Chemical inhibitors of c-Met receptor tyrosine kinase stimulate osteoblast differentiation and bone regeneration

Kim, J.W.,Lee, M.N.,Jeong, B.C.,Oh, S.H.,Kook, M.S.,Koh, J.T. North-Holland 2017 European journal of pharmacology Vol.806 No.-

<P>The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been recently introduced to negatively regulate bone morphogenetic protein (BMP)-induced osteogenesis. However, the effect of chemical inhibitors of c-Met receptor on osteoblast differentiation process has not been examined, especially the applicability of c-Met chemical inhibitors on in vivo bone regeneration. In this study, we demonstrated that chemical inhibitors of c-Met receptor tyrosine kinase, SYN1143 and SGX523, could potentiate the differentiation of precursor cells to osteoblasts and stimulate regeneration in calvarial bone defects of mice. Treatment with SYN1143 or SGX523 inhibited HGF-induced c-Met phosphorylation in MC3T3-E1 and C3H10T1/2 cells. Cell proliferation of MC3T3-E1 or C3H10T1/2 was not significantly affected by the concentrations of these inhibitors. Co-treatment with chemical inhibitor of c-Met and osteogenic inducing media enhanced osteoblast-specific genes expression and calcium nodule formation accompanied by increased Runx2 expression via c-Met receptor-dependent but Erk-Smad signaling independent pathway. Notably, the administration of these c-Met inhibitors significantly repaired critical-sized calvarial bone defects. Collectively, our results suggest that chemical inhibitors of c-Met receptor tyrosine kinase might be used as novel therapeutics to induce bone regeneration.</P>

c-Cbl-Mediated Neddylation Antagonizes Ubiquitination and Degradation of the TGF-β Type II Receptor

Zuo, W.,Huang, F.,Chiang, Y.,Li, M.,Du, J.,Ding, Y.,Zhang, T.,Lee, H.,Jeong, L.,Chen, Y.,Deng, H.,Feng, X.H.,Luo, S.,Gao, C.,Chen, Y.G. Cell Press 2013 Molecular cell Vol.49 No.3

Transforming growth factor β (TGF-β) is a potent antiproliferative factor in multiple types of cells. Deregulation of TGF-β signaling is associated with the development of many cancers, including leukemia, though the molecular mechanisms are largely unclear. Here, we show that Casitas B-lineage lymphoma (c-Cbl), a known proto-oncogene encoding an ubiquitin E3 ligase, promotes TGF-β signaling by neddylating and stabilizing the type II receptor (TβRII). Knockout of c-Cbl decreases the TβRII protein level and desensitizes hematopoietic stem or progenitor cells to TGF-β stimulation, while c-Cbl overexpression stabilizes TβRII and sensitizes leukemia cells to TGF-β. c-Cbl conjugates neural precursor cell-expressed, developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, to TβRII at Lys556 and Lys567. Neddylation of TβRII promotes its endocytosis to EEA1-positive early endosomes while preventing its endocytosis to caveolin-positive compartments, therefore inhibiting TβRII ubiquitination and degradation. We have also identified a neddylation-activity-defective c-Cbl mutation from leukemia patients, implying a link between aberrant TβRII neddylation and leukemia development.

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.

풍력 블레이드 복합재의 결함 탐상을 위한 NDE 모니터링기법

임광희(K. H. Im),김우진(W. J. Kim),정예원(Y. W. Jeong),조철현(C. H. Cho),김선규(S. K. Kim),조영태(Y. T. Cho) Korean Society for Precision Engineering 2021 한국정밀공학회 학술발표대회 논문집 Vol.2021 No.11월

Terahertz waves (T-ray) was extensively studied for the nondestructive evaluation of characterization of various and FRP composite materials for a use of wind energy. The composite materials are being utilized on the various areas. Here, T-rays were used to perform NDE when detecting defects in the trailing edge of a wind turbine blade. This study proposed a method to measure a refractive index of a composite, using T-rays (THz) and reviewed the characteristics of the T-ray E-field of a CFRP composite. Particularly, this study produced images to determine defects in the trailing edge of a wind turbine blade and compared and analyzed the images. The TOF of T-ray penetration was measured using a T-ray through-transmission mode to find the following characteristics of the blade. The trailing edge of a nonconductive wind turbine blade could transmit T-rays, enabling the measurement of refractive indices in a through-transmission mode. The effectiveness and limitations of T-ray for the NDE of composites are discussed.

