• Nutrition Research and Practice
• /
• 제4권4호
• /
• pp.276-282
• /
• 2010

The principal objective of this study was to evaluate the chemopreventive and therapeutic effects of a combination of all-trans-retinoic acid (RA) and knockdown of delta-like 1 homologue (Drosophila) (DLK1) on neuroblastoma, the most common malignant disease in children. As unfavorable neuroblastoma is poorly differentiated, neuroblastoma cell was induced differentiation by RA or DLK1 knockdown. Neuroblastoma cells showed elongated neurite growth, a hallmark of neuronal differentiation at various doses of RA, as well as by DLK1 knockdown. In order to determine whether or not a combination of RA and DLK1 knockdown exerts a greater chemotherapeutic effect on neuroblastoma, cells were incubated at 10 nM RA after being transfected with SiRNA-DLK1. Neuronal differentiation was increased more by a combination of RA and DLK1 knockdown than by single treatment. Additionally, in order to assess the signal pathway of neuroblastoma differentiation induced by RA and DLK1 knockdown, treatment with the specific MEK/ERK inhibitors, U0126 and PD 98059, was applied to differentiated neuroblastoma cells. Differentiation induced by RA and DLK1 knockdown increased ERK phosphorylation. The MEK/ERK inhibitor U0126 completely inhibited neuronal differentiation induced by both RA and DLK1 knockdown, whereas PD98059 partially blocked neuronal differentiation. After the withdrawal of inhibitors, cellular differentiation was fully recovered. This study is, to the best of our knowledge, the first to demonstrate that the specific inhibitors of the MEK/ERK pathway, U0126 and PD98059, exert differential effects on the ERK phosphorylation induced by RA or DLK1 knockdown. Based on the observations of this study, it can be concluded that a combination of RA and DLK1 knockdown increases neuronal differentiation for the control of the malignant growth of human neuroblastomas, and also that both MEK1 and MEK2 are required for the differentiation induced by RA and DLK1 knockdown.

• 한국항공우주학회지
• /
• 제49권4호
• /
• pp.321-328
• /
• 2021

본 연구에서는 우주 발사체의 복합재 추진제 탱크 구조의 경량 설계를 위하여 좌굴 Knockdown factor를 ABAQUS를 이용한 수치해석 기반으로 새롭게 도출하였다. 복합재 원통 구조의 다양한 두께비(R/t)와 세장비(L/R)를 적절히 고려하였으며, 기하학적 초기 결함을 Single Perturbation Load Approach를 이용하여 구현하였다. 두께비 = 500 및 세장비 = 2.04를 갖는 복합재 원통 구조의 모델의 경우, NASA의 기존 좌굴 설계 기준보다 약 84.38%만큼 좌굴 Knockdown factor가 높게 도출되어 본 연구의 좌굴 설계 기준을 이용할 경우 복합재 추진제 탱크의 경량 구조 설계가 가능함을 확인하였다. 더불어, 복합재 원통 구조의 두께비와 세장비가 각각 증가함에 따라 전역 좌굴 하중과 좌굴 Knockdown factor가 모두 감소하는 경향을 알 수 있었다.

• Composites Research
• /
• 제34권5호
• /
• pp.283-289
• /
• 2021

본 연구에서는 압축력을 받는 얇은 복합재 원통 구조에 대하여 기하학적 혹은 하중에 대한 초기 결함 모델을 이용하여 수치해석적으로 좌굴 Knockdown factor를 새롭게 도출하였다. 전역 좌굴이 발생하기 이전에 타원형상의 변형 형상을 갖는 복합재 원통 구조를 사용하였다. 복합재 원통 구조의 기하학적 초기 결함만 고려하기 위하여 Single Perturbation Load Approach를 이용하였으며, 기하학적 초기 결함과 더불어 하중 불균일을 함께 구현하기 위하여 Single Boundary Perturbation Approach를 사용하였다. 기하학적 초기 결함 모델의 좌굴 Knockdown factor는 NASA의 기존의 좌굴 Knockdown factor보다 약 84% 높게 도출되었으며, 좌굴 시험에 비하여서는 약 9% 낮게 도출되었다. 기하학적 초기 결함과 하중 불균일을 함께 고려하는 모델의 좌굴 Knockdown factor는 NASA의 좌굴 Knockdown factor에 비하여서는 약 75% 높게, 그리고 좌굴 시험보다 약 14% 낮게 계산되었다. 따라서, 본 연구의 좌굴 설계 기준은 고려된 초기 결함 모델과 상관없이 기존의 좌굴 설계 기준에 비하여 경량 설계의 제공이 가능함과 동시에 좌굴 시험 대비 적절히 보수적인 설계 기준을 제공할 수 있음을 확인하였다.

• 한국항공우주학회지
• /
• 제48권9호
• /
• pp.653-661
• /
• 2020

본 논문에서는 우주 발사체 추진제 탱크 구조인 등방성 격자 원통 구조의 경량 설계를 위하여 축 방향의 압축력과 내부 압력을 함께 고려하여 좌굴 Knockdown factor를 수치해석 연구를 통하여 새롭게 정립하였다. 등방성 격자 원통 구조의 유한요소 모델링 및 비선형 후좌굴 해석을 위하여 비선형 유한요소 해석 프로그램인 ABAQUS를 사용하였다. 본 연구 결과, 축 방향의 압축력과 500 kPa의 내부 압력을 함께 받는 등방성 격자 원통 구조의 전역 좌굴 하중 및 좌굴 Knockdown factor가 축 방향의 압축력만을 받는 원통 구조에 비해 각각 304% 및 53%만큼 증가하였다. 따라서 발사체 탱크 구조의 좌굴 설계 시, 내부 압력과 압축력을 함께 고려한 본 연구의 좌굴 Knockdown factor를 이용할 경우, 내부 압력을 고려하지 않은 설계에 비하여 경량 구조 설계가 가능함을 확인하였다.

