• Genomics & Informatics
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• v.19 no.1
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• pp.2.1-2.10
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• 2021

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

• JSTS:Journal of Semiconductor Technology and Science
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• v.13 no.4
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• pp.291-302
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• 2013

NAND flash memory (NFM) based storage devices, e.g. Solid State Drive (SSD), are rapidly replacing conventional storage devices, e.g. Hard Disk Drive (HDD). As NAND flash memory technology advances, its specification has evolved to support denser cells and larger pages and blocks. However, efforts to fully understand their impacts on design objectives such as performance, power, and cost for various applications are often neglected. Our research shows this recent trend can adversely affect the design objectives depending on the characteristics of applications. Past works mostly focused on improving the specific design objectives of NFM based systems via various architectural solutions when the specification of NFM is given. Several other works attempted to model and characterize NFM but did not access the system-level impacts of individual parameters. To the best of our knowledge, this paper is the first work that considers the specification of NFM as the design parameters of NAND flash storage devices (NFSDs) and analyzes the characteristics of various synthesized and real traces and their interaction with design parameters. Our research shows that optimizing design parameters depends heavily on the characteristics of applications. The main contribution of this research is to understand the effects of low-level specifications of NFM, e.g. cell type, page size, and block size, on system-level metrics such as performance, cost, and power consumption in various applications with different characteristics, e.g. request length, update ratios, read-and-modify ratios. Experimental results show that the optimized page and block size can achieve up to 15 times better performance than the conventional NFM configuration in various applications. The results can be used to optimize the system-level objectives of a system with specific applications, e.g. embedded systems with NFM chips, or predict the future direction of NFM.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5337-5341
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• 2015

Background: Individual susceptibility to cancer has been attributed to polymorphisms in xenobiotic metabolizing genes. To evaluate the association of the Leu432Val polymorphism of cytochrome P4501B1 (CYP1B1) with esophageal squamous cell carcinoma (ESCC), we conducted a case control study in Kashmir, India, an area with a relatively high incidence of ESCC. Materials and Methods: We recruited 404 histopathologically confirmed ESCC cases, and an equal number of controls, individually matched for sex, age and district of residence to respective cases. Information was obtained on various dietary, lifestyle and environmental factors in face to face interviews, using a structured questionnaire, from each subject. Genotypes were analysed by polymerase chain reaction, restriction fragment length polymorphism and sequencing of randomly selected samples. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: Among the three possible variants, we did not find any Leu432Leu genotype of CYP1B1 in the study population and the genotypic distribution of Val432Val and Leu432Val carriers was nearly equal in both cases (89.6% and 10.4%) and controls (88.9% and 11.1%) respectively. We did not find any risk associated with this polymorphism in the current study (OR = 0.64; 95% CI: 0.55 - 1.64). Conclusions: The study indicates that (Leu432Val) polymorphism of CYP1B1, is not associated with ESCC risk. However, replicative studies with larger sample size are needed to substantiate the findings.

• Transactions of the Korean Society of Mechanical Engineers B
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• v.37 no.11
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• pp.971-975
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• 2013

In general, the solar photovoltaic power increases with higher solar insolation. However, the solar cell generation efficiency reduces because the solar cell surface is heated by solar insolation. According to advanced research, with a $1^{\circ}C$ increase in the solar cell surface temperature, the generation efficiency decreases by ~0.5%. To solve this problem, we conducted experiments in which we attempted to reduce the solar cell surface temperature using a water jet spray. In this study, we found the long-term experimental results of increases in solar power generation. The experimental results show a comparison of the site with and without cooling and cleaning equipment being installed. The results of the long-term experiments show that solar photovoltaic power generation is increased by at least 13% up to 19% with cooling and cleaning.

• Journal of Korea Water Resources Association
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• v.33 no.3
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• pp.341-350
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• 2000

The objectives of this study are to develop a state-space form of stochastic dynamic storage function routing model and to test the model performance for real-time flow forecast. The selected study area is the main Han River starting from Paldang Dam site to Indogyo station and the 13 flood events occurred from 1987 to 1998 are selected for computing model parameters and testing the model performance. It was shown that the optimal model parameters are quite different depending on Hood events, but the values used on field work also give reasonable results in this study area. It is also obvious that the model performance from the stochastic-dynamic model developed in this study gives more accurate and reliable results than that from the existing deterministic model. Analysis for allowable forecast lead time leads that under the current time step the reasonable predicted downstream flows in 5 hours time advance are obtained from the stochastic dynamic model on relatively less lateral inflow event in the study area.

