Subacute toxicity and toxicokinetics study of DHP107, an oral paclitaxel formulation with once-weekly dosing in mice

Kim, Ji-Young,Lee, Sunyeong,Kim, Yongbum,Jeong, Eun Ju,Lee, In-Hyun,Son, Min-Hee,Lee, Jae Young,Kim, Sang Kyum,Moon, Kyoung-Sik Elsevier 2019 Regulatory toxicology and pharmacology Vol.103 No.-

<P><B>Abstract</B></P> <P>DHP107, an oral formulation of paclitaxel, is effectively and systemically absorbed in intestinal endothelial cells. Although the <I>in vivo</I> efficacy of DHP107 has been reported, the potential toxicity of DHP107 has not been evaluated. Therefore, this study was conducted to evaluate the toxicity and toxicokinetics of DHP107 orally administered to ICR mice at 25, 50, and 100 mg/kg via once-weekly dosing for six weeks. DHP107-related clinical signs were observed in both sexes at 100 mg/kg. There were significant increases in the number of platelets and percentages of reticulocytes and basophils in male mice. Also in males, there was a significant decrease in the absolute and relative weights of testes, epididymides, kidneys, and heart. Relative spleen weights were significantly increased in males treated with doses ≥50 mg/kg which had histopathological correlates. These changes were reversible after a two-week recovery period with the exception of the findings in the reproductive organs. Systemic exposure to paclitaxel increased with DHP107 doses in single and multiple dosing with no marked differences between sexes. In conclusion, the target organs were determined to be the reproductive and hematopoietic organs in male mice, suggesting of sex difference and the NOAEL of DHP107 was established to be < 25 mg/kg for males and 50 mg/kg for females.</P> <P><B>Highlights</B></P> <P> <UL> <LI> DHP107 is an oral cancer therapy containing paclitaxel as a single active ingredient. </LI> <LI> The target organs of DHP107 were reproductive and hematopoietic organs. </LI> <LI> The systemic exposure was increased dose-dependently. </LI> <LI> The NOAEL of DHP107 was under 25 mg/kg for males, and 50 mg/kg for females. </LI> </UL> </P>

A Novel Capacitorless DRAM Cell Using Superlattice Bandgap-Engineered (SBE) Structure With 30-nm Channel Length

Sunyeong Lee,Ja Sun Shin,Jaeman Jang,Hagyoul Bae,Daeyoun Yun,Jieun Lee,Dae Hwan Kim,Dong Myong Kim IEEE 2011 IEEE TRANSACTIONS ON NANOTECHNOLOGY Vol.10 No.5

<P>We propose a novel SiGe superlattice bandgap-engineered (SBE) capacitorless dynamic random access memory (DRAM) cell with 30-nm channel length as a next-generation DRAM cell with high storage density and long retention time for practical implementation by 2-D technology computer-aided design simulation. The SBE capacitorless DRAM cell uses a common source structure and different metal layers for the top gate word line (WL) from the bottom gate WL to realize a 6F<SUP>2</SUP> feature size. Thanks to the Si<SUB>0.8</SUB>Ge<SUB>0.2</SUB> superlattice quantum well and silicon dioxide (SiO<SUB>2</SUB>) physical barrier, we obtained 213 μA/μm for the sensing margin and about 10 ms for the retention time.</P>

A Novel Self-Aligned 4-Bit SONOS-Type Nonvolatile Memory Cell With T-Gate and I-Shaped FinFET Structure

Sunyeong Lee,Yong Woo Jeon,Tsu-Jae King Liu,Dae Hwan Kim,Dong Myong Kim IEEE 2010 IEEE transactions on electron devices Vol.57 No.8

