• Journal of Korean Neurosurgical Society
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• 제61권4호
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• pp.441-449
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• 2018

Objective : Notch receptors are heterodimeric transmembrane proteins that regulate cell fate, such as differentiation, proliferation, and apoptosis. Dysregulated Notch pathway signaling has been observed in glioblastomas, as well as in other human malignancies. Nerve growth factor (NGF) is essential for cell growth and differentiation in the nervous system. Recent reports suggest that NGF stimulates glioblastoma proliferation. However, the relationship between NGF and Notch1 in glioblastomas remains unknown. Therefore, we investigated expression of Notch1 in a glioblastoma cell line (U87-MG), and examined the relationship between NGF and Notch1 signaling. Methods : We evaluated expression of Notch1 in human glioblastomas and normal brain tissues by immunohistochemical staining. The effect of NGF on glioblastoma cell line (U87-MG) was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. To evaluate the relationship between NGF and Notch1 signaling, Notch1 and Hes1 expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. To confirm the effects of NGF on Notch1 signaling, Notch1 and Hes1 small interfering RNAs (siRNAs) were used. Results : In immunohistochemistry, Notch1 expression was higher in glioblastoma than in normal brain tissue. MTT assay showed that NGF stimulates U87-MG cells in a dose-dependent manner. RT-PCR and Western blot analysis demonstrated that Notch1 and Hes1 expression were increased by NGF in a dose-dependent manner. After transfection with Notch1 and Hes1 siRNAs, there was no significant difference between controls and 100 nM $NGF-{\beta}$, which means that U87-MG cell proliferation was suppressed by Notch1 and Hes1 siRNAs. Conclusion : These results indicate that NGF stimulates glioblastoma cell proliferation via Notch1 signaling through Hes 1.

• 대한치과교정학회지
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• 제19권1호
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• pp.77-93
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• 1989

The purpose of the present study were to disclose whether the depth of the mandibular antegonial notch can be used as an indicator of mandibular growth potential. The patients composed of 76 samples and were classified following 3 groups, based on the depth of mandibular antegonial notch : Deep notch group (more than 3mm), Neutral notch group (1-3mm), Shallow notch group (less than 1mm). For each case, the first lateral cephalograms were taken prior to the start of treatment and the second films 3-4 years after. The results were as follows; 1. Deep notch group had a shorter corpus, less ramus height and greater genial angle than did Shallow notch group. 2. Deep notch group had a more retrusive mandibular position than Shallow notch group. 3. Deep notch group had longer total anterior facial height and longer anterior lower facial height group. 4. Deep notch group grow vertical clockwise growth pattern, while Shallow notch group grow horizontal counterclockwise growth pattern. 5. Deep notch group had less mandibular growth than Shallow notch group during observation period.

• Journal of Biosystems Engineering
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• 제1권1호
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• pp.64-72
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• 1976

This experimental work was carried out to investigate the fatigue bending strength on various shapes and sizes of notches of the domestically manufactured steel plate. The notch types tested were a circular hole, U-and V-notches. The S-N diagram for different notch shapes were discussed in relation to plan bending strength and stress concentration factor of notches .The results of the experiments are summarized as follows : (1) The difference between stress concentration factor and notch factor was greater as the radium of notch root became smaller, and these values approached to an identical value as the radium of notch root increased. (2) It was shown that the plane bending fatigue limit of bar without notch for the hotrolled steel having the tensile strength of 33.1kg/$mm^2$was 17.0kg/$mm^2$. (3) U-and V-notch had a greater effect of stress concentration factor on the endurance limit, but O-hole showed the same effect only for $\o\pm2mm$. (4) For the same radius of notch root, U-notch showed a lower value of fatigue limit compared to V-notch and O-hole.