• Physical Therapy Rehabilitation Science
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• v.13 no.1
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• pp.78-85
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• 2024

Objective: This Study aimed to examine the changes in muscle activity of trunk muscles by performing three squat exercises on normal adults. Design: cross-sectional study Methods: Thirty-two adult subjects participated in this study. General squat, overhead squat, and overhead squat combined with abdominal stabilization were randomly performed for 5 seconds, 3 times, to calculate the average muscle activation. Muscle activation was normalized using electrodes on the rectus abdominis, external oblique, internal oblique, and erector spinae muscles to measure maximum voluntary isometric contraction (MVIC) for 5 seconds, repeated 3 times each. Results: There was a significant difference in the mean and maximal muscle activity of the bilateral erector spinae (ES) when comparing the squat to the overhead squat (p<0.05). There was a significant difference (p<0.05) in the mean and maximal muscle activity of the bilateral external oblique (EO) when comparing the overhead squat to the overhead squat combined with the abdominal stabilization technique. When comparing the squat to the overhead squat with abdominal stabilization, there was a significant difference in the mean and maximum muscle activity of the bilateral RA, EO, and left Internal oblique (IO) (p<0.05), and there was a significant difference in the maximum muscle activity of the bilateral erector spinae (ES) (p<0.05). Post hoc tests showed significant differences between squatting methods for the RA, EO, IO, and ES (p<0.017). Conclusion: The results of this study showed that squats combined with abdominal stabilization were more effective at activating core muscles than squats or overhead squats alone.

• Korean Journal of Adult Nursing
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• v.12 no.2
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• pp.245-255
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• 2000

The purpose of this study is to compare the physical health, anxiety and depression of the Dan-Jeon Breathing trained group with those of a non-trained group and to analyze the relationship between the training period of Dan-Jeon Breathing method and physical health, anxiety, and depression. The number of people in the Dan-Jeon Breathing trained group over 3 months was 149 and in the non-trained group 142. Data were collected from August to October 1999. As tools, 35 physical symptom questions were chosen from The Cornell Medical Index modified by Nam(1965) and from the Symptom Checklist-90-Revision(SCL-90-R) by Kim(1984); 10 questions on anxiety and 13 questions on depression were used in the study. The statistics of the study were gathered by using SPSS Window; the analysis was made by applying $X^2$-test, t-test, Pearson correlation, ANOVA and Scheffe tests. The results were as follows. 1. The Dan-Jeon Breathing trained group had lower physical symptom score and showed less anxiety and depression than the non-trained group, which supported the 1st, 2nd, 3rd hypotheses. 2. The longer the training period of Dan-Jeon Breathing, the lower the physical symptom score, which supports the 4th hypothesis, but the 5th and, 6th hypotheses were not supported because anxiety and depression did not get lower as the training period of Dan-Jeon Breathing got longer. 3. The physical symptom score, anxiety and depression that were made by the general characteristics of Dan-Jeon Breathing trained group were analyzed. As a result, the physical symptom score of women was greater than that of men. Physical symptoms score and the rate of anxiety and depression were different by education levels. The degree of anxiety was different by age. Those who have a religion have a higher physical symtoms score than people who have no religion. There was no difference in physical health score, anxiety and depression according to marital status, economic status and occupations. The results suggest that the physical and mental health status of Dan-Jeon Breathing trained group is better than that of the non-trained group. Physical symptoms scores gets lower as the training period of Dan-Jeon Breathing gets longer which results in the improvement of physical health status.

• Journal of the Korean Society of Clothing and Textiles
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• v.30 no.3 s.151
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• pp.407-411
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• 2006

This study was carried out to investigate the physiological responses of obese children after a short-term wear training and education. A ten-week program was conducted on thirteen obese elementary school children of six boys and seven girls in the 4th to the 6th grade. During the program, the children were instructed to measure daily ambient temperature and weight of their clothing. Physiological responses of the sedentary children in 100$\%$ cotton short sleeved t-shirt (0.13clo) and T/C short pants(0.09clo) were observed in the climatic chamber of 23.0$\pm$0.5$^{circ}C$ and 50$\pm$5$\%$RH before and after program. During the experiment, internal ear temperature ($T_{ear}$), seven site skin temperatures, systolic blood pressure, diastolic blood pressure, heart rate, and subjective responses of thermal comfort and thermal sensation were measured every 5minutes. Mean skin temperature($T_{sk}$) and mean arterial pressure(MAP) were calculated. Obtained data are statistically analyzed and main results are as follows. There was highly significant correlation between the ambient temperature and the total clothing weight. $T_{ear}$ and MAP were reduced in the post-program compared to the pre-program. The obese girls felt slightly warmer than the obese boys and the girls were likely to prefer lower ambient temperature in the post-program than the pre-program. It was concluded that the 10 week wear training is apt to be more applicable to the obese girls than the obese boys. However, a more comprehensive study including. diverse measurements of deep body temperature with a long-term training would be needed to clarify the improvement of temperature adaptability in the obese children.

