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Protein-coding genes account for only ~2% of the human genome, whereas the vast majority of transcripts are non-coding RNAs (ncRNAs) including long ncRNAs (lncRNAs). A growing volume of literature has proposed that lncRNAs are important factors in cancer. Colon cancer-associated transcript-1 (CCAT1), an lncRNA, which was first identified in colon cancer, was previously shown to promote tumor development and be a negative prognostic factor in gastric cancer. However, the mechanism through which CCAT1 exerts its oncogenic activity remains largely unknown. Recently, a novel regulatory mechanism has been proposed in which RNAs can cross-talk with each other via competing shared for microRNAs (miRNAs). The proposed competitive endogenous RNAs could mediate the bioavailability of miRNAs on their targets, thus imposing another level of posttranscriptional regulation. In this study, we demonstrated that CCAT1 was upregulated in gallbladder cancer (GBC) tissues. CCAT1 silencing downregulated, whereas CCAT1 overexpression enhanced the expression of miRNA-218-5p target gene Bmi1 through competitively ‘spongeing’ miRNA-218-5p. Our data revealed that CCAT1 knockdown impaired the proliferation and invasiveness of GBC cells, at least in part through affecting miRNA-218-5p-mediated regulation of Bmi1. Moreover, CCAT1 transcript level was correlated with Bmi1 mRNA level in GBC tissues. Together, these results suggest that CCAT1 is a driver of malignancy, which acts in part through ‘spongeing’ miRNA-218-5p.

Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo . Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.

Multiple sclerosis (MS) is a complex demyelinating disease of the central nervous system. Current research has shown that at least in some cases, the primary insult in MS could be directed at the oligodendrocyte, and that the earliest immune responses are primarily via innate immune cells. We have identified a family of receptor protein tyrosine kinases, known as the TAM receptors (Tyro3, Axl and Mertk), as potentially important in regulating both the oligodendrocyte and immune responses. We have previously shown that Gas6, a ligand for the TAM receptors, can affect the severity of demyelination in mice, with a loss of signalling via Gas6 leading to decreased oligodendrocyte survival and increased microglial activation during cuprizone-induced demyelination. We hypothesised TAM receptor signalling would also influence the extent of recovery in mice following demyelination. A significant effect of the absence of Gas6 was detected upon remyelination, with a lower level of myelination after 4 weeks of recovery in comparison with wild-type mice. The delay in remyelination was accompanied by a reduction in oligodendrocyte numbers. To understand the molecular mechanisms that drive the observed effects, we also examined the effect of exogenous Gas6 in in vitro myelination assays. We found that Gas6 significantly increased myelination in a dose-dependent manner, suggesting that TAM receptor signalling could be directly involved in myelination by oligodendrocytes. The reduced rate of remyelination in the absence of Gas6 could thus result from a lack of Gas6 at a critical time during myelin production after injury. These findings establish Gas6 as an important regulator of both CNS demyelination and remyelination.

Structural evolution in nanoscale Cu 50 Zr 50 metallic glasses during high-pressure torsion is investigated using molecular dynamics simulations. Results show that the strong cooperation of shear transformations can be realized by high-pressure torsion in nanoscale Cu 50 Zr 50 metallic glasses at room temperature. It is further shown that high-pressure torsion could prompt atoms to possess lower five-fold symmetries and higher potential energies, making them more likely to participate in shear transformations. Meanwhile, a higher torsion period leads to a greater degree of forced cooperative flow. And the pronounced forced cooperative flow at room temperature under high-pressure torsion permits the study of the shear transformation, its activation and characteristics, and its relationship to the deformations behaviors. This research not only provides an important platform for probing the atomic-level understanding of the fundamental mechanisms of high-pressure torsion in metallic glasses, but also leads to higher stresses and homogeneous flow near lower temperatures which is impossible previously.

Multiple sclerosis (MS) is a debilitating, chronic demyelinating disease of the central nervous system affecting over 2 million people worldwide. The TAM family of receptor tyrosine kinases (TYRO3, AXL and MERTK) have been implicated as important players during demyelination in both animal models of MS and in the human disease. We therefore conducted an association study to identify single nucleotide polymorphisms (SNPs) within genes encoding the TAM receptors and their ligands associated with MS. Analysis of genotype data from a genome-wide association study which consisted of 1618 MS cases and 3413 healthy controls conducted by the Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) revealed several SNPs within the MERTK gene (Chromosome 2q14.1, Accession Number NG_011607.1) that showed suggestive association with MS. We therefore interrogated 28 SNPs in MERTK in an independent replication cohort of 1140 MS cases and 1140 healthy controls. We found 12 SNPs that replicated, with 7 SNPs showing p-values of less than 10(-5) when the discovery and replication cohorts were combined. All 12 replicated SNPs were in strong linkage disequilibrium with each other. In combination, these data suggest the MERTK gene is a novel risk gene for MS susceptibility.

