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Intravesical Instillation of c-MYC Inhibitor KSI-3716 Suppresses Orthotopic Bladder Tumor Growth
Jeong, K.C.,Kim, K.T.,Seo, H.H.,Shin, S.P.,Ahn, K.O.,Ji, M.J.,Park, W.S.,Kim, I.H.,Lee, S.J.,Seo, H.K. Williams and Wilkins Co 2014 The Journal of urology Vol.191 No.2
Purpose: c-MYC is a promising target for cancer therapy but its use is restricted by unwanted, devastating side effects. We explored whether intravesical instillation of the c-MYC inhibitor KSI-3716 could suppress tumor growth in murine orthotopic bladder xenografts. Materials and Methods: The small molecule KSI-3716, which blocks c-MYC/MAX binding to target gene promoters, was used as an intravesical chemotherapy agent. KSI-3716 action was assessed by electrophoretic mobility shift assay, chromatin immunoprecipitation, transcription reporter assay and quantitative reverse transcriptase-polymerase chain reaction. Inhibition of cell proliferation and its mechanism was monitored by cell cytotoxicity assay, EdU incorporation assay and flow cytometry. The in vivo efficacy of KSI-3716 was examined by noninvasive luminescence imaging and histological analysis after intravesical instillation of KSI-3716 in murine orthotopic bladder xenografts. Results: KSI-3716 blocked c-MYC/MAX from forming a complex with target gene promoters. c-MYC mediated transcriptional activity was inhibited by KSI-3716 at concentrations as low as 1 μM. The expression of c-MYC target genes, such as cyclin D2, CDK4 and hTERT, was markedly decreased. KSI-3716 exerted cytotoxic effects on bladder cancer cells by inducing cell cycle arrest and apoptosis. Intravesical instillation of KSI-3716 at a dose of 5 mg/kg significantly suppressed tumor growth with minimal systemic toxicity. Conclusions: The c-MYC inhibitor KSI-3716 could be developed as an effective intravesical chemotherapy agent for bladder cancer.
Kim, I,Kang, E S,Yim, Y S,Ko, S J,Jeong, S-H,Rim, J H,Kim, Y S,Ahn, C W,Cha, B S,Lee, H C,Kim, C H Nature Publishing Group 2011 The pharmacogenomics journal Vol.11 No.3
SLC30A8 encodes the β-cell-specific zinc transporter-8 (ZnT-8) expressed in insulin secretory granules. The single-nucleotide polymorphism rs13266634 of SLC30A8 is associated with susceptibility to post-transplantation diabetes mellitus (PTDM). We tested the hypothesis that the polymorphic residue at position 325 of ZnT-8 determines the susceptibility to cyclosporin A (CsA) suppression of insulin secretion. INS (insulinoma)-1E cells expressing the W325 variant showed enhanced glucose-stimulated insulin secretion (GSIS) and were less sensitive to CsA suppression of GSIS. A reduced number of insulin granule fusion events accompanied the decrease in insulin secretion in CsA-treated cells expressing ZnT-8 R325; however, ZnT-8 W325-expressing cells exhibited resistance to the dampening of insulin granule fusion by CsA, and transported zinc ions into secretory vesicles more efficiently. Both tacrolimus and rapamycin caused similar suppression of GSIS in cells expressing ZnT-8 R325. However, cells expressing ZnT-8 W325 were resistant to tacrolimus, but not to rapamycin. The Down's syndrome candidate region-1 (DSCR1), an endogenous calcineurin inhibitor, overexpression and subsequent calcineurin inhibition significantly reduced GSIS in cells expressing the R325 but not the W325 variant, suggesting that differing susceptibility to CsA may be due to different interactions with calcineurin. These data suggest that the ZnT-8 W325 variant is protective against CsA-induced suppression of insulin secretion. Tolerance of ZnT-8 W325 to calcineurin activity may account for its protective effect in PTDM.
김철수(C. S. Kim),안승호(S. H. Ahn),허원(C. S. Woo),정광우(K.W. Chung) 한국철도학회 2013 한국철도학회 학술발표대회논문집 Vol.2013 No.11
갱웨이 벨로우즈는 관절형 고속철도차량 곡선주행시 객차 끝단부 사이에 다양한 변위차를 고려하여 갱웨이 프레임에 장착된 이중 주름구조 네오프렌 고무부품이다. 본 연구에서는 고속철도차량 갱웨이 프레임의 안전성 연구일환으로서, 3축 회전변위(롤링, 요잉, 피칭 변위차)조건 및 혼합모드(롤링+요잉)조건하의 갱웨이 벨로우즈의 구조해석 결과로부터, 리그 시험(피로시험)의 가속 조건을 제안하고자 한다. The fatigue failure of the bellows of the articulated type high speed train (HST) has a harmful effect on the riding comfort for the passengers with the increase of noise and ringing in the ears due to airtightness failure during pass through a long tunnel. In this study, to assure the safety of gangway bellows of the HST, non-linear analysis of the gangway bellows considering triaxial angular displacement(rolling /yawing/pitching) between the carriage end parts are performed. Moreover, from the results of non-linear analysis, the accelerated condition of the rig test is proposed.
Deep Learning Based Tree Recognition rate improving Method for Elementary and Middle School Learning
Jung-Eun Choi(최정은),Hwan-Seung Yong(용환승) 한국컴퓨터정보학회 2019 韓國컴퓨터情報學會論文誌 Vol.24 No.12
본 연구의 목적은 수업 시 스마트기기에 적용할 수 있는 나무 이미지를 인식하고 분류하여 정확도를 측정할 수 있는 효율적인 모델을 제안하는 것이다. 2015개정 교육과정으로 개정되면서 초등학교 4학년 과학교과서의 학습 목표에서 스마트 기기 사용한 식물 인식이 새롭게 추가 되었다. 특히 나무 인식의 경우 다른 사물 인식과 달리 수형, 수피, 잎, 꽃, 열매의 부위별 특징이 있으며, 계절에 따라 모양 및 색깔의 변화를 거치므로 인식률에 차이가 존재한다. 그러므로 본 연구를 통해 컨볼루션 신경망 기반의 사전 학습된 인셉션V3모델을 이용하여 재학습 전 후의 나무 부위별 인식률을 비교한다. 또한 각 나무의 유형별 이미지 정확도를 결합시키는 방식을 통해 효율적인 나무 분류 방안을 제시하며 교육현장에서 사용하는 스마트기기에 적용 할 수 있을 것이라 기대한다. The goal of this study is to propose an efficient model for recognizing and classifying tree images to measure the accuracy that can be applied to smart devices during class. From the 2009 revised textbook to the 2015 revised textbook, the learning objective to the fourth-grade science textbook of elementary schools was added to the plant recognition utilizing smart devices. In this study, we compared the recognition rates of trees before and after retraining using a pre-trained inception V3 model, which is the support of the Google Inception V3. In terms of tree recognition, it can distinguish several features, including shapes, bark, leaves, flowers, and fruits that may lead to the recognition rate. Furthermore, if all the leaves of trees may fall during winter, it may challenge to identify the type of tree, as only the bark of the tree will remain some leaves. Therefore, the effective tree classification model is presented through the combination of the images by tree type and the method of combining the model for the accuracy of each tree type. I hope that this model will apply to smart devices used in educational settings.