LIME: Towards a Metadata Module for Ontolex

The OntoLex W3C Community Group has been working for more than a year on realizing a proposal for a standard ontol-ogy lexicon model. As the core-specification of the model is almost com-plete, the group started development of additional modules for specific tasks and use cases. We think that in many usage scenarios (e.g. linguistic enrichment, lo-calization and alignment of ontologies) the discovery and exploitation of linguis-tically grounded datasets may benefit from summarizing information about their linguistic expressivity. While the VoID vocabulary covers the need for general metadata about linked datasets, this more specific information demands a dedicated extension. In this paper, we fill this gap by introducing LIME (Linguistic Metadata), a new vocabulary aiming at completing the OntoLex standard with specifications for linguistic metadata.

Application of a Semantic Search Algorithm to Semi-Automatic GUI Generation

The Semantic Search research field aims to query metadata and to identify relevant subgraphs. While in traditional search engines queries are composed by lists of keywords connected through boolean operators, Semantic Search instead, requires the submission of semantic queries that are structured as a graph of concepts, entities and relations. Submission of this graph is however not trivial as while a list of keywords of interest can be provided by any user, the formulation of semantic queries is not easy as well. One of the main challenges of RDF Browsers lies in the implementation of interfaces that allow the common user to submit semantic queries by hiding their complexity. Furthermore a good semantic search algorithm is not enough to fullfil user needs, it is worthwhile to implement visualization methods which can support users in intuitively understanding why and how the results were retrieved. In this paper we present a novel solution to query RDF datasets and to browse the results of the queries in an appealing manner

Terminology extraction: an analysis of linguistic and statistical approaches

Are linguistic properties and behaviors important to recognize terms? Are statistical measures effective to extract terms? Is it possible to capture a sort of termhood with computation linguistic techniques? Or maybe, terms are too much sensitive to exogenous and pragmatic factors that cannot be confined in computational linguistic? All these questions are still open. This study tries to contribute in the search of an answer, with the belief that it can be found only through a careful experimental analysis of real case studies and a study of their correlation with theoretical insights

Senescence in hepatic stellate cells as a mechanism of liver fibrosis reversal: a putative synergy between retinoic acid and PPAR-gamma signalings

Hepatic stellate cells (HSCs), also known as perisinusoidal cells, are pericytes found in the perisinusoidal space of the liver. HSCs are the major cell type involved in liver fibrosis, which is the formation of scar tissue in response to liver damage. When the liver is damaged, stellate cells can shift into an activated state, characterized by proliferation, contractility and chemotaxis. The activated HSCs secrete collagen scar tissue, which can lead to cirrhosis. Recent studies have shown that in vivo activation of HSCs by fibrogenic agents can eventually lead to senescence of these cells, which would contribute to reversal of fibrosis although it may also favor the insurgence of liver cancer. HSCs in their non-active form store huge amounts of retinoic acid derivatives in lipid droplets, which are progressively depleted upon cell activation in injured liver. Retinoic acid is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A, generally required for growth and development. The precise function of retinoic acid and its alterations in HSCs has yet to be elucidated, and nonetheless in various cell types retinoic acid and its receptors (RAR and RXR) are known to act synergistically with peroxisome proliferator-activated receptor gamma (PPAR-gamma) signaling through the activity of transcriptional heterodimers. Here, we review the recent advancements in the understanding of how retinoic acid signaling modulates the fibrogenic potential of HSCs and proposes a synergistic combined action with PPAR-gamma in the reversal of liver fibrosis

From ESR to continuous CC-ESRR process: development in remelting technology towards better products and productivity

