• Genomics & Informatics
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• 제11권4호
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• pp.245-253
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• 2013

A radioresistant cell line was established by fractionated ionizing radiation (IR) and assessed by a clonogenic assay, flow cytometry, and Western blot analysis, as well as zymography and a wound healing assay. Microarray was performed to profile global expression and to search for differentially expressed genes (DEGs) in response to IR. H460R cells demonstrated increased cell scattering and acidic vesicular organelles compared with parental cells. Concomitantly, H460R cells showed characteristics of increased migration and matrix metalloproteinase activity. In addition, H460R cells were resistant to IR, exhibiting reduced expression levels of ionizing responsive proteins (p-p53 and ${\gamma}$-H2AX); apoptosis-related molecules, such as cleaved poly(ADP ribose) polymerase; and endoplasmic reticulum stress-related molecules, such as glucose-regulated protein (GRP78) and C/EBP-homologous protein compared with parental cells, whereas the expression of anti-apoptotic X-linked inhibitor of apoptosis protein was increased. Among DEGs, syntrophin beta 2 (SNTB2) significantly increased in H460R cells in response to IR. Knockdown of SNTB2 by siRNA was more sensitive than the control after IR exposure in H460, H460R, and H1299 cells. Our study suggests that H460R cells have differential properties, including cell morphology, potential for metastasis, and resistance to IR, compared with parental cells. In addition, SNTB2 may play an important role in radioresistance. H460R cells could be helpful in in vitro systems for elucidating the molecular mechanisms of and discovering drugs to overcome radioresistance in lung cancer therapy.

• Journal of Microbiology and Biotechnology
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• 제18권7호
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• pp.1317-1325
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• 2008

Viral safety is an important prerequisite for clinical preparations of plasma-derived pharmaceuticals. One potential way to increase the safety of therapeutic biological products is the use of a virus-retentive filter. In order to increase the viral safety of human antihemophilic factor IX, particularly in regard to non-enveloped viruses, a virus removal process using a polyvinylidene fluoride membrane filter (Viresolve NFP) has been optimized. The most critical factor affecting the filtration efficiency was operating pH and the optimum pH was 6 or 7. Flow rate increased with increasing operating pressure and temperature. Recovery yield in the optimized production-scale process was 96%. No substantial changes were observed in the physical and biochemical characteristics of the filtered factor IX in comparison with those before filtration. A 47-mm disk membrane filter was used to simulate the process performance of the production-scale cartridges and to test if it could remove several experimental model viruses for human pathogenic viruses, including human hepatitis A virus (HAV), porcine parvovirus (PPV), murine encephalomyocarditis virus (EMCV), human immunodeficiency virus type 1 (HIV), bovine viral diarrhea virus (BVDV), and bovine herpes virus (BHV). Non-enveloped viruses (HAV, PPV, and EMCV) as well as enveloped viruses (HIV, BVDV, and BHV) were completely removed during filtration. The log reduction factors achieved were $\geq$6.12 for HAV, $\geq$4.28 for PPV, $\geq$5.33 for EMCV, $\geq$5.51 for HIV, $\geq$5.17 for BVDV, and $\geq$5.75 for BHV. These results indicate that the virus filtration process successfully improved the viral safety of factor IX.

• 한국군사과학기술학회지
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• 제11권4호
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• pp.133-140
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• 2008

The purpose of this study is to provide response methods to minimize the damage from chemical terrorism in a naturally ventilated indoor system using several types of dispersion simulations. Three chemical warfare agents such as sarin(GB), phosgene and chlorine gas which have high potential to be used in terror or to be involved with accidents were selected in this simulation. Fire dynamic simulation based on Large Eddy Simulation which is effective because of less computational effort and detailed expression of the dispersion flow was adopted to describe the dispersion behavior of these agents. When the vent speed is 0.005m/s, the heights of 0.1 agent mass fraction are 0.9m for sarin, 1.0m for phosgene and 1.1m for chlorine gas, and the maximum mass fraction are 0.27 for all three agents. However, when the vent speed is increased to 0.05m/s, the heights of 0.1 agent mass fraction become 1.6m for all three agents and maximum mass fraction inside the room increase to 0.70 for sarin, 0.58 for phosgene and 0.53 for chlorine gas. It is shown that molecular weight of the agents has an important role for dispersion, and it is important to install ventilation system with height less than 1.6m to minimize the damage from chemical toxicity.

