• Title/Summary/Keyword: NOTCH

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Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System

  • Kim, Hyun Sik;Park, Young Han;Lee, Heui Seung;Kwon, Mi Jung;Song, Joon Ho;Chang, In Bok
    • Journal of Korean Neurosurgical Society
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    • v.64 no.5
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    • pp.716-725
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    • 2021
  • Objective : The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process. Methods : We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma. Results : Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA. Conclusion : These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation.

A Study on the Wear of Ceramic Tool in Finish Machining of STD11 Steel (STD11강의 다듬질절삭에 의한 세라믹공구의 마멸에 관한 연구)

  • 김광래
    • Journal of the Korean Society of Manufacturing Technology Engineers
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    • v.4 no.2
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    • pp.46-53
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    • 1995
  • In this study, Wear of a ceramic cutting tool for hardened STD11 steel was investigated. Under the finish machining condition. DOC notch wear of a ceramic cutting tool was mostly occurred earlier than flank and crater wear were proceeded. The relations of DOC notch wear, which was characteristically produced at the beginning of cutting. to cutting speed, feed, depth of cut, and nose radius of a ceramic cutting tool were examined. Effective approach angle, which is a function of cutting conditions, and boundary area were suggested, and then the influence of those was investigated, The following conclusions were obtained: (1)as cutting speed was increasing. DOC notch wear was decreasing (2) the cutting condition that magnitude of slendermess ratio was made small, was favorable for DOC notch wear, (3) as depth of cut was smaller, the influence of feed on DOC notch wear was also smaller, (4) DOC notch wear was mainly influenced by effective approach angle, but by boundary area in the range of low feed.

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A Comparative Study of the Fatigue Strength on Cruciform Joints by Local Stress Methods (십자형 용접부 피로강도 산정을 위한 국부응력법의 비교연구)

  • Yang, Park-Dal-Chi;Ahn, Jung-Hyun
    • Journal of the Society of Naval Architects of Korea
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    • v.47 no.4
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    • pp.573-579
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    • 2010
  • The notch effects on the fatigue strength of welded joints are both stress concentration and fatigue strength reduction. In the notch stress approach, the notch effects are usually approximated by introducing weld-bead parameters for the local detailed weld joints. In this paper, well-known notch stress approaches - critical distance method, area method and fictitious rounding method are presented for the fatigue strength of cruciform joints. The estimated results of the present methods are applied to the experiments performed in this study and reported in the references. The results of the application show that the fatigue-life scatterness of the experimental data expressed in the nominal stress is significantly reduced by introducing the effective fatigue stress of the present study.

Analysis of Fatigue Strength in Expansion Joint Weldment of Bridge (교량 신축이음창치 용접부의 피로강도 해석)

  • 이용복;정진성;박영근;김태윤;김호경;박상흡
    • Journal of Welding and Joining
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    • v.16 no.4
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    • pp.73-82
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    • 1998
  • This paper is especially concerned with the weldment between support beam and square bar that plays important roles in control box of Expansion Joint as a brdige structure. Fatigue strength ({TEX}$$\sigma$_{ult}${/TEX}) of the weldment is dependent on notch factor ({TEX}$K_{f}${/TEX}) become important factors to predict fatigue life. The fatigue notch sensitivity (η) for metals can be divided into two types ; high and low notch sensitivity. In this work, the Expansion Joint weldment was found to have low notch sensitivity. The maximum strain distribution during static loading is similar to the FEM analysis. Fatigue test of real structure was performed up to {TEX}$10^{6}${/TEX} cycles to be compared with predicted endurance limit.

