• Proceedings of the Korean Society for Bioinformatics Conference
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• 2000.11a
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• pp.74-82
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• 2000

Prostate cancer initially responds and regresses in response to androgen depletion therapy, but most human prostate cancers will eventually recur, and re-grow as an androgen independent tumor. Once these tumors become hormone refractory, they usually are incurable leading to death for the patient. Little is known about the molecular details of how prostate cancer cells regress following androgen ablation and which genes are involved in the androgen independent growth following the development of resistance to therapy. Such knowledge would reveal putative drug targets useful in the rational therapeutic design to prevent therapy resistance and control androgen independent growth. The application of genome scale technologies have permitted new insights into the molecular mechanisms associated with these processes. Specifically, we have applied functional genomics using high density cDNA microarray analysis for parallel gene expression analysis of prostate cancer in an experimental xenograft system during androgen withdrawal therapy, and following therapy resistance, The large amount of expression data generated posed a formidable bioinformatics challenge. A novel template based gene clustering algorithm was developed and applied to the data to discover the genes that respond to androgen ablation. The data show restoration of expression of androgen dependent genes in the recurrent tumors and other signaling genes. Together, the discovered genes appear to be involved in prostate cancer cell growth and therapy resistance in this system. We have also developed and applied tissue microarray (TMA) technology for high throughput molecular analysis of hundreds to thousands of clinical specimens simultaneously. TMA analysis was used for rapid clinical translation of candidate genes discovered by cDNA microarray analysis to determine their clinical utility as diagnostic, prognostic, and therapeutic targets. Finally, we have developed a bioinformatic approach to combine pharmacogenomic data on the efficacy and specificity of various drugs to target the discovered prostate cancer growth associated candidate genes in an attempt to improve current therapeutics.

• Composites Research
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• v.16 no.2
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• pp.62-67
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• 2003

Interfacial properties and damage sensing for the carbon fiber/epoxy-amine terminated (AT)-polyetherimide (PEI) composite were performed using microdroplet test and electrical resistance measurements. As AT-PEI content increased, the fracture toughness of epoxy-AT-PEI matrix increased, and interfacial shear strength (IFSS) increased due to the improved fracture toughness by energy absorption mechanisms of AT-PEI phase. The microdroplet in the carbon fiber/neat epoxy composite showed brittle microfailure mode. At 15 phr AT-PEI content ductile microfailure mode appeared because of improved fracture toughness. After curing, the change in electrical resistance $\Delta\textrm{R}$) with increasing AT-PEI content increased gradually because of thermal shrinkage. Under cyclic stress, in the neat epoxy case the reaching time until same stress was faster and their slope was higher than those of 15 phr AT-PEI. The result obtained from electrical resistance measurements under curing process and reversible stress/strain was correspondence well with matrix toughness properties.

• Molecules and Cells
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• v.39 no.12
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• pp.869-876
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• 2016

Cantharidin (CTD) is an active compound isolated from the traditional Chinese medicine blister beetle and displayed anticancer properties against various types of cancer cells. However, little is known about its effect on human chronic myeloid leukemia (CML) cells, including imatinib-resistant CML cells. The objective of this study was to investigate whether CTD could overcome imatinib resistance in imatinib-resistant CML cells and to explore the possible underlying mechanisms associated with the effect. Our results showed that CTD strongly inhibited the growth of both imatinib-sensitive and imatinib-resistant CML cells. CTD induced cell cycle arrest at mitotic phase and triggered DNA damage in CML cells. The ATM/ATR inhibitor CGK733 abrogated CTD-induced mitotic arrest but promoted the cytotoxic effects of CTD. In addition, we demonstrated that CTD downregulated the expression of the BCR-ABL protein and suppressed its downstream signal transduction. Real-time quantitative PCR revealed that CTD inhibited BCR-ABL at transcriptional level. Knockdown of BCR-ABL increased the cell-killing effects of CTD in K562 cells. These findings indicated that CTD overcomes imatinib resistance through depletion of BCR-ABL. Taken together, CTD is an important new candidate agent for CML therapy.

