo, non senza attriti con il CISE, il Ministero dell'Industria appoggiò la creazione del Comitato Nazionale per le Ricerche Nucleari (CNRN), incaricato di promuovere e occuparsi della fisica nucleare applicata. Alla presidenza fu nominato Francesco Giordani, chimico napoletano legato all'IRI ed agli ambienti del neo meridionalismo. Il Comitato, che solo nel 1960 fu mutato in CNEN (Comitato Nazionale per l'Energia Nucleare) ottenendo la necessaria personalità giuridica, dovette costantemente far fronte alle difficoltà derivanti dalla propria fragilità istituzionale e dalle continue tensioni con l'industria elettrica privata. Ciononostante, sotto la guida del suo Segretario Generale Felice Ippolito, riuscì a dar vita ad importanti realizzazioni (come il Sincrotrone di Frascati o il Centro di ricerche nucleari di Ispra) e diede l'impulso fondamentale che portò alla costruzione, nei primi anni '60, delle prime centrali nucleari in Italia. Questo “periodo aureo” della fisica nucleare applicata iniziò a finire nell’agosto del 1963 quando una dura campagna stampa prese a mettere in discussione le gestione di Ippolito che si ritrovò al centro di un “caso” che da mediatico si fece ben presto giuridico e portò, nel marzo del 1964, all'arresto del Segretario Generale del CNEN per irregolarità amministrative. “Il caso Ippolito”, lungi dall’essere solo un processo per un isolato caso di malversazione, di fatto sancì la fine della ricerca e dello sviluppo del nucleare in Italia, facendo piazza pulita non solo dei progetti di nuove centrali atomiche, ma anche di un certo tipo di gestione degli enti pubblici che aveva fatto dell’elasticità amministrativa il proprio punto di forza, laddove in seguito si impose la burocratizzazione e la lottizzazione politica. Nella tesi in esame ho tentato di individuare, all'interno di un campo di ricerca così vario e così ricco di spunti collocati a cavallo di più discipline storiche (storia e filosofia della scienza, dell'economica e dell'industria, della cultura e della politica, delle relazioni internazionali), alcuni snodi focali ed emblematici che permettessero di sviluppare un percorso di indagine su quello che appariva come un meraviglioso tentativo di far recuperare all'Italia il tempo perduto a causa del regime fascista, in termini di sviluppo tecnologico e scientifico, ma anche culturale e politico. Tale tentativo ottenne risultati di rilievo mondiale nel dopoguerra ma andò incontro ad una nuova sconfitta, nei primi anni '60, quando emerse l'incapacità dello Stato di riformare se stesso per tener dietro ai rapidi mutamenti, non solo tecnici, che la tecnologia d'eccellenza pretende per mantenersi tale. Fin dall'inizio ho individuato in Felice Ippolito il trait d'union tra i fatti caratterizzanti le vicende trattate. Interessato alla ricerca nucleare quale geologo esperto in prospezioni minerarie, in seguito venne nominato Segretario Generale del CNRN e si trovò a rivestire un ruolo chiave, emblematico e rappresentativo, all'interno di un complesso ambiente culturale composto da intellettuali, scienziati ed alti funzionari che parteciparono ad una rete di rapporti all'interno della quale si elaborarono delle organiche strategie di sviluppo per il Paese. Ippolito divenne referente e portavoce di una comunità scientifica che si caratterizzava in quegli anni per il suo rapporto estremamente dialettico e consapevole con tutte le componenti della società, dalla classe politica al mondo dell'industria e dell'economica, dal mondo della cultura alle classi subalterne. Per comprendere l'incontro tra Ippolito e la comunità dei fisici, ho ritenuto di iniziare la tesi con un accenno all'esperienza dei “ragazzi di via Panisperna” e di Enrico Fermi, in particolare. La partenza in treno di Fermi per Stoccolma, il 6 dicembre 1938, dove avrebbe ritirato il premio Nobel prima di espatriare negli Stati Uniti (in fuga dalle leggi razziali ma soprattutto dall'incapacità del regime fascista di comprenderne e sostenerne le iniziative), è stata presentata come evento