• Biomolecules & Therapeutics
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• 제30권1호
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• pp.19-27
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• 2022

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wild-type EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and third-generation EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.

• Tuberculosis and Respiratory Diseases
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• 제85권2호
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• pp.147-154
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• 2022

Background: The expression of calcium signaling pathway molecules is altered in various carcinomas, which are related to the proliferation and altered characteristics of cancer cells. However, changes in calcium signaling in anti-cancer drug-resistant cells (bearing a T790M mutation in epidermal growth factor receptor [EGFR]) remain unclear. Methods: Afatinib-mediated changes in the level of store-operated Ca²⁺ entry (SOCE)-related proteins and intracellular Ca²⁺ level in non-small cell lung cancer cells with T790M mutation in the EGFR gene were analyzed using western blot and ratiometric assays, respectively. Afatinib-mediated autophagic flux was evaluated by measuring the cleavage of LC3B-II. Flow cytometry and cell proliferation assays were conducted to assess cell apoptosis and proliferation. Results: The levels of SOCE-mediating proteins (ORAI calcium release-activated calcium modulator 1 [ORAI1], stromal interaction molecule 1 [STIM1], and sarco/endoplasmic reticulum Ca²⁺ ATPase [SERCA2]) decreased after afatinib treatment in non-small cell lung cancer cells, whereas the levels of SOCE-related proteins did not change in gefitinib-resistant non-small cell lung cancer cells (PC-9/GR; bearing a T790M mutation in EGFR). Notably, the expression level of SOCE-related proteins in PC-9/GR cells was reduced also responding to afatinib in the absence of extracellular Ca²⁺. Moreover, extracellular Ca²⁺ influx through the SOCE was significantly reduced in PC-9 cells pre-treated with afatinib than in the control group. Additionally, afatinib was found to decrease the level of SOCE-related proteins through autophagic degradation, and the proliferation of PC-9GR cells was significantly inhibited by a lack of extracellular Ca²⁺. Conclusion: Extracellular Ca²⁺ plays important role in afatinib-mediated autophagic degradation of SOCE-related proteins in cells with T790M mutation in the EGFR gene and extracellular Ca²⁺ is essential for determining anti-cancer drug efficacy.

• Journal of the Korean Statistical Society
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• 제26권1호
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• pp.147-154
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• 1997

An infinite dam with a compound Poisson input having exponential jumps is considered. As an output policy, we adopt the $P_{\lambda}$$^{M}$ Policy. After assigning costs to the dam we obtain the long-rum average cost per unit time of operating the dam and find the optimal values of .lambda. and M which minimize the long-run average cost.t.

• Tuberculosis and Respiratory Diseases
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• 제85권2호
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• pp.155-164
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• 2022

Background: The remarkable efficacy of osimertinib in non-small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy. Methods: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed. Results: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7-50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30-0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12-0.45; p<0.001) were independently associated with a prolonged PFS with osimertinib. Conclusion: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.

• 한국연소학회:학술대회논문집
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• 대한연소학회 2003년도 제27회 KOSCO SYMPOSIUM 논문집
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• pp.201-208
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• 2003

Wheat dust cloud를 $5{\times}5{\times}214.1cm^3$ square tube내부에 발생시켜 화염의 전달과 연소 한계에 관한 연구를 수행하였다. 사용된 미립자는 $160{\mu}m-300{\mu}m$의 크기로 분류되어 주로 사용되었고 $300{\mu}m-325{\mu}m$크기의 미립자가 더불어 사용되었다. 연소 튜브는 연료로 사용되는 미립자를 튜브의 상단에서부터 컨베이어 벨트를 사용해서 공급받아 튜브의 하단에서 전기코일을 사용하여 점화시키는 구조로 고안되었다. 화염의 최대 진행속도는 작은 크기와 보다 큰 크기의 미립자를 사용했을 때가 각각 523cm/sec와 373cm/sec로 측정되었다. 연소 속도는 입자의 크기와 집접도(concentration)에 따라 변화를 보였는데 최소 3cm/sec에서 최대 7.5cm/sec로 관측되었다. 그러나 화염의 두께는 놀랍게도 입자의 집접도와 큰 연관이 없어 보였는데, 이는 앞으로도 보다 많은 연구를 통한 검증이 필요하리라 생각된다. 끝으로 fuel rich flammability는 $790g/m^3$으로 stoichiometric mixture $230g/m^3$에 비교해 월등히 높은 값으로 관측되었다.

