• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.348-352
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• 2009

Over the last decade, the incidence of overweight and obesity has nearly doubled in many countries and is considered a pandemic. Obesity was identified as a major risk factor for cardiovascular disease as the same level as smoking and diabetes. Visceral fat is considered one of the key contributors to outcome and certain ethnic groups such as Asians seem to be more affected than others. Weight reduction through lifestyle changes was found to be impactful to improve overall health, but weight loss and maintenance thereof is limited and difficult to sustain. Surgical intervention demonstrated a greater weight loss in the severely obese and was associated with improved all-cause mortality. Despite numerous pharmacological targets and a high medical need, only few drugs have been successfully developed. Earlier studies with amphetamine-derived compounds showed significant weight loss but their critical safety profiles led to market withdrawals and disappointment. More recent compounds; orlistat - a lipase inhibitor, rimonabant - a cannaboid-1-receptor antagonist, and sibutramine - a combined serotonin/norepinephrine re-uptake inhibitor, all demonstrated similar significant efficacy; however, they carry specific safety profiles making them unsuitable for every patient. The main limitation of pharmacotherapy is the absence of clear benefit-risk assessments through outcome studies. Such a study - the SCOUT trial - was designed to compare sibutramine versus placebo and the effect on morbidity and mortality in nearly 10,000 obese patients with additional risk factors. Such studies could provide new scientific evidence for obesity treatment and may support future pharmacological approaches.

• CELLMED
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• v.2 no.3
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• pp.27.1-27.6
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• 2012

Red ginseng, which has a variety of biological and pharmacological activities including antioxidant, anti-inflammatory, antimutagenic and anticarcinogenic effects, has been used for thousands of years as a general tonic in traditional oriental medicine. Here, we tested the immune regulatory activities of hydrolyzed red ginseng by malted barley (HRG) on the expressions of receptor interacting proteins (Rip) 2 and $I{\kappa}B$ kinase-beta (IKK-${\beta}$) in mouse peritoneal macrophages. We show that HRG increased the activations of Rip 2 and IKK-${\beta}$ for the first time. When HRG was used in combination with recombinant interferon-${\gamma}$ (rIFN-${\gamma}$), there was a marked cooperative induction of nitric oxide (NO) production. The increased expression of inducible NO synthase from rIFN-${\gamma}$ plus HRG-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor-${\kappa}B$ (NF-${\kappa}B$). In addition, the treatment of peritoneal macrophages with rIFN-${\gamma}$ plus HRG caused significant increases in tumor necrosis factor (TNF)-${\alpha}$ mRNA expression and production. Because NO and TNF-${\alpha}$ play an important role in the immune function and host defense, HRG treatment can modulate several aspects of the host defense mechanisms as a result of the stimulations of the inducible nitric oxide synthase and NF-${\kappa}B$. In conclusion, our findings demonstrate that HRG increases the productions of NO and TNF-${\alpha}$ from rIFN-${\gamma}$-primed macrophages and suggest that Rip2/IKK-${\beta}$ plays a critical role in mediating these immune regulatory effects of HRG.

• The Journal of the Korean Society for Microbiology
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• v.34 no.5
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• pp.435-443
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• 1999

Orientia tsutsugamushi is obligate intracellular bacterium that grows within the cytoplasm of the eukaryotic host cells. Therefore capability of the attachment, entry into the host cell and intracellular survival should be critical process for oriential infection. In this study we investigated the cellular invasion mechanism of Orientia tsutsugamushi and the role of transmembrane heparan sulfate proteoglycan, which binds diverse components at the cellular microenvironment and is implicated as host cell receptors for a variety of microbial pathogens. First of all Orientia tsutsugamushi can invade a wide range of nonprofessional phagocytic cells including fibroblast, epithelial cells and endothelial cells of various host species, including Band T lymphocytes. Thus, it was postulated that the attachment of O. tsutsugamushi requires the recognition of ubiquitous surface structures of many kinds of host cells. Treatments with heparan sulfate and heparin inhibited the infection of Orientia tsutsugamushi in dose-dependent manner for L cell, mouse fibroblast, whereas other glycosaminoglycans such as chondroitin sulfate had no effect. Collectively, these findings provide strong evidence that initial interaction with heparan sulfate proteoglycan is required for the oriential invasion into host cells.

