• Geomechanics and Engineering
• /
• v.23 no.2
• /
• pp.151-163
• /
• 2020

Grouting method is an effective way of reinforcing cracked rock masses and plugging water gushing. Current grouting diffusion models are generally developed for horizontal cracks, which is contradictory to the fact that the crack generally occurs in rock masses with irregular spatial distribution characteristics in real underground environments. To solve this problem, this study selected a cement-sodium silicate slurry (C-S slurry) generally used in engineering as a fast-curing grouting material and regarded the C-S slurry as a Bingham fluid with time-varying viscosity for analysis. Based on the theory of fluid mechanics, and by simultaneously considering the deadweight of slurry and characteristics of non-uniform spatial distribution of viscosity of fast-curing grouts, a theoretical model of slurry diffusion in an oblique crack in rock masses at constant grouting rate was established. Moreover, the viscosity and pressure distribution equations in the slurry diffusion zone were deduced, thus quantifying the relationship between grouting pressure, grouting time, and slurry diffusion distance. On this basis, by using a 3-d finite element program in multi-field coupled software Comsol, the numerical simulation results were compared with theoretical calculation values, further verifying the effectiveness of the theoretical model. In addition, through the analysis of two engineering case studies, the theoretical calculations and measured slurry diffusion radius were compared, to evaluate the application effects of the model in engineering practice. Finally, by using the established theoretical model, the influence of cracking in rock masses on the diffusion characteristics of slurry was analysed. The results demonstrate that the inclination angle of the crack in rock masses and azimuth angle of slurry diffusion affect slurry diffusion characteristics. More attention should be paid to the actual grouting process. The results can provide references for determining grouting parameters of fast-curing grouts in engineering practice.

• Journal of KIISE:Computing Practices and Letters
• /
• v.9 no.3
• /
• pp.266-277
• /
• 2003

Every conceptual temporal rat relationship can be described using one of seven relations (before, meets, overlaps, during, starts, finishes, and equals ). The conceptual representation provides an efficient means for our multimedia authoring system to automatically fill in the necessary timing details. We developed a multimedia Presentation authoring system that supports a mechanism for conceptually representing the temporal relations of different media. Among the many editors that make up our system, the temporal relation editor provides users with an intuitive mechanism for representing the conceptual flow of a presentation by simple and direct graphical manipulations. Our system is based on the SMIL(Synchronized Multimedia Integration Language). The conceptual temporal relation editor and other editors of our system exchange their information in real-time and automatically generate SMIL codes through the SMIL Object Manager. Our system uses TRN(Temporal Relation Network) as its internal multimedia presentation representation. The TRN corresponds exactly to the structure seen in the graphical representation of the presentation. A parallel relationship found in a TRN can be collapsed into a single synchronization block. This facilitates the determination of the playing time of each component and can be the basic unit for reusability of already prepared blocks of presentation code.

• Genomics & Informatics
• /
• v.16 no.3
• /
• pp.52-58
• /
• 2018

In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials.

• Journal of Life Science
• /
• v.19 no.4
• /
• pp.520-525
• /
• 2009

Early onset of Batten disease (EBD), one of the most lethal neurodegenerative storage disorders of childhood, is caused by inactivating mutations in the Ceroid Lipofuscinosis, Neuronal (CLN1) gene. Neurogranin, a calmodulin-binding protein, is expressed in the brain and participates in the protein kinase C (PKC) signaling pathway. While oxidative stress is the suggested cause of neurodegeneration in EBD, its molecular mechanism(s) remains obscure. In this research, we examined the levels of neurogranin in the brain mRNA of wild-type (WT) mice and EBD knockout (KO) mice, as well as the proteins. We also performed neuronal cultures to measure the expression levels of neurgranin and phosphorylated-neurogranin with or without oxidative stress inducers and anti-oxidants. Results showed that neurogranin in both EBD KO mice brain mRNA and protein extracts decreased in an age dependent manner. However, high amounts of phosphorylated-neurogranin were detected in the 6-month brain. This pattern was also confirmed by cultured neurospheres samples. Moreover, neurospheres treated with $H_2O_2$, an oxidative stress inducer, showed increased phosphorylated-neurogranin patterns. Interestingly, this pattern returned to normal status when treated with N-acetyl-L-cystein, an anti-oxidant, after $H_2O_2$ treatment was performed. Our results suggest that the phosphorylation of neurogranin is affected by oxidative stress status in EBD, and appropriate anti-oxidant treatment will relieve hyper-phosphorylation of neurogranin.