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A Study on the Corrosion Fatigue Fracture of U-notch Radius (U-노치반경에 따른 부식피로 파괴거동)

  • 이장규;윤종희;인승현;우창기;신관수;최양호;박성완
    • Proceedings of the Korean Society of Machine Tool Engineers Conference
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    • 2002.10a
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    • pp.58-63
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    • 2002
  • This study has performed rotary bending fatigue testing that smooth specimen using SM45C materials and notched specimen whose radii were R6, R4 and R2, were processed in 3% NaCl aqueous solutions or in the air. The results are as followed; 1. In the air fatigue limit at 10$^{7}$ cycles remarkably reduced as notch radius goes small. 2. In 3% NaCl aqueous solution fatigue strength at 10$^{6}$ cycles also had large range of reduction as notch radius goes small. 3. Comparing fatigue strength in the air, fatigue strength at 10$^{6}$ cycles in 3% NaCl aqueous solution reduced by 46.2% at smooth specimen, 55.3% at R6 notch radius, 45.8% at R4 and 39.7% at R2 respectively. 4. The reason that fatigue strength reduced in the reduction of notch radius sire was because the surface of notch exposed in corrosion was small and consequently it was less corroded.

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An Adaptive Digital Notch Filter for Stabilization of Single-Phase Grid-Connected Inverters With LCL Filter (LCL 필터가 결합된 단상 계통연계형 인버터의 안정화를 위한 적응형 디지털 노치 필터)

  • Heo, Jin-Yong;Kim, Hak-Soo;Nho, Eui-Cheol
    • The Transactions of the Korean Institute of Power Electronics
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    • v.26 no.5
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    • pp.307-314
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    • 2021
  • Even though the LCL filters have superior harmonic attenuation ability to L filters, stability has always been an issue. The system could be unstable because of the resonance phenomenon, especially when digital controller is used. Adding a notch filter to the compensator is one approach to solve the problem. Resonance phenomenon can be inhibited by aligning notch frequency to system resonance frequency. However, resonance frequency variation can be obtained because the actual system has a nonstationary characteristic. Therefore, the system could be unstable, where the system parameters are changed when the conventional notch filter is used. An adaptive digital notch filter that stabilizes the system even system parameters are changed. Simulation and experiment results are provided to verify the validity of the proposed adaptive filter.

Inhibitory Effects of Harmine on Migration and Invasion of Human Breast Cancer Cells by Regulating Notch Signaling (Harmine의 Notch 신호전달 조절에 의한 유방암세포주 이동 및 침윤 억제 효과)

  • Yun, Jieun
    • Korean Journal of Pharmacognosy
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    • v.49 no.4
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    • pp.285-290
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    • 2018
  • Harmine, a beta-carboline alkaloid isolated from the seeds of Peganum harmala has been reported as a promising drug candidate for cancer therapy. However, the effect of harmine on breast cancer remains still unclear. In this study, the effect of harmine on the cell proliferation, migration, and invasion of breast cancer MDA-MB231 cells and the underlying mechanism were investigated. The results indicated that harmine inhibited the proliferation MDA-MB231 cells in a dose-dependent manner and markedly suppressed migration and invasion of MDA-MB231 cells. The mechanism involved in part through Notch signaling. The Notch activity was significantly inhibited by harmine treatment and harmine suppressed the expression of Jagged1 which is a key ligand to activate Notch signaling. These findings suggest a novel mechanism of harmine on anti-cancer activity and harmine may act as a potential therapeutic drug for breast cancer treatment.

siRNA-mediated Silencing of Notch-1 Enhances Docetaxel Induced Mitotic Arrest and Apoptosis in PCa Cells