simbolico e metaforico della perdita di un primo “treno per la modernità” da parte dell'Italia. L'attenzione è stata posta soprattutto su chi rimase sulla banchina di quella stazione, ovvero Edoardo Amaldi, che pur con molti dubbi alla fine scelse di rimanere in Italia diventando il punto di riferimento per eccellenza, in virtù del suo carisma scientifico ed umano, della comunità dei fisici italiani nel dopoguerra. In particolare ho messo in evidenza il rafforzarsi in Amaldi di un punto di vista autonomo su quello che doveva essere il rapporto tra la ricerca scientifica ed il mondo della politica e dell'industria. Mentre oltreoceano Fermi delegava al Governo la valutazione etica e la gestione dei risultati del proprio lavoro scientifico, in Italia il suo allievo Amaldi fin dal dopoguerra iniziò a tessere una rete di rapporti, con l'industria e le aziende controllate dallo Stato, caratterizzati da alcuni principi imprescindibili. Quando gli industriali elettrici privati lo chiamarono al CISE, Amaldi pose perentorie condizioni alla propria partecipazione, come la difesa della sua autonomia scientifica, il rifiuto di ogni principio di segretezza, ed il fatto che la ricerca doveva andare a beneficio dell'intera collettività e non a vantaggio di pochi gruppi privati. Dopo aver delineato alcuni elementi della figura di Amaldi, ho concentrato il mio interesse su Ippolito e sui suoi rapporti con l'ambiente culturale napoletano, liberale e meridionalista, di cui anche Francesco Giordani faceva parte. Attraverso la bibliografia e gli archivi dell'ente, ho esaminato la nascita del CNRN sull'asse Ippolito-Giordani-Pietro Campilli (il Ministro dell'Industria che sostenne il progetto) e di seguito l'insorgere delle tensioni con il CISE e l'industria privata. L'obiettivo è stato di mettere in evidenza l'estrema “coerenza” dell'incontro tra i fisici rappresentati da Amaldi e la politica scientifica portata avanti da Ippolito e Giordani, capaci di soddisfarne sia le ambizioni tecnico scientifiche che etiche e politiche. Con un capitolo intermedio, su tematiche di politica nucleare internazionale, ho introdotto il tema dell'iniziatica Atoms for peace, lanciata dal Presidente americano Eisenhower, che prospettava una politica di disarmo atomico fondata sulla socializzazione della tecnologia nucleare ad uso civile. Rinunciando a proporre un inquadramento storiografico e critico complessivo, ho scelto di render conto della rappresentazione offerta da uno dei protagonisti di quegli anni, ovvero il francese Bertrand Goldschmidt, che influenzò grandemente il punto di vista di Ippolito e degli Amici del Mondo (cui Ippolito si legò) e che oggi testimonia in maniera particolarmente efficace il clima di “euforia atomica” che determinò allora fondamentali scelte di politica energetica europea. L'iniziativa Atoms for Peace diede l'occasione ad Ippolito di avviare un'intesa collaborazione con l'ambiente culturale che ruotava attorno alla rivista «Il Mondo» diretta da Mario Pannunzio e che in quel momento si presentava come la fucina, di stampo liberale radicale, dei progetti politici che portarono in seguito al Centrosinistra. Ripercorrendo le pagine della rivista ho messo in evidenza un percorso di progressiva presa di coscienza sulla questione nucleare. Se fino all'iniziativa Atoms for Peace erano considerate solo le applicazioni militari di tale tecnologia, in seguito e anche grazie all'intervento di Ippolito, il dibattito sul nucleare venne connesso alla questione della produzione energetica vista nella prospettiva della lotta contro i monopoli e per la nazionalizzazione del settore. Su questi temi centrali in quella fase politica (sulla nazionalizzazione del settore elettrico si giocò la battaglia fondamentale per il Centrosinistra), Ippolito in particolare, a metà degli anni '50, iniziò a tessere un discorso unitario tra crescente richiesta energetica, sviluppo della tecnologia nucleare e necessaria nazionalizzazione. Coerenti a questa linea iniziarono ad apparire su «Il Mondo» i “Dialoghi