Structural and Temperature-Dependent Electrical/Optical Behaviors of Hot-Wall Deposited BaGa2Se4 Layers

J. J. Bang,홍광준,T. S. Jeong,C. J. Youn 한국물리학회 2018 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.73 No.1

The characteristic behavior of hot-wall deposited BaGa2Se4 layers was investigated as a function of temperature. The structural quality of the layers was found to be affected by tensile strain due to the coincidence-lattice mismatch. The carrier mobility showed an aspect of two scattering mechanisms. As the temperature was increased to 100 K, the mobility increased as a function of T1 due to impurity scattering. Also, at temperatures higher than 100 K, its behavior was reduced to two different-temperature slopes caused by lattice scattering. One was a function of T−3/2 at T > 200 K, and the other was a function of T−1/2 for 100 < T > 200 K. From the behavior of log n(T) versus 1/T, three donor-trap levels due to native defects were observed. By tracking the spectral photocurrent (PC) behavior with decreasing temperature, we found that the three PCpeak positions shifted toward shorter wavelengths and their intensities were dramatically decreased. These spectral PC peaks were due to the band-to-band transition. These band-gap variation were well matched by Eg(T) = Eg(0)−2.06×10 −3T2/(T +230.7). By the selection rule, the crystal-field and the spin-orbit splitting were found to be 0.2031 and −0.2259 eV, respectively. In the log Jph versus 1/T plot, we found that the spectral PC-intensity behavior was related to two donor-trap levels by comparing with the carrier concentration results. In conclusion, the dramatic decrease in the spectral PC intensity was attributed to trapping centers.

FAM83H mutations cause ADHCAI and alter intracellular protein localization.

Lee, S-K,Lee, K-E,Jeong, T-S,Hwang, Y-H,Kim, S,Hu, J C-C,Simmer, J P,Kim, J-W Journal of Dental Research, Inc 2011 Journal of dental research Vol.90 No.3

<P>Mutations in a family with sequence similarity 83 member H (FAM83H) cause autosomal-dominant hypocalcification amelogenesis imperfecta (ADH CAI). All FAM83H ADHCAI-causing mutations terminate translation or shift the reading frame within the specific exon 5 segment that encodes from Ser(287) to Glu(694). Mutations near Glu(694) cause a milder, more localized phenotype. We identified disease-causing FAM83H mutations in two families with ADHCAI: family 1 (g.3115C>T, c.1993 C>T, p.Q665X) and family 2 (g.3151C>T, c.2029 C>T, p.Q677X). We also tested the hypothesis that truncation mutations alter the intracellular localization of FAM83H. Wild-type FAM83H and p.E694X mutant FAM83H fused to green fluorescent protein (GFP) localized in the cytoplasm of HEK293T cells, but the mutant FAM83H proteins (p.R325X, p.W460X, and p.Q677X) fused to GFP localized mainly in the nucleus with slight expression in the cytoplasm. We conclude that nuclear targeting of the truncated FAM83H protein contributes to the severe, generalized enamel phenotype.</P>

승화법에 의한 CdS 단결정 성장

정태수,김현숙,유평렬,신영진,신현길,김택성,정철훈,이훈,신영신,강신국,정경수,홍광준,Jeong, T. S.,Kim, H. S.,Yu, P. Y.,Shin, Y. J.,Shin, H. K.,Kim, T. S.,Jeong, C. H.,Lee, H.,SHin, Y. S.,Kang, S. K.,Jeong, K. S.,Hong, K. J. 한국결정성장학회 1993 韓國結晶成長學會誌 Vol.3 No.2

