• Molecules and Cells
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• v.43 no.3
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• pp.236-250
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• 2020

Currently, many available anti-cancer therapies are targeting apoptosis. However, many cancer cells have acquired resistance to apoptosis. To overcome this problem, simultaneous induction of other types of programmed cell death in addition to apoptosis of cancer cells might be an attractive strategy. For this purpose, we initially investigated the inhibitory role of TRIP-Br1/XIAP in necroptosis, a regulated form of necrosis, under nutrient/serum starvation. Our data showed that necroptosis was significantly induced in all tested 9 different types of cancer cell lines in response to prolonged serum starvation. Among them, necroptosis was induced at a relatively lower level in MCF-7 breast cancer line that was highly resistant to apoptosis than that in other cancer cell lines. Interestingly, TRIP-Br1 oncogenic protein level was found to be very high in this cell line. Up-regulated TRIP-Br1 suppressed necroptosis by repressing reactive oxygen species generation. Such suppression of necroptosis was greatly enhanced by XIAP, a potent inhibitor of apoptosis. Our data also showed that TRIP-Br1 increased XIAP phosphorylation at serine87, an active form of XIAP. Our mitochondrial fractionation data revealed that TRIP-Br1 protein level was greatly increased in the mitochondria upon serum starvation. It suppressed the export of CypD, a vital regulator in mitochondria-mediated necroptosis, from mitochondria to cytosol. TRIP-Br1 also suppressed shikonin-mediated necroptosis, but not TNF-α-mediated necroptosis, implying possible presence of another signaling pathway in necroptosis. Taken together, our results suggest that TRIP-Br1/XIAP can function as onco-proteins by suppressing necroptosis of cancer cells under nutrient/serum starvation.

• Journal of Pharmacopuncture
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• v.22 no.1
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• pp.28-34
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• 2019

Background: Breast cancer is a complex, heterogeneous disease and one of the most common malignancies in women worldwide. The efficacy of chemotherapy as an important breast cancer treatment option has been severely limited because of the inherent or acquired resistance of cancer cells. The molecular chaperone heat shock protein 90 (HSP90) upregulated in response to cellular stress is required for functions such as conformational maturation, activation and stability in more than 200 client proteins, mostly of the signaling type. In this study, the expression of HSP90 isoforms including $HSP90{\alpha}$ and $HSP90{\beta}$ in breast cancer cell lines before and after treatment with doxorubicin (DOX) was assessed. Material and Methods: The cell cytotoxicity of DOX in MDA-MB-231 and MCF-7 cell lines was determined using the MTT assay. immunofluorescence and western blotting techniques were used to determine the expression of $HSP90{\beta}$ in the cell lines before and after DOX treatment. Immunofluorescence was also conducted to ascertain the expression of $HSP90{\alpha}$. Results: The MTT assay results showed that the MDA-MB-231 cells ($IC_{50}=14.521{\mu}M$) were more sensitive than the MCF-7 cells ($IC_{50}=16.3315{\mu}M$) to DOX. The immunofluorescence results indicated that the expression of $HSP90{\alpha}$ in both cell lines decreased after exposure to DOX. The western blot and immunofluorescence analyses showed that $HSP90{\beta}$ expression decreased in the MCF-7 cells but increased in the MDA-MB-231 cells after DOX treatment. Conclusion: The obtained results suggested that $HSP90{\alpha}$ and $HSP90{\beta}$ expression levels were reduced in the MCF-7 cells after exposure to DOX. In the MDA-MB-231 cells, $HSP90{\alpha}$ expression was reduced while $HSP90{\beta}$ was found to be overexpressed following DOX treatment.

• Nuclear Engineering and Technology
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• v.54 no.8
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• pp.3117-3129
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• 2022

Deeply understanding the phase change of thin liquid sodium film inside wick pore is very important for further studying high-temperature sodium heat pipe's heat transfer. For the first time, the evaporation and condensation of thin liquid sodium film are investigated by the Lennard-Jones potential of molecular dynamics. Based on the startup and normal operation of the sodium heat pipe, three different cases are simulated. First, the equilibrium is achieved and the Mass Accommodation Coefficients of the three cases are 0.3886, 0.2119, 0.2615 respectively. Secondly, the non-equilibrium is built. The change of liquid film thickness, the number of gas atoms, the net evaporation flux (J_net), the heat transfer coefficient (h) at the liquid-gas interface are acquired. Results indicate that the magnitude of the J_net and the h increase with the basic equilibrium temperature. In 520-600 K (the startup of the heat pipe), the h has approached 5-6 W m^-2 K^-1 while liquid film thickness is in 11-13 nm. The fact shows that during the initial startup of the sodium heat pipe, the thermal resistance at the liquid-gas interface can't be negligible. This work is the complement and extension for macroscopic investigation of heat transfer inside sodium heat pipe. It can provide a reference for further numerical simulation and optimal design of the sodium heat pipe in the future.

