3D 프린팅 소재 화학물질의 독성 예측을 위한 Data-centric XAI 기반 분자 구조 Data Imputation과 QSAR 모델 개발

유창규,정찬혁,김상윤,허성구,SHAHZEBTARIQ,신민혁 한국화학공학회 2023 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.61 No.4

As accessibility to 3D printers increases, there is a growing frequency of exposure to chemicals associated with 3D printing. However, research on the toxicity and harmfulness of chemicals generated by 3D printing is insufficient, and the performance of toxicity prediction using in silico techniques is limited due to missing molecular structure data. In this study, quantitative structure-activity relationship (QSAR) model based on data-centric AI approach was developed to predict the toxicity of new 3D printing materials by imputing missing values in molecular descriptors. First, MissForest algorithm was utilized to impute missing values in molecular descriptors of hazardous 3D printing materials. Then, based on four different machine learning models (decision tree, random forest, XGBoost, SVM), a machine learning (ML)-based QSAR model was developed to predict the bioconcentration factor (Log BCF), octanol-air partition coefficient (Log Koa), and partition coefficient (Log P). Furthermore, the reliability of the data-centric QSAR model was validated through the Tree-SHAP (SHapley Additive exPlanations) method, which is one of explainable artificial intelligence (XAI) techniques. The proposed imputation method based on the MissForest enlarged approximately 2.5 times more molecular structure data compared to the existing data. Based on the imputed dataset of molecular descriptor, the developed data-centric QSAR model achieved approximately 73%, 76% and 92% of prediction performance for Log BCF, Log Koa, and Log P, respectively. Lastly, Tree-SHAP analysis demonstrated that the data-centric-based QSAR model achieved high prediction performance for toxicity information by identifying key molecular descriptors highly correlated with toxicity indices. Therefore, the proposed QSAR model based on the data-centric XAI approach can be extended to predict the toxicity of potential pollutants in emerging printing chemicals, chemical process, semiconductor or display process.

납(Pb)이 생쥐 신장조직의 미세구조에 미치는 영향

劉昌奎,崔林淳 연세대학교 자연과학연구소 1986 學術論文集 Vol.17 No.-

This study was made to investigate the ultrastructural changes of the male mouse(ICR strain) kidney tissue affected by lead(Pb). Pb, as a form of Pb(CH_3COO)_2 was injected within the peritoneal cavity at the time interval of 24 hrs, 48 hrs and 72 hrs form injection time. In the meantime, electron microscopy was used to investigate the histologic changes occured in control animals, experimental animals. In kidney cells of experimental animals, changes of the nuclear chromatin were little, but cristae of mitochondria presented in cytoplasm was impaired, vacuolation was risen, thoseby many vacuole was formed. Especially, in the case of 5 mg/kg and 10mg/kg Pb concentration, mitochondrial presented in cytoplasm was considerably deformed. While, with 20 mg/kg of Pb(CH_3COO)_2, it was observed that normal structure was presented in the nucleus, electrodensity in cytoplasm was decreased mostly, but mitochondrial deform was slightly decreased.

Modeling, multiresolution analysis and process monitoring for an integrated wastewater treatment management system