수직 2단 전기로를 제작하고 결정성장관에 꼬리관을 연결하여 seed 결정없이 승화 방법으로 CdS 결정을 성장하였다. 이때 시료부분과 성장부분의 온도차 ${\Delta}T$가 이론적인 값 $14.7^{\circ}C$와 비교해서 실험적으로 얻은 값이 $15^{\circ}C$ 로 아주 일치하는 값을 나타내었다. 이때 꼬리관의 온도를 $110^{\circ}C$로 시간당 0.38mm 정도로 빨리 결정성장관을 끌어 올려 결정을 성장하였다. 분말법의 X-선 회절무늬와 Laue 배면 반사법의 Laue 무늬로부터 성장된 결정이 육방정이고 결정성장관의 길이 방향으로 c축을 갖는 단결정임을 확인하였다. 또한 CdS 단결정은 상온에서 전자 이동도와 운반자 밀도는 각각 $316cm^2/V{\cdot}sec$와 $2.90{\times}10^{16}cm^{-3}$정도이였다. We has made 2-zone vertical electric furnace and has been grown CdS single crystal by sublimation method in crystal growth tube with tail tube without seed crystal for growth. While it has been growing, temperature difference ${\Delta}T$ of source and growth part has nearly agreed with theoritical value $14.7^{\circ}C$and experimental value $15^{\circ}C$ Then, crystal of best quality has been grown, when temperature of tail tube has been $110^{\circ}C$, in spite of quickly pulling up crystal growth tube a degree O.38mm per hour. The grown crystal have had hexagonal structure and single crystal with c-axis to length of crystal growth tube from X- ray diffraction pattern of powder method and Laue pattern of back reflection Laue method. Also, the mobility and carrier density from Hall effect measurement have been $316cm^2/V{\cdot}sec$ and $2.90{\times}10^{16}cm^{-3}$ at the room temperature, respectively.

Investigation of the Structural, Electrical, and Optical Properties of MnAl2Se4 Layers Grown Using the Hot-Wall Deposition Technique

S. H. You,K. J. Hong,J. W. Jeong,T. S. Jeong,C. J. Youn,J. D. Moon 한국물리학회 2016 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.69 No.4

MnAl2Se4 layers were grown using the hot-wall deposition technique with an attached reservoir tail. Precise control of the vapor pressure in the reservoir was thought to play an important role in the grown of a stoichiometric layer. From the relation between the reciprocal temperature and the carrier concentration, we extracted the dominant trap level as 96.1 meV in the high-temperature region and 13.9 meV in the middle-temperature region. Thus, from a log-log plot between the mobility and the temperature, the mobility showed the different temperature-dependent decreases of the mobility at temperatures above 100 K: T−1/2 in the temperature range of 100 < T < 225 K and T−3/2 in the temperature of T > 225 K. The mobility decreased in proportion to T1 in the low-temperature range of T < 100 K. By analyzing the optical absorption results, the bandgap variation matched Eg(T) = Eg(0) − 3.19 × 10−3 T2/(T + 488) well, where Eg(0) is estimated to be 3.5616 eV. Consequently, low-temperature growth of MnAl2Se4 layers was achieved by using the hot-wall deposition technique.

AA2219-T87 알루미늄 합금 마찰교반용접부의 용접속도 변경에 따른 기계적 특성 변화

신민철(M.C. Shin),유준태(J.T. Yoo),이상훈(S.H. Lee),윤종훈(J.H. Yoon),박충희(C.H. Park),정연희(Y.H. Jeong) 대한용접·접합학회 2023 대한용접학회 특별강연 및 학술발표대회 개요집 Vol.2023 No.10

Effect of Thermal Annealing on the Characteristics of Phosphorus-Implanted ZnO Crystals

Jeong, T. S.,Yu, J. H.,Mo, H. S.,Kim, T. S.,Lim, K. Y.,Youn, C. J.,Hong, K. J.,Kim, H. S. Springer Science + Business Media 2014 Journal of electronic materials Vol.43 No.7

A P-doped ZnO surface layer on undoped ZnO wafers was prepared by phosphorus (P) ion implantation. Hall effect measurement revealed p-type conduction in such layers annealed at 800A degrees C. This indicates that acceptor levels are present in P-doped ZnO, even though the ZnO is still n-type. Micro-Raman scattering in -z(xy)z geometry was conducted on P-implanted ZnO. The E (2) (high) mode shift observed toward the high-energy region was related to compressive stress as a result of P-ion implantation. This compressive stress led to the appearance of an A (1)(LO) peak, which is an inactive mode. This A (1)(LO) peak relaxed during thermal annealing in ambient oxygen at temperatures higher than 700A degrees C. The P2p(3/2) peak observed at 135.6 eV by x-ray photoelectron spectroscopy is associated with chemical bond formation leading to 2(P2O5) molecules. This indicates that implanted P ions substituted Zn sites in the ZnO layer. In photoluminescence spectroscopy, the P-related peaks observed at energies ranging between 3.1 and 3.5 eV originated from (A(0), X) emission, because of P-Zn-2V(Zn) complexes acting as shallow acceptors. The acceptor level was observed to be 126.9 meV above the valence band edge. Observation of this P-related emission indicates that ion implantation results in acceptor levels in the P-doped ZnO layer. This suggests that the P2O5 bonds are responsible for the p-type activity of P-implanted ZnO.