  • Ye, Qi-Fa;Zhang, Yi-Chuan;Peng, Xiao-Qing;Long, Zhi;Ming, Ying-Zi;He, Le-Ye
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2485-2489
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    • 2012
  • Purpose: Notch is an important signaling pathway that regulates cell fate, stem cell maintenance and the initiation of differentiation in many tissues. It has been reported that activation of Notch-1 contributes to tumorigenesis. However, whether Notch signaling might have a role in chemoresistance of prostate cancer is unclear. This study aimed to investigate the effects of Notch-1 silencing on the sensitivity of prostate cancer cells to docetaxel treatment. Methods: siRNA against Notch-1 was transfected into PC-3 prostate cancer cells. Proliferation, apoptosis and cell cycle distribution were examined in the presence or absence of docetaxel by MTT and flow cytometry. Expression of $p21^{waf1/cip1}$ and Akt as well as activation of Akt in PC-3 cells were detected by Western blot and Real-time PCR. Results: Silencing of Notch-1 promoted docetaxel induced cell growth inhibition, apoptosis and cell cycle arrest in PC-3 cells. In addition, these effects were associated with increased $p21^{waf1/cip1}$ expression and decreased Akt expression and activation in PC-3 cells. Conclusion: Notch-1 promotes chemoresistance of prostate cancer and could be a potential therapeutic target.

Analysis of notch depth and loading rate effects on crack growth in concrete by FE and DIC

  • Zhu, Xiangyi;Chen, Xudong;Lu, Jun;Fan, Xiangqian
    • Computers and Concrete
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    • v.24 no.6
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    • pp.527-539
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    • 2019
  • In this paper, the fracture characteristics of concrete specimens with different notch depths under three-point flexural loads are studied by finite element and fracture mechanics methods. Firstly, the concrete beams (the size is 700×100×150 mm) with different notch depths (a=30 mm, 45 mm, 60 mm and 75 mm respectively) are tested to study the influence of notch depths on the mechanical properties of concrete. Subsequently, the concrete beams with notch depth of 60 mm are loaded at different loading rates to study the influence of loading rates on the fracture characteristics, and digital image correlation (DIC) is used to monitor the strain nephogram at different loading rates. The test results show that the flexural characteristics of the beams are influenced by notch depths, and the bearing capacity and ductility of the concrete decrease with the increase of notch depths. Moreover, the peak load of concrete beam gradually increases with the increase of loading rate. Then, the fracture energy of the beams is accurately calculated by tail-modeling method and the bilinear softening constitutive model of fracture behavior is determined by using the modified fracture energy. Finally, the bilinear softening constitutive function is embedded into the finite element (FE) model for numerical simulation. Through the comparison of the test results and finite element analysis, the bilinear softening model determined by the tail-modeling method can be used to predict the fracture behavior of concrete beams under different notch depths and loading rates.

Evaluation of the antegonial notch related to the mandibular morphology and the curve of Spee in anteroposterior relation (전후방적 분류에 따른 하악 형태 및 Spee 만곡에 대한 antegonial notch의 관계 평가)

  • Son, J-H;Kim, Y-H;Kook, Y-A
    • The Journal of the Korean dental association
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    • v.45 no.8 s.459
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    • pp.483-490
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    • 2007
  • The aim of this study was to investigate the relationship between the mandibular antegonial notch and the mandibular morphology, and the curve of Spee in anteroposterior skeletal relationship. Pre-treatment lateral cephalograms were obtained from 80(male 34, female 46) adult orthodontic patients and the samples were classified into 3 categories by ANB angle($0^{\circ}$$\leq$ANB< $4^{\circ}$ Class I, $4^{\circ}$$\leq$ANB Class II, ANB< $0^{\circ}$ Class III). The curve of Spee was measured directly from the pre-treatment mandibular study cast of each patient included in this study. Pearson correlation coefficient test and multiple regression analysis in each group revealed the following results; 1. Antegonial notch depth was positively correlated with hoth lower anterior facial height(ANS-Me) in skeletal Class I, II and III groups and Id-Me height in skeletal Class I and II groups. 2. A statistically significant negative correlation was found between the depth of the antegonial notch and the curve of Spee in the Class III group. 3. Significant relationship was not found between the antegonial notch depth and any of the other cephalometric variables such as mandibular body length(Go-Gn) and ramus height(Co-Go). As antegonial notch depth increased, more vertical growth of the mandible was observed. Antegonial notch can be used as a predictor of vertical mandibular growth in the diagnosis and treatment planning of malocclusion.

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