Search

Results on the Rayleigh to Compton ratio (R/C) for elements and compounds with low atomic number (5 6 Z 6 12) are presented. These materials are difficult to identify and characterize with other radiological techniques because of their very close linear attenuation coefficients. A transportable setup for R/C measurements was assembled and tested. This comprises an X-ray tube, in which the output radiation is partially ‘‘converted’’ to monochromatic radiation emitted by a secondary target. The experimental results are compared with theory, determined through coherent and incoherent scattering cross sections.

L'articolo descrive e discute i risultati di una ricerca qualitativa condotta in quattro quartieri della città di Lecce, finalizzata alla comprensione della diffusione di una condizione di insicurezza. La ricerca ha consentito di mettere in discussione gli approcci più diffusi nelle scienze sociali per la spiegazione dell'insicurezza urbana, mostrando che né la distribuzione dei fenomeni criminali, né la collocazione abitativa nello spazio urbano sono di per sé determinanti nella percezione di una paura del crimine: quanto piuttosto la condizione socio-culturale dei cittadini e le condizioni dei legami sociali di cui si possono giovare.

Aim of this study was to analyse diffusion tensor imaging (DTI) datasets in order to identify damaged areas or disorders of the brain in a semi-automatic way. For this purpose, a software tool has been developed: it takes in input the fractional anisotropy (FA) map of a (damaged) brain and, after several steps involving the comparison between the two brain hemispheres, it gives back, as output, a binary mask with a ROI (Region of Interest) that shows the probably damaged area. In the same way, starting from the MR image without diffusion weighting (b0), we find another ROI that we compare with the one previously detected from the FA map. Then we overlay these ROIs onto both the FA map and the image without diffusion weighting, trying to quantify how well the ROIs cover the pathological tissue. This procedure was repeated on a few patients (healthy and pathological ones). The algorithm worked well, showing as a preliminary result that FA maps allow a neater detection of the pathological tissue if compared to MR images without diffusion weighting.

An instrument for detecting and monitoring potential frescos detachments has been developed. It is based on Compton backscattered photons and is made of an X-ray tube, a detector system and a translation system. The device has been employed on standard samples with different and known detachments in order to achieve the optimum set-up. The results of the optimization process are presented.

the zooplankton of two adjacent coastal lakes has been compared. some difference emerged, over all in the species composition

the presence of resting stages from plankton organisms has been ascertained in the mud sediments of mar Piccolo. the first cm of sediment was richer than the other ones

A mobile instrument has been developed for the detection and mapping of detachments in frescos by using Compton back scattered photons. The instrument is mainly composed of a high energy X-ray tube, an X-ray detection system and a translation table. The instrument was first applied to samples simulating various detachment situations, and then transferred to the Vatican Museum to detect detachments and inhomogeneities in the stanza di Eliodoro, one of the ‘‘Raphaels stanze’’.

// Stefania Cannito 1,* , Cristian Turato 2,* , Claudia Paternostro 1 , Alessandra Biasiolo 2 , Sebastiano Colombatto 3 , Irene Cambieri 4 , Santina Quarta 2 , Erica Novo 1 , Elisabetta Morello 1 , Gianmarco Villano 2 , Silvano Fasolato 2 , Tiziana Musso 5 , Ezio David 6 , Ignazia Tusa 7 , Elisabetta Rovida 7 , Riccardo Autelli 1 , Antonina Smedile 8 , Umberto Cillo 9 , Patrizia Pontisso 2 and Maurizio Parola 1 1 Department of Clinical and Biological Sciences, Unit of Experimental Medicine and Interuniversity Center for Liver Pathophysiology, University of Torino, Italy 2 Department of Medicine, University of Padova, Italy 3 Department of Oncology, University of Torino, Italy 4 Department of Plastic Surgery and Burn Unit Skin Bank, CTO Hospital, Torino, Italy 5 Department of Public Health and Pediatric Sciences, University of Torino, Italy 6 Pathology Unit, San Giovanni Battista Hospital, Torino, Italy 7 Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Firenze, Italy 8 Gastroenterology and Hepatology Division, San Giovanni Battista Hospital, Torino, Italy 9 Unit of Hepatobiliary Surgery and Liver Transplantation, University of Padova, Italy * These authors contributed equally to this work Correspondence: Maurizio Parola, email: // Keywords : SERPINB3, hypoxia, hepatocellular carcinoma, HIF-2α, reactive oxygen species Received : September 01, 2014 Accepted : December 09, 2014 Published : December 10, 2014 Abstract SERPINB3 is a cysteine-proteases inhibitor up-regulated in a significant number of cirrhotic patients carrying hepatocellular carcinoma (HCC) and recently proposed as a prognostic marker for HCC early recurrence. SERPINB3 has been reported to stimulate proliferation, inhibit apoptosis and, similar to what reported for hypoxia, to trigger epithelial-to-mesenchymal transition (EMT) and increased invasiveness in liver cancer cells. This study has investigated whether SERPINB3 expression is regulated by hypoxia-related mechanisms in liver cancer cells. Exposure of HepG2 and Huh7 cells to hypoxia up-regulated SERPINB3 transcription, protein synthesis and release in the extracellular medium. Hypoxia-dependent SERPINB3 up-regulation was selective (no change detected for SERPINB4) and operated through hypoxia inducible factor (HIF)-2α (not HIF-1α) binding to SERPINB3 promoter, as confirmed by chromatin immuno-precipitation assay and silencing experiments employing specific siRNAs. HIF-2α-mediated SERPINB3 up-regulation under hypoxic conditions required intracellular generation of ROS. Immuno-histochemistry (IHC) and transcript analysis, performed in human HCC specimens, revealed co-localization of the two proteins in liver cancer cells and the existence of a positive correlation between HIF-2α and SERPINB3 transcript levels, respectively. Hypoxia, through HIF-2α-dependent and redox-sensitive mechanisms, up-regulates the transcription, synthesis and release of SERPINB3, a molecule with a high oncogenic potential.