• Asian-Australasian Journal of Animal Sciences
• /
• v.31 no.5
• /
• pp.650-657
• /
• 2018

Objective: The study investigated the biological functions and mechanisms for controlling cashmere growth of Liaoning cashmere goat by ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) and decorin (DCN) genes. Methods: cDNA library of Liaoning cashmere goat was constructed in early stages. OCIAD2 and DCN genes related to cashmere growth were identified by homology analysis comparison. The expression location of OCIAD2 and DCN genes in primary and secondary hair follicles (SF) was performed using in situ hybridization. The expression of OCIAD2 and DCN genes in primary and SF was performed using real-time polymerase chain reaction (PCR). Results: In situ hybridization revealed that OCIAD2 and DCN were expressed in the inner root sheath of Liaoning cashmere goat hair follicles. Real-time quantitative PCR showed that these genes were highly expressed in SF during anagen, while these genes were highly expressed in primary hair follicle in catagen phase. Melatonin (MT) inhibited the expression of OCIAD2 and promoted the expression of DCN. Insulin-like growth factors-1 (IGF-1) inhibited the expression of OCIAD2 and DCN, while fibroblast growth factors 5 (FGF5) promoted the expression of these genes. MT and IGF-1 promoted OCIAD2 synergistically, while MT and FGF5 inhibited the genes simultaneously. MT+IGF-1/MT+FGF5 inhibited DCN gene. RNAi technology showed that OCIAD2 expression was promoted, while that of DCN was inhibited. Conclusion: Activation of bone morphogenetic protein (BMP) signaling pathway up-regulated OCIAD2 expression and stimulated SF to control cell proliferation. DCN gene affected hair follicle morphogenesis and periodic changes by promoting transforming growth $factor-{\beta}$ ($TGF-{\beta}$) and BMP signaling pathways. OCIAD2 and DCN genes have opposite effects on $TGF-{\beta}$ signaling pathway and inhibit each other to affect the hair growth.

• Korean Journal of Clinical Laboratory Science
• /
• v.48 no.3
• /
• pp.176-182
• /
• 2016

When inflammatory reaction is in progress, the macrophages release inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and product inflammatory mediators, including inducible nitric oxide synthase (iNOS) and prostaglandin E2 (PGE2). We conducted this study to evaluate the anti-inflammatory efficacy on each water extract of Acanthopanacis cortex, Achyranthes radix, and Eucommiae cortex, and to investigate whether they inhibit the expression of pro-inflammatory cytokine. Acanthopanacis cortex, Achyranthes radix, and Eucommiae cortex were extracted with water and freeze-dried. Acanthoside D, 20-hydroxyecdysone, and pinoresinol diglucoside as an index material were analyzed by high-performance liquid chromatography (HPLC) to ensure that the components of each extracts were extracted well. RAW 264.7 cell line, stimulated with lipopolysaccharide (LPS) to cause an inflammatory response, was treated with each water extract at various concentrations to determine the anti-inflammatory efficacy. Then, the anti-inflammatory efficacy was confirmed by a nitric oxide (NO) assay, and the mRNA expression levels of pro-inflammatory cytokines were measured by real time PCR. As a result, the indicator materials were detected from each extract, and Acanthopanacis cortex water extract (ACWE) and Achyranthes radix water extract (ARWE) were shown to have a high activity than Eucommiae cortex water extract (ECWE) in NO assay. In Korea, traditionally it prescribed a combination of medicinal herbs. This study confirmed the anti-inflammatory response of these medicinal plants in arthritis and its synergistic effect when used in combination with western medicine.