• 한국전기전자재료학회논문지
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• 제13권5호
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• pp.451-457
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• 2000

Experimental investigations on the effect of two kinds of additives ; aqueous NaOH solution and ammonia(NH$_3$) for removal of NOx and SO$_2$ simultaneously by corona discharge were carried out. The simulated combustion flue gas was[NO(0.02[%])-SO$_2$(0.08[%])-$CO_2$-Air-$N_2$] Volume percentage of aqueous NaOH solution used was 20[%] and $N_2$flow rate was 2.5[$\ell$/min] for bubbling aqueous NaOH solution Ammonia gas(14.81[%]) balanced by argon was diluted by air. NH$_3$ molecular ratios(MR) based on [NH$_3$] and [NO+SO$_2$] were 1, 1.5 and 2.5 The vapour of aqueous NaOH solution and NH$_3$was introduced to the main simulated combustion flue gas duct through injection systems which were located at downstream of corona discharge reactor. NOx(NO+NO$_2$) removal rate by injecting the vapour of aqueous NaOH solution was much better than that by injecting NH$_3$however SO$_2$removal rate by injecting NH$_3$was much better than that by injecting the vapour of aqueous NaOH SO$_2$removal rate slightly increased with increasing applied voltage. When the vapour of aqueous NaOH solution and NH$_3$were simultaneously injection NOx and SO$_2$ removal rate were significantly increased.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2013년도 제45회 하계 정기학술대회 초록집
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• pp.277.1-277.1
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• 2013

Molecular diagnostics consists of three processes, which are a sample pretreatment, a nucleic acid amplification, and an amplicon detection. Among three components, sample pretreatment is an important process in that it can increase the limit of detection by purifying nucleic acid in biological sample from contaminants that may interfere with the downstream genetic analysis such as nucleic acid amplification and detection. To achieve point-of-care virus detection system, the sample pretreatment process needs to be simple, rapid, and automatic. However, the commercial RNA extraction kits such as Rneasy (Qiagen) or MagnaPure (Roche) kit are highly labor-intensive and time-consuming due to numerous manual steps, and so it is not adequate for the on-site sample preparation. Herein, we have developed a rotary microfluidic system to extract and purify the RNA without necessity of external mechanical syringe pumps to allow flow control using microfluidic technology. We designed three reservoirs for sample, washing buffer, and elution buffer which were connected with different dimensional microfluidic channels. By controlling RPM, we could dispense a RNA sample solution, a washing buffer, and an elution buffer successively, so that the RNA was captured in the sol-gel solid phase, purified, and eluted in the downstream. Such a novel rotary sample preparation system eliminates some complicated hardwares and human intervention providing the opportunity to construct a fully integrated genetic analysis microsystem.

• Molecules and Cells
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• 제40권5호
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• pp.363-370
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• 2017

Extrahepatic cholangiocarcinoma (ECC), a malignant tumor of biliary origin, has a poor prognosis with limited treatment options. The KRAS oncogene is the most commonly mutated gene in ECC and one of the factors that predicts a poor prognosis and low survival rate. L1 cell adhesion molecule (L1CAM) is expressed in ECC cells and acts as an independent poor prognostic factor in predicting patient survival. In this study we investigate the functional significance of L1CAM in ECC cells with activating KRAS mutation. We selected an ECC cell line, EGI-1, with activating KRAS mutation, and then confirmed its expression of L1CAM by RT-PCR, western blot analysis, and flow cytometry. The suppression of L1CAM expression (using a specific lentivirus-delivered shRNA) significantly decreased the migratory and invasive properties of EGI-1 cells, without altering their proliferation or survival. Analyses of signaling effectors in L1CAM-depleted and control EGI-1 cells indicated that L1CAM suppression decreased the levels of both phosphorylated MKK4 and total MKK4, together with c-Jun N-terminal kinase (JNK) phosphorylation. Further, exposure to a JNK inhibitor (SP600125) decreased migration and invasion of EGI-1 cells. These results suggest that L1CAM promotes cellular migration and invasion via the induction of MKK4 expression, leading to JNK activation. Our study is the first to demonstrate a functional role for L1CAM in ECC carrying the activating KRAS mutation. Given that KRAS is the most commonly mutated oncogene in ECC, L1CAM may serve as an attractive therapeutic target for ECC cells with activating KRAS mutation.

• Molecules and Cells
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• 제43권9호
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• pp.813-820
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• 2020

NB4 cell, the human acute promyelocytic leukemia (APL) cell line, was treated with various concentrations of arsenic trioxide (ATO) to induce apoptosis, measured by staining with 7-amino-actinomycin D (7-AAD) by flow cytometry. 2', 7'-dichlorodihydro-fluorescein-diacetate (DCF-DA) and MitoSOX™ Red mitochondrial superoxide indicator were used to detect intracellular and mitochondrial reactive oxygen species (ROS). The steady-state level of SO₂ (Cysteine sulfinic acid, Cys-SO₂H) form for peroxiredoxin 3 (PRX3) was measured by a western blot. To evaluate the effect of sulfiredoxin 1 depletion, NB4 cells were transfected with small interfering RNA and analyzed for their influence on ROS, redox enzymes, and apoptosis. The mitochondrial ROS of NB4 cells significantly increased after ATO treatment. NB4 cell apoptosis after ATO treatment increased in a time-dependent manner. Increased SO₂ form and dimeric PRX3 were observed as a hyperoxidation reaction in NB4 cells post-ATO treatment, in concordance with mitochondrial ROS accumulation. Sulfiredoxin 1 expression is downregulated by small interfering RNA transfection, which potentiated mitochondrial ROS generation and cell growth arrest in ATO-treated NB4 cells. Our results indicate that ATO-induced ROS generation in APL cell mitochondria is attributable to PRX3 hyperoxidation as well as dimerized PRX3 accumulation, subsequently triggering apoptosis. The downregulation of sulfiredoxin 1 could amplify apoptosis in ATO-treated APL cells.