• BMB Reports
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• 제48권8호
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• pp.431-437
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• 2015

Notch signaling plays a pivotal role in cell fate determination, cellular development, cellular self-renewal, tumor progression, and has been linked to developmental disorders and carcinogenesis. Notch1 is activated through interactions with the ligands of neighboring cells, and acts as a transcriptional activator in the nucleus. The Notch1 intracellular domain (Notch1-IC) regulates the expression of target genes related to tumor development and progression. The Notch1 protein undergoes modification after translation by posttranslational modification enzymes. Phosphorylation modification is critical for enzymatic activation, complex formation, degradation, and subcellular localization. According to the nuclear cycle, Notch1-IC is degraded by E3 ligase, FBW7 in the nucleus via phosphorylation-dependent degradation. Here, we summarize the Notch signaling pathway, and resolve to understand the role of phosphorylation in the regulation of Notch signaling as well as to understand its relation to cancer. [BMB Reports 2015; 48(8): 431-437]

• 대한치과교정학회지
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• 제19권1호
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• pp.123-135
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• 1989

This study was undertaken to investigate the relationship between the depth of antegonial notch and the craniofacial morphology, and to predict the mandibular growth direction & potential in class III malocclusion. The computerized analyses were carried out on longitudinal lateral cephalometric radiographs of 50 children with class III malocclusion, divided into two groups ; 30 deep notch subjects (more than 2.6mm) and 20 shallow notch subjects (less than 1.5mm). The conclusions were as follows: 1. The mandibular growth direction in deep notch group was more vertically directed than in shallow notch group. 2. Deep notch group had shorter anterior & posterior cranial base than shallow notch group. 3. There was not significant difference between deep & shallow notch groups in the amount of mandibular growth during treatment period. 4. Notch depth increased in both deep & shallow notch groups during treatment period.

• Archives of Plastic Surgery
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• 제37권1호
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• pp.7-11
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• 2010

Purpose: Vascular endothelial growth factor (VEGF) is known as a growth factor of endothelium and fibroblast. The purpose is to know the VEGF effects on fibroblast proliferation and fibroblast's notch receptor expression. Methods: CCD-986sk fibroblast was purchased from the Korean Cell Bank and was used in XTT assay for proliferation and wound healing assay for migration. Immunofluorescent (IF) staining and western blotting were used in testing notch expression of fibroblast. Semiquantitative RT-PCR was used in checking notch 1 mRNA production by fibroblast. Student-t test was used for analyzing results. Results: Cell proliferation assay using XTT showed significant higher proliferation in VEGF treated fibroblast, $2.324{\pm}0.0026$ vs. $2.463{\pm}0.017$ (p=0.002). Wound healing assay showed longer migration in VEGF treated fibroblast (p=0.062). The fluorescence was brighter in VEGF treated cells of notch 1 IF staining. Notch 1 expressions and mRNA productions increased more in VEGF treated cells. Conclusion: VEGF stimulates fibroblast to proliferate, migrate and to express Notch 1 simultaneously. Notch receptor could be related to VEGF mediated wound healing.

• Molecules and Cells
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• 제27권1호
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• pp.15-19
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• 2009

Notch signaling is controlled at multiple levels. In particular, stabilized Notch receptor activation directly affects the transcriptional activations of Notch target genes. Although some progress has been made in terms of defining the regulatory mechanism that alters Notch stability, it has not been determined whether Notch1/NICD stability is regulated by $GSK-3{\alpha}$. Here, we show that Notch1/NICD levels are significantly regulated by $GSK-3{\beta}$ and by $GSK-3{\alpha}$. Treatment with LiCl (a specific GSK-3 inhibitor) or the overexpression of the kinase-inactive forms of $GSK-3{\alpha}/{\beta}$ significantly increased Notch1/NICD levels. Endogenous NICD levels were also increased by either $GSK-3{\alpha}/{\beta}$- or $GSK-3{\alpha}$-specific siRNA. Furthermore, it was found that $GSK-3{\alpha}$ binds to Notch1. Deletion analysis showed that at least three Thr residues in Notch1 (Thr-1851, 2123, and 2125) are critical for its response to LiCl, which increased not only the transcriptional activity of endogenous NICD but also Hes1 mRNA levels. Taken together, our results indicate that $GSK-3{\alpha}$ is a negative regulator of Notch1/NICD.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.291-297
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• 2013