• Nutrition Research and Practice
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• v.4 no.4
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• pp.259-269
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• 2010

Resistance training (RT) is associated with reduced risk of low grade inflammation related diseases, such as cardiovascular disease and type 2 diabetes. The majority of the data studying cytokines and exercise comes from endurance exercise. In contrast, evidence establishing a relationship between RT and inflammation is more limited. This review focuses on the cytokine responses both following an acute bout, and after chronic RT. In addition, the effect of RT on low grade systemic inflammation such as individuals at risk for type 2 diabetes is reviewed. Cytokines are secreted proteins that influence the survival, proliferation, and differentiation of immune cells and other organ systems. Cytokines function as intracellular signals and almost all cells in the body either secrete them or have cytokine receptors. Thus, understanding cytokine role in a specific physiological situation such as a bout of RT can be exceedingly complex. The overall effect of long term RT appears to ameliorate inflammation, but the specific effects on the inflammatory cytokine, tumor necrosis factor alpha are not clear, requiring further research. Furthermore, it is critical to differentiate between chronically and acute Interleukin-6 levels and its sources. The intensity of the RT and the characteristics of the training protocol may exert singular cytokine responses and as a result different adaptations to exercise. More research is needed in the area of RT in healthy populations, specifically sorting out gender and age RT acute responses. More importantly, studies are needed in obese individuals who are at high risk of developing low grade systemic inflammatory related diseases. Assuring adherence to the RT program is essential to get the benefits after overcoming the first acute RT responses. Hence RT could be an effective way to prevent, and delay low grade systemic inflammatory related diseases.

• Journal of Environmental Science International
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• v.19 no.8
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• pp.971-981
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• 2010

The objectives of this study were to measure ambient total gaseous mercury (TGM) concentrations in Seoul, to analyze the characteristics of TGM concentration, and to identify of possible source areas for TGM using back-trajectory based hybrid receptor models like PSCF (Potential Source Contribution Function) and RTWC (Residence Time Weighted Concentration). Ambient TGM concentrations were measured at the roof of Graduate School of Public Health building in Seoul for a period of January to October 2004. Average TGM concentration was $3.43{\pm}1.17\;ng/m^3$. TGM had no notable pattern according to season and meteorological phenomena such as rainfall, Asian dust, relative humidity and so on. Hybrid receptor models incorporating backward trajectories including potential source contribution function (PSCF) and residence time weighted concentration (RTWC) were performed to identify source areas of TGM. Before hybrid receptor models were applied for TGM, we analysed sensitivities of starting height for HYSPLIT model and critical value for PSCF. According to result of sensitivity analysis, trajectories were calculated an arrival height of 1000 m was used at the receptor location and PSCF was applied using average concentration as criterion value for TGM. Using PSCF and RTWC, central and eastern Chinese industrial areas and the west coast of Korea were determined as important source areas. Statistical analysis between TGM and GEIA grided emission bolsters the evidence that these models could be effective tools to identify possible source area and source contribution.

• Nutrition Research and Practice
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• v.14 no.2
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• pp.95-101
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• 2020

BACKGROUND/OBJECTIVES: Folate plays a critical role in DNA synthesis and methylation. Intracellular folate homeostasis is maintained by the enzymes folylpolyglutamate synthase (FPGS) and γ-glutamyl hydrolase (GGH). FPGS adds glutamate residues to folate upon its entry into the cell through a process known as polyglutamylation to enhance folate retention in the cell and to maintain a steady supply of utilizable folate derivatives for folate-dependent enzyme reactions. Thereafter, GGH catalyzes the hydrolysis of polyglutamylated folate into monoglutamylated folate, which can subsequently be exported from the cell. The objective of this review is to summarize the scientific evidence available on the effects of intracellular folate homeostasis-associated enzymes on cancer chemotherapy. METHODS: This review discusses the effects of FPGS and GGH on chemosensitivity to cancer chemotherapeutic agents such as antifolates, such as methotrexate, and 5-fluorouracil. RESULTS AND DISCUSSION: Polyglutamylated (anti)folates are better substrates for intracellular folate-dependent enzymes and retained for longer within cells. In addition to polyglutamylation of (anti)folates, FPGS and GGH modulate intracellular folate concentrations, which are an important determinant of chemosensitivity of cancer cells toward chemotherapeutic agents. Therefore, FPGS and GGH affect chemosensitivity to antifolates and 5-fluorouracil by altering intracellular retention status of antifolates and folate cofactors such as 5,10-methylenetetrahydrofolate, subsequently influencing the cytotoxic effects of 5-fluorouracil, respectively. Generally, high FPGS and/or low GGH activity is associated with increased chemosensitivity of cancer cells to methotrexate and 5-fluorouracil, while low FPGS and/or high GGH activity seems to correspond to resistance to these drugs. Further preclinical and clinical studies elucidating the pharmocogenetic ramifications of these enzyme-induced changes are warranted to provide a framework for developing rational, effective, safe, and customized chemotherapeutic practices.

