816 research outputs found
The control of collisional tectonics over valley morphology: the case of the largest glacier in the European Alps
Restauro: Conoscenza, Progetto, Cantiere, Gestione
La SIRA, società scientifica che riunisce anzitutto coloro che, nelle università italiane, lavorano nel campo restauro, con i propri studi, la ricerca e l’insegnamento, ha l’obiettivo statutario di promuovere “lo studio e la valorizzazione del patrimonio culturale in ambito scientifico, accademico, civile ed educativo”. I volumi raccolgono i contributi al II Convegno tenutorsi a Bologna a settembre 2018 cui ha partecipato un consistente numero di studiosi in vario modo impegnati nell’Università italiana. L’intenzione fondamentale era fare luce sul rapporto esistente – o possibile – tra i molti aspetti che influenzano il ‘concreto fare restauro’ e che, nel loro articolarsi, possono determinare il successo o l’insuccesso delle attività che connotano il suo sviluppo: conoscenza, programmazione e fattibilità economica, progetto, cantiere e successiva gestione dei beni coinvolti
Decentralizing Electric Vehicle Supply Chains: Value Proposition and System Design
Distributed ledger technologies are transforming existing business models and business relationships. In particular, blockchain allows non-trusting parties to manage a shared database in a decentralized way and improve the transparency, authenticity, and reliability of the exchanged data. Nonetheless, decentralized paradigms are not yet well established, resulting in only a fraction of blockchain-based applications being successful in the long term.In this paper, we present a blockchain-based solution for the electric vehicle supply chain that we designed in the context of the CONCORDIA project of the European Cybersecurity Competence Network. We describe the goals, the value proposition, the main design choices, and the architecture of our system. Moreover, we discuss the electric vehicle supply chain, analyzing the improvements and limitations introduced by our blockchain-based solution. We analyze our solution from the managerial and technical points of view through a lean business methodology for blockchain solutions. In particular, we developed an economic impact assessment to evaluate the potential costs and revenues of the application of blockchain technology in a supply chain context. Although the blockchain system is inspired by the supply chain of a multinational automotive company, it can be applied to any other multi-actor supply chain
Numerical Investigation on the Thermo-Mechanical Behavior of HTS Tapes and Experimental Testing on Their Critical Current
This work extends to second generation Rare-Earth Barium-Copper-Oxide ((Re)BCO) tapes an experimental proce- dure previously developed to analyze the impact of double bending at room temperature on the performance of Bismuth-Strontium- Calcium-Copper-Oxide (BSCCO) tapes. The modified procedure is applied to measure the critical current of a commercial (Re)BCO tape subjected to bending around a cylindrical mandrel first on one side, then on the other side, followed by the cooldown to cryogenic temperature. In the bending phase, mandrels of decreasing diame- ter are used to identify the minimum curvature leading to a signif- icant reduction of the tape critical current. Furthermore, a novel finite element model is developed to complement the experimental results. The model simulates the double bending at room tempera- ture, the following straightening of the sample, and its cooldown to cryogenic conditions. The coupled thermo-mechanical numerical model together with the temperature-dependent mechanical prop- erties allow investigating the combination of thermal contraction effects and bending loads in the whole domain of the problem. The experimental and numerical results obtained help to give a better insight in the distribution of the strain and stress components inside the (Re)BCO tape and to evaluate their impact on the conductor electrical performance in relevant operating condition
LPS-induced TNF-α factor mediates pro-inflammatory and pro-fibrogenic pattern in non-alcoholic fatty liver disease
Lipopolysaccharide (LPS) is currently considered one of the major players in non-alcoholic fatty liver disease (NAFLD) pathogenesis and progression. Here, we aim to investigate the possible role of LPS-induced TNF-α factor (LITAF) in inducing a pro-inflammatory and pro-fibrogenic phenotype of non-alcoholic steatohepatitis (NASH).We found that children with NAFLD displayed, in different liver-resident cells, an increased expression of LITAF which correlated with histological traits of hepatic inflammation and fibrosis. Total and nuclear LITAF expression increased in mouse and human hepatic stellate cells (HSCs). Moreover, LPS induced LITAF-dependent transcription of IL-1β, IL-6 and TNF-α in the clonal myofibroblastic HSC LX-2 cell line, and this effect was hampered by LITAF silencing. We showed, for the first time in HSCs, that LITAF recruitment to these cytokine promoters is LPS dependent. However, preventing LITAF nuclear translocation by p38MAPK inhibitor, the expression of IL-6 and TNF-α was significantly reduced with the aid of p65NF-ĸB, while IL-1β transcription exclusively required LITAF expression/activity. Finally, IL-1β levels in plasma mirrored those in the liver and correlated with LPS levels and LITAF-positive HSCs in children with NASH.In conclusion, a more severe histological profile in paediatric NAFLD is associated with LITAF over-expression in HSCs, which in turn correlates with hepatic and circulating IL-1β levels outlining a panel of potential biomarkers of NASH-related liver damage. The in vitro study highlights the role of LITAF as a key regulator of the LPS-induced pro-inflammatory pattern in HSCs and suggests p38MAPK inhibitors as a possible therapeutic approach against hepatic inflammation in NASH