How to determine topological relationships is one of the most important operations on fuzzy spatiotemporal data. The proposed strategies impose strict restrictions on structure and data types of fuzzy spatiotemporal data, and fall short in their abilities to handle fuzzy attributes extension and fuzzy time extension. To overcome these limitations, in this paper, we first establish a fuzzy spatiotemporal data model based on XML. Then, we propose strategies of transforming two general fuzzy spatiotemporal data trees into one binary fuzzy spatiotemporal data tree. In succession, an effective algorithm to match the desired twigs is proposed after extending the region coding scheme to compatible with fuzzy spatiotemporal data. Our approach adopts XML twig pattern technique to determine topological relationship continuously so that it can reduce unnecessary execution time of querying the desired nodes. More importantly, we use a pointer array to eliminate unnecessary execution time of twig matching. Finally, the experimental results demonstrate the performance advantages of our approach.

XML has become the standard for publishing and exchanging data on the Web. Since most of the business data nowadays are stored in structured databases including relational and object-oriented databases (OODB), it is of significance to automate the transformation process and generate the XML data containing information from existing databases. At the same time, information imprecision and uncertainty exist in many practical applications, and for this reason, fuzzy data modeling has been extensively investigated in various data models. As such, there is an increasing need to effectively publish fuzzy structured data as fuzzy XML documents for Web-based applications. In this paper, we take a significant step in a fundamental consolidation of fuzzy XML. In particular, we are interested in finding an XML schema that best describes the existing fuzzy object-oriented schema. To accomplish this, we first offer mapping formalisms to capture the semantics of fuzzy XML Schema and fuzzy object-oriented schema. To allow for better and platform independent sharing of data stored in an object-oriented format, we investigate the formal transformation from fuzzy OODB to fuzzy XML and develop a set of rules to assist in the transformation process.

The eXtensible Markup Language (XML) has reached a wide acceptance as the relevant standardization for representing and exchanging data on the Web. Unfortunately, XML covers the syntactic level but lacks semantics, and thus cannot be directly used for the Semantic Web. Currently, finding a way to utilize XML data for the Semantic Web is challenging research. As we have known that ontology can formally represent shared domain knowledge and enable semantics interoperability. Therefore, in this paper , we investigate how to represent and reason about XML with ontologies. Firstly , we give formalized representations of XML data sources, including Document Type Definitions (DTDs), XML Schemas, and XML documents. On this basis , we propose formal approaches for transforming the XML data sources into ontologies, and we also discuss the correctness of the transformations and provide several transformation examples. Furthermore , following the proposed approaches, we implement a prototype tool that can automatically transform XML into ontologies. Finally , we apply the transformed ontologies for reasoning about XML, so that some reasoning problems of XML may be checked by the existing ontology reasoners.

Since semi-structured documents (e.g., XML) could benefit greatly from database support and more specifically from object-oriented (OO) database management systems, we study the methodology of reengineering XML to object-oriented databases when database migration occurs in this paper. In particular, considering the need of processing the imprecise and uncertain information existing in practical applications, we investigate the problem of migrating fuzzy XML to fuzzy object-oriented databases. To find the object-oriented schema that best describes the existing fuzzy XML schema (DTD), we devise a comprehensive approach centering on a set of mapping rules. Such reengineering practices could not only provide a significant consolidation of the interoperability between fuzzy OO and fuzzy XML modeling techniques, but also develop the practical design methodology for fuzzy OO databases.

Information imprecision and uncertainty exist in many real-world applications and for this reason fuzzy data management has been extensively investigated in various database management systems. Currently, introducing native support for XML data in relational database management systems (RDBMs) has attracted considerable interest with a view to leveraging the powerful and reliable data management services provided by RDBMs. Although there is a rich literature on XML-to-relational storage, none of the existing solutions satisfactorily addresses the problem of storing fuzzy XML data in RDBMs. In this paper, we study the methodology of storing and querying fuzzy XML data in relational databases. In particular, we present an edge-based approach to shred fuzzy XML data into relational data. The unique feature of our approach is that no schema information is required for our data storage. On this basis, we present a generic approach to translate path expression queries into SQL for processing XML queries.