• Nuclear Engineering and Technology
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• 제42권6호
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• pp.620-635
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• 2010

In this paper we describe current activities on the project Multi-Scale Modeling and Analysis of convective boiling (MSMA), conducted jointly by the Paul Scherrer Institute (PSI) and the Swiss Nuclear Utilities (Swissnuclear). The long-term aim of the MSMA project is to formulate improved closure laws for Computational Fluid Dynamics (CFD) simulations for prediction of convective boiling and eventually of the Critical Heat Flux (CHF). As boiling is controlled by the competition of numerous phenomena at various length and time scales, a multi-scale approach is employed to tackle the problem at different scales. In the MSMA project, the scales on which we focus range from the CFD scale (macro-scale), bubble size scale (meso-scale), liquid micro-layer and triple interline scale (micro-scale), and molecular scale (nano-scale). The current focus of the project is on micro- and meso-scales modeling. The numerical framework comprises a highly efficient, parallel DNS solver, the PSI-BOIL code. The code has incorporated an Immersed Boundary Method (IBM) to tackle complex geometries. For simulation of meso-scales (bubbles), we use the Constrained Interpolation Profile method: Conservative Semi-Lagrangian $2^{nd}$ order (CIP-CSL2). The phase change is described either by applying conventional jump conditions at the interface, or by using the Phase Field (PF) approach. In this work, we present selected results for flows in complex geometry using the IBM, selected bubbly flow simulations using the CIP-CSL2 method and results for phase change using the PF approach. In the subsequent stage of the project, the importance of effects of nano-scale processes on the global boiling heat transfer will be evaluated. To validate the models, more experimental information will be needed in the future, so it is expected that the MSMA project will become the seed for a long-term, combined theoretical and experimental program.

• Journal of Applied Biological Chemistry
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• 제62권2호
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• pp.129-135
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• 2019

Salvia miltiorrhiza Radix is cultivated in Korea and China and is traditionally used to treat cardiovascular diseases. In this study, we developed and validated a quantitative analysis method for S. miltiorrhiza Radix using high-performance liquid chromatography (HPLC). Identification was performed using ultra performance liquid chromatography-tandem mass spectrometry. For quantitative analysis, we used seven marker compounds. Separation conditions for HPLC were optimized using an ODS column with gradient conditions of 1% formic acid in distilled water and 1% formic acid in acetonitrile, with a flow rate of 0.8 mL/min and a detection wavelength of 280 nm. This method showed good linearity ($R^2=0.9998$), precision (relative standard deviation ${\leq}3.3%$), accuracy (recovery of 94.16-102.89%), limit of detection ($7.53{\mu}g/mL$), and limit of quantification ($23.71{\mu}g/mL$). This approach successfully quantified marker compounds in S. miltiorrhiza Radix. The individual marker compounds were identified by comparing the molecular masses and retention times with does standard compounds. Marker compound contents of S. miltiorrhiza Radix were investigated with different cultivation regions. Seven marker compounds were detected and quantified in all samples. Among them, salvianolic acid B showed the highest contents and it ranged from 4.13 to 7.15%. The salvianolic acid B content (7.15%) of marker compound was the highest in Bonghwa, and the tanshinone IIA content (1.90%) was the highest in Pohang. The results of marker compounds and developed method were intended to provide a favorable reference for the study of S. miltiorrhiza Radix from different regions of Korea.

• 한방비만학회지
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• 제19권1호
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• pp.1-11
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• 2019

Objectives: The purpose of the present study was to evaluate the preventive effects of ethanol extract of Polygalae radix (EEPR) against oxidative stress (hydrogen peroxide, $H_2O_2$)-induced DNA damage and apoptosis in Chang liver cells. Methods: Chang liver cells were pretreated with various concentrations of EEPR and then challenged with 0.5 mM $H_2O_2$. The cell viability and apoptosis were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry analysis, respectively. The levels of reactive oxygen species (ROS), mitochondrial membrane potentials (MMPs) and adenosine tri-phosphate (ATP) contents were measured. Expression levels of Bcl-2 and Bax were also determined using Western blot analysis. Results: The results showed that the decreased survival rate induced by $H_2O_2$ could be attributed to the induction of DNA damage and apoptosis accompanied by the increased production of ROS, which was remarkably protected by EEPR. In addition, the loss of $H_2O_2$-induced MMPs and ATP contents was significantly attenuated in the presence of EEPR. The inhibitory effect of EEPR on $H_2O_2$-induced apoptosis was associated with up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio. Conclusions: Our data prove that EEPR protects Chang liver cells against $H_2O_2$-induced DNA damage and apoptosis by scavenging ROS and thus suppressing the mitochondrial-dependent apoptosis pathway.