• Korean Journal of Acupuncture
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• v.32 no.3
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• pp.116-123
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• 2015

Objectives : The present study was designed to investigate effects and molecular mechanisms of Atractylodes macrocephala Koidzumi extracts(AMK) on the improvement of adipocyte dysfunction induced by TNF-${\alpha}$ in 3T3-L1 adipocytes. We examined whether AMK could directly influence the inflammation and insulin resistance in 3T3-L1 adipocytes. Methods : Potential roles of AMK in the lipolysis, production of inflammatory adipokines and ROS, expression and phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein, and expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ were investigated in this study. Results : Our data demonstrated that TNF-${\alpha}$ significantly increased lipolysis, levels of MCP-1, IL-6, and ROS and phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein, while TNF-${\alpha}$ reduced the expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ in adipocytes, suggesting that TNF-${\alpha}$ induced a condition with the occurrence of inflammation and insulin resistance. Those alterations induced by TNF-${\alpha}$ were prevented by the treatment of AMK. AMK down-regulated the phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein and up-regulated the expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ on TNF-${\alpha}$-induced inflammation and insulin resistance. Conclusions : Thus, our results indicate that AMK can be used to prevent from the TNF-${\alpha}$-induced adipocyte dysfunction through MAPK, $NF{\kappa}B$ and $PPAR{\gamma}$ pathways.

• Journal of Microbiology
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• v.45 no.4
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• pp.286-290
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• 2007

The purpose of this study was to investigate the prevalence and genetic mechanisms of erythromycin resistance in staphylococci. A total of 102 erythromycin resistant non-duplicate clinical isolates of staphylococci [78. coagulase negative stapylococci (CNS), 24 Staphylococcus aureus] were collected between October 2003 and August 2004 in Istanbul Faculty of Medicine in Turkey. The majority of the isolates were from blood and urine specimens. Antimicrobial susceptibilities were determined by the agar dilution procedure and the resistance phenotypes by the double disk induction test. A multiplex PCR was performed, using primers specific for erm(A), erm(B), erm(C), and msrA genes.. Among the 78 CNS isolates, 57.8% expressed the $MLS_{B}-constitutive$, 20.6% the $MLS_{B}-inducible$, and 21.6% the $MS_B$ phenotypes. By PCR, 78.2% of these isolates harbored the erm(C) gene, 8.9% erm(A), 6.4% erm(B), and 11.5% msrA genes. In S. aureus, the constitutive $MLS_B$ (58.3 %) was more common than the inducible phenotype (20.8%). erm(A) was detected in 50% and erm(C) in 62.5% of the isolates, while 37.5% contained both erm(A) and erm(C). erm(C)-associated macrolide resistance was the most prevalent in CNS, while ermC) and erm(A, C) was the most prevalent in S. aureus.

• Membrane and Water Treatment
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• v.1 no.4
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• pp.297-316
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• 2010

Membrane fouling is one of the major operational concerns of membrane processes which results in loss of productivity. This paper investigates the ultrafiltration (UF) results of synthetic oil-in-water (o/w) emulsion using flat sheets of polysulfone (PSf) membrane synthesized with four different compositions. The aim is to identify the mechanisms responsible for the observed permeate flux reduction with time for different PSf membranes. The experiments were carried out at four transmembrane pressures i.e., 68.9 kPa, 103.4 kPa, 137.9 kPa and 172.4 kPa. Three initial oil concentrations i.e., 75 $mgL^{-1}$, 100 $mgL^{-1}$ and 200 $mgL^{-1}$ were considered. The resistance-in-series (RIS) model was applied to interpret the data and on that basis, the individual resistances were evaluated. The significances of these resistances were studied in relation to parameters, namely, transmembrane pressure and initial oil concentration. The total resistance to permeate flow is found to increase with increase in both transmembrane pressure and initial oil concentration while for higher oil concentration, resistance due to concentration polarization is found to be the prevailing resistance. The applicability of the constant pressure filtration models to the experimental data was also tested to explain the blocking process. The study shows that intermediate pore blocking is the dominant mechanism at the initial period of UF while in the later period, the fouling process is found to approach cake filtration like mechanism. However, the duration of pore blocking mechanism is different for different membranes depending on their morphological and permeation properties.

• The Plant Pathology Journal
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• v.37 no.4
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• pp.315-328
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• 2021

Fusarium and Rhizoctonia genera are important pathogens of many field crops worldwide. They are constantly evolving and expanding their host range. Selecting resistant cultivars is an effective strategy to break their infection cycles. To this end, we screened a collection of Medicago truncatula accessions against Fusarium oxysporum, Fusarium solani, and Rhizoctonia solani strains isolated from different plant species. Despite the small collection, a biodiversity in the disease response of M. truncatula accessions ranging from resistant phenotypes to highly susceptible ones was observed. A17 showed relative resistance to all fungal strains with the lowest disease incidence and ratings while TN1.11 was among the susceptible accessions. As an initiation of the characterization of resistance mechanisms, the antioxidant enzymes' activities, at the early stages of infections, were compared between these contrasting accessions. Our results showed an increment of the antioxidant activities within A17 plants in leaves and roots. We also analyzed the responses of a population of recombinant inbred lines derived from the crossing of A17 and TN1.11 to the infection with the same fungal strains. The broad-sense heritability of measured traits ranged from 0.87 to 0.95, from 0.72 to 0.96, and from 0.14 to 0.85 under control, F. oxysporum, and R. solani conditions, respectively. This high estimated heritability underlines the importance of further molecular analysis of the observed resistance to identify selection markers that could be incorporated into a breeding program and thus improving soil-borne pathogens resistance in crops.

