• Molecules and Cells
• /
• 제45권10호
• /
• pp.718-728
• /
• 2022

Splicing factor B subunit 4 (SF3B4), a component of the U2-pre-mRNA spliceosomal complex, contributes to tumorigenesis in several types of tumors. However, the oncogenic potential of SF3B4 in lung cancer has not yet been determined. The in vivo expression profiles of SF3B4 in non-small cell lung cancer (NSCLC) from publicly available data revealed a significant increase in SF3B4 expression in tumor tissues compared to that in normal tissues. The impact of SF3B4 deletion on the growth of NSCLC cells was determined using a siRNA strategy in A549 lung adenocarcinoma cells. SF3B4 silencing resulted in marked retardation of the A549 cell proliferation, accompanied by the accumulation of cells at the G0/G1 phase and increased expression of p27, p21, and p53. Double knockdown of SF3B4 and p53 resulted in the restoration of p21 expression and partial recovery of cell proliferation, indicating that the p53/p21 axis is involved, at least in part, in the SF3B4-mediated regulation of A549 cell proliferation. We also provided ubiquitination factor E4B (UBE4B) is essential for p53 accumulation after SF3B4 depletion based on followings. First, co-immunoprecipitation showed that SF3B4 interacts with UBE4B. Furthermore, UBE4B levels were decreased by SF3B4 depletion. UBE4B depletion, in turn, reproduced the outcome of SF3B4 depletion, including reduction of polyubiquitinated p53 levels, subsequent induction of p53/p21 and p27, and proliferation retardation. Collectively, our findings indicate the important role of SF3B4 in the regulation of A549 cell proliferation through the UBE4B/p53/p21 axis and p27, implicating the therapeutic strategies for NSCLC targeting SF3B4 and UBE4B.

• BMB Reports
• /
• 제51권2호
• /
• pp.57-58
• /
• 2018

An accurate diagnostic marker for detecting early-stage hepatocellular carcinoma (eHCC) is clinically important, since early detection of HCC remarkably improves patient survival. From the integrative analysis of the transcriptome and clinicopathologic data of human multi-stage HCC tissues, we were able to identify barrier-to-autointegration factor 1 (BANF1), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) and splicing factor 3b subunit 4 (SF3B4) as early HCC biomarkers which could be detected in precancerous lesions of HCC, with superior capabilities to diagnose eHCC compared to the currently popular HCC diagnostic biomarkers: GPC3, GS, and HSP70. We then showed that SF3B4 knockdown caused G1/S cell cycle arrest by recovering $p27^{kip1}$ and simultaneously suppressing cyclins, and CDKs in liver cancer cells. Notably, we demonstrated that aberrant SF3B4 overexpression altered the progress of splicing progress of the tumor suppressor gene, kruppel like factor 4 (KLF4), and resulted in non-functional skipped exon transcripts. This contributes to liver tumorigenesis via transcriptional inactivation of $p27^{kip1}$ and simultaneous activation of Slug genes. Our results suggest that SF3B4 indicates early-stage HCC in precancerous lesions, and also functions as an early-stage driver in the development of liver cancer.

• BMB Reports
• /
• 제48권3호
• /
• pp.127-128
• /
• 2015

Tumor metastasis involves circulating and tumor-initiating capacities of metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction-mediated self-renewal and circulating tumor cell (CTC) capacities were mechanistically explored. TM4SF5-dependent sphere growth was correlated with $CD133^+$, $CD24^-$, ALDH activity, and a physical association between CD44 and TM4SF5. The TM4SF5/CD44 interaction activated c-Src/STAT3/ Twist1/ B mi1 signaling for spheroid formation, while disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5-positive cells were identified circulating in blood 4 to 6 weeks after orthotopic liver-injection. Anti-TM4SF reagents blocked their metastasis to distal intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes self-renewal and CTC properties supported by $CD133^+/TM4SF5^+/CD44^+^{(TM4SF5-bound)}/ALDH^+/CD24^-$ markers during HCC metastasis.

• 한국산업융합학회 논문집
• /
• 제16권1호
• /
• pp.1-8
• /
• 2013

In case that W/B is 20%, 30%, 40% respectively, the effects of additive and shrinkage reducing agent on the autogenous shrinkage for high strengthen concrete through the substitution of FA and SF analysis were obtained as following conclusions. When the ratio of FA increased, the compressive strength of high strengthen concrete is decreased in the early times. As the ratio of SF increase, the compressive strength also increased. Comparing with PC(Portland Cement) for 7 days curing, the strength is 13.8% of FA10 + SR0.5 and 19.2% of FA15 + SR0.5 decreased when W/B is 20%, and 6.1% of SF7.5 + SR0.5, 4.8% of SF15 + SR0.5, the strength are increased. In case that W/B is 30%, 13.1% of FA10 + SR0.5 19.1% of FA15 + SR0.5 the strength is decreased and 4.1% of SF 7.5 + SR0.5, 7.2% of SF15 + SR0.5 the strength are increased. In case of W/B 40%, 4.3% of FA10 + SR0.5, and 8.7% of FA15 + SR0.5, the strength is decreased and 3.3% of SF7.5 + SR0.5, 6.3% SF15 + SR0.5 the strength is increased. When the ratio of SR is 0.5%, autogenous shrinkage strain of OPC concrete appeared $-417{\times}10-6$ in 56days curing, the shrinkage strain is decreased 23.7%. The reducing effects of autogenous shrinkage when the mineral and shrinkage agent are used are the same as ones when only shrinkage agent used.

