On the lower semicontinuous envelope of functionals defined on polyhedral chains

In this note we prove an explicit formula for the lower semicontinuous envelope of some functionals defined on real polyhedral chains. More precisely, denoting by $H \colon \mathbb{R} \to \left[ 0,\infty \right)$ an even, subadditive, and lower semicontinuous function with $H(0)=0$, and by $\Phi_H$ the functional induced by $H$ on polyhedral $m$-chains, namely \Phi_{H}(P) := \sum_{i=1}^{N} H(\theta_{i}) \mathcal{H}^{m}(\sigma_{i}), \quad\mbox{for every }P=\sum_{i=1}^{N} \theta_{i} [[ \sigma_{i} ]] \in\mathbf{P}_m(\mathbb{R}^n), we prove that the lower semicontinuous envelope of $\Phi_H$ coincides on rectifiable $m$-currents with the $H$-mass \mathbb{M}_{H}(R) := \int_E H(\theta(x)) \, d\mathcal{H}^m(x) \quad \mbox{ for every } R= [[ E,\tau,\theta ]] \in \mathbf{R}_{m}(\mathbb{R}^{n}). Comment: 14 page

Effect of Cold Rolling on Microstructural and Mechanical Properties of a Dual-Phase Steel for Automotive Field

A new advanced dual-phase (DP) steel characterized by ferrite and bainite presence in equal fractions has been studied within this paper. The anisotropy change of this steel was assessed as a progressively more severe cold rolling process was introduced. Specifically, tensile tests were used to build a strain-hardening curve, which describes the evolution of this DP steel's mechanical properties as the thinning level increases from 20 to 70% with 10% step increments. As expected, the cold rolling process increases mechanical properties, profoundly altering the material's microstructure, which was assessed in depth using Electron Backscatter Diffraction (EBSD) analysis coupled with the Kernel Average Misorientation (KAM) maps. At the same time, the process strongly modifies the material planar anisotropy. Microstructural and mechanical assessment and the Kocks-Mecking model applied to this steel evidenced that a 50% strain hardening makes the DP steel isotropic. The material retains or resumes anisotropic behavior for a lower or higher degree of deformation. Furthermore, the paper evaluated the forming limit of this DP steel and introduced geometric limitations to testing the thin steel plates' mechanical properties

Empirical fragility curves for settlement-affected buildings: Analysis of different intensity parameters for seven hundred masonry buildings in The Netherlands

The analysis and prediction of damage to buildings resting on highly compressible fine-grained "soft soils" containing (organic) clay and peat are key issues to be addressed for a proper management of subsidence-affected urban areas. Among the probabilistic approaches suggested in literature, those oriented to the generation of empirical fragility curves are particularly promising provided that a comprehensive dataset for both the subsidence-related intensity (SRI) parameters and the corresponding damage severity to buildings is available. Following this line of thought, in the present paper, a rich sample of more than seven hundred monitored (by remote sensing) and surveyed masonry buildings – mainly resting with their (shallow or piled) foundations on soft soils – is analysed in four urban areas of The Netherlands. Probabilistic functions in the form of fragility curves for building damage are retrieved for three different SRI parameters (i.e., differential settlement, rotation and deflection ratio) derived from the processing of Synthetic Aperture Radar (SAR) images by way of a differential interferometric (DInSAR) technique in combination with the severity levels of the damage recorded from the visual inspection of over 700 masonry buildings. As a novelty with respect to earlier similar studies, the work points out the methodological steps to be followed in order to identify the most appropriate SRI parameter among the selected ones. Thus, the objective of the paper is to improve the existing geotechnical forecasting tools for subsidence-affected urban areas, in order to target areas that require more detailed investigations/analyses and/or to select/prioritize foundation repairing/replacing measures

HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2

Hepatitis C virus (HCV) infection is a leading cause of liver fibrosis, especially in developing countries. The process is characterized by the excess accumulation of ECM that may lead, over time, to hepatic cirrhosis, liver failure and also to hepatocarcinoma. The direct role of HCV in promoting fibroblasts trans-differentiation into myofibroblasts, the major fibrogenic cells, has not been fully clarified. In this study, we found that HCV derived from HCV-infected patients infected and directly induced the trans-differentiation of human primary fibroblasts into myofibroblasts, promoting fibrogenesis. This effect correlated with the activation of GLI2, one of the targets of Hedgehog signaling pathway previously reported to be involved in myofibroblast generation. Moreover, GLI2 activation by HCV correlated with a reduction of autophagy in fibroblasts, that may further promoted fibrosis. GLI2 inhibition by Gant 61 counteracted the pro-fibrotic effects and autophagy inhibition mediated by HCV, suggesting that targeting HH/GLI2 pathway might represent a promising strategy to reduce the HCV-induced fibrosis

Diversity Assessment and DNA-Based Fingerprinting of Sicilian Hazelnut (Corylus avellana L.) Germplasm

