• Ocean Systems Engineering
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• 제4권4호
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• pp.263-278
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• 2014

The spudcan requires the suitable design considering the soil, platform, and environmental conditions. Its shape needs to be designed to secure sufficient reaction of soil so that it can prevent overturning accidents. Its shape also has to minimize the installation and extraction time. Even in the same soil condition, the reaction of soil may be different depending on the shape of spud can, mainly the slope of top and bottom plates. Therefore, in this study, the relation between the slope of plates and the reaction of soil with and without water jetting is analyzed to better understand their interactions and correlations. For the investigation, a wind turbine installation jack-up rig (WTIJ) is selected as the target platform and the Gulf of Mexico is considered as the target site. A multi layered (sand overlying two clays) soil profile is applied as the assumed soil condition and the soil-structure interaction (SSI) analysis is performed by using ANSYS to analyze the effect of the slope change of the bottom plate and water jetting on the reaction of soil. This kind of investigation and simulation is needed to develop optimal and smart spudcan with water-jetting control in the future.

• 통합자연과학논문집
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• 제4권3호
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• pp.202-209
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• 2011

Tuberculosis is a major health problem in humans because of its multidrug resistance and discovering new treatments for this disease is urgently required. The synthesis of isoprenoids in Mycobacterium tuberculosis has been reported as an interesting pathway to target. In this context, 2C-methyl-D-erythritol 4-phosphate (MEP) pathway of M. tuberculosis has drawn attention. The MEP pathway begins with the condensation of glyceraldehyde 3-phosphate and pyruvate forming 1-deoxy-D-xylulose 5-phosphate (DXP) which is catalyzed by 1-deoxy-D-xylulose 5-phosphate synthase (DXS). As there is no X-ray structure was reported for this target, comparative modeling was used to generate the three dimensional structure. The structure was further validated by PROCHECK, VERIFY-3D, PROSA, ERRAT and WHATIF. Molecular docking studies was performed with the substrate (Thiamine pyrophosphate) and the reported inhibitor 2-methyl-3-(4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolol[1,5-a]pyrimidin-7-one) against the developed model to identify the crucial residues in the active site. This study may further be useful to provide structure based drug design.

• Biomolecules & Therapeutics
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• 제26권5호
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• pp.458-463
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• 2018

The phosphorylation of JNK is known to induce insulin resistance in insulin target tissues. The inhibition of JNK-JIP1 interaction, which interferes JNK phosphorylation, becomes a potential target for drug development of type 2 diabetes. To discover the inhibitors of JNK-JIP1 interaction, we screened out 30 candidates from 4320 compound library with In Cell Interaction Trap method. The candidates were further confirmed and narrowed down to five compounds using the FRET method in a model cell. Among those five compounds, Acebutolol showed notable inhibition of JNK phosphorylation and elevation of glucose uptake in diabetic models of adipocyte and liver cell. Structural computation showed that the binding affinity of Acebutolol on the JNK-JIP1 interaction site was comparable to the known inhibitor, BI-78D3. Our results suggest that Acebutolol, an FDA-approved beta blocker for hypertension therapy, could have a new repurposed effect on type 2 diabetes elevating glucose uptake process by inhibiting JNK-JIP1 interaction.

• The Plant Pathology Journal
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• 제22권4호
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• pp.369-374
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• 2006

To characterize benzimidazole-resistant and -sensitive Monilinia fructicola populations, the fungal isolates were obtained from peach plants showing brown rot and bloosom blight. Benzimidazole-sensitive isolates did not grow on potato dextrose agar(PDA) amended with $\geq1.0{\mu}g$ active ingredient(a.i.)/ml of the fungicides. However, benzimidazole-resistant isolates grew on PDA regardless of the tested concentrations of fungicides. Benzimidazole-resistant isolates did not grow on diethofencarb-PDA, but sensitive isolates grew on the same PDA. In the nucleotide sequences of $\beta$-tubulin gene, only codon 198(GAG: glutamic acid), a target site for benzimidazole, was replaced with GCG(alanine) in all of the resistant isolates, and this substitution seems to play an important role in the development of resistance. Other interesting codons such as 165(GCT), 200(TTC), and 241(GCT) were not changed among the isolates. Benzimidazole-resistant and -sensitive isolates were clustered clearly in random amplified polymerphic DNA analyses and the results revealed that low levels of genetic diversity between benzimidazole-sensitive and -resistant isolates of M. fructicola in the investigated regions.

• Molecules and Cells
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• 제20권1호
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• pp.1-16
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• 2005

The peptidyl transferase center (PTC) is located in a protein free environment, thus confirming that the ribosome is a ribozyme. This arched void has dimensions suitable for accommodating the 3'ends of the A-and the P-site tRNAs, and is situated within a universal sizable symmetry-related region that connects all ribosomal functional centers involved in amino-acid polymerization. The linkage between the elaborate PTC architecture and the A-site tRNA position revealed that the A-to P-site passage of the tRNA 3'end is performed by a rotatory motion, which leads to stereochemistry suitable for peptide bond formation and for substrate mediated catalysis, thus suggesting that the PTC evolved by genefusion. Adjacent to the PTC is the entrance of the protein exit tunnel, shown to play active roles in sequence-specific gating of nascent chains and in responding to cellular signals. This tunnel also provides a site that may be exploited for local co-translational folding and seems to assist in nascent chain trafficking into the hydrophobic space formed by the first bacterial chaperone, the trigger factor. Many antibiotics target ribosomes. Although the ribosome is highly conserved, subtle sequence and/or conformational variations enable drug selectivity, thus facilitating clinical usage. Comparisons of high-resolution structures of complexes of antibiotics bound to ribosomes from eubacteria resembling pathogens, to an archaeon that shares properties with eukaryotes and to its mutant that allows antibiotics binding, demonstrated the unambiguous difference between mere binding and therapeutical effectiveness. The observed variability in antibiotics inhibitory modes, accompanied by the elucidation of the structural basis to antibiotics mechanism justifies expectations for structural based improved properties of existing compounds as well as for the development of novel drugs.

