Small RNAs Targeting Transcription Start Site Induce Heparanase Silencing through Interference with Transcription Initiation in Human Cancer Cells

Heparanase (HPA), an endo-h-D-glucuronidase that cleaves the heparan sulfate chain of heparan sulfate proteoglycans, is overexpressed in majority of human cancers. Recent evidence suggests that small interfering RNA (siRNA) induces transcriptional gene silencing (TGS) in human cells. In this study, transfection of siRNA against −9/+10 bp (siH3), but not −174/−155 bp (siH1) or −134/−115 bp (siH2) region relative to transcription start site (TSS) locating at 101 bp upstream of the translation start site, resulted in TGS of heparanase in human prostate cancer, bladder cancer, and gastric cancer cells in a sequence-specific manner. Methylation-specific PCR and bisulfite sequencing revealed no DNA methylation of CpG islands within heparanase promoter in siH3-transfected cells. The TGS of heparanase did not involve changes of epigenetic markers histone H3 lysine 9 dimethylation (H3K9me2), histone H3 lysine 27 trimethylation (H3K27me3) or active chromatin marker acetylated histone H3 (AcH3). The regulation of alternative splicing was not involved in siH3-mediated TGS. Instead, siH3 interfered with transcription initiation via decreasing the binding of both RNA polymerase II and transcription factor II B (TFIIB), but not the binding of transcription factors Sp1 or early growth response 1, on the heparanase promoter. Moreover, Argonaute 1 and Argonaute 2 facilitated the decreased binding of RNA polymerase II and TFIIB on heparanase promoter, and were necessary in siH3-induced TGS of heparanase. Stable transfection of the short hairpin RNA construct targeting heparanase TSS (−9/+10 bp) into cancer cells, resulted in decreased proliferation, invasion, metastasis and angiogenesis of cancer cells in vitro and in athymic mice models. These results suggest that small RNAs targeting TSS can induce TGS of heparanase via interference with transcription initiation, and significantly suppress the tumor growth, invasion, metastasis and angiogenesis of cancer cells

Evaluation of partner companies based on fuzzy inference system for establishing virtual enterprise consortium

4th International Conference on Operations Research and Enterprise Systems (2015 : Lisbon; Portugal)Virtual Enterprise (VE) is one of the growing trends in agile manufacturing concepts. Under this platform companies with different skills and core competences are cooperate with each other in order to accomplish a manufacturing goal. Success of VE, as a consortium, highly depends on the success of its partners. So it is very important to choose the most appropriate companies to enroll in VE. In this study a Fuzzy Inference System (FIS) based approach is developed to evaluate and select the potential enterprises. The evaluation is conducted based on four main criteria; unit price, delivery time, quality and past performance. These criteria are considered as inputs of FIS and specific membership functions are designed for each. By applying fuzzy rules the output of the model, partnership chance, is calculated. In the end, the trustworthy of the model is tested and verified by comparing it with fuzzy-TOPSIS technique providing a sample. © Springer International Publishing Switzerland 2015.Institute for Systems and Technologies of Information, Control and Communication (INSTICC

Enterprise competence organization schema: publishing the published competences

This article was published in the journal Proceedings of the Institution of Mechanical Engineers, Part B: Journal of Engineering Manufacture [Sage © IMechE]. The definitive version is available at: http://dx.doi.org/10.1177/09544054JEM2097Competence is a standardized way to define the profile of an enterprise. Understanding and auditing competences acquired, required, and desired by a company and further representing them in a structured manner is a beneficial step for enhancing the company's performance. Ontology is emerging as an effective tool to structure competences for comprehensive and transportable machine understanding. In the present paper, ECOS (Enterprise Competence Organization Schema) is presented as a mechanism to capture enterprise competence in a manner understandable by computers. The objective behind this concept is to create a web of machine-readable pages describing basic information and competences of enterprises with sets of interconnected data and semantic models. The ECOS ontology captures enterprise competences using a consistent and comprehensive list of concepts and vocabulary and converts them into a semantic web resource using the Web Ontology Language (OWL). The novel concept of an ECOS-card and ECOS-form is proposed and used for developing and publishing enterprise competences. Examples from real-life enterprise applications of ECOS are also shown in the paper