• 제목/요약/키워드: ATF4

검색결과 93건 처리시간 0.024초

1,25-dihydroxyvitamin D3 affects thapsigargin-induced endoplasmic reticulum stress in 3T3-L1 adipocytes

  • Dain Wi;Chan Yoon Park
    • Nutrition Research and Practice
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    • 제18권1호
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    • pp.1-18
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    • 2024
  • BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress in adipose tissue causes an inflammatory response and leads to metabolic diseases. However, the association between vitamin D and adipose ER stress remains poorly understood. In this study, we investigated whether 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) alleviates ER stress in adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)2D3 after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr. RESULTS: Treatment with 1,25(OH)2D3 during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)2D3 treatment suppressed mRNA levels of Ddit3, sXbp1, and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3, sXbp1, and Atf4 following 1,25(OH)2D3 administration was not observed in Vdr-knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)2D3 inhibited transcription of Ddit3, sXbp1, Atf4, Bip, and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)2D3 treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes. CONCLUSIONS: Our data suggest that 1,25(OH)2D3 prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr. In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.

LEU+ loaded APR1400 using accident tolerant fuel cladding for 24-month two-batch fuel management scheme

  • Husam Khalefih;Taesuk Oh;Yunseok Jeong;Yonghee Kim
    • Nuclear Engineering and Technology
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    • 제55권7호
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    • pp.2578-2590
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    • 2023
  • In this work, a 24-month two-batch fuel management strategy for the APR1400 using LEU + has been investigated, where enrichments of 5.9 and 5.2 w/o are utilized in lieu of the conventional 4-5 w/o UO2 fuel. In addition, an Accident Tolerant Fuel (ATF) clad based on the swaging technology is applied to APR1400 fuel assemblies. In this special ATF clad design, both outer and inner SS316 layers protect the conventional zircaloy clad. Erbia (Er2O3) is introduced as a burnable absorber with two-fold goals to lower the critical boron concentration in the long-cycle LEU + loaded core as well as to handle the LEU + fuel in the existing front-end fuel facilities without renewing the license. Two types of fuel assemblies with different loading of gadolinia (Gd2O3) are considered to control both the reactivity and the core radial power distribution. The erbia burnable absorber is uniformly admixed with UO2 in all fuel pins except for the gadolinia-bearing ones. In this study, two core designs were devised with different erbia loading, and core performance and safety parameters were evaluated for each case in comparison with a core design without any burnable absorbers. The core analysis was done using the two-step method. First, cross-sections are generated by the SERPENT 2 Monte Carlo code, and the 3-D neutronic analysis is performed with an in-house multi-physics nodal code KANT.

3 차원 프린팅 기술을 이용한 신개념 경수로 핵연료 기술 개발에 관한 연구 (Development of Innovative Light Water Reactor Nuclear Fuel Using 3D Printing Technology)

  • 김효찬;김현길;양용식
    • 한국정밀공학회지
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    • 제33권4호
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    • pp.279-286
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    • 2016
  • To enhance the safety of nuclear reactors after the Fukushima accident, researchers are developing various types of accident tolerant fuel (ATF) to increase the coping time and reduce the generation of hydrogen by oxidation. Coated cladding, an ATF concept, can be a promising technology in view of its commercialization. We applied 3D printing technology to the fabrication of coated cladding as well as of coated pellets. Direct metal tooling (DMT) in 3D printing technologies can create a coated layer on the tubular cladding surface, which maintains stability during corrosion, creep, and wear in the reactor. A 3D laser coating apparatus was built, and parameter studies were carried out. To coat pellets with erbium using this apparatus, we undertook preliminary experiments involving metal pellets. The adhesion test showed that the coated layer can be maintained at near fracture strength.

마늘성분 Allicin에 의해 차별적으로 발현되는 유전자군의 발현 분석 (Analysis of Differentially Expressed Genes by Allicin in Human Colorectal Cancer Cell)

  • 김경호;김민정;김종식;표석능;김병오
    • 한국미생물·생명공학회지
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    • 제38권4호
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    • pp.442-447
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    • 2010
  • 본 연구에서는 마늘성분 allicin에 의한 항암 기전 및 화학적 암 예방법의 분자 생물학적 기전을 이해하기 위한 연구의 일환으로, 마늘성분 중의 하나인 allicin이 인체 대장암 세포주 HCT116의 증식에 미치는 영향을 확인하였다. allicin의 처리에 따라 세포사멸이 나타나며 생존율이 감소함을 확인하였다. 또한 oligo DNA microarray 실험을 통하여 allicin에 의해 발현되는 유전자 중 발현양의 차이를 보인 유전자중 2배 이상 up-regulation된 유전자는 7,840개, 2배 이상 down-regulation 된 유전자는 10,010개로 각각 분류 되었다. 이 중, ATF3유전자의 발현을 확인하였고, 또 다른 항암유전자인 NAG-1 유전자의 발현을 RT-PCR로 확인하였다. 그 결과, allicin처리에 의해 항암유전자인 ATF3의 발현과 NAG1 유전자의 발현이 증가함을 확인하였다. 또한 p53 HCT116 세포주를 이용하여 allicin에 의한 NAG1 단백질의 발현을 확인한 결과, allicin은 p53 유전자 의존적으로 NAG-1 단백질을 발현함을 확인하였다. 결론적으로 allicin은 세포주기나 세포사멸에 관련된 많은 유전자들의 발현 변화를 유도함으로써 암세포 성장억제 활성을 갖는 것으로 사료된다.