This work describes the development of the Electro Slag Remelting process at Valbruna, starting in the 1997 with an innovative INTECO ESR plant equipped with protective gas hood (for inert atmosphere remelting), electrode change system and fully computer controlled. The second step was made a couple of years later when the plant was upgraded to ESRR® (Electro Slag Rapid Remelting). With this new feature Acciaierie Valbruna was able to obtain ready to roll remelted billets (145, 160 and 200 mm square), getting rid of the traditional forging or blooming operations needed in case of traditional ESR ingot remelting. This was surely a dramatic cut off in product cost accounting and production lead time without loosing any of the special characteristics typical of ESR products. Unfortunately the ESRR® process, very promising in terms of cycle complexity reduction and quality of the product, because of its “batch-type” operation, was uneconomical in regard of productivity of the plant and not feasible in industrial scale. The final step of this development was made at the beginning of 2002 when t he ESRR® plant was upgraded again and equipped with an innovative INTECO automatic manipulator, which resulted in a continuous process. This was the birth of the very first CC-ESRR® (continuous casting electro slag rapid remelting) plant in the world. The first part of this paper focuses o n the development of processes and equipment, giving a brief description of ESR, ESRR® and CC-ESRR® process while the second part describes the results of a series of test remelting used for product and CC-ESRR® process characterization

Amphiregulin activates human hepatic stellate cells and is upregulated in non alcoholic steatohepatitis

Amphiregulin (AR) involvement in liver fibrogenesis and hepatic stellate cells (HSC) regulation is under study. Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular cancer (HCC). Our aim was to investigate ex vivo the effect of AR on human primary HSC (hHSC) and verify in vivo the relevance of AR in NAFLD fibrogenesis. hHSC isolated from healthy liver segments were analyzed for expression of AR and its activator, TNF- converting enzyme (TACE). AR induction of hHSC proliferation and matrix production was estimated in the presence of antagonists. AR involvement in fibrogenesis was also assessed in a mouse model of NASH and in humans with NASH. hHSC time dependently expressed AR and TACE. AR increased hHSC proliferation through several mitogenic signaling pathways such as EGFR, PI3K and p38. AR also induced marked upregulation of hHSC fibrogenic markers and reduced hHSC death. AR expression was enhanced in the HSC of a murine model of NASH and of severe human NASH. In conclusion, AR induces hHSC fibrogenic activity via multiple mitogenic signaling pathways, and is upregulated in murine and human NASH, suggesting that AR antagonists may be clinically useful anti-fibrotics in NAFLD

Efficacy and epigenetic interactions of novel DNA hypomethylating agent guadecitabine (SGI-110) in preclinical models of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a deadly malignancy characterized at the epigenetic level by global DNA hypomethylation and focal hypermethylation on the promoter of tumor suppressor genes. In most cases it develops on a background of liver steatohepatitis, fibrosis, and cirrhosis. Guadecitabine (SGI-110) is a second-generation hypomethylating agent, which inhibits DNA methyltransferases. Guadecitabine is formulated as a dinucleotide of decitabine and deoxyguanosine that is resistant to cytidine deaminase (CDA) degradation and results in prolonged in vivo exposure to decitabine following small volume subcutaneous administration of guadecitabine. Here we found that guadecitabine is an effective demethylating agent and is able to prevent HCC progression in pre-clinical models. In a xenograft HCC HepG2 model, guadecitabine impeded tumor growth and inhibited angiogenesis, while it could not prevent liver fibrosis and inflammation in a mouse model of steatohepatitis. Demethylating efficacy of guadecitabine on LINE-1 elements was found to be the highest 8 d post-infusion in blood samples of mice. Analysis of a panel of human HCC vs. normal tissue revealed a signature of hypermethylated tumor suppressor genes (CDKN1A, CDKN2A, DLEC1, E2F1, GSTP1, OPCML, E2F1, RASSF1, RUNX3, and SOCS1) as detected by methylation-specific PCR. A pronounced demethylating effect of guadecitabine was obtained also in the promoters of a subset of tumor suppressors genes (CDKN2A, DLEC1, and RUNX3) in HepG2 and Huh-7 HCC cells. Finally, we analyzed the role of macroH2A1, a variant of histone H2A, an oncogene upregulated in human cirrhosis/HCC that synergizes with DNA methylation in suppressing tumor suppressor genes, and it prevents the inhibition of cell growth triggered by decitabine in HCC cells. Guadecitabine, in contrast to decitabine, blocked growth in HCC cells overexpressing macroH2A1 histones and with high CDA levels, despite being unable to fully demethylate CDKN2A, RUNX3, and DLEC1 promoters altered by macroH2A1. Collectively, our findings in human and mice models reveal novel epigenetic anti-HCC effects of guadecitabine, which might be effective specifically in advanced states of the disease