• 대한전자공학회논문지SD
• /
• 제42권5호
• /
• pp.55-62
• /
• 2005

본 논문에서는 공간-주파수 OFDM (SF-OFDM) 기법을 위한 효율적인 심볼 검출 알고리즘이 제안되고, 이를 기반으로 하는 SF-OFDM 무선 LAN 기저대역 프로세서의 구현 결과가 제시된다. SF-OFDM 기법에서 부반송파의 개수가 적은 경우 부채널간 간섭이 발생하게 되며, 이러한 간섭은 다이버시티 시스템의 성능을 크게 저하시킨다. 제안된 알고리즘은 부채널간 간섭을 병렬적으로 제거함으로써 기존 알고리즘에 비해 큰 성능 이득을 얻는다. 컴퓨터 모의실험을 통한 비트오류율 (BER) 성능 평가 결과 두개의 송${\cdot}$수신 안테나를 사용하는 경우 10-4의 BER에서 기존 알고리즘에 비해 약 3 dB의 성능이득을 얻음을 확인하였다. 제안된 심볼 검출 알고리즘이 적용된 SF-OFDM 무선 LAN 시스템의 패킷오류율 (PER), link throughput 및 coverage 성능이 분석되었다. 최대 전송률의 $80\%$를 목표 throughput으로 설정 했을 때, SF-OFDM 기반 무선 LAN 시스템은 기존의 IEEE 802.11a 무선 LAN 시스템에 비해 약 5.95 dB의 SNR 이득과 3.98 미터의 coverage 이득을 얻을 수 있었다. 제안된 알고리즘이 적용된 SF-OFDM 무선 LAN 기저대역 프로세서는 하드웨어 설계 언어를 통해 설계되었으며, 0.18um 1.8V CMOS 표준 셀 라이브러리를 통해 합성되었다. 제시된 division-free 하드웨어 구조와 함께, 구현된 프로세서의 총 게이트 수는 약 945K개였으며, FPGA 테스트 시스템을 통해 실시간 검증 및 평가되었다.

• 미생물학회지
• /
• 제37권4호
• /
• pp.245-252
• /
• 2001

MLS (macrolide-lincosamide-streptogramin B) 항생제 내성인자 단백질인 Erm 단백질들은 아미노산 서열 중 그 동일성과 유사성이 높아 구조적으로도 동등한 단백질의 한 집단을 형성한다. 최근 X-ray crystallography에 의해 구조가 결정된 ErmC\` 및 ErmAM 단백질의 구조에 근거하여 ErmSF 단백질도 catalytic domain과 substrate binding domain으로 구분하였고 N-terminal end에 존재하는 catalytic domain의 대량생산을 다양한 pET 발현 vector를 사용하여 시도하였다. 그리고 catalytic domain을 coding하는 DNA 절편은 세 종류를 사용하였다: DNA 절편 1은 Met 1부터 Glu 186까지를 coding하고 DNA 절편 2는 Arg 60부터 Glu 186까지의 정보를 가진 DNA이고 DNA 절편 3은 Arg 60부터 Arg 240까지를 encoding하는 DNA이다. 사용된 다양한 발현 vector중에서 pET19b는 DNA 절편 3, pET23b는 DNA 절편 1과 2를 성공적으로 대량생산하였다. 그러나 대량생산된 catalytic domain들은 불용성 단백질 집합체인 inclusion body를 형성하였다. ErmSF catalytic domain들의 용해성 단백질의 생산을 위하여 chaperone GroESL과 Thioredoxin의 동시 발현 및 배양온도를 $22^{\circ}C$로 낮추어 시도했으나 대량 발현된 단백질의 용해에는 도움을 얻지 못하였다.