The characterization of plant genetic resources is a precondition for genetic improvement and germplasm management. The increasing use of molecular markers for DNA-based genotype signature is crucial for variety identification and traceability in the food supply chain. We collected 75 Sicilian hazelnut accessions from private and public field collections, including widely grown varieties from the Nebrodi Mountains in north east Sicily (Italy). The germplasm was fingerprinted through nine standardized microsatellites (SSR) for hazelnut identification to evaluate the genetic diversity of the collected accessions, validating SSR discrimination power. We identified cases of homonymy and synonymy among acquisitions and the unique profiles. The genetic relationships illustrated by hierarchical clustering, structure, and discriminant analyses revealed a clear distinction between local and commercial varieties. The comparative genetic analysis also showed that the Nebrodi genotypes are significantly different from the Northern Italian, Iberian, and Turkish genotypes. These results highlight the need and urgency to preserve Nebrodi germplasm as a useful and valuable source for traits of interest employable for breeding. Our study demonstrates the usefulness of molecular marker analysis to select a reference germplasm collection of Sicilian hazelnut varieties and to implement certified plants’ production in the supply chain

Neuropilin 1mediates keratinocyte growth factor signaling in adipose-derived stem cells: potential involvement in adipogenesis

Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs

DNMT3B in vitro knocking-down is able to reverse embryonal rhabdomyosarcoma cell phenotype through inhibition of proliferation and induction of myogenic differentiation

Aberrant DNA methylation has been frequently observed in many human cancers, including rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. To date, the expression and function of the de novo DNA methyltransferase (DNMT) 3B in RMS have not yet been investigated. Our study show for the first time a significant up-regulation of DNMT3B levels in 14 RMS tumour samples and 4 RMS cell lines in comparison to normal skeletal muscle. Transfection of RD and TE671 cells, two in vitro models of embryonal RMS (ERMS), with a synthetic DNMT3B siRNA decreased cell proliferation by arresting cell cycle at G1 phase, as demonstrated by the reduced expression of Cyclin B1, Cyclin D1 and Cyclin E2, and by the concomitant up-regulation of the checkpoint regulators p21 and p27. DNMT3B depletion also impaired RB phosphorylation status and decreased migratory capacity and clonogenic potential. Interestingly, DNMT3B knock-down was able to commit ERMS cells towards myogenic terminal differentiation, as confirmed by the acquisition of a myogenic-like phenotype and by the increased expression of the myogenic markers MYOD1, Myogenin and MyHC. Finally, inhibition of MEK/ERK signalling by U0126 resulted in a reduction of DNMT3B protein, giving evidence that DNMT3B is a down-stream molecule of this oncogenic pathway.Taken together, our data indicate that altered expression of DNMT3B plays a key role in ERMS development since its silencing is able to reverse cell cancer phenotype by rescuing myogenic program. Epigenetic therapy, by targeting the DNA methylation machinery, may represent a novel therapeutic strategy against RMS

Silencing of Keratinocyte Growth Factor Receptor Restores 5-Fluorouracil and Tamoxifen Efficacy on Responsive Cancer Cells

BACKGROUND: Keratinocyte growth factor receptor (KGFR) is a splice variant of the FGFR2 gene expressed in epithelial cells. Activation of KGFR is a key factor in the regulation of physiological processes in epithelial cells such as proliferation, differentiation and wound healing. Alterations of KGFR signaling have been linked to the pathogenesis of different epithelial tumors. It has been also hypothesized that its specific ligand, KGF, might contribute to the development of resistance to 5-fluorouracil (5-FU) in epithelial cancers and tamoxifen in estrogen-positive breast cancers. METHODOLOGY/PRINCIPAL FINDINGS: Small interfering RNA was transfected into a human keratinocyte cell line (HaCaT), a breast cancer derived cell line (MCF-7) and a keratinocyte primary culture (KCs) to induce selective downregulation of KGFR expression. A strong and highly specific reduction of KGFR expression was observed at both RNA (reduction = 75.7%, P = 0.009) and protein level. KGFR silenced cells showed a reduced responsiveness to KGF treatment as assessed by measuring proliferation rate (14.2% versus 39.0% of the control cells, P<0.001) and cell migration (24.6% versus 96.4% of the control cells, P = 0.009). In mock-transfected MCF-7 cells, KGF counteracts the capacity of 5-FU to inhibit cell proliferation, whereas in KGFR silenced cells KGF weakly interferes with 5-FU antiproliferative effect (11.2% versus 28.4% of the control cells, P = 0.002). The capacity of 5-FU to induce cell death is abrogated by co-treatment with KGF, whereas in KGFR silenced cells 5-FU efficiently induces cell death even combined to KGF, as determined by evaluating cell viability. Similarly, the capacity of tamoxifen to inhibit MCF-7 and KCs proliferation is highly reduced by KGF treatment and is completely restored in KGFR silenced cells (12.3% versus 45.5% of the control cells, P<0.001). CONCLUSIONS/SIGNIFICANCE: These findings suggest that selective inhibition of the KGF/KGFR pathway may provide a useful tool to ameliorate the efficacy of the therapeutic strategies for certain epithelial tumors