• Pediatric Infection and Vaccine
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• v.12 no.2
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• pp.140-148
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• 2005

Purpose : To characterize the epidemiology and clinical features of invasive pneumococcal infections in Korean children. Methods : One hundred ninety four cases of invasive pneumococcal infections diagnosed at the Seoul National University Children's Hospital from October 1985 to December 2003 were analysed retrospectively. All isolates were screened for resistance to penicillin by oxacillin disc diffusion test. Serotypes were determined for 125 isolates. Results : The types of infection were bacteremia without focus 84/194(43%), meningitis 36/194(19%), pneumonia with bacteremia 36/194(19%), peritonitis 24/194(12%), other focal infections 3/194(2%). Fifty seven percent(110/194) of the episodes developed in the immunocompromised and 20%(37/194) were nosocomially acquired. The patients younger than 2 years of age was 60% in the immunocompetent patients and 25% in the immunocompromised patients. The overall case fatality rate was 7%. All the isolates by 1988 were susceptible to penicillin screened by oxacillin disk. Penicillin resistance was first detected in 1989(20%), and then increased rapidly; 89% in 1995, 69% in 1996, and 80~100% thereafter. The seven most frequently isolated serotypes were 23F, 19F, 14, 6B, 6A, 9V and 19A, which accounted for 70% of total isolates. Conclusion : S. pneumoniaeis an important cause of morbidity and mortality in children. Invasive infections caused by S. pneumoniae most often occurred in infants and young children, while they are frequent in older immunocompromised children as well. This is the largest case series on invasive pneumococcal infections in Korean children.

• Journal of the Korea Concrete Institute
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• v.17 no.6 s.90
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• pp.947-953
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• 2005

Previous test results showed that the current ASTM(American Standard for Testing and Materials) grip adapter for GFRP(Glass Fiber Reinforced Polymer) rebar was not fully successful in developing the design tensile strength of GFRP rebars with reasonable accuracy. It is because the current ASTM grip adapter which is composed of a pair of rectangular metal blocks of which inner faces are grooved along the longitudinal direction does not take into account the various geometric characteristics of GFRP rebar such as surface treatment, shape of bar cross section as well as physical characteristics such as poisson effect, elastic modulus in the transverse direction and so on. The objective of this paper is to provide how to proportion the optimum diameter of inner groove in ASTM grip adapter to develop design tensile strength of GFRP rebar. The proportioning of inner groove in ASTM grip adapter is based on the force equilibrium of GFRP rebar between tensile capacity and minimum frictional resistance required along the grip adapter. The frictional resistance of grip adapter is calculated based on the compressive strain compatibility in radial direction induced by the difference between diameter of GFRP rebar and inner groove In ASTM grip. All testing procedures were made according to the CSA S806-02 recommendations. From the preliminary test results on round-type GFRP rebars, it was found that maximum tensile loads acquired under the same testing conditions is highly affected by the diameter of inner groove in ASTM grip adapter. The grip adapter with specific dimension proportioned by proposed method recorded the highest tensile strength among them.

