Mechanisms producing different precipitation patterns over north‐eastern Italy: insights from HyMeX‐SOP1 and previous events

During the first HyMeX Special Observation Period (SOP1) field campaign, the target site of north‐eastern Italy (NEI) experienced a large amount of precipitation, locally exceeding the climatological values and distributed among several heavy‐rainfall episodes. In particular, two events that occurred during the last period of the campaign drew our attention. These events had common large‐scale patterns and a similar mesoscale setting, characterised by southerly low‐level flow interacting with the Alpine orography, but the precipitation distribution was very different. During Intensive Observing Period IOP18 (31 October–1 November 2012), convective systems were responsible for intense rainfall mainly located over a flat area of the eastern Po Valley, well upstream of the orography. Conversely, during IOP19 (4/5 November 2012), heavy precipitation affected only the Alpine area. In addition to IOP18 and IOP19, the present study analyses other heavy‐precipitation episodes that display similar characteristics and which occurred over NEI during the autumn of recent years. A high‐resolution (2 km grid spacing) non‐hydrostatic NWP model and available observations are used for this purpose. The two different observed precipitation patterns are explained in terms of interaction between the impinging flow and the Alps. Depending on the thermodynamic profile, convection can be triggered when the impinging flow is forced to rise over a pre‐existing cold‐air layer at the base of the orography. In this situation a persistent blocked‐flow condition and upstream convergence are responsible for heavy rain localized over the plain. Conversely, if convection does not develop, flow‐over conditions are established and heavy rain affects the Alps. Numerical parameters proposed in the literature are used to support the analysis. Finally, the role of evaporative cooling beneath the convective systems is evaluated. It turns out that the stationarity of the systems upstream of the Alps is mainly attributable to persistent blocked‐flow conditions, while convective outflow slightly modifies the location of precipitation

Ferritin heavy chain Is the host factor responsible for HCV-Induced inhibition of apoB-100 production and is required for efficient viral infection

Hepatic fat export occurs by apolipoprotein B-100-containing lipoprotein production, whereas impaired production leads to liver steatosis. Hepatitis C virus (HCV) infection is associated to dysregulation of apoB-100 secretion and steatosis; however, the molecular mechanism by which HCV affects the apoB-100 secretion is not understood. Here, combining quantitative proteomics and computational biology, we propose ferritin heavy chain (Fth) as being the cellular determinant of apoB-100 production inhibition. By means of molecular analyses, we found that HCV nonstructural proteins and NS5A appear to be sufficient for inducing Fth up-regulation. Fth in turn was found to inhibit apoB-100 secretion leading to increased intracellular degradation via proteasome. Notably, intracellular Fth down-regulation by siRNA restores apoB-100 secretion. The inverse correlation between ferritin and plasma apoB-100 concentrations was also found in JFH-1 HCV cell culture systems (HCVcc) and HCV-infected patients. Finally, Fth expression was found to be required for robust HCV infection. These observations provide a further molecular explanation for the onset of liver steatosis and allow for hypothesizing on new therapeutic and antiviral strategies

A three-parameter model for fatigue crack growth data analysis

A three-parameters model for the interpolation of fatigue crack propagation data is proposed. It has been validated by a Literature data set obtained by testing 180 M(T) specimens under three different loading levels. In details, it is highlighted that the results of the analysis carried out by means of the proposed model are more smooth and clear than those obtainable using other methods or models. Also, the parameters of the model have been computed and some peculiarities have been picked out

A four-parameters model for fatigue crack growth data analysis

A four-parameters model for interpolation of fatigue crack growth data is presented. It has beenvalidated by means of both data produced by the Authors and data collected from Literature. The proposedmodel is an enhanced version of a three-parameters model already discussed in a previous work that has beensuitably modified in order to overcome some drawbacks raised when applied to a quite wider experimental dataset. Results of validation study have also revealed that the new model, besides interpolating accurately crackgrowth data, allows to identify the presence of anomalies in the data sets. For this reason, by a suitable filter tobe chosen depending on the size and number of anomalies, it can be used to remove them and obtain sigmoidalcrack propagation curves smoother than those obtained when the current analysis techniques are used. In theend, possible model parameters correlations are analysed

About the certification of railway rails

When the compliance with the European Code of some rail steel has to be verified, the need ofcarrying out the experimental activities in accordance with several testing Standards forces the operator both tosolve the problems related to the choice of a suitable testing practice and often to interpret subjectivelyStandards guidelines. This does not facilitate the comparability and/or the quality of the results produced byseveral laboratories. With reference to a series of fatigue, fracture toughness and fatigue crack growth testscarried out by the authors on specimens extracted from rails, the main lacks in the current standards, related toboth the choice of the control parameters and the testing procedures, are pointed out. Regarding the crackgrowth testing, several procedures to compute the crack growth rates to be compared with the limits prescribedby the Code are proposed. These procedures have been applied to a data set produced during theaforementioned testing activity, in order to highlight, by comparison of the results obtained by them, thesignificant differences in the crack growth rate estimates and the magnitude of the errors that can be done dueto the lacks in the standard practices currently adopted