plutonici” di Ernesto Rossi che testimoniavano i rapporti sempre più stretti tra Ippolito e la rivista, nel contesto delle vicissitudini politiche che portarono alla nascita del Partito Radicale ed ai convegni degli Amici del Mondo “La lotta contro i monopoli” e “Atomo ed elettricità”. Usando gli atti dei convegni e analizzando i molti articoli in merito apparsi sulla rivista, ho messo in evidenza il processo che portò, a partire dalle posizioni antistataliste sempre sostenute sulle pagine di «Il Mondo» in particolare da Rossi, al definirsi della presa di posizione nazionalizzatrice espressa durante il convegno “La lotta contro i monopoli”. Del seminario “Atomo ed elettricità” ho ritenuto di particolare interesse l'identificazione operata dai relatori tra esigenze tecnico-scientifiche dell'energia nucleare e opzione nazionalizzatrice che portò ad una lettura prettamente politica delle scelte tecniche da operare in materia di filiere tecnologiche. Lettura che, come evidenzieremo, Ippolito non condividerà a favore di un approccio che preferisce le soluzioni particolari alle analisi universali. Atoms for Peace comporta un rilancio generale della politica nucleare italiana anche in termini di “gara atomica” tra ricerca e sviluppo pubblici e privati. In particolare, ho esaminato il crescente clima di ostilità tra il CNRN e l'industria privata (l'Edison in particolare) e le cause che portarono alle dimissioni di Giordani dalla Presidenza del Comitato. In un capitolo titolato “Come Mattei all'Agip” ho delineato le difficoltà istituzionali che dovette affrontare Ippolito da segretario plenipotenziario del CNRN ed il conseguente sviluppo di un modus operandi problematico che ebbe importanti conseguenze nella creazione del “caso” che sarebbe esploso. Tra le molte vicissitudini del CNRN ho seguito soprattutto il processo che portò alla costruzione delle prime centrali atomiche in Italia con particolar attenzione alla collaborazione tra CNRN e Banca Mondiale che portò alla costruzione della centrale di Garigliano e che sintetizzò istanze meridionaliste e nucleariste. Con il capitolo “Dal CNRN al CNEN” ho esaminato il percorso politico che portò alla nascita del CNEN nel contesto delle trattative per il primo Governo di Centrosinistra e della nazionalizzazione dell'energia elettrica. L'obiettivo è stato in particolare mettere in evidenza le tensioni che andarono delineandosi all'interno del nuovo ente elettrico, l'ENEL, tra le posizioni rappresentate dal Direttore Generale Angelini ed il consigliere Ippolito. Negli ultimi due capitoli ho riassunto in modo antologico l'aspetto più ampiamente trattato dalla storiografia esistente sul tema, ovvero il “caso” mediatico e giuridico che prese il nome del Segretario Generale del CNEN e che portò alla sua incarcerazione. Oltre alla fase processuale, ho ricostruito il quadro politico e gli avvenimenti che portarono alla messa in stato di accusa di Ippolito, nell'estate del 1963, ed alla sua incarcerazione l'anno successivo, che ebbero come diretta conseguenza il drastico ridimensionamento dei programmi nucleari del CNEN. Infine ho proposto un'analisi delle ipotesi interpretative date al “caso Ippolito” evidenziando anche alcuni aspetti che, per varie ragioni, non sono stati ancora indagati. In ultima analisi il presente studio tenta di mettere in luce la complessità della materia trattata che, pur prestandosi per molte ragioni alle semplificazioni complottistiche e dietrologiche di stampo giornalistico, risulta incomprensibile senza una contestualizzazione capace di connettere il percorso della fisica nucleare italiana (che a partire dall'esperienza dei “ragazzi di via Panisperna” tende a pensarsi e muoversi come una “comunità” portatrice di propri interessi e ideali), il dibattito filosofico, culturale e tecnico sulle ragioni e sui mezzi dell'intervento dello Stato nell'economia e sul ruolo di intellettuali e scienziati nella società, ed infine la storia politica italiana, europea ed internazionale che portò alla nascita del Centrosinistra.