<P>We propose a novel 4-bit self-aligned SONOS-type nonvolatile memory (NVM) cell with a T-gate and I-shaped FinFET structure for practical implementation with high storage density and better reliability. In order to obtain enhanced reliability characteristics, a modified Fowler-Nordheim tunneling mechanism is employed for programming along the channel length direction, while a band-to-band hot hole injection is used for erasing along the channel width direction. With separated paths for program and erase, improved device performance is obtained with sensing margin. In order to improve the immunity to second-bit effects, the gate-induced drain leakage current method, which is a charge detection method and highly sensitive to the locally stored charges, is employed for the reading of the stored data. In terms of the scalability, we confirmed by 2-D technology computer-aided design simulation that the proposed NVM cell with channel length <I>L</I> = 50 nm operates with enough sensing margin and high-density ( ~ 5 F<SUP>2</SUP>/bit) NVM by the crossed cell array architecture.</P>

유아예술교육에 대한 교사의 개념도 분석

김선영 ( Sunyeong Kim ),이진화 ( Jinwha Lee ) 사단법인 아시아문화학술원 2021 인문사회 21 Vol.12 No.6

본 연구는 2019 개정 누리과정 예술경험 교육내용에 대한 유아교사의 지식 정도를 분석하기 위해 A광역시에 위치한 어린이집, 유치원 3-5세 담임교사 총 45명을 대상으로 개념도를 작성하였다. 개념도를 분석한 결과 유아교사의 예술경험 교육내용의 상위개념은 총 134개였고, ‘미술’과 ‘음악’, ‘움직임과 춤’의 개념에 대해 많은 비중을 두고 있었다. 종속개념은 음악이 116개, 미술이 108개로 움직임과 춤, 동극, 감상에 비해 약4배 이상 많은 것으로 나타났다. 본 연구 결과를 토대로 유아들에게 교과 형태로 예술교육을 제공하는 것에 대한 교사의 반성적 고찰이 필요하다는 사실을 지적하면서, 단순모방이나 재연학습을 넘어 유아들의 미적 감성을 함양시키기 위해 교사 스스로 미적 감성을 함양하는 자세가 필요하다는 점을 제안하였다. 이를 위해 예비교사와 현직교사의 예술교육의 내용지식을 강화하고, 이를 유아들과 함께 공유하고 활용할 수 있도록 예비교사와 현직교사를 대상으로 하는 교사교육 프로그램 제공이 필요하다는 점을 강조하였다. The purpose of the study to analyze the level of early childhood teacher’s knowledge on art experience education, 45 teachers from daycare centers and kindergartens located in A metropolitan city wrote a concept map. According to the analysis of the concept map, there were a total of 134 upper-level terms concepts in the education contents of art experience of early childhood teachers, and much emphasis was placed on the concepts of “art”, “music”, and “movement and dance.” The subordinate concepts include 116 music and 108 in art, which was four times more than movement, dance, bronze, and appreciation. Based on this study, it suggested that efforts should be made to reflect on providing art education to early childhood by dividing them as subjects. Teachers must have an attitude of cultivating their own aesthetic sensibility in order to provide an education that develops children’s aesthetic sensibility beyond simple imitation or replay learning. And also, pre- and in service teacher education programs should be provided so that they can strengthen and utilize content knowledge to preemptively understand art education and share it with young children.

Optical Charge Pumping Technique for Extracting Interface States of Nano-Scale SONOS Flash Memories

Lee Sunyeong,김대환,Choi Chang-Min,Jeon Ki-Chan,Kang Gu-Cheol,Kim Dong Myong,Kim Kwan-Young,Kim Se-Woon,Lee Jang-Uk,Lee Jong Duk,Park Jun-Hyun,박병국,Park So-Ra,Roh Kang-Seob,Seo Seung-Hwan,Shin Hyungcheol 한국물리학회 2007 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.51 No.III

The optical charge pumping (CP) technique is proposed as a simple and fast method for extracting the energy distribution of interface trap, $D_{it}$, of silicon-oxide-nitride-oxide-silicon (SONOS) flash memories. It is based on the optical response of a subthreshold slope of a SONOS memory cell transistor and is more effectively applicable to nano-scale emerging devices than the conventional CP technique, because no electrical pulse is required during extraction and because the current is measured not from the substrate, but from the drain contact. This means that a large gate current can be easily corrected by monitoring both the gate current and the drain current, no parasitic effect is caused by excluding the pulse measurement setup, and the extraction of $D_{it}$ in devices on silicon-on-insulator substrates is possible. The results applied to SONOS memories show that the generation rate of interface traps with program/erase cycles is higher in the NAND flash scheme rather than in the NOR flash scheme.

