• Molecules and Cells
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• 제40권1호
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• pp.45-53
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• 2017

Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of ${\beta}-catenin$, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1945-1952
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• 2015

Inflammatory bowel disease (IBD) is a disease strongly associated with colorectal cancer (CRC) as a well-known precancerous condition. Alterations in DNA methylation and mutation in K-ras are believed to play an early etiopathogenic role in CRC and may also an initiating event through deregulation of molecular signaling. Epigenetic silencing of APC and SFRP2 in the WNT signaling pathway may also be involved in IBD-CRC. The role of aberrant DNA methylation in precancerous state of colorectal cancer (CRC) is under intensive investigation worldwide. The aim of this study was to investigate the status of promoter methylation of MGMT-B, APC1A and SFRP2 genes, in inflamed and normal colon tissues of patients with IBD compared with control normal tissues. A total of 52 IBD tissues as well as corresponding normal tissues and 30 samples from healthy participants were obtained. We determined promoter methylation status of MGMT-B, SFRP2 and APC1A genes by chemical treatment with sodium bisulfite and subsequent MSP. The most frequently methylated locus was MGMT-B (71%; 34 of 48), followed by SFRP2 (66.6 %; 32 of 48), and APC1A (43.7%; 21 of 48). Our study demonstrated for the first time that hypermethylation of the MGMT-B and the SFRP2 gene promoter regions might be involved in IBD development. Methylation of MGMT-B and SFRP2 in IBD patients may provide a method for early detection of IBD-associated neoplasia.

• Structural Monitoring and Maintenance
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• 제2권3호
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• pp.269-282
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• 2015

Civil structures should be designed with the lowest cost and longest lifetime possible and without service failure. The efficient and sustainable use of materials in building design and construction has always been at the forefront for civil engineers and environmentalists. Timber is one of the best contenders for these purposes particularly in terms of aesthetics; fire protection; strength-to-weight ratio; acoustic properties and seismic resistance. In recent years, timber has been used in commercial and taller buildings due to these significant advantages. It should be noted that, since the launch of the modern building standards and codes, a number of different structural systems have been developed to stabilise steel or concrete multistorey buildings, however, structural analysis of high-rise and multi-storey timber frame buildings subjected to lateral loads has not yet been fully understood. Additionally, timber degradation can occur as a result of biological decay of the elements and overloading that can result in structural damage. In such structures, the deficient members and joints require strengthening in order to satisfy new code requirements; determine acceptable level of safety; and avoid brittle failure following earthquake actions. This paper investigates performance assessment and damage assessment of older multi-storey timber buildings. One approach is to retrofit the beams in order to increase the ductility of the frame. Experimental studies indicate that Sprayed Fibre Reinforced Polymer (SFRP) repairing/retrofitting not only updates the integrity of the joint, but also increases its strength; stiffness; and ductility in such a way that the joint remains elastic. Non-linear finite element analysis ('pushover') is carried out to study the behaviour of the structure subjected to simulated gravity and lateral loads. A new global index is re-assessed for damage assessment of the plain and SFRP-retrofitted frames using capacity curves obtained from pushover analysis. This study shows that the proposed method is suitable for structural damage assessment of aged timber buildings. Also SFRP retrofitting can potentially improve the performance and load carrying capacity of the structure.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2185-2193
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• 2016

Background: The pathogenesis of sporadic colorectal cancer (CRC) is influenced by the patient genetic background and environmental factors. Based on prior understanding, these are classified in two major pathways of genetic instability. Microsatellite instability (MSI) and CPG island methylator phenotype (CIMP) are categorized as features of the hypermethylated prototype, and chromosomal instability (CIN) is known to be indicative of the non-hypermethylated category. Secreted frizzled related protein 2 (SFRP2), APC1A in WNT signaling pathway and the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), are frequently hypermethylated in colorectal cancer. Detection of methylated DNA as a biomarker by easy and inexpensive methods might improve the quality of life of patients with CRC via early detection of cancer or a precancerous condition. Aim: To evaluate the rate of SFRP2 and MGMT hypermethylation in both polyp tissue and serum of patients in south Iran as compared with matched control normal population corresponding samples. Materials and Methods: Methylation-specific PCR was used to detect hypermethylation in DNA extracted from 48 polypoid tissue samples and 25 healthy individuals. Results: Of total polyp samples, 89.5% had at least one promoter gene hypermethylation. The most frequent methylated locus was SFRP2 followed by MGMT-B (81.2 and 66.6 percent respectively). Serologic detection of hypermethylation was 95% sensitive as compared with polyp tissue. No hypermethylation was detected in normal tissue and serum and its detection in patients with polyps, especially of serrated type, was specific. Conclusions: Serologic investigation for detection of MGMT-B, SFRP2 hypermethylation could facilitate prioritization of high risk patients for colonoscopic polyp detection and excision.

• Bulletin of the Korean Chemical Society
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• 제32권7호
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• pp.2377-2384
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• 2011

Azo-acenaphthylene oligomers with repeating acenaphthylene units "n" up to 4, 5, 7, 17 and 19 have been prepared successfully using nitroxide mediated Stable Free Radical Polymerization (SFRP). Azo-acenaphthylene oligomers, reversibly end-capped by the stable nitroxide 2,2,6,6-tetramethyl-1-piperidinoxyl (TEMPO), were further reacted via radical addition to 4-(naphthalenemethoxy)styrene monomer for diblock co-polymer formation. Characterization of the oligomers and diblock co-polymers was accomplished using MALDI-MS supported by GPC (Gel Permeation Chromatography) and $^1H$ NMR spectrometry. MALDI-MS afforded definitive results by providing an inter-peak interval of 152 (m/z), corresponding to acenaphthylene monomer, and inter-peak interval of 260 (m/z) for the naphthalenemethoxystyrene monomer unit in block copolymers. Our study opens the way to control the number of repeat units in the oligomers. Further these oligomers can be tailored with various monomers for the formation of block copolymers.