• Childhood Kidney Diseases
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• v.10 no.1
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• pp.18-26
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• 2006

Purpose : Empirical antimicrobial treatment is indicated before bacteriological results are available for young children with febrile UTI to minimize renal scarring. To ensure appropriate therapy, knowledge of the prevalence of causative organisms and their susceptibility patterns to antimicrobials is mandatory. We performed a retrospective analysis investigating the local prevalence and resistance patterns of uropathogens, primarily E. coli, isolated from community-acquired UTIs. Methods : A total of 103 positive urine cultures from children with febrile UTI collected at Bundang CHA General Hospital from February 2004 to February 2005 were analyzed. Inclusion criteria were fever higher than $37.5^{\circ}C$, significant bacteriuria with single strain growth of at least 10s colony forming units/mL urine, and leukocyturia >5/HPF. Results : E. coli(89.3%) was the leading uropathogen followed by Enterococcus spp.(3.9%) Klebsiella spp.(2.9%), Citrobctcter spp.(1.9%) and Enterobacter spp.(1.9%). E. coli strains revealed a low proportion of antimicrobial susceptibility to ampicillin(AMP; 27.2%) ampicillinsulbactam(AMS; 34.8%) and trimethoprim-sulfamethoxazole(SXT; 65.2%). Susceptibility patterns to cephalosporins were as follows; cefazolin(1st generation; 91.3%), cefoxitin(2nd; 100%), ceftriaxone(3rd; 97.8%) and cefepime(4th; 97.8%). Three E. coli isolates produced ex tended - spectrum beta-lactamase(ESBL). Conclusion : Empirical treatment with AMP, AMS and SXT, which are commonly used in pediatric clinics, is not recommended for childhood UTI due to high incidence of resistance. The high level of susceptibility to cephalosporins makes these drugs reasonable alternatives. However the emergence of ESBL-producers, even though they are quite few, may have an impact on cephalosporin treatment in the future. (J Korean Soc Pediatr Nephrol 2006;10:18-26)

• Journal of Plant Biotechnology
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• v.35 no.3
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• pp.169-176
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• 2008

Salicylic acid(SA) is a phytohormone that is related to plant defense mechanism. The SA accumulation is triggered by abiotic and biotic stresses. SA acts as a signal molecular compound mediating systemic acquired resistance and hypersensitive response in plant. Although the role of SA has been studied extensively, an understanding of the SA regulatory mechanism is still lacking in plants. In order to comprehend SA regulatory mechanism, we have been transformed with a SID2 promoter:GUS::LUC fusion construct into siz1-2 mutant and wild plant(Col-0). SIZ1 encodes SUMO E3 ligase and negatively regulates SA accumulation in plants. SID2(SALICYLIC ACID INDUCTION DEFICIENT2) is a crucial enzyme of SA biosynthesis. The Arabidopsis SID2 gene encodes isochorismate synthase(ICS) that controls SA level by conversion of chorismate to isochorismate. We compared the regulation of SID2 in wild-type and siz1-2 transgenic plants that express SID2 promoter:GUS::LUC constructs respectively. The expressions of $\beta$-GLUCURONIDASE and LUCIFERASE were higher in siz 1-2 transgenic plant without any stress treatment. SID2 promoter:GUS::LUC/siz1-2 transgenic plant will be used as a starting material for isolation of siz1-2 suppressor mutants and genes involved in SA-mediated stress signaling pathway.

• Childhood Kidney Diseases
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• v.16 no.1
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• pp.38-45
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• 2012

Purpose: The incidence of community-acquired urinary tract infection (UTI) due to extended-spectrum ${\beta}$-lactamase producing $Escherichia$ $coli$ (ESBL(+) $E.$ $coli$) has increased worldwide. ESBL causes resistance to various types of the newer ${\beta}$-lactam antibiotics, including the expanded spectrum cephalosporins and monobactams. We aimed to investigate the severity of UTI and associated genitourinary malformations in children with febrile UTI caused by ESBL(+) $E.$ $coli$. Methods: We retrospectively reviewed the medical records of 290 patients diagnosed as febrile UTI caused by $E.$ $coli$ between January 2008 and October 2010 at Korea University Medical center. We classified the patients into two groups with ESBL(+) and ESBL(-) $E.$ $coli$ group according to the sensitivity of urine culture. Fever duration, admission period, white blood cell (WBC) counts and C-reactive protein (CRP) in peripheral blood, the presence of hydronephrosis, cortical defects, vesicoureteral reflux (VUR) and renal scar were compared between the two groups. Results: Patients with ESBL(+) $E.$ $coli$ were 32, and those with ESBL(-) $E.$ $coli$ were 258. If we excluded those tested with a sterile urine bag, patients with ESBL(+) $E.$ $coli$ were 22, and those with ESBL(-) $E.$ $coli$ were 212. Whether the results of sterile urine bag tests were included or not, there was no significant difference in all parameters between the two groups statistically. Conclusion: Our data shows that ESBL(+) $E.$ $coli$ may not be related to the severity of UTI and associated genitourinary malformations.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.31-39
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• 2011