• Clinical and Experimental Reproductive Medicine
• /
• v.33 no.4
• /
• pp.253-263
• /
• 2006

Objective: Identification of the regulatory mechanism for arrest and initiation of primordial follicular growth is crucial for female fertility. Previously, we found 15 expressed sequence tags (ESTs) that were specifically abundant in the day-S-subtracted cDNA library and that the B357 clone was novel. The present study was conducted to obtain the whole sequence of the novel gene including B357 and to characterize its mRNA and protein expression in mouse ovary and testis. Methods: The extended sequence of the 2,965-bp cDNA fragment for the clone B357 was named ${\underline{5}}-{\underline{d}}ay-{\underline{o}}vary-{\underline{s}}pecific\;gene-{\underline{1}}$ (5DOS1) and submitted to GenBank (accession number ${\underline{AY751521}}$). Expression of 5DOS1 was characterized in both female and male gonads at various developmental stages by Northern blotting, real-time RT-PCR, in situ hybridization, Western blotting, and immunohistochemistry. Results: The 5DOS1 transcript was highly expressed in the adult testis, brain, and muscle as compared to the other tissues. In the ovary, the 5DOS1 transcript was detected in all oocytes from primordial to antral follicles, and highly expressed at day 5 after birth and decreased thereafter. In contrast, expression of 5DOS1 showed a gradual increase during testicular development and its expression was limited to various stages of male germ cells except spermatogonia. Conclusions: This is the first report on the expression and characterization of the 5DOS1 gene in the mouse gonads. Further functional analysis of the 5DOS1 protein will be required to predict its role in gametogenesis.

• Journal of KIISE:Computing Practices and Letters
• /
• v.15 no.10
• /
• pp.752-760
• /
• 2009

Emerging peer-to-peer systems benefit from the large amount of resources provided by many peers. However, many peer-to-peer systems or applications suffer from malicious peers and it is not guaranteed that peers are always online. Micropayment systems are accounting and charging mechanism for buying services, so we can apply them to solve these problems. In the past the majority of micropayment system uses a centralized broker but the problem with most existing micropayment system is a heavy load on the broker. For instance, when an owner of the coin is offline, the broker delegates the owner and handles payment messages. It occurs frequently because of characteristic of peer-to-peer system and is another load of the broker. In this paper we introduce DPay, a peer-to-peer micropayment system that uses distributed hash table (DHT) for storing encrypted payment messages and increases scalability and reduces the load of broker by removing downtime protocol. We show the idea of real-time double spending detection in DPay and report the results of several evaluations in order to compare DPay and other payment scheme. In simulation result, the load of broker in DPay is reduced by 30% on average of other previous payment scheme. We expect that DPay can apply various peer-to-peer systems because it provides a real-time double spending detection and stores more secure payment messages.

• The Journal of Pediatrics of Korean Medicine
• /
• v.30 no.4
• /
• pp.29-59
• /
• 2016

