Il debito commerciale in Italia: quanto contano le motivazioni finanziarie?

Trade credit arises from delayed payments between firms. It is not easy to identify its determinants since they are connected to organisational,technical, commercial and financial factors.In this paper we empirically examine the determinants of the usage of trade credit by Italian industrial firms. We use an original database that contains detailed information from an ad hoc survey of Bank of Italy on trade credit, from Italian Central Credit Register on banking relations and from firmsÂ’ balance sheet.The focus of the paper concerns the role of financial reasons among the determinants of trade credit demand. The Bank of Italy survey shows that financial motives are less frequent than transactive ones; nevertheless we find a positive correlation between financial reasons and the amount of accounts payable, while the opposite occurs for firms that delay the payments to their suppliers in order to control the quality of purchased goods. The main findings of our empirical analysis are: i) financial determinants of trade credit demand are more frequent among firms in financial distress (rationed firms, firms with lower unused lines of credit and firms with a higher cost of credit); ii) firms in financial distress and firms in trouble have more accounts payable; iii) finally, these firms do not obtain from their suppliers a higher amount of accounts payable (or more delayed payments) but they are able to increase their usage of trade credit by paying over the due date.trade credit,corporate finance,credit rationing

Development of a HPLC-UV method for the simultaneous determination of intracellular glutathione species in human cells

In the present work, an HPLC-UV method was set-up to allow the simultaneous quantification of the reduced-GSH, oxidised-GSSG and nitroso-GSNO glutathione species. Chromatographic separation was achieved on YMC ODS-A C18 column (150 × 4.6 mm, 5 μm), coupled to a Guard-c precolumn (YMC-Pack, 10 × 1-4,0 mm). The eluted compounds were detected at 215 nm by UV-detector, by keeping the column oven at room temperature while the auto-sampler temperature was maintained at 4°C. A fractional factorial design has been applied for the optimization of the mobile phase resulting in baseline separated peaks within 6 minutes. In-house validation was evaluated by linearity, limits of detection (LODs), limits of quantification (LOQs), reproducibility, repeatability and recovery. The detection and quantification limits obtained for standard solutions were below 0.2 μM and 0.6 μM, respectively (RSD values below 2%). The developed method was applied to the measurement of GSH, GSSG and GSNO in human pulmonary cells (A549) exposed to limonene, limonene oxide solubilized into the culture medium and to NO2 as gas phase. Results show an increase in GSH levels, without significant changes in GSSG, when cells were exposed to limonene oxide, while cells exposed to NO2 resulted in a significant increase of GSNO amount. Detection limits were of 1 μM for the glutathione species measured in A549 cells, with RSD values below 2.5%. In conclusion, the present HPLC-UV method can be readily used to measure in a rapid, simultaneous and accurate way the status of GSH, GSSG and GSNO in human cells, their simultaneous quantification helping to better predict the potential impact of chemicals on human health.JRC.I.1-Chemical Assessment and Testin

Repression of Esophageal Neoplasia and Inflammatory Signaling by Anti-miR-31 Delivery In Vivo.

BACKGROUND: Overexpression of microRNA-31 (miR-31) is implicated in the pathogenesis of esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary zinc deficiency. Using a rat model that recapitulates features of human ESCC, the mechanism whereby Zn regulates miR-31 expression to promote ESCC is examined. METHODS: To inhibit in vivo esophageal miR-31 overexpression in Zn-deficient rats (n = 12-20 per group), locked nucleic acid-modified anti-miR-31 oligonucleotides were administered over five weeks. miR-31 expression was determined by northern blotting, quantitative polymerase chain reaction, and in situ hybridization. Physiological miR-31 targets were identified by microarray analysis and verified by luciferase reporter assay. Cellular proliferation, apoptosis, and expression of inflammation genes were determined by immunoblotting, caspase assays, and immunohistochemistry. The miR-31 promoter in Zn-deficient esophagus was identified by ChIP-seq using an antibody for histone mark H3K4me3. Data were analyzed with t test and analysis of variance. All statistical tests were two-sided. RESULTS: In vivo, anti-miR-31 reduced miR-31 overexpression (P = .002) and suppressed the esophageal preneoplasia in Zn-deficient rats. At the same time, the miR-31 target Stk40 was derepressed, thereby inhibiting the STK40-NF-κΒ-controlled inflammatory pathway, with resultant decreased cellular proliferation and activated apoptosis (caspase 3/7 activities, fold change = 10.7, P = .005). This same connection between miR-31 overexpression and STK40/NF-κΒ expression was also documented in human ESCC cell lines. In Zn-deficient esophagus, the miR-31 promoter region and NF-κΒ binding site were activated. Zn replenishment restored the regulation of this genomic region and a normal esophageal phenotype. CONCLUSIONS: The data define the in vivo signaling pathway underlying interaction of Zn deficiency and miR-31 overexpression in esophageal neoplasia and provide a mechanistic rationale for miR-31 as a therapeutic target for ESCC

Migration of Polycyclic Aromatic Hydrocarbons (PAHs) from plastic and rubber articles