Purpose : This study was performed for the purpose of finding causative organisms and clinical features of septic arthritis or acute osteomyelitis in children. Methods : The study involved a retrospective review of the medical records of 63 microbiologically confirmed cases of acute pyogenic arthritis and osteomyelitis. All of the cases were brought about by community-associated infections and managed at the Seoul National University Children's Hospital or Seoul National University Bundang Hospital from June 2003 to July 2009. Results : The median age of all cases was 60 months and there were 35 males and 28 females. Major involved joints included the hip joint (15 cases), knee joint (7 cases), shoulder joint (4 cases), and elbow joint (4 cases). Also, major involved bones included the femur (20 cases), tibia (13 cases), humerus (7 cases), and radius (7 cases). Staphylococcus aureus was the most commonly identified causative organism, accounting for 49 cases (77.8%). Of the 49 isolates of S. aureus, methicillin-resistant S. aureus (MRSA) accounted for 8 cases (16.3%). Group B streptococcus spp. (GBS) and Salmonella spp. accounted for 3 cases, respectively. Nafcillin or cefazolin was often prescribed as an initial empirical antibiotic. There were 9 cases that were managed by a regimen that included vancomycin as the first choice. Fifty four cases (85.7%) recovered without any complications. Methicillin-sensitive S. aureus (MSSA), responsible for 41 cases, caused chronic complications in 3 cases. Of 8 cases caused by MRSA, 1 case showed chronic complication. There were no fatal cases. Conclusion : S. aureus remains the most common organism causing acute pyogenic arthritis and osteomyelitis of childhood acquired in the community. The high prevalence of methicillin resistance among S. aureus should be considered carefully in the selection of initial empirical antibiotics.

• KSBB Journal
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• v.20 no.5 s.94
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• pp.376-382
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• 2005

Avermectin (AVM) $B_{1a}$ produced by Streptomyces avermitilis via polyketide pathway is a secondary metabolite with powerful anthelmintic and insecticidal activities, thus being used as an efficient agent in the field of agriculture and animal health. It has been reported that a precursor for AVM $B_{1a}$ biosynthesis was isoleucine and the biosynthetic pathway of AVM $B_{1a}$ was closely similar to that of fatty acid. Based on understanding of the biosynthetic pathway of AVM $B_{1a}$, we intended to screen various mutants resistant against O-methyl threonine (OMT), an isoleucine-anti metabolite, and/or mutants resistant against p-fluoro phenoxy acetic acid (pFAC), an inhibitor of fatty acid biosynthesis. It was inferred that these mutants could produce AVM $B_{1a}$ more efficiently, due to the acquired capability of not only overproducing isoleucine intracellularly but also channelling metabolized carbon-sources into the polyketide pathway, thus leading to enhanced biosynthesis of AVM $B_{1a}$. The resulting mutant (PFA-1 strain) resistant against 100 ppm of pFAC was able to produce approximately 42 fold higher amount of AVM $B_{1a}$ compared to the parallel mother strain (4,200 vs. 100 units/l). In addition, through the process of continuous strain improvement program carried out by gradually increasing the OMT concentration, it was possible to obtain a more attractive mutant with greater AVM $B_{1a}$ production capacity (9,000 units/l). Notable was that significantly higher producer (12,000 units/l) could be selected through further screening of the resistant mutants, this time, to even higher concentration of PFAC. Meanwhile, through the analysis of AVM Bla production histograms (i.e., number of strains according to their AVM $B_{1a}$ biosynthetic ability) for the earlier strains in comparison with the high producers having the characteristics of resistance to OMT and pFAC, it was found that production stability of the high-yielding producers were remarkably improved, as demonstrated by the fact that larger proportion of the mutated strains had greater capability of AVM $B_{1a}$ biosynthesis ($71\%$ in the range between 5,000 and 7,000 units/L; $47\%$ in the range between 6,000 and 7,000 units/l). Based on these consequences, it was concluded that the rational screening strategy based on the understanding of the biosynthetic pathway of AVM $B_{1a}$ was very effective in obtaining high-yielding mutants with the features of enhanced production stability.