Hepatitis C virus production requires apolipoprotein A-I and affects its association with nascent low-density lipoproteins

Background/aims The life cycle of hepatitis C virus (HCV) is intimately linked to the lipid metabolism of the host. In particular, HCV exploits the metabolic machinery of the lipoproteins in several steps of its life cycle such as circulation in the bloodstream, cell attachment and entry, assembly and release of viral particles. However, the details of how HCV interacts with and influences the metabolism of the host lipoproteins are not well understood. A study was undertaken to investigate whether HCV directly affects the protein composition of host circulating lipoproteins. Methods A proteomic analysis of circulating very low-, low- and high-density lipoproteins (VLDL, LDL and HDL), isolated from either in-treatment naive HCV-infected patients or healthy donors (HD), was performed using two-dimensional gel electrophoresis and tandem mass spectrometry (MALDI-TOF/TOF). The results obtained were further investigated using in vitro models of HCV infection and replication. Results A decreased level of apolipoprotein A-I (apoA-I) was found in the LDL fractions of HCV-infected patients. This result was confirmed by western blot and ELISA analysis. HCV cellular models (JFH1 HCV cell culture system (HCVcc) and HCV subgenomic replicons) showed that the decreased apoA-I/LDL association originates from hepatic biogenesis rather than lipoprotein catabolism occurring in the circulation, and is not due to a downregulation of the apoA-I protein concentration. The sole non-structural viral proteins were sufficient to impair the apoA-I/LDL association. Functional evidence was obtained for involvement of apoA-I in the viral life cycle such as RNA replication and virion production. The specific siRNA-mediated downregulation of apoA-I led to a reduction in both HCV RNA and viral particle levels in culture. Conclusions This study shows that HCV induces lipoprotein structural modification and that its replication and production are linked to the host lipoprotein metabolism, suggesting apoA-I as a new possible target for antiviral therapy

Transverse strength of railway tracks : Part 1. planning and experimental setup

© Gruppo Italiano Frattura 2014. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/Several studies have been carried out until now by various Research Agencies and Railway Administrations to quantify the effects of the track-bed geometrical characteristics on the transverse strength of the track. Unfortunately, not all the possible scenarios in terms of track components, track-bed cross profile, operating conditions etc. have been investigated and not all the relevant variables have been directly measured. Therefore data available from the literature have different degrees of reliability. With the aim of enlarging the knowledge on the track stability and covering much of the possible relevant scenarios, an experimental research program has been developed in the framework of a cooperation between RFI, Italcertifer and DII. In order to perform the investigation under quite general conditions and to reduce the experimentation costs, n. 28 significant scenarios have been identified and reproduced on as many independent track segments. By applying on each track segment a transversal load, the strength of the ballast-sleeper interface has been determined. The results relative to the first four scenarios are presented in terms of applied load vs. lateral track displacement diagrams and in more synthetic numerical tables.Peer reviewe

Antigiardial activity of novel triazolyl-quinolone-based chalcone derivatives:when oxygen makes the difference

Giardiasis is a common diarrheal disease worldwide caused by the protozoan parasite Giardia intestinalis. It is urgent to develop novel drugs to treat giardiasis, due to increasing clinical resistance to the gold standard drug metronidazole (MTZ). New potential antiparasitic compounds are usually tested for their killing efficacy against G. intestinalis under anaerobic conditions, in which MTZ is maximally effective. On the other hand, though commonly regarded as an ‘anaerobic pathogen,’ G. intestinalis is exposed to relatively high O2 levels in vivo, living attached to the mucosa of the proximal small intestine. It is thus important to test the effect of O2 when searching for novel potential antigiardial agents, as outlined in a previous study [Bahadur et al. (2014) Antimicrob. Agents Chemother. 58, 543]. Here, 45 novel chalcone derivatives with triazolyl-quinolone scaffold were synthesized, purified, and characterized by high resolution mass spectrometry, 1H and 13C nuclear magnetic resonance and infrared spectroscopy. Efficacy of the compounds against G. intestinalis trophozoites was tested under both anaerobic and microaerobic conditions, and selectivity was assessed in a counter-screen on human epithelial colorectal adenocarcinoma cells. MTZ was used as a positive control in the assays. All the tested compounds proved to be more effective against the parasite in the presence of O2, with the exception of MTZ that was less effective. Under anaerobiosis eighteen compounds were found to be as effective as MTZ or more (up to three to fourfold); the same compounds proved to be up to >100- fold more effective than MTZ under microaerobic conditions. Four of them represent potential candidates for the design of novel antigiardial drugs, being highly selective against Giardia trophozoites. This study further underlines the importance of taking O2 into account when testing novel potential antigiardial compounds

Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation

The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell-derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17-producing T cells (Th17). In vivo analysis of lymph nodes hosting T-cell priming in experimental autoimmune encephalomyelitis revealed activated MCs, Tregs, and Th17 cells displaying tight spatial interactions, further supporting the occurrence of an MC-mediated inhibition of Treg suppression in the establishment of Th17-mediated inflammatory responses. © 2009 by The American Society of Hematology