Polycyclic Aromatic Hydrocarbons (PAHs) constitute a large group of chemically related substances many of which are known carcinogens. To minimise human exposure there are already several pieces of EU legislation which limit their presence in certain food products, as well as in water and ambient air. Under the REACH regulation (EC 1907/2006 Annex XVII, Entry 50), eight priority PAHs have for some time been restricted in extender oils used in tyres. Although not added deliberately to consumer products, PAHs can still be present as impurities. An amendment of the above mentioned legislation (Regulation EU 1272/2013) establishes content limits for the eight PAHs of 0.5 mg kg-1 for plastic and rubber components of toys/childcare articles, and 1 mg kg-1 for all other consumer articles, in direct and prolonged, or short-term repetitive, contact with the skin or oral cavity. In May 2016 DG JRC and DG GROW signed an Administrative Arrangement (AA 34003) known as the STANPAHs project. The main objective of this contract was for the JRC to provide scientific support in the implementation and potential amendment of the restriction on polycyclic aromatic hydrocarbons, in particular concerning paragraphs 5 and 6 of entry 50 of Annex XVII to the REACH legislation. The main objectives of the project were: a) to gain a better understanding of the migration behaviour of certain PAHs in plastic and rubber components of articles, and b) to develop a reliable methodology to determine PAH migration from these matrices, under conditions simulating, to the best possible extent, dermal contact (including the oral cavity). This report presents the outcomes of the experimental studies carried out at JRC and the achievements towards fulfilling these objectives. A set of manufactured polymeric plastic and rubber matrices, to be used as test materials in the project, has been chosen based on criteria such as their frequency of use in articles within the scope of the restriction and the likelihood of the presence of high PAH contents (e.g. due to their content in carbon black or extender oils). Various grades and types of ingredients known to be PAH sources were used in the formulation of the manufactured ad-hoc materials. The test materials included low density polyethylene (LDPE), polystyrene (PS) and polyvinyl chloride (PVC) as plastic matrices, and ethylene-propylene diene monomer (EPDM), natural rubber-butadiene rubber (NR-BR) and silicone as rubber matrices. Moreover, recycled granules (coated and uncoated) originating from end-of-life tyres produced before and after 2010 as well as rubber tiles made of the recycled coated granules were also made available for this study. The content of each of the eight restricted PAHs was measured by using a method developed in-house based on Randall hot extraction, purification by Solid Phase Extraction based on Molecular Imprinted Polymers, and Gas Chromatography Mass Spectrometry determination. A number of experimental studies were undertaken to generate data and information to improve the knowledge on migration of the target PAHs. Migration parameters operated in the STANPAHs project to estimate migration rates were as follows: dynamic mode at 40°C for 24 hours using a variety of migration media including artificial aqueous simulants, modified biosimulants formulations with lipidic content such as skin surface film liquid (SSFL), and 20% ethanol in water. According to scientific literature the use of 20% ethanol as the migration medium proved to correlate well with human skin absorption. Using these conditions, migration of the target PAHs into artificial sweat (EN1811) and artificial saliva (DIN53160-1) was not detected in any of the materials studied. Moreover none of the plastic polymeric materials led to detectable release of the target PAHs in any of the migration media used in this study (i.e. artificial sweat and saliva, skin surface film liquid (SSFL), and 20% ethanol solution). Similarly the tests with silicone materials did not result in detectable migration. Only the rubber matrices containing Distillate Aromatic Extract (DAE) as extender oil showed detectable migration when using 20% ethanol as the migration solution. In addition, the release of PAHs from coated recycled rubber granules was lower than from the uncoated granules suggesting that the coating acts as a barrier to chemical migration. According to industrial partners DAE is not used by European industries for manufacturing of parts of articles intended for skin contact. The materials containing DAE, although not representative for marketed products, have been made available to facilitate migration testing method development. The migration test method using 20% ethanol has been validated in-house and shows good method performance allowing the determination of PAH at trace level. Furthermore it has been considered for an initial inter-laboratory comparison study (ILC) aiming to investigate method applicability and transferability in a variety of laboratories. The within-laboratory precision, expressed as the relative standard deviation for repeatability (RSDr), and the between-laboratory precision, expressed as the relative standard deviation for reproducibility (RSDR) were assessed. In general the RSDR ranged from 28 to 113% and the RSDr from 7 to 23%. It is worth remembering that the level of PAH migration was very close to the quantification limit of the method and therefore this variability can be expected. Similar values have been reported in a recent German study with the participation of 9 laboratories on the migration of PAHs from rubber materials in contact with aqueous ethanol. The fact that better values of RSDr and RSDR were obtained for chrysene and benzo(e)pyrene that had the highest concentrations in the final migration solutions and that the analysis of the control solution used in this exercise showed a good reproducibility (RSDR% <10%), shows the possibility to reduce the variability between laboratories with a revised operating procedure in terms of injection volume and/or elution volume. In conclusion this report makes available new data and scientific information on the migration behaviour of certain PAHs from selected plastic and rubber polymeric matrices, in support of the European Commission's legal obligation to review the PAHs restriction under REACH. Standard operating procedures for quantification of the content of each of the eight restricted PAHs as well as their migration into 20% ethanol have been developed. Moreover the information gathered in STANPAHs (e.g. literature search), the ad-hoc manufactured materials still available, as well as the JRC in-house analysis method for PAH content could be of great benefit to accelerate the work towards standardisation of PAH content analysis in consumer products that has been recently undertaken by the European Standardisation Committee following a request by DG GROW.JRC.F.2-Consumer Products Safet

