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Design, synthesis and anticancer activity of fluorocyclopentenyl-purines and – pyrimidines
Yoon, Ji-seong,Jarhad, Dnyandev B.,Kim, Gyudong,Nayak, Akshata,Zhao, Long Xuan,Yu, Jinha,Kim, Hong-Rae,Lee, Ji Yun,Mulamoottil, Varughese A.,Chandra, Girish,Byun, Woong Sub,Lee, Sang Kook,Kim, Yong-Ch Elsevier 2018 European journal of medicinal chemistry Vol.155 No.-
<P><B>Abstract</B></P> <P>Based on the potent anticancer activity of 6′-fluorocyclopentenyl-cytosine <B>2b</B> in phase IIa clinical trials for the treatment of gemcitabine-resistant pancreatic cancer, we carried out a systematic structure-activity relationship study of 6′-fluorocyclopentenyl-pyrimidines <B>3a</B>-<B>i</B> and -purines <B>3j</B>-<B>o</B> to discover novel anticancer agents. We also synthesized the phosphoramidate prodrug <B>3p</B> of adenine derivative <B>1b</B> to determine if the anticancer activity depended on the inhibition of DNA and/or RNA polymerase in cancer cells and/or on the inhibition of <I>S</I>-adenosylhomocysteine (SAH) hydrolase. All of the synthesized pyrimidine nucleosides exhibited much less potent anticancer activity <I>in vitro</I> than the cytosine derivative <B>2b</B>, acting as RNA and/or DNA polymerase inhibitor, indicating that they could not be efficiently converted to their triphosphates for anticancer activity. Among all the synthesized purine nucleosides, adenine derivative <B>1b</B> and <I>N</I> <SUP>6</SUP>-methyladenine derivative <B>3k</B> showed potent anticancer activity, showing equipotent inhibitory activity as the positive control, neplanocin A (<B>1a</B>) or Ara-C. However, the phosphoramidate prodrug <B>3p</B> showed less anticancer activity than <B>1b</B>, indicating that it did not act as a RNA and/or DNA polymerase inhibitor like <B>2b</B>. This result also demonstrates that the anticancer activity of <B>1b</B> largely depends on the inhibition of histone methyltransferase, resulting from strong inhibition of SAH hydrolase. The deamination of the <I>N</I> <SUP>6</SUP>-amino group, the addition of the bulky alkyl group at the <I>N</I> <SUP>6</SUP>-amino group, or the introduction of the amino group at the C2 position almost abolished the anticancer activity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Eighteen 6′-fluorocyclopentenyl-pyrimidines and -purines were designed and synthesized. </LI> <LI> The mechanism of action of the cytosine analog <B>2b</B> is related to the inhibition of DNA/RNA polymerase. </LI> <LI> The mechanism of action of the adenosine analogs, <B>1b</B> and <B>3k</B> is related to the inhibition of SAH hydrolase. </LI> <LI> The inhibition of SAH hydrolase is associated with the inhibition of histone methyltransferase. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
The Efficacy of Bisphosphonates for Prevention of Osteoporotic Fracture: An Update Meta-analysis
Byun, Ji-Hye,Jang, Sunmee,Lee, Sumin,Park, Suyeon,Yoon, Hyun Koo,Yoon, Byung-Ho,Ha, Yong-Chan The Korean Society for Bone and Mineral Research 2017 대한골대사학회지 Vol.24 No.1
<P><B>Background</B></P><P>The efficacy of bisphosphonates for osteoporotic fracture has been consistently reported in recent randomized controlled trials (RCTs) enrolling hundreds of patients. The objective of this study was to update knowledge on the efficacy of available bisphosphonates in the prevention of vertebral and non-vertebral fractures.</P><P><B>Methods</B></P><P>An approach “using systematic reviews” on PubMed and Cochrane Library was taken. Twenty-four RCTs investigating the effects of bisphosphonates for the prevention of osteoporotic fracture were included in final analysis. A pairwise meta-analysis was conducted with a random effects model. Subgroup analysis was performed according to the type of bisphosphonate.</P><P><B>Results</B></P><P>The use of bisphosphonate decrease the risk of overall osteoporotic fracture (odds ratio [OR] 0.62; <I>P</I><0.001), vertebral fracture (OR 0.55; <I>P</I><0.001) and non-vertebral fracture (OR 0.73; <I>P</I><0.001). Subgroup analysis indicated that zoledronic acid showed the lowest risk reduction (OR 0.61; <I>P</I><0.001) for overall osteoporotic fractures but no significance was observed for etidronate (OR 0.34; <I>P</I>=0.127).</P><P><B>Conclusions</B></P><P>This update meta-analysis re-confirmed that bisphosphonate use can effectively reduce the risk of osteoporotic fracture. However, there is a lack of evidence regarding etidronate for the prevention of osteoporotic fracture.</P>