• Mycobiology
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• 제38권3호
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• pp.215-218
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• 2010

Azoles are currently the most widely used class of antifungal drugs clinically, and are effective for treating fungal infections. Target site of azoles is ergosterol biosynthesis in fungal cell membrane, which is absent in the mammalian host. However, the development of resistance to azole treatments in the fungal pathogen has become a significant challenge. Here, we report the identification and functional characterization of a UPC2 homolog in the human pathogen Cryptococcus neoformans. UPC2 plays roles in ergosterol biosynthesis, which is also affected by the availability of iron in Saccharomyces cerevisiae and Candida albicans. C. neoformans mutants lacking UPC2 were constructed, and a number of phenotypic characteristics, including antifungal susceptibility and iron utilization, were analyzed. No differences were found between the mutant phenotypes and wild type, suggesting that the role of C. neoformans UPC2 homolog may be different from those in S. cerevisiae and C. albicans, and that the gene may have a yet unknown function.

• BMB Reports
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• 제46권3호
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• pp.131-138
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• 2013

During cancer progression, bone marrow derived myeloid cells, including immature myeloid cells and macrophages, progressively accumulate at the primary tumour site where they contribute to the establishment of a tumour promoting microenvironment. A marked infiltration of macrophages into the stromal compartment and the generation of a desmoplastic stromal reaction is a particular characteristic of pancreatic ductal adenocarcinoma (PDA) and is thought to play a key role in disease progression and its response to therapy. Tumour associated macrophages (TAMs) foster PDA tumour progression by promoting angiogenesis, metastasis, and by suppressing an anti-tumourigenic immune response. Recent work also suggests that TAMs contribute to resistance to chemotherapy and to the emergence of cancer stem-like cells. Here we will review the current understanding of the biology and the pro-tumourigenic functions of TAMs in cancer and specifically in PDA, and highlight potential therapeutic strategies to target TAMs and to improve current therapies for pancreatic cancer.

• 미생물학회지
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• 제27권4호
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• pp.317-322
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• 1989

A gene can be selectively overexpressed in E. coli by utilizing the phage T7 RNA polymerase's stringent recognition and active transcription of the T7 promoter. The T7 expression system was constructed such that the T7 RNA polymerase gene is under the control of lacUV5 promoter in one plasmid, and that the target gene, the promoterless chloramphenicol acetyltransferase (CAT) gene with E. coli ribosome binding site is under the control of T7 promoter in the other plasmid. Only the E. coli cells containing both plasmids show high resistance to chloramphenicol. When the copy number of the runaway plasmid containing the polymerase gene was varied by a temperature shift, amounts of the CAT protein synthesized upon induction was correspondingly changed as shown in SDS gel electrophoresis.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.51-55
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• 2016

Phytochemical investigation of Pistacia integerrima has highlighted isolation of two known compounds naringenin (1) and dihydrokaempferol (2). A crude extract and these isolated compounds were here evaluated for their effects on reversion of multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). The multidrug resistance P-glycoprotein is a target for chemotherapeutic drugs from cancer cells. In the present study rhodamine-123 exclusion screening test on human mdr1 gene transfected mouse gene transfected L5178 and L5178Y mouse T-cell lymphoma cells showed excellent MDR reversing effects in a dose dependent manner. In-silico molecular docking investigations demonstrated a common binding site for Rhodamine123, and compounds naringenin and dihydrokaempferol. Our results showed that the relative docking energies estimated by docking softwares were in satisfactory correlation with the experimental activities. Preliminary interaction profile of P-gp docked complexes were also analysed in order to understand the nature of binding modes of these compounds. Our computational investigation suggested that the compounds interactions with the hydrophobic pocket of P-gp are mainly related to the inhibitory activity. Moreover this study s a platform for the discovery of novel natural compounds from herbal origin, as inhibitor molecules against the P-glycoprotein for the treatment of cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3123-3128
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• 2014

The liver is normally the major site of glucose metabolism in intact organisms and the most important target organ for the action of insulin. It has been widely accepted that insulin resistance (IR) is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). However, the relationship between IR and drug resistance in liver cancer cells is unclear. In the present study, IR was induced in HepG2 cells via incubation with a high concentration of insulin. Once the insulin-resistant cell line was established, the stability of HepG2/IR cells was further tested via incubation in insulin-free medium for another 72h. Afterwards, the biological effects of insulin resistance on adhesion, migration, invasion and sensitivity to cis-platinum (DDP) of cells were determined. The results indicated that glucose consumption was reduced in insulin-resistant cells. In addition, the expression of the insulin receptor and glucose transportor-2 was downregulated. Furthermore, HepG2/IR cells displayed markedly enhanced adhesion, migration, and invasion. Most importantly, these cells exhibited a lower sensitivity to DDP. By contrast, HepG2/IR cells exhibited decreased adhesion and invasion after treatment with the insulin sensitizer pioglitazone hydrochloride. The results suggest that IR is closely related to drug resistance as well as adhesion, migration, and invasion in HepG2 cells. These findings may help explain the clinical observation of limited efficacy for chemotherapy on a background of IR, which promotes the invasion and migration of cancer cells.