• The Journal of Asian Finance, Economics and Business
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• 제8권3호
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• pp.905-915
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• 2021

This study examines the relationship between financial behavior, financial literacy, self-efficacy, and self-coping among emerging adults. The study population is 790 respondents from 11 Credit Counselling and Debt Management (CCDM). Statistical Package for Social Science (SPSS) was used to analyze Pearson Correlation and Multiple regression. It was used to determine the relationships and recognize determinants of emerging adults' financial behavior respectively. In this study, financial literacy, self-efficacy, self-coping, and financial behavior variables were entered into the regression. A total of 790 respondents aged 40 and below were selected. An independent sample t-test was administered to compare the financial behavior scores for females and males. The results reveal that there was significant difference in the mean of financial behavior scores for females (M = 87.20, SD = 18.00) and males (M = 89.70, SD = 16.80; t (765) = 2.010, p = 0.045, two-tailed). The multiple regression results indicate that the model explained 13.4% of the variance in financial behavior, which is predicted significantly by the model (F = 38.361, p = 0.000). This study will be beneficial to policymakers to improve living conditions and to promote good financial behavior, financial literacy, self-efficacy as well as self-coping especially for emerging adults in Malaysia.

• 동의생리병리학회지
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• 제35권4호
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• pp.117-123
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• 2021

Gefitinib, a first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), provides obvious clinical benefit in patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, patients ultimately develop gefitinib resistance which mainly caused by EGFR T790M secondary mutation. In the current study, we investigated whether the root extract of Scutellaria baicalensis (SB) overcomes gefitinib resistance. Gefitinib-resistant H1975 human NSCLC cells (EGFR L858R/T790M double mutant) were treated with gefitinib and/or ethanol extract of SB (ESB) to evaluate the effect of ESB on the gefitinib sensitivity. The cell viability was measured by MTT assay and trypan blue exclusion assay. The colony-forming ability was evaluated by anchorage-dependent colony formation assay. Combined treatment with gefitinib and ESB markedly decreased the cell viability and colony formation than single treatment with gefitinib or ESB in H1975 cells. In addition, cells treated with both gefitinib and ESB exhibited a significant increase of sub-G1 DNA content which indicates apoptotic cells compared with those treated with gefitinib or ESB alone. As a molecular mechanism, combined treatment with gefitinib and ESB strongly downregulated the phosphorylation of ERK and JNK than single treatment with gefitinib or ESB. Taken together, our results demonstrate that ESB sensitizes H1975 cells to gefitinib treatment. We cautiously propose that ESB can be used in combination with gefitinib for the advanced NSCLC patients with acquired resistance to EGFR TKIs.

• 한국정보처리학회:학술대회논문집
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• 한국정보처리학회 2015년도 추계학술발표대회
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• pp.787-790
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• 2015

스마트폰의 등장을 시작으로 사물과 인터넷의 결합이 급속히 진행되면서 다양하고 새로운 시장이 형성 되고 있다. 특히 모바일 네트워크가 확산되면서 소비자의 스마트 홈 시장에 대한 관심이 높아졌으며 다양한 기업들이 스마트 홈 시장에 진입하고 있다. 본 논문에서는 다양한 스마트 홈 기술을 소개한다. OneM2M, AllJoyn의 플랫폼 구조와 보안 표준을 살펴보고 IoTivity, Homekit, Thread의 특징을 분석하여 스마트 홈 기술의 동향을 분석한다.