XXIV Ciclo
1975

The content of this thesis illustrates the six months work done during my internship at TKH Security Solutions - Siqura B.V. in Gouda, Netherlands. The aim of this thesis is to investigate on convolutional neural networks possible usage, from two different point of view: first we propose a novel algorithm for person re-identification, second we propose a deployment chain, for bringing research concepts to product ready solutions. In existing works, the person re-identification task is assumed to be independent of the person detection task. In this thesis instead, we consider the two tasks as linked. In fact, features produced by an object detection convolutional neural network (CNN) contain useful information, which is not being used by current re-identification methods. We propose several solutions for learning a metric on CNN features to distinguish between different identities. Then the best of these solutions is compared with state of the art alternatives on the popular Market-1501 dataset. Results show that our method outperforms them in computational efficiency, with only a reasonable loss in accuracy. For this reason, we believe that the proposed method can be more appropriate than current state of the art methods in situations where the computational efficiency is critical, such as embedded applications. The deployment chain we propose in this thesis has two main goals: it must be flexible for introducing new advancement in networks architecture, and it must be able to deploy neural networks both on server and embedded platforms. We tested several frameworks on several platforms and we ended up with a deployment chain that relies on the open source format ONNX.

O objetivo deste trabalho foi realizar a dosimetria de filtros dinâmicos aprimorados (“Enhanced Dynamic Wedge” – EDW). Isso foi feito com dois intuitos: 1) a avaliação da implementação clínica do filtro dinâmico aprimorado considerando-se suas vantagens e desvantagens; e 2) a comparação entre a eficiência e a melhor aplicabilidade de três sistemas dosimétricos diferentes em conjunto com o filtro dinâmico aprimorado. Os sistemas dosimétricos utilizados foram: o Sistema de Imagem de Feixe (“Beam Image System” – BIS2G), da Scanditronix-Wellhöfer, uma câmara de ionização cilíndrica de 0,6 cm3 do tipo Farmer, e um arranjo linear de câmaras de ionização múltiplas (“Ionization Chamber Linear Detector Array”) com 23 câmaras de ionização cilíndricas de 0,14 cm3, tipo Farmer. Com o Sistema de Imagem de Feixe – BIS2G foi possível obter curvas de fluência que permitiram analisar a simetria dos perfis de fluência, linearidade da dose, efeito da taxa de dose e efeito da gravidade, características diretamente ligadas à qualidade do funcionamento do filtro dinâmico aprimorado, além de ter sido possível também calcular o fator filtro para campos simétricos. Com a câmara de ionização mediu-se a porcentagem de dose em profundidade - PDP e calculou-se o fator filtro para campos simétricos e campos assimétricos (uma das vantagens do EDW). Com o arranjo linear de câmaras de ionização múltiplas foi possível obter curvas de isodose que permitiram a verificação da simetria e a comparação com os resultados obtidos com o BIS2G, além do cálculo do fator filtro para campos simétricos. O fator filtro calculado através de medidas tomadas com os três sistemas foi também comparado com resultados obtidos por dois formalismos, de Gibbons1 e de Klein et al 2, bem conhecidos da literatura e que serviram para a validação dos resultados e deste trabalho. Destas comparações verificou-se que os ângulos do filtro dinâmico aprimorado que apresentam maior diferença entre resultados obtidos e os formalismos foram os ângulos de 45º e de 60º em relação ao método de Klein et al que apresentaram diferenças de 2,1% em relação ao BIS2G, 1,9% em relação à câmara de ionização e 1,1% em relação ao arranjo linear de câmaras de ionização.
The purpose of this work was to accomplish the dosimetry of Enhanced Dynamic Wedge (EDW). It was carried out with two intents: 1) the evaluation of the clinical implementation of the EDW considering its advantages and disadvantages, and 2) the comparison among the efficiency and the better applicability of three different dosimetric systems in a set with the EDW. The dosimetric systems used were: the Beam Image System (BIS2G), from Scanditronix-Wellhöfer, a cylindrical ionization chamber of 0.6 cm3, type Farmer, and an ionization chamber linear detector array, composed by 23 cylindrical ionization chamber of 0.14 cm3, type Farmer. With the BIS2G was possible to plot graphs of fluence that allowed to analyze the symmetry of the graphs of fluence, linearity of the dose, dose rate effect, and gravity effect, features directly connected to the quality of the working of the EDW, further on having been possible to calculate the wedge factor for symmetric fields. With the ionization chamber it was measured the PDP and it was calculated the wedge factor for symmetric and asymmetric fields (one advantage of EDW). With the array it was possible to plot graphs of isodosis that allowed the checking of the symmetry and the comparison with the results obtained with the BIS2G, besides the calculation of the wedge factor for symmetric fields. The wedge factors obtained from the measurements of the three systems were also compared with the results of the formalisms, of Gibbons1 and of Klein et al 2, both well known if the literature, and that were used to validate the results and the work. From these comparisons was verified that the angles of the EDW that show more difference between the results and the formalisms were the 46º and 60º angles related to the method of Klein et al, which show differences of 2.12% related to BIS2G, 1.92% related to the ionization chamber, and 1.10% related to ionization chamber linear detector array.