Notch1 has been reported to be highly expressed in triple-negative and other subtypes of breast cancer. Mutant p53 (R280K) is overexpressed in MDA-MB-231 triple-negative human breast cancer cells. The present study aimed to determine whether the mutant p53 can be a potent transcriptional activator of the Notch1 in MDA-MB-231 cells, and explore the role of this mutant p53-Notch1 axis in curcumin-induced apoptosis. We found that curcumin treatment resulted in an induction of apoptosis in MDA-MB-231 cells, together with downregulation of Notch1 and its downstream target, Hes1. This reduction in Notch1 expression was determined to be due to the decreased activity of endogenous mutant p53. We confirmed the suppressive effect of curcumin on Notch1 transcription by performing a Notch1 promoter-driven reporter assay and identified a putative p53-binding site in the Notch1 promoter by EMSA and chromatin immunoprecipitation analysis. Overexpression of mutant p53 increased Notch1 promoter activity, whereas knockdown of mutant p53 by small interfering RNA suppressed Notch1 expression, leading to the induction of cellular apoptosis. Moreover, curcumin-induced apoptosis was further enhanced by the knockdown of Notch1 or mutant p53, but it was decreased by the overexpression of active Notch1. Taken together, our results demonstrate, for the first time, that Notch1 is a transcriptional target of mutant p53 in breast cancer cells and suggest that the targeting of mutant p53 and/or Notch1 may be combined with a chemotherapeutic strategy to improve the response of breast cancer cells to curcumin.

• Structural Engineering and Mechanics
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• 제69권1호
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• pp.51-67
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• 2019

In this paper, the anisotropy of tensile behaviours of layered rocks consisting internal notch has been investigated using particle flow code. For this purpose, firstly calibration of PFC2D was performed using Brazilian tensile strength. Secondly Brazilian test models consisting bedding layer was simulated numerically. Thickness of layers was 10 mm and layered angularity was $90^{\circ}$, $75^{\circ}$, $60^{\circ}$, $45^{\circ}$, $30^{\circ}$, $15^{\circ}$ and $0^{\circ}$. The strength of bedding interface was too high. Each model was consisted of one internal notch. Notch length is 1 cm, 2 cm and 4 cm and notch angularities are $60^{\circ}$, $45^{\circ}$, $30^{\circ}$, $15^{\circ}$ and $0^{\circ}$. Totally, 90 model were tested. The results show that failure pattern was affected by notch orientation and notch length. It's to be noted that layer angle has not any effect on the failure pattern. Also, Brazilian tensile strength is affected by notch orientation and notch length.

• Journal of the Korean Wood Science and Technology
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• 제26권4호
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• pp.6-12
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• 1998

Test results of domestic softwood lumber were presented to examine the notch effect of beams and compare to present AIJ(Architecture Institute of Japan) formula in notched wood member especially positioned in bottom side (tension side) of a beam. Notched lumber was tested under following condition : each specimen supported simply, and subjected to third-point loading at points of 1/3 of the span length. Notch was located opposite side to loading direction and notch depth were 1/6, 1/4, 1/3 of beam depth. Deflection and load were measured by digital dial guage each in 25kgf increment. Bending test results were as follows; Mpro/Mmax range (proportional and maxium bending moment ratio in notched beam) was 0.5 - 0.65. It was considered that maxium bending moment was about 1.5 times to proportional bending moment in notched beam and showed same tendency in the test result of ordinary wood specimens. AU standard formula for the tension side notch, Mmat = 0.6 ${\times}$ (Zo $\sigma$), the constant 0.6 was suitble for notch ratio(notch depth to beam depth) 1/6, but this ratio for 1/4, and 1/3 was not. So it is preferable to accept smaller value than 0.6 for notch ratio more than 1/3. These experiment results showed critical effect in tension side notched wood beam especially in greater than notch ratio 1.3 of wood beam. From the above results, it is recommened to revise design formula adoptable to domestic wood constructon member with tension side notched member.