• 한국산림과학회지
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• 제79권2호
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• pp.162-172
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• 1990

가산일대(架山一帶)에 대해 삼림환경형분류(森林環境型分類)(Habitat Type 분류(分類))를 적용(適用)한 결과(結果) 다음과 같이 요약(要約)할 수 있었다. 1. 소나무/철쭉 삼림환경형(森林環境型)(PIDE/RHSC H.T.) : 산릉선부(山陵線部)와 사면상부(斜面上部)에 분포(分布)하는 지형적(地形的) 극성상(極盛相)이다. 하층(下層)에 철쭉꽃이 잘 나타난다. 2. 서어나무/실새풀 삼림환경형(森林環境型)(CALA/CAAR H.T.) : 계곡(溪谷)을 낀 사면하부(斜面下部)에 분포(分布)하며 사면상부(斜面上部)와 능선부(陵線部)의 소나무림과 접하고 있다. 하층(下層)에 실새풀이 잘 나타난다. 3. 신갈나무/산거울 삼림환경형(森林環境型)(QUMO/CAHU H.T.) : 산성외부(山城外部)의 사면(斜面)에 분포(分布)하며 해발(海拔) 600-790m에 이른다. 하층(下層)에 산거울이 잘 나타난다. 4. 신갈나무/실새풀 삼림환경형(森林環境型)(QUMO/CAAR H.T.) : 산성내부(山城內部)의 평정봉(平頂峰)에 분포(分布)하며 해발(海拔) 700-870m에 이른다. 하층(下層)에 실새풀이 많다. 5. 물푸레나무/물봉선 산림환경형(森林環境型)(FRRH/IMTE H.T.) : 계곡부(溪谷部)에 분포(分布)하며 하층(下層)에 물 물봉선이 잘 나타난다. 6. 층층나무/백당나무 삼림환경형(森林環境型)(COCO/VISA H.T.) : 계곡부(溪谷部)와 계곡(溪谷) 근원지(根源地)에 분포(分布)하며 해발(海拔) 780-830m에 이른다. 하층(下層)에 백당나무가 잘 나타난다.

• 한국산림과학회지
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• 제95권4호
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• pp.443-452
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• 2006

다릅나무 임분의 입지 환경과 해발고에 따른 생장량을 비교하기 위해 강원도 평창군 중왕산에서 $30m{\times}30m$ 크기의 조사구 28곳을 선정해서 식생 및 입지 환경 특성을 조사했다. 또한 해발고가 약 100 m 간격으로 있는 5곳의 조사구에서 각 2그루씩 다릅나무를 선발해서 수간석해했다. 다릅나무는 주로 해발 790~1,170 m 사이의 북향의 능선 또는 사면에서 출현했다. 다릅나무의 입지는 A층 깊이가 평균 21.2 cm로 깊고, A층 수분 함량은 35.6%로 높은 편이며, 토양 비옥도가 낮은 지역이었다. 다릅나무와 함께 중요치가 높은 수종은 신감나무, 물푸레나무, 당단풍나무, 고로쇠나무, 느릅나무, 피나무, 사사나무 등이었다. 중왕산 지역의 다릅나무림은 TWINSPAN에 의해 다릅나무-사시나무 군락, 다릅나무-느릅나무 군락(이상 건조형), 다릅나무-피나무 군락, 다릅나무-쪽동백나무 군락(이상 습윤형)으로 나누어졌다. 군락유형별 ha당 개체수는 습윤형 군락이 건조형 군락보다 많았다. 한편, 다릅나무의 연간 수고 생장량은 10년까지 급격한 증가를 보이다가 점차 감소했으며, 초기 수고 생장이 빨라 초기 침입수종의 생장전략을 보여줬다. 또한 다릅나무는 수령 40년 이상에서도 주변목의 고사로 경쟁이 완화되면 재적 생장량이 크게 증가하는 특성을 보였으며, 수령 50년 이후 경제성 있게 수확할 수 있는 것으로 판단됐다.