Objectives PRAL (Prunus armeniaca Linne Var) has been known to suppress allergic reaction. However, the cellular target and its mechanism of action were unclear. This study was designed to investigate the effect of PRAL on RBL-2H3 mast cell, which is PMA-Ionomycin-induced activated in vitro and the effect of PRAL on the MNC/Nga mice that are DNCB-induced activated in vivo. Methods In this study, IL-4, IL-13 production were examined by ELISA analysis; IL-4, IL-13, IL-31, IL-31Ra, $TNF-{\alpha}$ and GM-CSF mRNA expression were examined by Real-time PCR; manifestations of AP-1 and MAPKs transcription factors were examined by western blotting in vitro. Then skin rashes have been evaluated and verified the distribution of mast cells by H&E and toluidine blue. Also, WBC, eosinophil and neutrophil, IgE level in serum, $IFN-{\gamma}$, IL-4, IL-5 in the splenocyte culture supernatant, the absolute cell numbers of $CD4^+$, $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$, $CD3^+CD69^+$ in the Axillary Lymph Node (ALN), PBMCs and dorsal skin and IL-5, IL-13, IL-31, IL-31Ra in the dorsal skin by Real-time PCR were all evaluated from the NC/BNga mice. Results As a result of this study, the mRNA expression of IL-4, IL-13, IL-31, IL-31Ra and $TNF-{\alpha}$ and IL-4, IL-13 production, shown in ELISA analysis, were suppressed by PRAL. Results from the western blot analysis showed decrease on the expression of mast-cell-specific transcription factors, including AP-1 and p-JNK, p-ERK. Histological examination showed that infiltration levels of immune cells in the skin of the AD-induced NC/Nga mice were improved by PRAL orally adminstration. Orally- administered PRAL group also showred decreased level of IgE in the serum. This group has shown decreased the level of IL-4, IL-5, but shown elevated $IFN-{\gamma}$ level in the splenocyte culture supernatant. The same group also has shown decreased cell numbers of $CD4^+$, $CD8^+$, $CD3^+CD69^+$ in the ALN, and $CD4^+$, $Gr-1^+CD11b^+$ in the dorsal skin. PRAL oral adminstration increased cell numbers of $CD4^+$, but decreased cell numbers of $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$ in the PBMCs. Conclusions Obtained results suggest that PRAL can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis (AD) induced in the NC/Nga mice. This may play an important role in recovering AD symptoms and suppressing pruritus.

• Molecular & Cellular Toxicology
• /
• v.5 no.1
• /
• pp.32-43
• /
• 2009

Acetaminophen (APAP) overdose is known to cause severe hepatotoxicity mainly through the depletion of glutathione. In this study, we compared the cytotoxic effects of APAP on both a normal murine hepatic cell line, BNL CL.2, and its SV40-transformed cell line, BNL SV A.8. Gene expression profiles for APAP-treated cells were also obtained using microarray and analyzed to identify differences in genes or profiles that may explain the differences of susceptibility to APAP in these cell lines. These two cell lines exhibited different susceptibilities to APAP (0-$5,000{\mu}M$); BNL SV A.8 cells were more susceptible to APAP treatment compared to BNL CL.2 cells. A dose of $625{\mu}M$ APAP, which produced significant differences in cytotoxicity in these cell lines, was tested. Microarray analysis was performed to identify significant differentially expressed genes (DEGs) irrespective of APAP treatment. Genes up-regulated in BNL SV A.8 cells were associated with immune response, defense response, and apoptosis, while down-regulated genes were associated with catalytic activity, cell adhesion and the cytochrome P450 family. Consistent with the cytotoxicity data, no significant DEGs were found in BNL CL.2 cells after treatment with $625{\mu}M$ APAP, while cell cycle arrest and apoptosis-related genes were up-regulated in BNL SV A.8 cells. Based on the significant fold-changes in their expression, a genes were selected and their expressions were confirmed by quantitative real-time RT-PCR; there was a high correlation between them. These results suggest that gene expression profiles may provide a useful method for evaluating drug sensitivity of cell lines and eliciting the underlying molecular mechanism. We further compared the genes identified from our current in vitro studies to the genes previously identified in our lab as regulated by APAP in both C57BL/6 and ICR mice in vivo. We found that a few genes are regulated in a similar pattern both in vivo and in vitro. These genes might be useful to develop as in vitro biomarkers for predicting in vivo hepatotoxicity. Based on our results, we suggest that gene expression profiles may provide useful information for elucidating the underlying molecular mechanisms of drug susceptibility and for evaluating drug sensitivity in vitro for extrapolation to in vivo.