• 한국통신학회논문지
• /
• 제30권4C호
• /
• pp.283-289
• /
• 2005

본 논문에서는 공간-주파수 OFDM (SF-OFDM) 전송 다이버시티 기법을 위한 효율적인 심볼 검출 알고리즘이 제안되었다. SF-OFDM 전송 다이버시티 기법에서 부반송파의 수가 적은 경우 부채널간 간섭이 발생하게 되며, 이러한 간섭은 다이버시티 시스템의 성능을 크게 저하시킨다. 제안된 알고리즘은 부채널간 간섭을 병렬 혹은 순차적으로 제거함으로써 기존 알고리즘에 비해 큰 성능 이득을 얻는다. 컴퓨터 모의실험을 통한 비트오류율 (BER) 성능 평가 결과. 두개의 송수신 안테나를 사용하는 경우, $10^{-4}$의 BER에서 약 3 dB의 성능 이득을 얻을 수 있음을 확인하였다. 제안된 알고리즘이 적용된 심볼 검출기는 하드웨어 설계 언어를 통해 설계되었고, $0.18{\mu}m$ 1.8V CMOS 표준 셀 라이브러리를 이용하여 합성되었다. 제시된 하드웨어 구조와 함께 설계된 SF-OFDM-PIC 심볼 검출기는 약 140K개의 논리 게이트로 구성되었고, SF-OFDM-SIC 검출기는 129K개의 논리 게이트로 합성되었다.

• 폴리머
• /
• 제38권1호
• /
• pp.54-61
• /
• 2014

Bombyx mori silk fibroin(SF)과 블렌드 필름을 만들기 위하여 키토산에 1,3-propanesultone을 반응시켜 수용성 sulfobetaine chitosan(SCs)을 제조하였다. 여러 가지 비율의 SF/SCs 블렌드 필름을 B. mori SF와 SCs의 수용액을 혼합하여 제조하였다. 수용액으로부터 얻어진 SF/SCs 블렌드 필름의 구조와 형태 변화는 분광학적 및 열적 분석을 통해 규명하였다. SF와 SCs의 혼합 비율에 따른 인공 피부나 화상치료 목적의 비이오재료로서의 물리적 및 기계적 성질에 미치는 영향을 조사하였다. X-선 분석으로 두 생체고분자 사이에 좋은 친화성을 보여주고 있음을 알 수 있었으며 기계적 성질도 SCs의 함량이 증가하면 크게 증가하였다. $37^{\circ}C$에서 phosphate buffered saline solution 용액 중에서 in vitro 분해 실험을 8주 동안 시행한 결과 46.4%가 분해됨을 알 수 있었다. MC3T3-E1 세포에 의한 독성 실험 결과 무독성을 나타내 주었으며, 3일의 배양 후 SF/SCs 필름의 상대 세포 수는 최적화된 tissue culture plastic보다 약간 낮게 나타남을 알 수 있었다.

• 대한전기학회논문지:전기기기및에너지변환시스템부문B
• /
• 제49권3호
• /
• pp.152-158
• /
• 2000

This paper deal with the experimental discussion about the impulse and AC dielectric strength of SF6 gas insulated transformer. Test sample is measured the dielectric breakdown voltage about modeling of the first and second section which is the weakest for surge voltage. The AC breakdown voltage is appeared 1.4 times than impulse breakdown voltage, so we can estimate that the impulse breakdown voltage is severe to AC breakdown voltage, and when the impulse is applied, in case of lmm tapping with Nomex paper, the characteristics of dielectric breakdown voltage is same to that in oil immersed transformer when SF6 gas pressure is 2.2kg/$cm^2$G.

• 대한간학회지
• /
• 제24권4호
• /
• pp.384-391
• /
• 2018

Backgrounds/Aims: The objective of our study was to determine the epidemiological, laboratory, and serological characteristics of patients with chronic hepatitis B virus (HBV) infection and normal transaminases. The study also aimed to evaluate liver damage by measuring the liver fibrosis (LF) grade and to identify possible factors associated with the presence of fibrosis. Methods: A retrospective observational study was conducted in patients with chronic HBV infection and classified as inactive carriers or immune-tolerant. Epidemiological variables of age, sex, immigrant, alcohol consumption, and body mass index (BMI), as well as virological variables (HBV DNA) and transaminase level were collected throughout the follow-up. The LF grade was evaluated by transient elastography. The cutoff value for significant fibrosis (SF) was liver stiffness ${\geq}7.9kPa$. Results: A total of 214 patients were included in the analysis, and 62% of them had a BMI ${\geq}25kg/m^2$. During follow-up, 4% of patients showed transaminase elevation (<1.5 times normal). Most patients had a viral DNA level <2,000 IU/mL (83%). Data on LF were available in 160 patients; of these, 14% had SF, 9% F3, and 6% F4. The variables associated with the presence of SF were transaminase alteration during follow-up, as 23% of patients with SF had elevated transaminases versus 3% of patients without SF (P<0.005), and BMI, as the vast majority of patients with SF (88%) had a BMI ${\geq}25kg/m^2$ versus 56% of patients without SF (P<0.05). Conclusions: In patients with chronic HBV infection and normal transaminases, liver damage does not seem to be related to DNA levels, alcohol consumption, or immigrant status. SF seems to be associated with transaminase alteration during follow-up and elevated BMI. It is therefore recommended to measure LF grade with validated non-invasive methods in such patients.