D-P-S-I-R기법을 이용한 기후변화로 인한 국내 온열질환 취약성 분석

장현빈 호서대학교 일반대학원 2024 국내석사

최근 지구온난화로 인해 여름철 폭염일수의 빈도가 증가함에 따라 온열질환자의 수도 증가하는 추세이다. 질병관리청의 온열질환자 신고현황 연보에 따르면 2011~2023년 온열질환자의 수는 약 21,000명으로 나타났고, 2018년을 기준으로 ‘재난 및 안전관리 기본법’을 개정해 폭염을 자연재난에 포함 시키며 인해 폭염 예방에 관심이 대두되고 있다. 이에 본 연구에는폭염 취약성 분석을 위해 D-P-S-I-R (Driver force–Pressure–State–Impact–Response)기법을 활용하였다. 2011년부터 2020년까지10년 단위 대한민국 행정구역 별 기온, 습도, 온열질환자, 무더위 쉼터 등 데이터를 수집하여 D-P-S-I-R 기법을 이용해 취약성분석을 실시하였고, 최종적으로 전국 폭염 취약성 지수를 도출했다. 폭염 취약성 결과를 통해 취약한 지역에 대해 선제적인 대비가 가능하고, 효과적으로 폭염에 대응할 수 있는 시스템을 구축 할 수 있을 것으로 기대된다. The increasing frequency of summer heat waves due to global warming has led to a rise in the number of patients with heat-related illnesses. According to the annual report on heat patients by the Korea Centers for Disease Control and Prevention, about 21,000 cases were reported between 2011 and 2023. In 2018, the “Framework Act on Disaster and Safety Management” was revised toclassify heat waves as natural disasters, highlighting the need for preventing measures. Therefore, this study employed the driverforce–pressure–state–impact–response (D-P-S-I-R) technique to analyze heat wave vulnerability from 2011 to 2020. Using data on temperature, humidity, heat-related patients, and heat shelters, a national heat wave vulnerability index was developed. The results aim to facilitate preemptive preparation for vulnerable areas and establish an effective response system for managing heat waves.

Cudrania tricuspidata extract and its active compound kaempferol-7-O-glucoside attenuate muscle atrophy by regulating protein turnover