Tumorigenicity Evaluation of Umbilical Cord Blood-derived Mesenchymal Stem Cells

Park, Sang-Jin,Kim, Hyun-Jung,Kim, Woojin,Kim, Ok-Sun,Lee, Sunyeong,Han, Su-Yeon,Jeong, Eun Ju,Park, Hyun-shin,Kim, Hea-Won,Moon, Kyoung-Sik Korean Society of ToxicologyKorea Environmental Mu 2016 Toxicological Research Vol.32 No.3

Mesenchymal stem cells (MSCs) have been identified in multiple types of tissue and exhibit characteristic self-renewal and multi-lineage differentiation abilities. However, the possibility of oncogenic transformation after transplantation is concerning. In this study, we investigated the tumorigenic potential of umbilical cord blood-derived MSCs (hUCB-MSCs) relative to MRC-5 and HeLa cells (negative and positive controls, respectively) both in vitro and in vivo. To evaluate tumorigenicity in vitro, anchorage-independent growth was assessed using the soft agar colony formation assay. hUCB-MSCs and MRC-5 cells formed few colonies, while HeLa cells formed a greater number of larger colonies, indicating that hUCB-MSCs and MRC-5 cells do not have anchorage-independent proliferation potential. To detect tumorigenicity in vivo, hUCB-MSCs were implanted as a single subcutaneous injection into BALB/c-nu mice. No tumor formation was observed in mice transplanted with hUCB-MSCs or MRC-5 cells based on macro- and microscopic examinations; however, all mice transplanted with HeLa cells developed tumors that stained positive for a human gene according to immunohistochemical analysis. In conclusion, hUCB-MSCs do not exhibit tumorigenic potential based on in vitro and in vivo assays under our experimental conditions, providing further evidence of their safety for clinical applications.

Separate Extraction of Source, Drain, and Substrate Resistances in MOSFETs With Parasitic Junction Current Method

Hagyoul Bae,Seok Cheon Baek,Sunyeong Lee,Jaeman Jang,Ja Sun Shin,Daeyoun Yun,Hyojong Kim,Dae Hwan Kim,Dong Myong Kim IEEE 2010 IEEE electron device letters Vol.31 No.11

<P>The separate extraction of asymmetric source (<I>R</I><SUB>S</SUB>) and drain (<I>R</I><SUB>D</SUB>) resistances caused by the variations in the layout, process, and device degradation is important in the practical modeling and characterization of MOSFETs and their integrated circuits. We propose a simple “parasitic junction current method” (PJCM) for the separate extraction of <I>R</I><SUB>S</SUB>, <I>R</I><SUB>D</SUB>, and <I>R</I><SUB>SUB</SUB> (substrate resistance) in MOSFETs. We applied the proposed PJCM to n-channel MOSFETs with different <I>W</I>/<I>L</I> combinations and verified its usefulness in the robust extraction of <I>R</I><SUB>S</SUB>, <I>R</I><SUB>D</SUB>, and <I>R</I><SUB>SUB</SUB>.</P>

Effects of the DNA repair inhibitors, cytosine arabinoside and 3‑aminobenzamide, on the frequency of radiation‑induced micronuclei, nuclear buds, and nucleoplasmic bridges

Yoon Hee Cho,Yang Jee Kim,Sunyeong Lee,Kyung‑in Joung,Hai Won Chung,Sunmi Kim,Su Young Kim 한국유전학회 2020 Genes & Genomics Vol.42 No.6