The molecular background of hepatocellular carcinoma (HCC) is highly heterogeneous, and biomarkers predicting response to treatments are an unmet clinical need. We investigated miR-30e-3p contribution to HCC phenotype and response to sorafenib, as well as the mutual modulation of TP53/MDM2 pathway, in HCC tissues and preclinical models. MiR-30e-3p was downregulated in human and rat HCCs, and its downregulation associated with TP53 mutations. TP53 contributed to miR-30e-3p biogenesis, and MDM2 was identified among its target genes, establishing an miR-30e-3p/TP53/MDM2 feedforward loop and accounting for miR-30e-3p dual role based on TP53 status. EpCAM, PTEN, and p27 were demonstrated as miR-30e-3p additional targets mediating its contribution to stemness and malignant features. In a preliminary cohort of patients with HCC treated with sorafenib, increased miR-30e-3p circulating levels predicted the development of resistance. In conclusion, molecular background dictates miR-30e-3p dual behavior in HCC. Mdm2 targeting plays a predominant tumor suppressor function in wild-type TP53 contexts, whereas other targets such as PTEN, p27, and EpCAM gain relevance and mediate miR-30e-3p oncogenic role in nonfunctional TP53 backgrounds. Increased circulating levels of miR-30e-3p predict the development of sorafenib resistance in a preliminary series of patients with HCC and deserve future investigations. Significance: The dual role of miR-30e-3p in HCC clarifies how the molecular context dictates the tumor suppressor or oncogenic function played by miRNAs.

Background and aims: Cholangiocarcinoma (CCA) is a form of primary liver cancer with limited therapeutic options. Recently, cancer stem cells (CSCs) have been proposed as a driving force of tumour initiation and dissemination, thus representing a crucial therapeutic target. The protease inhibitor SerpinB3 (SB3) has been identified in several malignancies including hepatocellular carcinoma. SB3 has been involved in the early events of hepatocarcinogenesis and is highly expressed in hepatic progenitor cells and in a mouse model of liver progenitor cell activation. However, only limited information on the possible role of SB3 in CCA stem-like compartment is available. Methods: Enrichment of CCA stem-like subset was performed by sphere culture (SPH) in CCA cell lines (CCLP1, HUCCT1, MTCHC01 and SG231). Quantitative RT-PCR and Western blotting were used to detect SB3 in both SPH and parental monolayer (MON) cells. Acquired CSC-like features were analysed using an endogenous and a paracrine in vitro model, with transfection of SB3 gene or addition of recombinant SB3 to cell medium respectively. SB3 tumorigenic role was explored in an in vivo mouse model of CCA by subcutaneous injection of SB3-transfected MON (MONSB3+) cells in immune-deficient NOD-SCID/IL2Rgnull (NSG) mice. SB3 expression in human CCA sections was investigated by immunohistochemistry. Overall survival (OS) and time to recurrence (TTR) analyses were carried out from a transcriptome database of 104 CCA patients. Results: SB3, barely detected in parental MON cells, was overexpressed in the same CCA cells grown as 3D SPH. Notably, MONSB3+ showed significant overexpression of genes associated with stemness (CD24, CD44, CD133), pluripotency (c-MYC, NOTCH1, STAT3, YAP, NANOG, BMI1, KLF4, OCT4, SOX2), epithelial mesenchymal transition (β-catenin, SLUG) and extracellular matrix remodelling (MMP1, MMP7, MMP9, ADAM9, ADAM10, ADAM17, ITGB3). SB3-overexpressing cells showed superior spherogenic capacity and invasion ability compared to control. Importantly, MONSB3+ exhibited activation of MAP kinases (ERK1/2, p38, JNK) as well as phosphorylation of NFκB (p65) in addition to up-regulation of the proto-oncogene β-catenin. All these effects were reversed after transient silencing of SB3. According to the in vitro finding, MONSB3+ cells retained high tumorigenic potential in NSG mice. SB3 overexpression was observed in human CCA tissues and analysis of OS as well as TTR indicated a worse prognosis in SB3+ CCA patients. Conclusion: These findings indicate a SB3 role in mediating malignant phenotype of CCA and identify a new therapeutic target.