Endoplasmic reticulum stress in periimplantation embryos

  • Michalak, Marek;Gye, Myung Chan
    • Clinical and Experimental Reproductive Medicine
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    • 제42권1호
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    • pp.1-7
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    • 2015
  • Stress coping mechanisms are critical to minimize or overcome damage caused by ever changing environmental conditions. They are designed to promote cell survival. The unfolded protein response (UPR) pathway is mobilized in response to the accumulation of unfolded proteins, ultimately in order to regain endoplasmic reticulum (ER) homeostasis. Various elements of coping responses to ER stress including Perk, Ask1, Bip, Chop, Gadd34, Ire1, Atf4, Atf6, and Xbp1 have been identified and were found to be inducible in oocytes and preimplantation embryos, suggesting that, as a normal part of the cellular adaptive mechanism, these coping responses, including the UPR, play a pivotal role in the development of preimplantation embryos. As such, the UPR-associated molecules and pathways may become useful markers for the potential diagnosis of stress conditions for preimplantation embryos. After implantation, ER stress-induced coping responses become physiologically important for a normal decidual response, placentation, and early organogenesis. Attenuation of ER stress coping responses by tauroursodeoxycholate and salubrinal was effective for prevention of cell death of cultured embryos. Further elucidation of new and relevant ER stress coping responses in periimplantation embryos might contribute to a comprehensive understanding of the regulation of normal development of embryonic development and potentiation of embryonic development in vitro.

위성통신용 광대역 저잡음증폭기의 구현 및 성능평가에 관한 연구 (A Study on Implementation and Performance of the Low Noise Amplifier for Satellite Mobile Communication System)

  • 전중성;김동일;배정칠
    • 한국정보통신학회논문지
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    • 제4권1호
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    • pp.67-76
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    • 2000
  • 본 논문에서는 INMARSAT 수신주파수인 1525-1545 MHz와 전세계 측위 시스템 수신주파수 15751 MHz 대역에서 초고주파용 수신장치로 사용되는 L-BAND(1525-1575 MHz)용 저잡음증폭기를 저항 결합회로를 사용하여 구현하였다. 사용된 저항 결합회로는 반사되는 전력이 정합 회로내의 저항에서 소모되므로 반사계수가 작아지고, 안정도도 개선되며, 또한 저잡음증폭기의 설계시 입력단 정합이 용이하였다. 저잡음증폭기의 구현에는 GaAs FET인 ATF-10136과 내부정합된 MMIC인 VNA-25를 이용하였으며, 알루미늄 기구물 안에 초고주파 회로와 자기 바이어스 회로를 함께 장착시켰다. 이렇게 제작된 저잡음증폭기는 32 dB의 이득, 0.8 dB 이하의 잡음지수와 18.6 dBm의 P1dB 출력을 얻었다.

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Prediction of ballooning and burst for nuclear fuel cladding with anisotropic creep modeling during Loss of Coolant Accident (LOCA)

  • Kim, Jinsu;Yoon, Jeong Whan;Kim, Hyochan;Lee, Sung-Uk
    • Nuclear Engineering and Technology
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    • 제53권10호
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    • pp.3379-3397
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    • 2021
  • In this study, a multi-physics modeling method was developed to analyze a nuclear fuel rod's thermo-mechanical behavior especially for high temperature anisotropic creep deformation during ballooning and burst occurring in Loss of Coolant Accident (LOCA). Based on transient heat transfer and nonlinear mechanical analysis, the present work newly incorporated the nuclear fuel rod's special characteristics which include gap heat transfer, temperature and burnup dependent material properties, and especially for high temperature creep with material anisotropy. The proposed method was tested through various benchmark analyses and showed good agreements with analytical solutions. From the validation study with a cladding burst experiment which postulates the LOCA scenario, it was shown that the present development could predict the ballooning and burst behaviors accurately and showed the capability to predict anisotropic creep behavior during the LOCA. Moreover, in order to verify the anisotropic creep methodology proposed in this study, the comparison between modeling and experiment was made with isotropic material assumption. It was found that the present methodology with anisotropic creep could predict ballooning and burst more accurately and showed more realistic behavior of the cladding.