유창규,이인범 대한환경공학회 2005 대한환경공학회 학술발표논문집 Vol.2005 No.12

수종 중금속에 의한 생쥐 간조직의 미세구조에 관한 연구

劉昌奎,崔林淳 연세대학교 자연과학연구소 1986 學術論文集 Vol.16 No.-

Hg와 Cu가 생체에 미치는 영향을 조사하기 위하여 ICR 계통의 숫 생쥐를 사용하여 각각 상이한 농도의 시료를 투여한 후 간조직 세포에서 일어나는 조직학적 변화를 관찰하였다. 생리적 식염수(0.86% NaCl Soln.)만을 투여한 대조군에서는 대체로 정상적인 구조를 하고 있는 핵과 전자밀도가 높은 세포 소기관들의 뚜렷한 형태를 관찰할수 있었으나, HgCl_2를 처리한 경우 1 mg을 투여하여 24 시간 및 48 시간 경과 후에는 핵질 내부의 인과 염색질이 분산되었고 세포질의 전자밀도도 낮아졌으며, 특히 mitochondria의 내부구조가 다소 변형 되었다. 5 mg의 처리군에서는 핵질 내부의 염색질이 분산되어 핵막 주위로 응집되었고, 세포질의 전자밀도는 낮아졌으며 mitochondria 내부가 대체로 붕괴되었다. 10 mg의 같은 시료를 투여 하였을때는 염색질이 핵막 주변 부위에 응집 분산됨은 여전하였고 과량의 glycogen과립들이 세포질 부위에서 관찰 되었다. CuSO_4를 투여한 경우에는 1 mg을 투여하여 24 시간 및 48시간 경과 후에는 대체로 핵질 내부의 염색질 응집과 세포질의 mitochondria가 퇴행 및 공포화 하는 경향으로 나타났다. 5 mg의 동시료를 처리한 경우에는 세포질내의 전자밀도가 대체로 낮아졌고 특히 소포체에 부착된 ribosome의 유리현상이 뚜렷하였다. CuSO_4 10mg을 투여한 군에서는 다소 회복되는 경향을 보여 심한 변화는 없었으나 glycogen 과립들의 수는 증가 하였다. This study was investigated to effects of Hg and Cu on individuals. The male mice of ICR strain were used and histological changes were observed in the hepatic cell following different concentrations of metal injection. In controls with 0.86% NaCl soln., normal structures were seen in nucleus, and cell organelles with normal structures had high electrodensity. After 24 hours and 48 hours treatment with 1 mg of HgCl_2, both nucleus and chromatin dispersed within nucleoplasm, decreased electrodensity of cytoplasm was observed, and especially internal structures of mitochondria were slightly transformed. In the case of 5 mg/kg injection, chromatin within nucleoplasm was dispersed, and aggregated around the nuclear membrane. The electrodensity of the cytoplasm was decreased and the clear disruption was occured in mitochondria. With 10 mg/kg, cytoplasm was aggregated and dispersed around the nuclear membrane, much glycogen granules presented in cytoplasm. When CuSO_4 1 mg/kg injection was performed, after 24 hours and 48 hours, aggregation of chromatin was seen, and mitochondria of cytoplasm were vacuolated. With 5 mg of CuSO_4, the electrodensity of cytoplasm was generally decreased, and endoplasmic reticulum bound ribosomes were profoundly segregated. At 10 mg of CuSO_4, recovery was more and less begun, and few alterations were severe. The number of glycogen granules increased.

산업체의 용수 및 폐수 최소화를 위한 Water pinch 기술동향 및 사례연구

유창규,이태영,이인범,문정기,전희동 대한환경공학회 2005 대한환경공학회 학술발표논문집 Vol.2005 No.12

생쥐의 Alkaline Phosphatase 활성에 미치는 in vivo와 in vitro에서의 인삼 Saponin과 그 분획물의 영향

劉昌奎,鄭魯八 연세대학교 자연과학연구소 1979 學術論文集 Vol.4 No.-

인대사에 관계하는 alkaline phosphatase(AP)의 활성에 미치는 영향을 알기 위하여 인삼(Panax ginseng C.A. Meyer)의 total saponins(T), butanol extracted saponins(B), diol계(DS), 와 triol계 saponin(TS)을 주사한 후 4시간, 12시간에 숫생쥐(Mus musoulus L.)의 소장과 콩팥에서 AP활성의 변화 및 소장의 AP활성에 대한 인삼성분의 in vitro에서의 영향을 관찰하였다. (1) 4시간후 소장에서의 AP활성은 35.9%(T) 69.9%(B), 56.4%(DS)와 34.4%(TS)의 유의성 있는 증가를 나타내었으며, 콩팥에서는 3.0%(TS)를 제외하고는 31.1%(T), 63.2%(B), 35.5%(DS)모두가 유의성 있게 증가하였다. (2) 12시간후 소장에서는 61.6%(T), 43.8%(B), 37.9%(DS), 24.7%(TS)로 모두가 유의성 있게 증가하였으며, 콩팥에서는 56.6%(T)를 제외하고는 모두가 유의성 없는 약간의 활성증가만 일으켰다. (3) In vitro 실험에서, 4×10^-5%(T), 2×10^-5%(B)와 1×10^-5%(DS와TS)의 농도에서 AP의 최고활성을 나타냈고, 그 전후 농도에서는 증가가 다소 감소하였다. 그리고 4×10^-5%의 DS와TS농도에서는 AP활성이 -36.4%와 -30.7%로 감소되는 현상이 나타났다. Influence of Korean Ginseng(Panax ginseng C.A. Meyer) extracts in saline on the activity of alkaline phosphatase(AP) produced in intestine and kidney of the male mice(Mus musoulus L.) was studied in vitro by injection of ginseng fraction in mice and in vitro by treatment of enzyme with ginseng extracts. Mice were injected with 0.1mg of total saponins(T), 0.02mg of butanol extracted saponins(B), 0.01mg of diol fraction(DS), and triol fraction(TS) saponin per 10g of weight of mice. AP activities in intestine and kidney at 4 and 12 hour intervals after injection were determined and the results are as follow: (1) In the 4 hour series the activites of AP were significantly increased in intestine; 35.9% (T), 69.9%(B), 56.4% (DS), and 34.4% (TS) relative to the saline control and in kidney 31.1% (T), 63.2% (B), 35.5% (DS), 3.0% (TS). (2) In the 12 hour series, the AP activities in intestine were also increased; 61.6% (T), 43.8% (B), 37.9% (DS), 24.7% (TS). In kidney, however, the increment of AP activities were not significant except the lot of total saponin (T). (3) In vitro experiment with small intestine homogenate, maximum AP activities were seen at 4×10^-5% (T), 2×10^-5% (B), and 1×10^-5% (DS & TS) of saponin concentrations, but they were decreased at higher or lower saponin concentrations. At 4×10^-5% of DS and TS concentrations, for instance, the AP activities were decreased by 36.4% and 30.7% respectively from the saline controls.