• 한국콘크리트학회:학술대회논문집
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• 한국콘크리트학회 2006년도 추계 학술발표회 논문집
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• pp.137-140
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• 2006

In this study, a seismic performance of reinforced concrete columns strengthened by a sprayed fiber reinforced polymer (SFRP) is investigated. For this purpose, six column specimens approximately scaled into 2/3, are designed and tested under a constant axial load, 10% of the nominal axial strength of column, and pseudo-static reversed cyclic lateral loading system. Four specimens are strengthened by Sprayed FRP using different combinations of short fibers (carbon or glass fiber) and resins (epoxy or vinyl esther). For comparison, the test investigated in this study also includes a specimen strengthened using carbon fiber reinforced polymer (CFRP), and also a control specimen without strengthening. The results revealed that specimens strengthened using SFRP showed a improved structure behavior, compared to control specimen, in terms of strength, ductility, lateral drift capacity, and energy-absorbtion capacity. In addition, compared to the specimen strengthened using CFRP, Sprayed FRP-strengthened specimens reasonably showed a equivalent seismic performance.

• Journal of Radiation Protection and Research
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• 제41권2호
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• pp.117-121
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• 2016

Background: Definition and grouping of initiating events (IEs) are important basics for probabilistic safety assessment (PSA). An IE in a spent fuel reprocessing plant (SFRP) is an event that probably leads to the release of dangerous material to jeopardize workers, public and environment. The main difference between SFRPs and nuclear power plants (NPPs) is that hazard materials spread diffusely in a SFRP and radioactive material is just one kind of hazard material. Materials and Methods: Since the research on IEs for NPPs is in-depth around the world, there are several general methods to identify IEs: reference of lists in existence, review of experience feedback, qualitative analysis method, and deductive analysis method. While failure mode and effect analysis (FMEA) is an important qualitative analysis method, master logic diagram (MLD) method is the deductive analysis method. IE identification in SFRPs should be consulted with the experience of NPPs, however the differences between SFRPs and NPPs should be considered seriously. Results and Discussion: The plutonium uranium reduction extraction (Purex) process is adopted by the technics in a model reprocessing plant. The first extraction cycle (FEC) is the pivotal process in the Purex process. Whether the FEC can function safely and steadily would directly influence the production process of the whole plant-production quality. Important facilities of the FEC are installed in the equipment cells (ECs). In this work, IEs in the FEC process were identified and categorized by FMEA and MLD two methods, based on the fact that ECs are containments in the plant. Conclusion: The results show that only two ECs in the FEC do not need to be concerned particularly with safety problems, and criticality, fire and red oil explosion are IEs which should be emphatically analyzed. The results are accordant with the references.

• 한국산업융합학회 논문집
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• 제11권2호
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• pp.93-98
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• 2008

Steel fibre reinforced concrete (SFRC) were considered a new technology for the construction industry. However today this technology has found wider acceptance among the construction industry. Currently, steel fibres are used in varied segments in many application areas across different segments in the construction industry, especially in tunneling, airports, warehouses, etc. Time and safety are the main factors are among the various advantages which renders steel fibres superior to the competing product. For fibers reinforcing, The maximum load carrying capacity is controlled by fibers pulling out of the composite because fiber reinforcing does not have a deformed surface like larger steel reinforcing bars. The study demonstrated that above concept is applicable and effective in concrete structure by analytical study. The analytical result appears that SFRP have the potential to significantly increase the strength of existing concrete structures, while at the same time dramatically improving their fracture energy characteristics.

• BMB Reports
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• 제37권6호
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• pp.741-748
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• 2004

The hepatitis C virus is associated with the development of liver cirrhosis and hepatocellular carcinomas. Among the 10 polyproteins produced by the virus, no function has been clearly assigned to the non-structural 5A (NS5A) protein. This study was designed to identify the hepatocellular proteins that interact with NS5A of the HCV. Yeast two-hybrid experiments were performed with a human liver cDNA prey-library, using five different NS5A derivatives as baits, the full-length NS5A (NS5A-F, amino acid (aa) 1~447) and its four different derivatives, denoted as NS5A-A (aa 1~150), -B (aa 1~300), -C (aa 300~447) and D (aa 150~447). NS5A-F, NS5A-B and NS5A-C gave two, two and 10 candidate clones, respectively, including an AHNAK-related protein, the secreted frizzled-related protein 4 (SFRP4), the N-myc downstream regulated gene 1 (NDRG1), the cellular retinoic acid binding protein 1 (CRABP-1), ferritin heavy chain (FTH1), translokin, tumor-associated calcium signal transducer 2 (TACSTD2), phosphatidylinositol 4-kinase (PI4K) and $centaurin{\delta}$ 2 ($CENT{\delta}2$). However, NS5A-A produced no candidates and NS5A-D was not suitable as bait due to transcriptional activity. Based on an in vitro binding assay, CRABP-1, PI4K, $CENT{\delta}2$ and two unknown fusion proteins with maltose binding protein (MBP), were confirmed to interact with the glutathione S-transferase (GST)/NS5A fusion protein. Furthermore, the interactions of CRABP-1, PI4K and $CENT{\delta}2$ were not related to the PXXP motif (class II), as judged by a domain analysis. While their biological relevance is under investigation, the results contribute to a better understanding of the possible role of NS5A in hepatocellular signaling pathways.

• International Journal of Stem Cells
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• 제16권3호
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• pp.342-355
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• 2023

Background and Objectives: Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and play important role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. Methods and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identify new cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. Conclusions: Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.