• Structural Engineering and Mechanics
• /
• 제87권5호
• /
• pp.419-429
• /
• 2023

This study conducts numerical analyses of a thin-walled composite cylinder under axial compression and internal pressure of 10 kPa. Numerical vibration correlation technique and nonlinear postbuckling analyses are conducted using the nonlinear finite element analysis program, ABAQUS. The single perturbation load approach and measured imperfection data are used to represent the geometric initial imperfection of thin-walled composite cylinder. The buckling knockdown factors are derived using present initial imperfection and analysis methods under axial compression without and with the internal pressure. Furthermore, the buckling knockdown factors are compared with the buckling test and computation time are calculated. In this study, derived buckling knockdown factors in present study have difference within 10% as compared with the buckling test. It is shown that nonlinear postbuckling analysis can derive relatively accurate buckling knockdown factor of present thin-walled cylinders, however, numerical vibration correlation technique derives reasonable buckling knockdown factors compared with buckling test. Therefore, this study shows that numerical vibration correlation technique can also be considered as an effective numerical method with 21~91% reduced computation time than nonlinear postbuckling analysis for the derivation of buckling knockdown factors of present composite cylinders.

• Animal Bioscience
• /
• 제37권4호
• /
• pp.567-575
• /
• 2024

Objective: This study aimed to identify genes regulated by cyclin dependent kinases 5 (CDK5) that participate in hair pigmentation in mice. Methods: The mRNA expression profiles of skin samples from CDK5-knockdown mice were constructed using high-throughput RNA sequencing and compared with those of wild-type mice. Results: In total, 8,002 known genes were differentially expressed between CDK5-knockdown and wild-type mice. Of these, 3,658 were upregulated and 4,344 were downregulated in the skin of CDK5-knockdown mice. An additional 318 previously unknown genes were also differentially expressed, with 171 downregulated and 147 upregulated genes in the skin of CDK5-knockdown mice. Of the known genes expressed in mouse skin, 80 were associated with hair color, with 61 showing lower expression and 19 exhibiting higher expression in skin of CDK5-knockdown mice. Importantly, the expression of the tyrosinase-related protein 1 (TYRP1) and the calcium signaling pathway were also found to be regulated by CDK5, suggesting that pigmentation is regulated by CDK5 via the calcium signaling pathway and TYRP1. Conclusion: The transcriptome profiles obtained from the skin of CDK5-knockdown mice compared to wild-type mice provide a valuable resource to help understand the mechanism by which CDK5 regulates melanogenesis in mice and other animals.

• Animal cells and systems
• /
• 제16권3호
• /
• pp.183-189
• /
• 2012

It has been suggested that chromatin is organized into the stable structures that provide fundamental units of chromosome architecture in interphase mammalian cells. The stable structures of chromatin can be visualized as replication foci when replicating DNA is labeled with thymidine analogs. Previously, we showed that the chromosome territory expanded after BAF53 knockdown. In this study, we found that BAF53 is required for the formation of replication foci. DNA replication was not impaired in BAF53 knockdown cells, suggesting that the decrease in the number of replication foci is due to disintegration of replication foci, but not suppression of DNA replication. The attractive forces that maintain structural integrity of replication foci could be disrupted by BAF53 knockdown, and it may be responsible, at least in part, for the expansion of chromosome territories after BAF53 knockdown.

• BMB Reports
• /
• 제48권10호
• /
• pp.583-588
• /
• 2015

Microtubule actin crosslinking factor 1 (MACF1), a widely expressed cytoskeletal linker, plays important roles in various cells by regulating cytoskeleton dynamics. However, its role in osteoblastic cells is not well understood. Based on our previous findings that the association of MACF1 with F-actin and microtubules in osteoblast-like cells was altered under magnetic force conditions, here, by adopting a stable MACF1-knockdown MC3T3-E1 osteoblastic cell line, we found that MACF1 knockdown induced large cells with a binuclear/multinuclear structure. Further, immunofluorescence staining showed disorganization of F-actin and microtubules in MACF1-knockdown cells. Cell counting revealed significant decrease of cell proliferation and cell cycle analysis showed an S phase cell cycle arrest in MACF1-knockdown cells. Moreover and interestingly, MACF1 knockdown showed a potential effect on cellular MTT reduction activity and mitochondrial content, suggesting an impact on cellular metabolic activity. These results together indicate an important role of MACF1 in regulating osteoblastic cell morphology and function.

• Molecules and Cells
• /
• 제38권9호
• /
• pp.789-795
• /
• 2015

A chromosome territory is composed of chromosomal subdomains. The internal structure of chromosomal subdomains provides a structural framework for many genomic activities such as replication and DNA repair, and thus is key to determining the basis of their mechanisms. However, the internal structure and regulating proteins of a chromosomal subdomain remains elusive. Previously, we showed that the chromosome territory expanded after BAF53 knockdown. Because the integrity of chromosomal subdomains is a deciding factor of the volume of a chromosome territory, we examined here the effect of BAF53 knockdown on chromosomal subdomains. We found that BAF53 knockdown led to the disintegration of histone H2B-GFP-visualized chromosomal subdomains and BrdU-labeled replication foci. In addition, the size of DNA loops measured by the maximum fluorescent halo technique increased and became irregular after BAF53 knockdown, indicating DNA loops were released from the residual nuclear structure. These data can be accounted for by the model that BAF53 is prerequisite for maintaining the structural integrity of chromosomal subdomains.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권11호
• /
• pp.6757-6760
• /
• 2013

Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer. Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drug-sensitivity. Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells. MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells.