Editor’s Highlight: A Genome-wide Screening of Target Genes Against Silver Nanoparticles in Fission Yeast

Lee, Ah-Reum,Lee, Sook-Jeong,Lee, Minho,Nam, Miyoung,Lee, Sol,Choi, Jian,Lee, Hye-Jin,Kim, Dong-Uk,Hoe, Kwang-Lae ACADEMIC PRESS 2018 TOXICOLOGICAL SCIENCES Vol.161 No.1

<P><B>Abstract</B></P><P>To identify target genes against silver nanoparticles (AgNPs), we screened a genome-wide gene deletion library of 4843 fission yeast heterozygous mutants covering 96% of all protein encoding genes. A total of 33 targets were identified by a microarray and subsequent individual confirmation. The target pattern of AgNPs was more similar to those of AgNO<SUB>3</SUB> and H<SUB>2</SUB>O<SUB>2</SUB>, followed by Cd and As. The toxic effect of AgNPs on fission yeast was attributed to the intracellular uptake of AgNPs, followed by the subsequent release of Ag<SUP>+</SUP>, leading to the generation of reactive oxygen species (ROS). Next, we focused on the top 10 sensitive targets for further studies. As described previously, 7 nonessential targets were associated with detoxification of ROS, because their heterozygous mutants showed elevated ROS levels. Three novel essential targets were related to folate metabolism or cellular component organization, resulting in cell cycle arrest and no induction in the transcriptional level of antioxidant enzymes such as Sod1 and Gpx1 when 1 of the 2 copies was deleted. Intriguingly, <I>met</I>9 played a key role in combating AgNP-induced ROS generation via NADPH production and was also conserved in a human cell line.</P>

Development of Worm-like Polymeric Drug Carriers with Multiple Ligands for Targeting Heterogeneous Breast Cancer Cells

Lee, A-Hyeong,Oh, Kyung-Taek,Baik, Hye-Jung,Lee, Bo-Reum,Oh, Young-Taik,Lee, Don-Haeng,Lee, Eun-Seong Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.8

In this study, wormorm-like polymeric micelles were construted from poly(L-lactic acid)-b-poly(ethyelen glycol) (PLLA-b-PEG) block copolymers via worm-like (or cylindrical) self- assembly that consisted of a relatively long PLLA block ($M_n$ 7K Daltons) at the core and a relatively short PEG block ($M_n$ 2K Daltons) as the shell. Several cancer-targeting moieties (such as folate, cobalamin, and cyclic arginine-glycine-aspartic (RGD) peptide) were chemically coupled with the succinylated or maleimided PEG block of PLLA-b-PEG to act as a cancer cell-specific targeting ligand for breast cancer. The worm-like micelles with muplite cancer cell-specific ligands proved to be successful in recognizing different breast cancer cells at once. This has the potential to aid in cancer-specific drug delivery and to be used as an effective treatment for breast cancer.

Study of Cu-X alloy seed layer on ITO for copper-plated silicon heterojunction solar cells

Lee, Sang Hee,Lee, Doo Won,Kim, Han Jun,Lee, Ah Reum,Lee, Soo Hong,Lim, Kyoung-jin,Shin, Won-suk Elsevier 2018 Materials science in semiconductor processing Vol.87 No.-

<P><B>Abstract</B></P> <P>For the reduction of optical loss and contact material cost in silicon heterojunction (SHJ) solar cells, copper plating has been considered as a suitable metallization technique. Usually, a metal seed layer is deposited on an indium tin oxide (ITO) prior to copper plating for adhesive contact between copper and ITO. As a requirement of suitable seed layer material, contact resistivity (ρ<SUB>c</SUB>) between the seed and the ITO is also important, as well as the adhesion, because high series resistance results in fill factor loss. In this study, we applied alloy seed layers which were deposited by co-evaporating copper with other metals (Cu-X). Contact resistivity values of the samples were extracted by using transfer length method (TLM). Also, tape tests were carried out to simply confirm the adhesion of contacts with different seed layers. Among the Cu-X alloy seed materials, the Cu-Ni alloy film resulted in good adhesion to the ITO as well as low average contact resistivity under 1 mΩ cm<SUP>2</SUP>.</P>

Investigation of Metal Co-evaporated Copper Seed Layers for Copper-Plated Heterojunction Solar Cells

Lee, Sang Hee,Lee, Doo Won,Lee, Ah Reum,Kim, Han Jun,Lee, Soo Hong 한국물리학회 2018 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol. No.

<P>For the reduction of optical loss and contact material cost in silicon heterojunction (SHJ) solar cells, copper plating has been considered as a suitable metallization technique. However, a plated copper contact on an indium-tin-oxide (ITO) generally has low a reliability of adhesion. For this reason, proper seed layer materials are required for adhesive copper plating. As a requirement for a suitable seed layer material, the contact resistance between the seed and the ITO is also important, as well as the adhesion, because high series resistance results in a low fill factor. In this research, we deposited a seed layer by co-evaporating copper with other metals (Cu-X). The contact resistivity (rho (c) ) of the Cu-X deposited on ITO was evaluated by using the transfer length method (TLM). In order to confirm the influence of the work function of the Cu-X, we measured the contact potential difference (CPD) by using photoemission in an air system (PAS). Moreover, phase and we analyzed the crystallite size by using X-ray diffraction (XRD) measurement.</P>

Identification of a New Cytotoxic Biflavanone from Selaginella doederleinii

LEE, Na-Youn,MIN, Hye-Young,LEE, Jun,NAM, Joo-Won,LEE, Yoo-Jin,HAN, Ah-Reum,Adam WIRYAWAN,Wahyu SUPRAPTO,LEE, Sang Kook,SEO, Eun-Kyoung 이화여자대학교 약학연구소 2009 藥學硏究論文集 Vol.- No.19

A new biflavanone, 2,2˝,3,3˝-tetrahydrorobustaflavone 7,4´,7˝-trimethyl ether (1) was isolated from the whole plant of Selaginella doederleinii H_(IERON). (Selaginellaceae) together with the known biflavonoid, robustaflavone 7,4´,7˝-trimethyl ether (2) as the cytotoxic constituents against the three human cancer cell lines, HCT, NCI-H358, and K562. The structure of the new compound 1 was elucidated by spectral analysis including various 1D- and 2D-NMR experiments.

Characterization of the InGaN/GaN Multi-Quantum-Wells Light-Emitting Diode Grown on Patterned Sapphire Substrate with Wide Electroluminescence Spectrum

Lee, Ah Reum,Jeon, Hunsoo,Lee, Gang-Seok,Ok, Jin-Eun,Jo, Dong-Wan,Kim, Kyoung Hwa,Yi, Sam Nyung,Yang, Min,Ahn, Hyung Soo,Cho, Chae-Ryong,Kim, Suok-Whan,Lee, Jae-Hak,Ha, Hong-Ju IOP Publishing 2011 Japanese journal of applied physics Vol.50 No.1

Knockdown of vps54 aggravates tamoxifen-induced cytotoxicity in fission yeast

Lee, Sol,Nam, Miyoung,Lee, Ah-Reum,Baek, Seung-Tae,Kim, Min Jung,Kim, Ju Seong,Kong, Andrew Hyunsoo,Lee, Minho,Lee, Sook-Jeong,Kim, Seon-Young,Kim, Dong-Uk,Hoe, Kwang-Lae Korea Genome Organization 2021 Genomics & informatics Vol.19 No.4

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)-positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) 'biological process' terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7 breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including 'cell cycle' (cdc2, rik1, pas1, and leo1), 'signaling' (sck2, oga1, and cki3), and 'vesicle-mediated transport' (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the 'signaling' GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

Systematic Target Screening Revealed That Tif302 Could Be an Off - Target of the Antifungal Terbinafi ne in Fission Yeast

( Sol Lee ),( Miyoung Nam ),( Ah-reum Lee ),( Jaewoong Lee ),( Jihye Woo ),( Nam Sook Kang ),( Anand Balupuri ),( Minho Lee ),( Seon-young Kim ),( Hyunju Ro ),( Youn-woong Choi ),( Dong-uk Kim ),( Kwa 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.2

We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the Erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.

거울을 활용한 미러링 코칭이 자유형 스트로킹 변화에 미치는 영향

이보람(Lee, Bo-Ram),윤소미(Yun, Somi),정아름(Jung, Ah-Reum),이윤빈(Lee, Yun Bin),이희진(Lee, Hee Jin),이대택(Lee, Dae Daek) 한국웰니스학회 2020 한국웰니스학회지 Vol.15 No.4