• International Journal of Highway Engineering
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• v.16 no.5
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• pp.109-119
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• 2014

PURPOSES : The control delay in seconds per vehicle is the most important traffic operational index to evaluate the level of service of signalized intersections. Thus, it is very critical to calculate accurate control delay because it is used as a basic quantitative evidence for decision makings regarding to investments on traffic facilities. The control delay consists of time-in-queue delay, acceleration delay, and deceleration delay so that it is technically difficult to directly measure it from fields. Thus, diverse analysis tools, including CORSIM, SYNCHRO, T7F, VISTRO, etc. have been utilized so far. However, each analysis tool may use a unique methodology in calculating control delays. Therefore, the estimated values of control delays may be different by the selection of an analysis tool, which has provided difficulties to traffic engineers in making solid judgments. METHODS : This study was initiated to verify the feasibility of diverse analysis tools, including HCM methodology, CORSIM, SYNCHRO, T7F, VISTRO, in calculating control delays by comparing estimated control delays with that measured from a field. RESULTS : As a result, the selected tools produced quite different values of control delay. In addition, the control delay value estimated using a calibrated CORSIM model was closest to that measured from the field. CONCLUSIONS : First, through the in-depth experiment, it was explicitly verified that the estimated values of control delay may depend on the selection of an analysis tool. Second, among the diverse tools, the value of control delay estimated using the calibrated microscopic traffic simulation model was most close to that measured from the field. Conclusively, analysts should take into account the variability of control delay values according to the selection of a tool in the case of signalized intersection analysis.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.1-14
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• 2011

Tuberculosis is a disease with high morbidity and mortality in children worldwide. Despite the decrease in the incidence of tuberculosis in Korea, more than 30,000 new patients are diagnosed each year. Active tuberculosis is less frequent in children compared to adults but the risk of miliary tuberculosis and CNS tuberculosis is much higher. The diagnosis of tuberculosis in children and adolescents is difficult due to the nonspecific symptoms upon presentation. Diagnostic work up is based on the confirmation of tuberculosis infection by tuberculin skin test, abnormal radiologic findings, and contact with an adult with active tuberculosis. Anti-tuberculosis medications are prescribed according to the drug susceptibility of the index patient. Latent tuberculosis infection plays an important role in adult tuberculosis by reactivation. Thus, it is critical to accurately diagnose latent tuberculosis in children to prevent reactivation in adulthood. Korean guidelines for diagnosis and treatment of tuberculosis in children and adolescents provide evidence based recommendations in the optimal diagnosis and treatment for active and latent tuberculosis in children and adolescents based on the current Korean situation.

• Journal of Microbiology and Biotechnology
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• v.18 no.6
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• pp.1197-1202
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• 2008

Recent studies provide some evidence that the HtrA2 protein is intimately associated with the pathogenesis of neurodegenerative disorders and that endoplasmic reticulum (ER) quality control and ER stress-associated cell death play critical roles in neuronal cell death. However, little is known about the intimate relationship between HtrA2 and ER stress-associated cellular responses. In the present study, we have demonstrated that the HtrA2 protein level was gradually and significantly increased by up to to-fold in the mitochondria under tunicamycin (Tm)-induced ER stress, which eventually promoted cell death through the release of HtrA2 into the cytoplasm. Using an ecdysone-inducible mammalian expression system, we demonstrate that the extent of cell death in 293-HtrA2 cells was approximately 20 times higher under Tm-induced ER stress, indicating that the increase in the HtrA2 protein level in the mitochondria itself is necessary but not sufficient for the promotion of cell death. Taken together, these results suggest that HtrA2 may serve as a mediator of ER stress-induced apoptosis and ER-mitochondrial cross-talk in some cellular processes.

• Journal of Educational Research in Mathematics
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• v.15 no.2
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• pp.197-213
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• 2005

There are not a few mathematical terms used as the undefined terms in school mathematics. The purpose of this study is to investigate critically the undefined mathematical terms in elementary school mathematics textbooks of Korea. As the result, the following suggestions are proposed. Firstly, It is not proper to use the terms which mathematics curriculum does not allow to use in elementary school math as the undefined terms in elementary school mathematics textbooks. Secondly, everyday-based undefined terms must be defined in elementary school mathematics textbook if their mathematical meanings are different from their everyday-based meanings. Thirdly, we need to consider the consistency when we use the undefined terms in elementary school mathematics. Fourthly, undefined terms should be define newly when the contexts in which they are used are changed or expanded. Finally, in elementary school mathematics textbooks, it is needed to define some purely mathematical undefined terms that there is no evidence which shows students grasp well their meaning.