The only first-line treatment approved for advanced hepatocellular carcinoma (HCC) is sorafenib. Since many patients experience drug resistance, the discovery of more effective therapeutic strategies represents an unmet clinical need. MicroRNA (MiR)-122 is downregulated in most HCCs, while oncogenic SerpinB3 is upregulated. Here, we assessed the relationship between miR-122 and SerpinB3 and their influence on cell phenotype and sorafenib resistance in HCC. A bioinformatics analysis identified SerpinB3 among hypothetical miR-122 targets. In SerpinB3-overexpressing HepG2 cells, miR-122 transfection decreased SerpinB3 mRNA and protein levels, whereas miR-122 inhibition increased SerpinB3 expression. Luciferase assay demonstrated the interaction between miR-122 and SerpinB3 mRNA. In an HCC rat model, high miR-122 levels were associated with negative SerpinB3 expression, while low miR-122 levels correlated with SerpinB3 positivity. A negative correlation between miR-122 and SerpinB3 or stem cell markers was found in HCC patients. Anti-miR-122 transfection increased cell viability in sorafenib-treated Huh-7 cells, while miR-122 overexpression increased sorafenib sensitivity in treated cells, but not in those overexpressing SerpinB3. In conclusion, we demonstrated that miR-122 targets SerpinB3, and its low levels are associated with SerpinB3 positivity and a stem-like phenotype in HCC. MiR-122 replacement therapy in combination with sorafenib deserves attention as a possible therapeutic strategy in SerpinB3-negative HCCs.

SERPINB3 has been found in chronic liver damage and hepatocellular carcinoma, but not in normal liver. By direct mRNA sequencing, a new SERPINB3 polymorphism (SCCA-PD) has been identified, presenting the substitution Gly351Ala in the reactive center loop of the protein. The prevalence of the SCCA-PD isoform has been found to be significantly higher in patients with cirrhosis than in patients with chronic liver disease and in normal subjects. The aim of this study was to investigate the biological and functional activity of SERPINB3 isoforms using in vitro models. HepG2 and Huh7 cells lines were transfected with plasmid vectors containing wild-type SERPINB3 or its polymorphic variant SCCA-PD and their expression at transcriptional and protein level was determined. To assess the functional activity, both recombinant proteins were produced and kinetic analysis was carried out using papain and cathepsin-L as target proteases. In addition, the inhibition of JNK kinase activity by SERPINB3 isoforms was assessed. The crystal structure of wild-type SERPINB3 at 2.7 Å resolution was used for preparation of refined 3D models of the two isoforms. The results showed that transcriptional activity and protein expression of the two isoforms were similar in both transfected cell lines. Both SERPINB3 preparations exerted a dose-dependent protease inhibitory activity, but the effect of SCCA-PD was higher than that of the wild-type isoform. This result was supported by 3D modelling, where increased hydrophobic profile of the SCCA-PD isoform, introduced by the G351A mutation, was detected. In addition, at high protein concentration, SCCA-PD revealed a 16% higher inhibitory effect on c-Jun phosphorylation by JNK1, compared with wild-type SERPINB3. In conclusion, the single amino acid substitution in the SERPINB3 reactive site loop improves the functional activity of SCCA-PD isoform. This different antiprotease activity might favor disease progression in patients carrying this polymorphism.

A logboat was found in year 2009 in the river Piave (Ponte Piave - TV). Two timber samples were submitted for dendrochronological and radiocarbon analysis. The logboat dates back to the Early Middle Ages (IX century). Una piroga monossile è stata rinvenuta nel 2009 nel fiume Piave (Ponte Piave - TV). Due campioni sono stati sottoposti ad analisi dendrocronologiche e radiocarboniche. Dai dati emersi la piroga risale all’Alto Medioevo (IX sec.).

A mobile instrument has been developed for the detection and mapping of detachments in frescos by using Compton back scattered photons. The instrument is mainly composed of a high energy X-ray tube, an X-ray detection system and a translation table. The instrument was first applied to samples simulating various detachment situations, and then transferred to the Vatican Museum to detect detachments and inhomogeneities in the stanza di Eliodoro, one of the "Raphael's stanze". © 2005 Elsevier B.V. All rights reserved.