99 research outputs found

    Vulnerabilità sismica di viadotti autostradali

    Get PDF
    Negli ultimi anni la comunità tecnico-scientifica ha rivolto un interesse crescente nei confronti delle tematiche inerenti alla valutazione della vulnerabilità sismica delle costruzioni esistenti. In quest’ampio panorama spiccano, per importanza strategica e complessità tecnica, i viadotti della rete autostradale. La maggior parte di questi manufatti è stata realizzata tra gli anni ’60 e ’70 con approcci progettuali che ignoravano le attuali conoscenze nel campo dell’ingegneria sismica. Pertanto, è emersa la necessità di indagare con moderne tecniche di analisi le effettive capacità resistenti di queste strutture, traendone conclusioni circa il loro livello di sicurezza in occasione di un terremoto. Nell’applicazione sistematica a più manufatti di una rete, è stato adottato un approccio basato sull’analisi “pushover” multi-modale che permette di tenere in conto sia il comportamento non lineare, dovuto ai complessi fenomeni di ridistribuzione delle azioni che avvengono in campo post-elastico, sia la complessità della risposta dinamica del sistema, dovuta alle diverse forme modali significative della struttura. A tal proposito, si è implementata una routine automatica che, appoggiandosi ai risultati ottenuti dal software FEM, esegue in automatico le combinazioni modali e le verifiche degli elementi costruttivi, riducendo in modo considerevole i tempi di lavoro e garantendo un maggiore controllo dei risultati. Gli indici di rischio così ottenuti vengono riassunti in opportune schede di analisi di vulnerabilità sismica (fornite e raccolte dalla Protezione Civile)

    A tetracationic porphyrin with dual anti-prion activity

    Get PDF
    Prions are deadly infectious agents made of PrPSc, a misfolded variant of the cellular prion protein (PrPC) which self-propagates by inducing misfolding of native PrPC. PrPSc can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, hampering the development of effective therapies. We identified Zn(II)-BnPyP, a tetracationic porphyrin that binds to distinct domains of native PrPC, eliciting a dual anti-prion effect. Zn(II)-BnPyP binding to a C-terminal pocket destabilizes the native PrPC fold, hindering conversion to PrPSc; Zn(II)-BnPyP binding to the flexible N-terminal tail disrupts N- to C-terminal interactions, triggering PrPC endocytosis and lysosomal degradation, thus reducing the substrate for PrPSc generation. Zn(II)-BnPyP inhibits propagation of different prion strains in vitro, in neuronal cells and organotypic brain cultures. These results identify a PrPC-targeting compound with an unprecedented dual mechanism of action which might be exploited to achieve anti-prion effects without engendering drug resistance

    NEDA—NEutron Detector Array

    Get PDF
    The NEutron Detector Array, NEDA, will form the next generation neutron detection system that has been designed to be operated in conjunction with γ-ray arrays, such as the tracking-array AGATA, to aid nuclear spectroscopy studies. NEDA has been designed to be a versatile device, with high-detection efficiency, excellent neutron-γ discrimination, and high rate capabilities. It will be employed in physics campaigns in order to maximise the scientific output, making use of the different stable and radioactive ion beams available in Europe. The first implementation of the neutron detector array NEDA with AGATA 1π was realised at GANIL. This manuscript reviews the various aspects of NEDA

    The domain architecture of large guanine nucleotide exchange factors for the small GTP-binding protein Arf