Soft sensor and adaptive model-based dissolved oxygen control for biological wastewater treatment process

유창규,이인범 대한환경공학회 2005 대한환경공학회 학술발표논문집 Vol.2005 No.12

생태산업단지의 사례연구 및 구축 전략

유창규,허순기,신지나,윤학모,박용준,전희동,이인범 대한환경공학회 2005 대한환경공학회 학술발표논문집 Vol.2005 No.12

高麗의 白丁 農民

유창규 전남사학회 1997 역사학연구 Vol.11 No.-

전자현미경을 이용한 중금속 Cadmium투여에 따른 생쥐비장조직의 미세구조에 관한 연구

劉昌奎,崔林淳 연세대학교 자연과학연구소 1987 學術論文集 Vol.19 No.-

Cadmium이 생쥐(ICR strain) 비장조직의 백수부위에 미치는 미세구조의 변화를 연구하기 위하여 cadmium을 CdCl_2 형태로 체중 ㎏당 1㎎과 5㎎씩을 생쥐의 복강에 처리한 후, 24시간, 48시간, 그리고 72시간 경과된 후로 구분하여 전자현미경을 사용하여 비장 백수부위의 림파구에서 일어나는 조직학적 변화를 관찰하였다. 생리적 식염수(0.86% NaCl soln.)만을 처리한 대조군에서는 대체로 정상형태의 림파구 핵과 비교적 밀도가 높은 세포질이 발견되나, 1㎎을 처리하였을 경우, 24시간이 경과하면서 세포질에 분포하는 mitochondria의 팽윤정도가 대조군보다 커졌으며, 48시간까지 지속되었다. 그러나, 핵, 소포체 등 다른 세포내 소기간에서의 형태변화는 관찰할 수 없었다. 5㎎을 처리하였을 경우에는 24시간이 경과하면서부터 lysosome이 출현하였고, lysosome은 48시간 및 72시간이 경과할 때까지 계속 존재하였다. 그러나 mitochondria의 경우는 1㎎처리군과 달리 다소 팽윤된 상태로 나타났으며, 핵질부에서는 염색질의 분산이 불규칙하게 관찰되었고 핵봉입체의 생성은 찾아 볼 수 없었다. 그러므로 cadmium의 급성중독에 의한 비장백수부위의 림파구에 있어서 형태학적 변화는 크지 않으나 효소의 활성 작용은 활발한 것으로 보여진다. In study of the cadmium effects on the white pulp of mouse spleen(ICR strain), Cd was intraperitoneally injected as CdCl_2(1㎎ and 5㎎/㎏ body weight) and changes of lymphocyte structure observed at 24hrs, 48hrs, and 72hrs elapsed. A group treated with saline(0.86% NaCl solution) only, showed normal lymphocyte nucleus and relatively dense cytoplasm. Those treated with 1㎎ CdCl_2, mitochondria when compared to controls were much swollen after 24hrs and this continued to 48hrs. No changes on other organelles were observed. Those treated with 5㎎ CdCl_2, lysosomes appeared after 24hrs and this continued to 48hrs and even after 72hrs. However, swollen mitochondria appeared with Cd, 5㎎/㎏ body weight, compared to 1㎎/㎏ body weight exposure and irregular chromosomal distribution was observed in nucleus but no inclusion bodies were found. Therefore, on acute exposure of lymphocytes of white pulp to Cd, morphological changes were not significant but effects on enzyme activity appeared significantly.