This thesis presents the results of an architectural study on the design of FPGA- based architectures for convolutional neural networks (CNNs). We have analyzed the memory access patterns of a Convolutional Neural Network (one of the biggest networks in the family of deep learning algorithms) by creating a trace of a well-known CNN architecture and by developing a trace-driven DRAM simulator. The simulator uses the traces to analyze the effect that different storage patterns and dissonance in speed between memory and processing element, can have on the CNN system. This insight is then used create an initial design for a layer architecture for the CNN using an FPGA platform. The FPGA is designed to have multiple parallel-executing units. We design a data layout for the on-chip memory of an FPGA such that we can increase parallelism in the design. As the number of these parallel units (and hence parallelism) depends on the memory layout of input and output, particularly if parallel read and write accesses can be scheduled or not. The on-chip memory layout minimizes access contention during the operation of parallel units. The result is an SoC (System on Chip) that acts as an accelerator and can have more number of parallel units than previous work. The improvement in design was also observed by comparing post synthesis loop latency tables between our design and one with a single unit design. This initial design can help in designing FPGAs targeted for deep learning algorithms that can compete with GPUs in terms of performance.

Genetic variation within the cannabinoid 1 receptor (CB1R) locus (CNR1) has been repeatedly associated with drug addiction pathologies. Genomic annotation of CNR1 indicates the vast majority of this genetic variation likely results in altered transcriptional regulation of the CNR1 gene as a mechanistic link to the disease phenotype. There is a lack of information describing the regulation of CNR1 transcription and the potential impact of disease-associated variation within the CNR1 locus on its transcriptional regulation. This study investigates the impact of an evolutionary conserved regulatory region of CNR1, termed ECR1, and the disease-associated variation contained within, on the transcriptional activity of the cognate CNR1 promoter region. Reporter assays conducted in primary hippocampal cells demonstrate that CNR1 promoter exhibits variable transcriptional activity during periods of CB1R signalling and cell depolarisation. Coupled to allelic variants of ECR1, the CNR1 promoter shows significant changes in transcriptional activity under resting conditions indicating that disease-associated variation within ECR1 may decrease CNR1 transcription. Further, alleles of ECR1 can drive allele-specific transcriptional responses from the CNR1 promoter during periods of CB1R stimulation and cell depolarisation. The results highlight the potential for disease-associated regulatory variation of the CNR1 locus to create stratified transcriptional responses to specific cell signalling scenarios and putatively to clinical strategies employing pharmacological agents. Furthermore, investigation of DNA-protein interactions at the allelic ECR1 region demonstrate that disease-associated variation within ECR1 alters DNA-protein interactions within the nucleus consistent with a decrease in transcriptional activity in the disease-associated allele variant. Collectively the current work supports the hypothesis that disease-associated variation within the ECR1 regulatory region of the CNR1 locus has the capacity to significantly impact on CNR1 promoter transcriptional activity. It is posited that allele-specific transcriptional effects may have a major impact on the susceptibility of individuals to drug addiction or on responses to clinical pharmacological treatments.

Les bacteries propioniques laitieres et en particulier celles de l'espece propionibacterium freudenreichii, jouent un role majeur dans l'etape de l'affinage des fromages a pate pressee cuite, type emmental par leur intervention dans l'ouverture de la pate et certainement dans la proteolyse du caille. Or la proteolyse due en partie a des peptidases intracellulaires implique la liberation de ces enzymes dans la pate par eclatement des bacteries nommees autolyse. Lors de cette these nous avons determine des parametres inducteurs de l'autolyse par une approche biochimique et ultrastructurale. Ainsi la capacite a l'autolyse depend de la souche consideree, du stade de croissance cellulaire, de l'absence de nutriment carbone, des conditions physicochimiques du milieu environnant (ph, nature des sels, temperature,). Les enzymes responsables de l'autolyse cellulaire (nommees autolysines), au nombre de 8 chez p. Freudenreichii, ont ete partiellement caracterisees (pm, resistance thermique, glycosylation). Des etapes de purification de ces autolysines ont ete franchies. Les resultats obtenus contribueront a un choix moins empirique des levains propioniques utilises en fromagerie

Breve introduzione alle reti neurali e al deep learning con descrizione dei sistemi utilizzati per i modelli e i test effettuati. Spiegazione del funzionamento dei sistemi creati ed esposizione dei risultati ottenuti.