지윤희(Yoon Hee Ji),배호석(Ho Seuk Bae),변기훈(Gi-Hoon Byun),김재수(Jea Soo Kim),김우식(Woo-Shik Kim),박상윤(Sang-Yoon Park) 한국해양공학회 2014 韓國海洋工學會誌 Vol.28 No.5
A multi-static SONAR system consists of the transmitters and receivers separately in space. The active target echoes are received along the transmitter-target-receiver path and depend on the shape and aspect angle of the submerged objects at each receiver. Thus, the target echo algorithm used with a mono-static system, in which the transmitter and receiver are located at the same position, has limits in simulating the target echoes for a multi-static SONAR system. In this paper, a target echo modeling procedure for a 3D submerged object in space is described based on the Kirchhoff approximation, and the SONAR system is extended to a multi-static SONAR system. The scattered field from external structures is calculated on the visible surfaces, which is determined based on the locations of the transmitter and receiver. A series of experiments in an acoustic water tank was conducted to measure the target echoes from scaled targets with a single transmitter and 16 receivers. Finally, the numerical results were compared with experimental results and shown to be useful for simulating the target echoes/target strength in a multi-static SONAR system.
쇼핑의 편의성 증진을 위한 오프라인 매장 전용 모바일 앱 서비스 제안 : 올리브영 매장을 중심으로
윤영서(Young-seo Yoon),김정윤(Jeong-yoon Kim),변수영(Su-young Byun),윤지수(Ji-soo Yoon) 한국HCI학회 2024 한국HCI학회 학술대회 Vol.2024 No.1
올리브영은 현재 높은 인지도와 매출 이익을 기록하고 있지만, 오프라인 매장 이용 고객의 불편사항은 꾸준히 존재하는 실정이다. 이를 해결하기 위해 본 연구는 설문조사와 인터뷰를 바탕으로 상품 관리 및 고객 안내 측면에서 발생하는 문제점을 확인한다. 이를 토대로 고객이 원하는 상품을 전자적인 형태의 장바구니로 담는 모바일 장바구니 앱 서비스를 제안한다.
[P498] Acquired dermal melanocytosis confined to the hand
( Ji-young Jun ),( Hyun Jeong Byun ),( Se Jin Oh ),( Seunghwan Oh ),( Ji-hye Park ),( Jong-hee Lee ),( Dong-yoon Lee ),( Joo-heung Lee ),( Jun-mo Yang ) 대한피부과학회 2017 대한피부과학회 학술발표대회집 Vol.69 No.1
Acquired dermal melanocytosis (ADM) classically occurs on the face of Asian women. However, extrafacial ADM is uncommon, especially those that are on the extremities. To our knowledge, there are only six cases of ADM confined to the hands. We present a 40-year-old Korean woman who has brown to blue pigmentation on left hand. The pigmentation was prominent on and around palmar creases and on the knuckle joints of the dorsum of a hand. She was both-handed, and denied any history of preceding trauma, inflammation, or occupational exposure to chemicals. Histopathological examination revealed scattered spindle-shaped cells with melanin granules and melanophages in the upper to middle dermis. We review the published work for ADM on the hands and suggest that ADM confined to hands may be a new entity.
Alitretinoin as a promising drug in two patients of recalcitrant Twenty Nail Dystrophy
( Ji Hye Heo ),( Seon Bok Lee ),( Hee Seong Yoon ),( Si Hyub Lee ),( Seung Dohn Yeom ),( Ji Won Byun ),( Jeonghyun Shin ),( Gwang Seong Choi ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.1
Twenty nail dystrophy is widespread trachyonychia involving all 20 nails. The cause of this is diverse and it can occur idiopathically. There are many treatment modalities reported but no standard evidence-based approaches. The use of topical and/or systemic corticosteroids or triamcinolone intralesional injection (TA ILI) in the nail matrix can be considered as a treatment modality. We experienced complete resolution in two cases of twenty nail dystrophy with oral alitretinoin 30 mg per day. Patient 1 was a 52-year-old woman with 3-month history of twenty nail dystrophy. She treated with systemic and topical anti-fungals for 4 months and TA ILI was administered monthly, but the symptoms worsened. Treatment with alitretinoin 30 mg per day was added. After 4 months, there was improvement of the nails, and the complete improvement was observed at the end of the treatment with a total of 9 months of alitretinoin. Patient 2 was a 62-year-old woman with 10-year history of twenty nail dystrophy. Previously she had treated with TA ILI, but it had not been effective. Treatment with alitretinoin 30 mg per day was added and the nails improved after 10 months. 18 months after the alitretinoin treatment, it was almost completely cured. To our best knowledge, this is the first case reports on improvement with alitretinoin treatment in idiopathic twenty nail dystrophy in dermatologic literature.