• IMMUNE NETWORK
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• v.8 no.1
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• pp.13-20
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• 2008

Background: Coptis chinensis rhizome has been used as a medicinal herb in traditional Oriental medicine. We investigated the effects of Coptis chinensis extract on inflammatory mediators and delayed type hypersensitivity in mice. Methods: The inhibitory effect of ethanolic extract of Coptis chinensis (CCE) on cell proliferation was evaluated using MTS assay. The lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the Con A-activated mouse splenocytes were cultured with various concentrations of CCE. Total nitric oxide (NO) production was determined by Griess reaction. The amounts of secreted prostaglandine E2 ($PGE_2$), interleukin (IL)-2 and IFN-${\gamma}$ were measured by ELISA. To investigate the in vivo anti-inflammatory effect of CCE, oxazolone-induced delayed type hypersensitivity (DTH) model was used. Results: The CCE at $100{\mu}g/ml$ significantly blocked the LPS-induced production of pro-inflammatory mediators (NO and PGE) in RAW264.7 macrophages. Also, it significantly inhibited cell proliferation and cytokine (IL-2 and IFN-${\gamma}$) production in splenocytes. Furthermore, when splenocytes from CCE fed mice (200 mg/kg for 2 weeks) were activated with Con A, cell proliferation and cytokine production were significantly inhibited. In addition, CCE decreased in vivo inflammation in oxazolone-induced DTH model mice. Conclusion: We suggest that Coptis chinensis can be used as an anti-inflammatory drug by exerting an inhibitory effect in inflammatory mediator- and cell-mediated inflammation.

• Journal of Ecology and Environment
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• v.41 no.11
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• pp.318-327
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• 2017

Background: A typical sewage treatment plant is designed for organic and nutrient removal from municipal sewage water and not targeted to eliminate micropollutants such as pesticides, pharmaceuticals, and nano-sized metals which become a big concern for sustainable human and ecological system and are mainly discharged from sewage treatment plant. Therefore, despite contaminant removal by wastewater treatment processes, there are still remaining environmental risks by untreated pollutants in STP (sewage treatment plant) effluents. This study performed aquatic toxicity tests of raw wastewater and treated effluents in two sewage treatment plants to evaluate toxicity reduction by wastewater treatment process and analyze concentration of contaminants to reveal potential toxic factors in STP effluents. Methods: Water samples were collected from each treatment steps of two STPs, and acute and chronic toxicity tests were conducted following USEPA (United States Environmental Protection Agency) and OECD (Organization for Economic Cooperation and Development) guidelines. Endpoints were immobility for mortality and reproduction effect for estrogenicity. Results: Acute $EC_{50}s$ (median effective concentration) of influents for Seungki (SK) and Jungnang (JN) STPs are $54.13{\pm}32.64%$ and $30.38{\pm}24.96%$, respectively, and reduced to $96.49{\pm}7.84%$ and 100%. Acute toxicity reduction was clearly correlated with SS (suspended solids) concentration because of filter feeding characteristics of test organisms. Chronic toxicity tests revealed that lethal effect was reduced and low concentration of influents showed higher number of neonates. However, toxicity reduction was not related to nutrient removal. Fecundity effect positively increased in treated wastewater compared to that in raw wastewater, and no significant differences were observed compared to the control group in JN final effluent implying potential effects of estrogenic compounds in the STP effluents. Conclusions: Conventional wastewater treatment process reduced some organics and nutritional compounds from wastewater, and it results in toxicity reduction in lethal effect and positive reproductive effect but not showing correlation. Unknown estrogenic compounds could be a reason causing the increase of brood size. This study suggests that pharmaceutical residues and nanoparticles in STP effluents are one of the major micropollutants and underline as one of estrogenic effect factors.