• Biomolecules & Therapeutics
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• v.29 no.4
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• pp.419-426
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• 2021

In this study, we aimed to investigate the effects of 8 weeks of treatment with a combination of evogliptin and leucine, a branched-chain amino acid, in mice with high-fat diet (HFD)-induced diabetes. Treatment with evogliptin alone or in combination with leucine reduced the body weight of the mice, compared to the case for those from the HFD control group. Long-term treatment with evogliptin alone or in combination with leucine resulted in a significant reduction in glucose intolerance; however, leucine alone did not affect postprandial glucose control, compared to the case for the mice from the HFD control group. Furthermore, the combination of evogliptin and leucine prevented HFD-induced insulin resistance, which was associated with improved homeostasis model assessment for insulin resistance, accompanied by markedly reduced liver fat deposition, hepatic triglyceride content, and plasma alanine aminotransferase levels. The combination of evogliptin and leucine increased the gene expression levels of hepatic peroxisome proliferator-activated receptor alpha, whereas those of the sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1 were not altered, compared to the case in the HFD-fed mice (p<0.05). Thus, our results suggest that the combination of evogliptin and leucine may be beneficial for treating patients with type 2 diabetes and hepatic steatosis; however, further studies are needed to delineate the molecular mechanisms underlying the action of this combination.

• Journal of Korean Society of Water and Wastewater
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• v.35 no.6
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• pp.425-436
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• 2021

In this study, chemically enhanced steam cleaning(CESC) was applied as a novel and efficient method for the control of organic and inorganic fouling in ceramic membrane filtration. The constant filtration regression model and the resistance in series model(RISM) were used to investigate the membrane fouling mechanisms. For total filtration, the coefficient of determination(R²) with an approximate value of 1 was obtained in the intermediate blocking model which is considered as the dominant contamination mechanism. In addition, most of the coefficient values showed similar values and this means that the complex fouling was formed during the filtration period. In the RISM, R _c/R _f increased about 4.37 times in chemically enhanced steam cleaning compared to physical backwashing, which implies that the internal fouling resistance was converted to cake layer resistance, so that the membrane fouling hardly to be removed by physical backwashing could be efficiently removed by chemically enhanced steam cleaning. The results of flux recovery rate showed that high-temperature steam may loosen the structure of the membrane cake layer due to the increase in diffusivity and solubility of chemicals and finally enhance the cleaning effect. As a consequence, it is expected that chemically enhanced steam cleaning can drastically improve the efficiency of membrane filtration process when the characteristics of the foulant are identified.

• Steel and Composite Structures
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• v.46 no.6
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• pp.773-791
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• 2023

Connections with damage concentrated to pre-selected components can enhance seismic resilience for moment resisting frames. These pre-selected components always yield early to dissipate energy, and their energy dissipation mechanisms vary from one to another, depending on their position in the connection, geometry configuration details, and mechanical characteristics. This paper presents behaviour insights on two types of beam-to-beam connections that the angles were designed as energy dissipation components, through the results of experimental study and finite element analysis. Firstly, an experimental programme was reviewed, and key responses concerning the working mechanism of the connections were presented, including strain distribution at the critical section, section force responses of essential components, and initial stiffness of test specimens. Subsequently, finite element models of three specimens were established to further interpret their behaviour and response that were not observable in the tests. The moment and shear force transfer paths of the composite connections were clarified through the test results and finite element analysis. It was observed that the bending moment is mainly resisted by axial forces from the components, and the dominant axial force is from the bottom angles; the shear force at the critical section is primarily taken by the slab and the components near the top flange. Lastly, based on the insights on the load transfer path of the composite connections, preliminary design recommendations are proposed. In particular, a resistance requirement, quantified by a moment capacity ratio, was placed on the connections. Design models and equations were also developed for predicting the yield moment resistance and the shear resistance of the connections. A flexible beam model was proposed to quantify the shear resistance of essential components.