Neutronic examination of the U-Mo accident tolerant fuel for VVER-1200 reactors

  • Semra Daydas;Ali Tiftikci
    • Nuclear Engineering and Technology
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    • 제56권7호
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    • pp.2625-2632
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    • 2024
  • In this study, we investigated the possibility of employing accident tolerant fuel (ATF) in VVER-1200/V491 assembly without gadolinium-containing fuel rods using the Monte Carlo code Serpent 1.1.7 with ENDF/B-VII cross-section library. The analysis involves assembly design with reflective boundary conditions. To compare the neutronic performances, U-5Mo, U-7.5Mo, U-10Mo, and U-15Mo fuels were chosen in addition to ordinary UO2 fuel. The concentration of 135Xe, 149Sm, fissile and fertile isotopes with burnup, reactivity feedback with fuel temperature variation, and β eff values were calculated. The results indicate that the fuel cycle length increases by 54.27% for U-5Mo, 32.6% for U-7.5Mo, and 13.8% for U-10Mo, while it decreases by 16.4% for U-15Mo fuel. Additionally, the effect of 95Mo content in natural Mo was investigated by reducing the 95Mo concentration. According to the results, each proposed fuel's fuel cycle length extended when the depletion ratio of 95Mo increased. Additionally, the calculations for reactivity feedback guarantee safe operating conditions for all U-xMo fuels.

비만에 의해 유도된 근형질세망 스트레스에서 유산소 운동에 의한 감소효과 (Aerobic Exercise Ameliorated High Fat Diet-induced Endoplasmic Reticulum Stress More Than Polyphenol Supplementation in Skeletal Muscle of Obese Mice)

  • 박종구;김용안;박희근;이왕록
    • 생명과학회지
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    • 제28권10호
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    • pp.1186-1192
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    • 2018
  • 비만에 의한 근형질세망 스트레스(Endoplasmic stress, ER stress) 발생은 비접힙 단백질의 축적으로 근육내 대사와 근기능 저하를 초래한다. 유산소 운동과 폴리페놀은 비만에 유도된 염증성 사이토카인과 ER stress를 감소시키는 것으로 잘 알려졌다. 그러나 신체활동과 약물에 의한 염증성 사이토카인과 ER stress 변인들의 변화에 선택적인 반응이 있는지에 대한 연구는 이루어지지 않았다. 따라서, 이 연구의 목적은 유산소 운동과 폴리페놀섭취에 따른 골격근내 ER stress 관련 변인에 우선적인 효과가 있는지 비교분석하고자 하였다. 이 연구의 목적을 위해 (1) 정상식이 그룹, (2) 60% 고지방식이 그룹, (3) 고지방식와 레스베라트롤 25 mg/kg 그룹, (4) 고지방식이와 크리신 50 mg/kg 투여 그룹, (5) 고지방식이와 운동 그룹으로 나누어 실시하였다. 레스베라트롤과 크리신 그룹은 16주간 경구 투여 하였고, 운동 그룹은 1일 40-60분간 10-14 m/min의 속도로 주 4일, 총 16주간 트레드밀 운동을 수행하였다. 운동그룹에서 $IRE1{\alpha}$, BIP/GRP78는 고지방 식이 그룹과 비교하여 유의하게 낮아졌다(p<0.05). 고지방식이와 레스베라트롤 투여 그룹에서 ATF6, $IRE1{\alpha}$, BIP/GRP78는 고지방식이 그룹과 비교하여 유의하게 낮아졌다(p<0.05). 고지방식이와 크리신 투여 그룹은 고지방식이 그룹과 비교하여 ATF6가 유의하게 낮아졌다(p<0.05). 이러한 결과는 유산소 운동과 레스베라트롤, 크리신 섭취에 의해 ER stress 관련 변인을 조절할 수 있다. 그러나 유산소 운동은 고지방 식이에 의해 유도되는 ER stress 개선이 더욱 효과적인 것으로 나타났다.

Involvement of Endoplasmic Reticulum Stress Response in the Neuronal Differentiation

  • Cho, Yoon-Mi;Jang, Yoon-Seong;Jang, Young-Min;Seo, Jin-Young;Kim, Ho-Shik;Lee, Jeong-Hwa;Jeong, Seong-Whan;Kim, In-Kyung;Kwon, Oh-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • 제11권6호
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    • pp.239-246
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    • 2007
  • Expressions of endoplasmic reticulum stress response (ERSR) genes were examined during the neuronal differentiation of rat fetal cortical precursor cells (rCPC) and rat pheochromocytoma PC12 cells. When rCPC were differentiated into neuronal cells for 7 days, early stem cell marker, nest in, expression was decreased from day 4, and neuronal markers such as neurofilament-L, -M and Tuj1 were increased after day 4. In this condition, expressions of BIP, ATF6, and phosphorylated PERK as well as their down stream signaling molecules such as CHOP, ATF4, XBP1, GADD34, Nrf2 and $p58^{IPK}$ were significantly increased, suggesting the induction of ERSR during neuronal differentiation of rCPC. ERSR was also induced during the differentiation of PC12 cells for 9 days with NGF. Neurofilament-L transcript was time-dependently increased. Both mRNA and protein levels of Tuj1 were increased after the induction, and the significant increase in NeuN was observed at day 9. Similar to the expression patterns of neuronal markers, BIP/GRP78 and CHOP mRNAs were highly increased at day 9, and ATF4 mRNA was also increased from day 7. These results strongly suggest the induction and possible role of ERSR in neuronal differentiation process. Further study to identify targets responsible for neuronal induction will be necessary.