몇가지 담수산동물(淡水産動物)에 대한 살충제 Cartap 의 급성독성에 관한 연구
변상지,최승윤,김광포 한국환경농학회 1984 한국환경농학회지 Vol.3 No.2
본 시험은 몇가지 淡水産動物에 대한 cartap의 急性毒性 發現에 미치는 動物의 種類, 水溫 및 pH의 영향을 검토하기 위하여 실시하였다. 공시된 담수산동물은 금붕어 (Carassius auratus LINNE), 왜 몰개 (Aphyocypris chinensis GU¨NTHERR), 미꾸리 (Misgurus anguillicaudatus CANTOR) 및 둥근물벼룩(Moina macrocopa STRAUS)이었다. 溶存酸素量과 물의 硬度는 각각 6∼8ppm, 22∼40ppm으로 고정하고, 水溫의 水準은 20℃, 25℃, 30℃이었고 pH値의 水準은 6, 7, 9이었다. 얻어진 시험 결과를 요약하면 다음과 같다. 1) 水溫 25℃, pH 7에서 cartap의 TLm (median tolerance limit)値는 금붕어, 왜몰개, 미꾸리에서 낮았고, 등근물벼룩에서 높았다, 금붕어에 대한 48시간 TLm値는 0.88ppm, 왜몰개는 0.26ppm, 미꾸리는 0.13ppm이었고, 등근물벼룩의 3시간 TLm値는 306ppm이었다. 2) pH値를 7로 고정하고, 수온을 20℃, 25℃, 30℃로 하였을 때, cartap의 TLm치는 금붕어와 왜몰개에서는 온도의 상승과 더불어 낮아졌으나 둥근물벼룩에서는 25℃에서 가장 높았고 30℃에서 가장 낮았다. 둥근물벼룩에 대한 3시간 TLm値는 20℃에서 107ppm, 25℃에서 306ppm, 30℃에서 77 ppm이었다. 3) 수온을 25℃로 고정하고 pH치를 6, 7, 9로 하였을 때, 금붕어와 왜몰개는 pH치가 높아질수록 TLm値도 높아졌으나, 둥근물벼룩은 높은 pH치에서 TLm치가 낮아졌다. 미꾸리의 사망율은 pH치가 커질수록 사망율이 현저히 증대하였다. 이상의 결과를 종합적으로 볼 때, cartap의 淡氷産動物에 대한 毒性發現度는 동물의 종류뿐만 아니라 水溫과 pH의 영향도 크게 받는데, 그 變化樣相은 要因에 따라 일정하지 않았다. The acute toxicity of an insecticide cartap to several species of freshwater animals was evaluated in the laboratory with special reference to the species specificity, effects of water temperatures and pH values. The aquatic animals tested were the Carassius auratus L., Aphyocypris chinensis GU¨NTHER, Misgurus anguillicaudatus CANTOR, Moina macrocopa STRAUS. The susceptibility of aquatic animals to cartap was different with the species of animals. At the water temperature of 25℃ and pH 7, TLm values of the insecticide to the C. auratus L., A. chinensis G. and M. anguillicaudatus were 0.88, 0.26 and 0.13 ppm in 48 hours, respectively, and to Moina macrocopa S., 306 ppm in 3 hrs. In the case of the three species of fish, TLm 48 values were significantly decreased with rise in temperature. In the case of water flea, where TLm value was 107 ppm at 20℃, there was no consistent response to temperature change, with the highest figure at 25℃ than at either 20 or 30℃. and the susceptibility of C.auratus L. and A. chinensis G. greatly decreased with the increase of pH in water. The toxicity to M. anguillicaudatus and M. macrocopa was significantly higher at pH 9 than at pH 6 or 7. In conclusion, the toxicological reactions of the freshwater animals to cartap were variably influenced by the water temperatures and pH values of water and species of animals.