Background Micronuclei (MN), nuclear bud (NBud), and nucleoplasmic bridge (NPB) are suggested as biomarkers for radiation exposure; however, they have not been extensively studied to understand the underlying mechanisms responsible for their formation. Objectives To (1) validate NBud and NPB within the cytokinesis-blocked micronucleus (CBMN) assay as biomarkers for radiation exposure and (2) determine the effects of the DNA repair inhibitors, cytosine arabinoside (Ara C) and 3-aminobenzamide (3-AB) on radiation-induced MN, NBud, and NPB formation. Methods Human blood samples were irradiated with 0–3 Gy X-rays and subsequently treated with Ara C and 3-AB. CBMN and chromosome aberration assays were carried out to measure MN, NBud, and NPB and dicentric chromosomes, respectively. Results The frequency of radiation-induced MN, NBud, and NPB increased in a dose-dependent manner. The frequency of MN, NBud, and NPB was highly and positively correlated with the dicentric chromosome, a standard biomarker for biodosimetry (r > 0.98, p < 0.0001). Furthermore, Ara C increased the frequency of MN, NBud, and NPB, whereas 3-AB increased the frequency of MN and NPB, but not NBud. Further, the potentiating effect of Ara C on the frequency of MN, NBud, and NPB was greater than that of 3-AB. Conclusion Our results validate NBuds and NPBs as independent valuable markers of radiation exposure. Additionally, we suggest that different mechanisms are likely involved in the formation of NBuds and NPBs following X-irradiation; however, additional studies are warranted to better understand the contribution of distinct DNA repair pathways to the formation of radiation-induced damages.

Tumorigenicity Evaluation of Umbilical Cord Blood-derived Mesenchymal Stem Cells

Sang-Jin Park,Hyun-Jung Kim,Woojin Kim,Ok-Sun Kim,Sunyeong Lee,Su-Yeon Han,Eun Ju Jeong,Hyun-shin Park,Hea-Won Kim,Kyoung-Sik Moon 한국독성학회 2016 Toxicological Research Vol.32 No.3

Mesenchymal stem cells (MSCs) have been identified in multiple types of tissue and exhibit characteristic self-renewal and multi-lineage differentiation abilities. However, the possibility of oncogenic transformation after transplantation is concerning. In this study, we investigated the tumorigenic potential of umbilical cord blood-derived MSCs (hUCB-MSCs) relative to MRC-5 and HeLa cells (negative and positive controls, respectively) both in vitro and in vivo. To evaluate tumorigenicity in vitro, anchorage-independent growth was assessed using the soft agar colony formation assay. hUCB-MSCs and MRC-5 cells formed few colonies, while HeLa cells formed a greater number of larger colonies, indicating that hUCBMSCs and MRC-5 cells do not have anchorage-independent proliferation potential. To detect tumorigenicity in vivo, hUCB-MSCs were implanted as a single subcutaneous injection into BALB/c-nu mice. No tumor formation was observed in mice transplanted with hUCB-MSCs or MRC-5 cells based on macroand microscopic examinations; however, all mice transplanted with HeLa cells developed tumors that stained positive for a human gene according to immunohistochemical analysis. In conclusion, hUCBMSCs do not exhibit tumorigenic potential based on in vitro and in vivo assays under our experimental conditions, providing further evidence of their safety for clinical applications.

Erratum: 달맞이순 (Oenothera laciniata) 에탄올 추출물 섭취가 고지방식이로 유도한 비만 마우스에서 항산화 및 비만억제효과

곽충실,김미주,김선기,박순영,김인규,강흔수,Kwak, Chung Shil,Kim, Mi-Ju,Kim, Sun Gi,Park, Sunyeong,Kim, In Gyu,Kang, Heun Soo 한국영양학회 2020 Journal of Nutrition and Health Vol.53 No.6