    Get PDF
    BACKGROUND: Small G proteins, which are essential regulators of multiple cellular functions, are activated by guanine nucleotide exchange factors (GEFs) that stimulate the exchange of the tightly bound GDP nucleotide by GTP. The catalytic domain responsible for nucleotide exchange is in general associated with non-catalytic domains that define the spatio-temporal conditions of activation. In the case of small G proteins of the Arf subfamily, which are major regulators of membrane trafficking, GEFs form a heterogeneous family whose only common characteristic is the well-characterized Sec7 catalytic domain. In contrast, the function of non-catalytic domains and how they regulate/cooperate with the catalytic domain is essentially unknown. RESULTS: Based on Sec7-containing sequences from fully-annotated eukaryotic genomes, including our annotation of these sequences from Paramecium, we have investigated the domain architecture of large ArfGEFs of the BIG and GBF subfamilies, which are involved in Golgi traffic. Multiple sequence alignments combined with the analysis of predicted secondary structures, non-structured regions and splicing patterns, identifies five novel non-catalytic structural domains which are common to both subfamilies, revealing that they share a conserved modular organization. We also report a novel ArfGEF subfamily with a domain organization so far unique to alveolates, which we name TBS (TBC-Sec7). CONCLUSION: Our analysis unifies the BIG and GBF subfamilies into a higher order subfamily, which, together with their being the only subfamilies common to all eukaryotes, suggests that they descend from a common ancestor from which species-specific ArfGEFs have subsequently evolved. Our identification of a conserved modular architecture provides a background for future functional investigation of non-catalytic domains

    ACAP-A/B Are ArfGAP Homologs in Dictyostelium Involved in Sporulation but Not in Chemotaxis

    Get PDF
    Arfs and Arf GTPase-activating proteins (ArfGAPs) are regulators of membrane trafficking and actin dynamics in mammalian cells. In this study, we identified a primordial Arf, ArfA, and two ArfGAPs (ACAP-A/B) containing BAR, PH, ArfGAP and Ankyrin repeat domains in the eukaryote Dictyostelium discoideum. In vitro, ArfA has similar nucleotide binding properties as mammalian Arfs and, with GTP bound, is a substrate for ACAP-A and B. We also investigated the physiological functions of ACAP-A/B by characterizing cells lacking both ACAP-A and B. Although ACAP-A/B knockout cells showed no defects in cell growth, migration or chemotaxis, they exhibited abnormal actin protrusions and ∼50% reduction in spore yield. We conclude that while ACAP-A/B have a conserved biochemical mechanism and effect on actin organization, their role in migration is not conserved. The absence of an effect on Dictyostelium migration may be due to a specific requirement for ACAPs in mesenchymal migration, which is observed in epithelial cancer cells where most studies of mammalian ArfGAPs were performed

    An alternative viewpoint on the nuclear structure towards 100Sn: Lifetime measurements in 105Sn

    No full text
    This work aims at presenting an alternative approach to the long standing problem of the B(E2) values in Sn isotopes in the vicinity of the N=Z double-magic nucleus Sn, until now predominantly measured with relativistic and intermediate-energy Coulomb excitation reactions. The direct measurement of the lifetime of low-lying excited states in odd-even Sn isotopes provides a new and precise guidance for the theoretical description of the nuclear structure in this region. Lifetime measurements have been performed in Sn for the first time with the coincidence Recoil Distance Doppler Shift technique. The lifetime results for the 7/2 first excited state and the 11/2 state, 2(Sn) ⊗ν1g multiplet member, are discussed in comparison with state-of-the-art shell model and mean field calculations, highlighting the crucial contribution of proton excitation across the core of Sn. The reduced transition probability B(E2) of the 11/2 core-coupled state points out an enhanced staggering with respect to the B(E2; 2→0) in the even-mass Sn and Sn isotopes

    On the seismic vulnerability evaluation of RC bridges exposed to corrosion

    No full text
    Recently, the engineering interest about the durability of existing reinforced concrete structures has significantly increased as confirmed by the conspicuous scientific literature. The results of these studies are influencing the development of new structural codes. Among the wide range of existing reinforced concrete structures, motorway viaducts stand out for their strategic relevance. Most of these structures were built between ’60 and ’70 years and, nowadays, the materials degradation phenomena are leading to strength capacity reduction, either in serviceability condition or in presence of exceptional loads such as the seismic action. In order to evaluate the degradation phenomena effects on the seismic vulnerability of motorway viaducts, this paper shows an efficient procedure to evaluate the seismic performance of reinforced concrete bridges starting from the modelling of the materials degradation, according to several scenarios, and by carrying out multimodal pushover analyses
    corecore