4D reconstruction of the Doldenhorn nappe-basement system in the Aar massif: Insights into late-stage continent-continent collision in the Swiss Alps
Exosome biogenesis in the protozoa parasite Giardia lamblia: A model of reduced interorganellar crosstalk
Extracellular vesicles (EVs) facilitate intercellular communication and are considered a promising therapeutic tool for the treatment of infectious diseases. These vesicles involve microvesicles (MVs) and exosomes and selectively transfer proteins, lipids, mRNAs, and microRNAs from one cell to another. While MVs are formed by extrusion of the plasma membrane, exosomes are a population of vesicles of endosomal origin that are stored inside the multivesicular bodies (MVBs) as intraluminal vesicles (ILVs) and are released when the MVBs fuse with the plasma membrane. Biogenesis of exosomes may be driven by the endosomal sorting complex required for transport (ESCRT) machinery or may be ESCRT independent, and it is still debated whether these are entirely separate pathways. In this manuscript, we report that the protozoan parasite, Giardia lamblia, although lacking a classical endo-lysosomal pathway, is able to produce and release exosome-like vesicles (ElV). By using a combination of biochemical and cell biology analyses, we found that the ElVs have the same size, shape, and protein and lipid composition as exosomes described for other eukaryotic cells. Moreover, we established that some endosome/lysosome peripheral vacuoles (PVs) contain ILV during the stationary phase. Our results indicate that ILV formation and ElV release depend on the ESCRT-associated AAA+-ATPase Vps4a, Rab11, and ceramide in this parasite. Interestingly, EIV biogenesis and release seems to occur in Giardia despite the fact that this parasite has lost most of the ESCRT machinery components during evolution and is unable to produce ceramide de novo. The differences in protozoa parasite EV composition, origin, and release may reveal functional and structural properties of EVs and, thus, may provide information on cell-to-cell communication and on survival mechanisms.Fil: Moyano, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Musso, Juliana Rita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Feliziani, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Frontera, Lorena Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Lanfredi-Rangel, Adriana. Centro de Pesquizas Gonzalo Monis. Fiocruz; BrasilFil: Lalle, Marco. Department Of Infectious Diseases, Foodborne And Neglec; ItaliaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin
Improved overall survival with Gemtuzumab Ozogamicin (GO) compared with best supportive care (BSC) in elderly patients with untreated acute myeloid leukemia (AML) not considered fit for intensive chemotherapy: final results from the randomized phase III study (AML-19) of the EORTC and gimema leukemia groups
peer reviewe
Prioritizing causal disease genes using unbiased genomic features
Background: Cardiovascular disease (CVD) is the leading cause of death in the developed world. Human genetic studies, including genome-wide sequencing and SNP-array approaches, promise to reveal disease genes and mechanisms representing new therapeutic targets. In practice, however, identification of the actual genes contributing to disease pathogenesis has lagged behind identification of associated loci, thus limiting the clinical benefits. Results: To aid in localizing causal genes, we develop a machine learning approach, Objective Prioritization for Enhanced Novelty (OPEN), which quantitatively prioritizes gene-disease associations based on a diverse group of genomic features. This approach uses only unbiased predictive features and thus is not hampered by a preference towards previously well-characterized genes. We demonstrate success in identifying genetic determinants for CVD-related traits, including cholesterol levels, blood pressure, and conduction system and cardiomyopathy phenotypes. Using OPEN, we prioritize genes, including FLNC, for association with increased left ventricular diameter, which is a defining feature of a prevalent cardiovascular disorder, dilated cardiomyopathy or DCM. Using a zebrafish model, we experimentally validate FLNC and identify a novel FLNC splice-site mutation in a patient with severe DCM. Conclusion: Our approach stands to assist interpretation of large-scale genetic studies without compromising their fundamentally unbiased nature. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0534-8) contains supplementary material, which is available to authorized users
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