Heterogeneity in circulating tumor cells : the relevance of the stem-cell subset

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process. The analysis of CTCs in patients has recently received widespread attention because of its clinical implications, particularly for precision medicine. Accumulated evidence documents a large heterogeneity in CTCs across patients. Currently, the most accepted view is that tumor cells with an intermediate phenotype between epithelial and mesenchymal have the highest plasticity. Indeed, the existence of a meta-stable or partial epithelial⁻mesenchymal transition (EMT) cell state, with both epithelial and mesenchymal features, can be easily reconciled with the concept of a highly plastic stem-like state. A close connection between EMT and cancer stem cells (CSC) traits, with enhanced metastatic competence and drug resistance, has also been described. Accordingly, a subset of CTCs consisting of CSC, present a stemness profile, are able to survive chemotherapy, and generate metastases after xenotransplantation in immunodeficient mice. In the present review, we discuss the current evidence connecting CTCs, EMT, and stemness. An improved understanding of the CTC/EMT/CSC connections may uncover novel therapeutic targets, irrespective of the tumor type, since most cancers seem to harbor a pool of CSCs, and disclose important mechanisms underlying tumorigenicity

The impact of the revised 17 O(p, \u3b1)14 N reaction rate on 17 O stellar abundances and yields

Context. Material processed by the CNO cycle in stellar interiors is enriched in 17O. When mixing processes from the stellar surface reach these layers, as occurs when stars become red giants and undergo the first dredge up, the abundance of 17O increases. Such an occurrence explains the drop of the 16O/17O observed in RGB stars with mass larger than solar mass 1:5M solar mass. As a consequence, the interstellar medium is continuously polluted by the wind of evolved stars enriched in 17O . Aims. Recently, the Laboratory for Underground Nuclear Astrophysics (LUNA) collaboration released an improved rate of the 17O(p; a)14N reaction. In this paper we discuss the impact that the revised rate has on the 16O/17O ratio at the stellar surface and on 17O stellar yields. Methods.We computed stellar models of initial mass between 1 and 20M solar mass and compared the results obtained by adopting the revised rate of the 17O(p; a)14N to those obtained using previous rates. Results. The post-first dredge up 16O/17O ratios are about 20% larger than previously obtained. Negligible variations are found in the case of the second and the third dredge up. In spite of the larger 17O(p; a)14N rate, we confirm previous claims that an extra-mixing process on the red giant branch, commonly invoked to explain the low carbon isotopic ratio observed in bright low-mass giant stars, marginally affects the 16O/17O ratio. Possible effects on AGB extra-mixing episodes are also discussed. As a whole, a substantial reduction of 17O stellar yields is found. In particular, the net yield of stars with mass ranging between 2 and 20 solar mass is 15 to 40% smaller than previously estimated. Conclusions. The revision of the 17O(p; a)14N rate has a major impact on the interpretation of the 16O/17O observed in evolved giants, in stardust grains and on the 17O stellar yields

Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update

In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH

Diabetes Alters Intracellular Calcium Transients in Cardiac Endothelial Cells

Diabetic cardiomyopathy (DCM) is a diabetic complication, which results in myocardial dysfunction independent of other etiological factors. Abnormal intracellular calcium ([Ca2+]i) homeostasis has been implicated in DCM and may precede clinical manifestation. Studies in cardiomyocytes have shown that diabetes results in impaired [Ca2+]i homeostasis due to altered sarcoplasmic reticulum Ca2+ ATPase (SERCA) and sodium-calcium exchanger (NCX) activity. Importantly, altered calcium homeostasis may also be involved in diabetes-associated endothelial dysfunction, including impaired endothelium-dependent relaxation and a diminished capacity to generate nitric oxide (NO), elevated cell adhesion molecules, and decreased angiogenic growth factors. However, the effect of diabetes on Ca2+ regulatory mechanisms in cardiac endothelial cells (CECs) remains unknown. The objective of this study was to determine the effect of diabetes on [Ca2+]i homeostasis in CECs in the rat model (streptozotocin-induced) of DCM. DCM-associated cardiac fibrosis was confirmed using picrosirius red staining of the myocardium. CECs isolated from the myocardium of diabetic and wild-type rats were loaded with Fura-2, and UTP-evoked [Ca2+]i transients were compared under various combinations of SERCA, sarcoplasmic reticulum Ca2+ ATPase (PMCA) and NCX inhibitors. Diabetes resulted in significant alterations in SERCA and NCX activities in CECs during [Ca2+]i sequestration and efflux, respectively, while no difference in PMCA activity between diabetic and wild-type cells was observed. These results improve our understanding of how diabetes affects calcium regulation in CECs, and may contribute to the development of new therapies for DCM treatment