장현빈 Graduate School, Yonsei University 2022 국내석사

근감소증(Muscle atrophy)은 노화, 영양부족 및 만성질환 등에 의해 유발되며, 근육량과 근기능이 모두 감소하는 것을 특징으로 한다. 근감소증은 삶의 질을 저하시킬뿐만 아니라, 당뇨, 비만, 골다공증과 같은 질병을 유발하므로, 근감소증을 예방하고 개선하는 것이 중요하다. 근육 내의 단백질은 근단백질의 합성과 분해 사이의 균형에 의해 조절된다. 근단백질의 합성은 저해되고 분해가 촉진될 경우 근감소증이 발생하게 된다. 꾸지뽕(Cudrania tricuspidata Bureau)은 뽕나무과에 속하며 한국, 중국, 일본에서 전통적으로 사용되어 왔다. 꾸지뽕 및 생리활성 성분 kaempferol-7-O-glucoside (KPG)는 항염, 항산화, 항암 등의 다양한 생리활성을 지니고 있다. 그러나, 꾸지뽕과 KPG의 근감소증 개선 효과에 대해서는 아직까지 연구된 바가 없다. 본 연구에서는 꾸지뽕 잎 추출물(C. tricuspidata leaves extract; CLE) 및 생리활성 성분 KPG의 근감소증 개선 효과를 검증하기 위하여 세포 모델로써 tumor necrosis factor-alpha (TNF-α)를 처리한 L6 근관세포, 동물 모델로써 부동화로 근감소증이 유도된 C57BL/6J 마우스를 이용하였다. TNF-α를 이용하여 근감소를 유도한 L6 근관세포에 CLE 20 및 40 μg/mL와 KPG 25 및 50 μM을 처리하여 세포 수준에서의 근기능 개선 효과를 확인하였다. CLE와 KPG 처리는 근아세포의 분화를 촉진하였을 뿐만 아니라 근단백질 합성에 관여하는 phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) 경로와 그 하위 인자인 mammalian target of rapamycin (mTOR), 70-kDa ribosomal protein S6 kinase (p70S6K), eukaryotic initiation factor 4E binding protein 1 (4EBP1)을 활성화하였다. 또한, CLE와 KPG는 근단백질 분해에 있어 중요한 전사 인자인 Forkhead box O3 (FoxO3)를 억제하여 근육 특이적 ubiquitin E3 ligase인 muscle RING-finger protein-1 (MuRF1)과 muscle atrophy F-box (MAFbx/atrogin-1)의 발현을 감소시켰다. CLE와 KPG는 nuclear factor kappa B (NF-κB) 경로와 염증성 사이토카인인 TNF-α, interleukin-6 (IL-6)의 생성을 억제하고, 항산화 효소인 catalase, superoxide dismutase (SOD) 및 glutathione peroxidase (GPx)의 발현을 상향 조절하였다. 동물모델에서는 C57BL/6J 마우스의 뒷다리를 1주일간 고정하여 근위축을 유도한 후, CLE 50 및 150 mg/kg/day를 1주일간 하루 1회씩 경구투여하였다. CLE는 부동화에 의해 감소한 마우스의 근력, 근지구력, 근육 부피 및 질량, 근단면적을 회복시켰다. 분자수준에서 CLE는 PI3K/Akt 경로를 촉진함으로써 mTOR/p70S6K/4EBP1 경로를 활성화하여 근단백질의 합성을 증가시켰고, 단백질 분해와 관련된 FoxO3를 비활성화하여 근단백질의 분해를 억제하였다. 또한, CLE는 염증 반응과 관련된 NF-κB 경로를 억제하여 염증성 사이토카인인 TNF-α와 IL-6의 발현을 하향 조절하였다. 종합적으로, 본 연구를 통해 CLE와 KPG가 근육 분화 및 근단백질 합성과 관련된 신호전달경로를 활성화하고, 근단백질 분해 및 염증 반응과 관련된 경로는 억제하며 항산화 효과를 촉진함으로써 근감소증을 개선에 효과가 있음을 확인하였다. 따라서, 꾸지뽕과 KPG는 근감소증 예방 및 개선 효과를 지니는 기능성 소재로 사용될 수 있을 것으로 기대된다. Skeletal muscle atrophy is a condition in which the muscle mass and function are decreased due to various causes, such as inflammation caused by chronic diseases and aging, physical inactivity, and malnutrition. Muscle atrophy not only causes other diseases, but also increases the mortality rate; hence, preventing and treating muscle atrophy are emerging as important tasks. Cudrania tricuspidata Bureau, also known as cudrang or mandarin melon berry, has been used as a traditional medicine in East Asian countries. It shows various biological activities, including anti-inflammatory, antioxidant, antitumor, hepatoprotective, and neuroprotective activities. Kaempferol-7-O-glucoside (KPG) is one of the main components of the leaves of C. tricuspidata that exerts anti-cancer, antioxidant, and anti-inflammatory effects. However, the protective effects of C. tricuspidata leaf extract (CLE) and KPG on muscle atrophy have not yet been reported. The present study investigated the effects of CLE and KPG on the inhibition of muscle atrophy in tumor necrosis factor alpha (TNF-α)-treated L6 myotubes and immobilization-induced C57BL/6J mice. CLE and KPG stimulated myoblast differentiation into myotubes by upregulating the myogenic regulatory factors, MyoD, myogenin and myosin heavy chain (MHC). Phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathway, which regulates both protein anabolism and catabolism, was activated by CLE and KPG in L6 myotubes. CLE and KPG also upregulated the mammalian target of rapamycin (mTOR) pathway and its downstream factors, 70-kDa ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E binding protein 1 (4EBP1), in TNF-α-treated L6 myotubes. Additionally, the mRNA expression levels of muscle-specific atrogenes, muscle RING-finger protein-1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin-1) were suppressed by CLE and KPG treatment by blocking the nuclear translocation of forkhead box O3 (FoxO3). CLE and KPG also downregulated the expression levels of proinflammatory cytokines, TNF-α and interleukin-6 (IL-6) by suppressing the nuclear factor kappa B (NF-κB) pathway and upregulating the levels of antioxidant enzymes, including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx), at the cellular level. The effect of CLE on muscle atrophy was investigated in hindlimb-immobilized C57BL/6J mice. CLE significantly recovered the grip strength and exercise capacity of immobilization-treated mice. Oral administration of CLE enhanced the hindlimb muscle volume, mass, and cross-sectional area of muscle fibers in C57BL/6J mice. At the molecular level, the PI3K/Akt/mTOR pathway was downregulated by immobilization, but activated with CLE in the tibialis anterior muscle. In contrast, phosphorylation of FoxO3 by CLE administration decreased the expression levels of ubiquitin E3 ligases, MuRF1 and atrogin-1. CLE also suppressed NF-κB, a transcription factor involved in the inflammatory response, consequently inhibiting TNF-α and IL-6 expression. Collectively, these results indicate that CLE and KPG improve muscle atrophy by regulating myogenesis, protein turnover-related pathways, inflammatory responses and antioxidant enzymes. Taken together, the current study suggests that C. tricuspidata and KPG may have potential to be used as pharmacological agents for preventing and alleviating muscle atrophy.

Application of Convolutional Neural Network to PWR Fuel Loading Pattern Optimization by Simulated Annealing

장현빈 부산대학교 대학원 2020 국내석사

Simulated Annealing (SA) algorithm is a widely used optimization method in the loading pattern (LP) optimization problems. However, the existing SA using neutronics code has a disadvantage of high computational cost. Therefore, the purpose of this paper is to reduce the computational cost of SA by applying prediction models using deep learning and Screening Technique. STREAM/RASTK 2.0 (ST/R2) code system was used to generate training data of prediction models and to perform 3D evaluation of SA. As a simple evaluation code to replace the existing neutronics code, the prediction models of neutronic design parameters using deep learning was developed. As input parameters of the training data, assembly fuel enrichment, fraction of Burnable Poison (BP), number of BP rods, and assembly burnup were selected because they can be obtained from the specifications of assembly without additional calculation. In addition, through performance comparison, Convolutional Neural Network (CNN) was adopted as deep learning method, and prediction models was developed to calculate the peaking factor and the cycle length of the Korean Standard Nuclear Power Plant (OPR-1000). The screening technique was developed to reduce computational cost by reducing the number of 3D evaluations in SA. The existing screening technique is a method of reducing computational cost through 2D evaluations instead of 3D evaluations using neutronics code. In this study, instead of 2D evaluations using neutronics code, the prediction models using deep learning that is faster than the existing code was applied as the simple evaluation code. By applying the prediction models to the screening technique, the computational cost can be further reduced. Also, uncertainty of the final LP due to the error of the prediction models can be reduced. For the design limit setting conditions, independent SA simulation with the screening technique were performed. As the results of the LP optimization using the simple evaluation code, the computational cost of optimization was greatly reduced.