본 연구는 자유형 스트로크를 교정하기 위해 수영장 바닥 거울을 사용한 코칭이 효과적인지 분석하는데 목적이 있다, 1년 이상 수영 강습을 받은 성인 30명을 무작위로 Mirror group(MG)과 No mirror group(NMG)으로 나누어 실시하였다. MG(men=12, 32.25±8.2 yrs, 175±5.5 ㎝, 70.9±9.2 ㎏; women=3, 37.6±13.7 yrs, 160.0±3.4 ㎝, 55.6±3.5 ㎏), NMG(men=7, 28.7±6.1 yrs, 176.2±3.7 ㎝, 72.4±14.4 ㎏; women=8, 38.8±14.6 yrs, 162.1±4.4 ㎝, 54.1±7.3 ㎏)은 2.43 m x 4.57 m x 1.37 m 크기의 인공 수조에서 자유형 1분을 실시하였다. 거울제공 여부와 시간의 상호작용이 스트로크 기준점과의 차이에 미치는 효과는 1차 검사에서 NMG: 6.0±3.982 ㎝, MG: 7.67±3.266 ㎝로 집단 간 차이가 1.67 ㎝인 반면, 2차 검사결과 NMG: 5.07±3.788 ㎝, MG: 2.47±3.502 ㎝ 로 집단 간 차이가 2.6 cm 로 나타나 통계적으로 유의하였다(F=20.627, p<.001). 거울 제공 여부와 시간에 따른 스트로크 빈도에 대한 분산분석 결과, 피드백 종류와 1차, 2차 검사의 상호작용이 스트로크 빈도에 미치는 효과는 1차 결과 NMG: 57.67±6.821 score, MG: 60.73±7.294 score에서 2차 결과 NMG: 56.33±6.586 score, MG: 53.67±5.447 score로 통계적으로 유의한 차이가 있는 것으로 나타났다(F=24.807, p<.001). 거울 제공 여부와 사전사후 검사 따른 스트로크 시간에 대한 분산분석을 실시한 결과, 피드백 종류와 1차, 2차 검사의 상호작용이 스트로크 시간에 미치는 효과는 1차 NMG: 2.04±.208 sec, MG: 2.05±.250sec에서 2차 NMG: 2.15±.287 sec, MG: 2.39±.307 sec로 통계적으로 유의한 차이가 나타났다(F=10.813, p<.01). This study analyzed whether coaching recreational swimmers using pool bottom mirror for correcting front crawl stroke is effective in achieving an intended stroke. Thirty adults who enrolled swimming lessons for more than 1 year participated and were randomly divided into two groups; mirror group (MG: 12 men; 32.3±8.2 yrs, 175.0±5.5 ㎝, 70.9±9.2 ㎏: 3 women; 37.6±13.7 yrs, 160.0±3.4 ㎝, 55.6±3.5 ㎏) and control group (CG: 7 men; 28.7±6.1 yrs, 176.2±3.7 ㎝, 72.4±14.4 ㎏: 8 women; 38.8±14.6 yrs, 162.1±4.4 ㎝, 54.1±7.3 ㎏). They performed front crawl twice in a swimming flume (2.43 × 4.57 × 1.37 meter) at their chosen speed (pace of 87.9±4.2 for men, 102.7±4.7 sec/100 meter for women). Their stroke was video recorded by an underwater camera (xnb-6001, Samsung, Korea) and dry land camera (gnd-6020R, Samsung, Korea). After their first trial and recording, individual stroke was evaluated and verbal feedback was given for correction targeting full arm range stroking. During second trial, MG had a mirror (81 × 151 ㎝) installed under the bottom of flume so that they could check their stroke. CG did not use mirror during second trial. An image analyzer (Dartfish, Swiss) was used to analyze the distance between reference point (RP: where fingertip was reached over Vastus lateralis during standing till on land) and fingertip as well as stroke time (time between left hand immersion cycle). Stroke frequency was counted cycles of both arms. Two trials were compared. The distance between RP and fingertip was 7.7±3.3 and 2.5±3.5 ㎝ in MG in 1st and 2nd trial, respectively (p<0.001) while it was 6.0±4.0 and 5.1±3.8 ㎝ in CG. The stroke frequency was 60.7±7.3 in MG and 57.7±6.8 freq/min in CG at 1st trial. It was decreased to 53.7±5.4 in MG (p<0.001), but not in CG (56.3±6.6 freq/min). The stroke time was increased from 2.1±0.3 to 2.4±0.3 sec in MG (p<0.01), but it was not changed in CG (2.1±0.2 vs. 2.2±0.3 sec)(F=10.813, p<.01).

딥러닝을 이용한 임의 관측지에서의 조위 예측

김해림(Haelim Kim),전용호(Yongho Jeon),박재형(Jaehyung Park),윤한삼(Hansam Yoon) 한국해양환경·에너지학회 2021 한국해양환경·에너지학회 학술대회논문집 Vol.2021 No.5

본 연구에서는 임의의 관측지에서의 조위를 예측하기 위하여 인근 조위 관측소의 조위 관측자료를 입력으로 하는 딥러닝 모델을 제시한다. 시계열 데이터 예측에 뛰어나다고 알려져 있는 순환신경망(RNN, Recurrent Neural Network) 모델을 사용하였으며, 모델의 훈련 및 검증을 위하여 울산 조위관측소와 부산 조위관측소의 조위 데이터를 이용하였다. 조위 예측의 정확도를 평가하기 위하여 평균 제곱급 오차(RMSE, Root Mean Square Error) 및 상관계수(CC, Correlation Coefficient)를 계산한 결과, 각각 5cm, 0.95로 높은 정확도가 나타났다. 또한 예측된 데이터를 조화 분해하여 실제 조위 데이터의 결과와 비교하였을 때 4대 분조 모두에서 진폭 정확도 95% 이상, 위상차 4° 이하가 나타났다. In this research, tidal level of an arbitrary station is predicted by using a deep learning model. RNN (Recurrent Neural Network) model is used and tidal level data of Ulsan tide station and Busan tide station is used for model training and validation. To evaluate the model performance, accuracy of the developed model is discussed in terms of root mean square error (RMSE) and correlation coefficient (CC) of the predicted tidal level. The results indicated that the model had a high accuracy. Also, harmonic analysis is conducted to compare similarities with observed data. As a result, accuracy of the amplitude was more than 95% and the phase difference was less than 4° in all four largeness tide value.