A definite trend in Biomedical Imaging is the one towards the integration of increasingly complex interpretative layers to the pure data acquisition process. One of the most interesting and looked-forward goals in the field is the automatic segmentation of objects of interest in extensive acquisition data, target that would allow Biomedical Imaging to look beyond its use as a purely assistive tool to become a cornerstone in ambitious large-scale challenges like the extensive quantitative study of the Human Brain. In 2019 Convolutional Neural Networks represent the state of the art in Biomedical Image segmentation and scientific interests from a variety of fields, spacing from automotive to natural resource exploration, converge to their development. While most of the applications of CNNs are focused on single-image segmentation, biomedical image data -being it MRI, CT-scans, Microscopy, etc- often benefits from three-dimensional volumetric expression. This work explores a reformulation of the CNN segmentation problem that is native to the 3D nature of the data, with particular interest to the applications to Fluorescence Microscopy volumetric data produced at the European Laboratories for Nonlinear Spectroscopy in the context of two different large international human brain study projects: the Human Brain Project and the White House BRAIN Initiative.

Objectives. To evaluate the association of cannabis use, genes of the endocannabinoid system and their interaction on clinical symptoms and cognitive performance in patients with a first-episode of pyschosis. Background. The role of both cannabis use and individual genetic background has been shown in the risk for psychosis. However, the influence of cannabis and variability at endocannabinoid genes on the psychosis outcome still remains inconclusive. Materials and Methods. The sample comprised 43 Caucasian individuals with a first-episode of psychosis (mean age(sd)=25.80(6.39) years, 76.7% males, 51.2% cannabis users).There were no differences in age and sex between cannabis users and non-users. Genetic variability was assessed by genotyping one Single Nucleotide Polymorphism (SNP) in each gene (CNR1-rs1049353 and CNR2-rs2501431). Clinical (PANSS, GAF) and neuropsychological (WAIS, WMS, BADS) scales were administered. Results and conclusions. Genotypic frequencies did not differ between cannabis users and non-users. Cannabis use was associated with better manipulative abilities (IQ-M-WAIS, p=0.029) and better executive function (BADS, p=0.036). CNR1-T allele carriers presented higher disorganized and negative syndrome scores (p=0.001 and p=0.044, respectively). The interaction models evidenced a combined effect of CNR1 and cannabis use on the negative syndrome-PANSS (p=0.037). These results suggest the role of cannabis use and genetic background on cognitive and psychopathological outcomes in first-episode psychosis. However, evidence is still scant, and further investigation in larger samples is needed.

The paper compares the development of the coupling between a viscous Reynolds-averaged Navier-Stokes (RANSE) method and an inviscid Boundary Element method (BEM) with application to the prediction of the propulsive performance of a propelled ship. The BEM computational model is implemented into the PRO-INS code developed by CNR-INSEAN. It is based on a boundary integral formulation for marine propellers in arbitrary onset non-cavitating and cavitating flow conditions. The RANSE approach is based on the unstructured finite-volume flow solver ISIS-CFD. An essential feature for full RANSE simulations with the ISIS-CFD code developed by ECN-CNRS is in the use of a sliding grid technique to simulate the real propeller rotating behind a ship hull. The STREAMLINE tanker and propeller are proposed as validation test case. Full RANSE simulations are performed for design speed only, while hybrid RANSE/BEM self-propulsion computations are performed for a speed range. Both computations are compared with experimental data and show good agreement for ship resistance and for propeller thrust and torque.

Deepfakes is a term used for resources which have been manipulated using new technology, in particular CNN [1]. This research presents the rationale for using KR (Knowledge Representation) mechanisms to identify, expose and prevent DeepFakes [1]https://doi.org/10.48550/arXiv.1905.00582