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Instruction Flow based Early Way Determination Technique for Low-power L1 Instruction Cache

  • Kim, Gwang Bok;Kim, Jong Myon;Kim, Cheol Hong
    • 한국컴퓨터정보학회논문지
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    • 제21권9호
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    • pp.1-9
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    • 2016
  • Recent embedded processors employ set-associative L1 instruction cache to improve the performance. The energy consumption in the set-associative L1 instruction cache accounts for considerable portion in the embedded processor. When an instruction is required from the processor, all ways in the set-associative instruction cache are accessed in parallel. In this paper, we propose the technique to reduce the energy consumption in the set-associative L1 instruction cache effectively by accessing only one way. Gshare branch predictor is employed to predict the instruction flow and determine the way to fetch the instruction. When the branch prediction is untaken, next instruction in a sequential order can be fetched from the instruction cache by accessing only one way. According to our simulations with SPEC2006 benchmarks, the proposed technique requires negligible hardware overhead and shows 20% energy reduction on average in 4-way L1 instruction cache.

꾸지뽕 신초 엽위별 잎 추출물의 항비만 효과 (Leaves of Cudrania tricuspidata on the Shoot Positional Sequence Show Different Inhibition of Adipogenesis Activity in 3T3-L1 Cells)

  • 박주하;궈루;강혜미;손병구;강점순;이용재;박영훈;제병일;최영환
    • 생명과학회지
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    • 제31권2호
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    • pp.209-218
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    • 2021
  • 본 연구는 꾸지뽕 신초에 부착된 잎을 6단계 즉 정아의 잎(L0), 정아부에서 하부의 순서대로 L1, L2, L3, L4 및 기부의 잎을 L5로 분류하여 채취하였다. 신초의 위치에 따라서 분류한 잎을 70% 에틸알콜로 추출한 다음 3T3-L1 cell line을 이용하여 지방분화 억제 효과를 스크린하고, 가장 효과가 좋았던 꾸지뽕 신초 정단잎(CTL0) 추출물의 작용기작을 규명하였다. 꾸지뽕 신초 정단잎(CTL0) 추출물의 지방분화 억제효과가 가장 좋았으며, 신초의 중간 잎인 CTL2까지는 정단 잎에서부터 중간 잎 추출물일수록 효과가 감소하였으며, 신초의 중간 하부 잎인 CTL3부터 기부 잎인 CTL5 추출물은 100 ㎍/ml의 고농도에서 효과가 없었다. 꾸지뽕 신초 정단잎(CTL0) 추출물을 12.5, 25 및 50 ㎍/ml의 농도로 처리하여 Oil Red O를 분석한 결과, 농도 의존적으로 3T3-L1세포의 지방분화를 억제시켰다. 3T3-L1 세포에 지방분화물질인 insulin, dexamethasone 및 rosiglitazone을 첨가한 분화배지(DM)에서는 배지내에 glucose의 함량이 낮았으나, CTL0 추출물의 처리는 배지에 glucose함량이 많이 남아있었기 때문에 세포내로 glucose의 흡수를 억제시켰으며, 세포내 중성지방의 함량도 감소하였다. CTL0처리는 전구지방세포에서 지방세포로 분화될 때에 주요 전사인자로 알려진 PPARγ와 PPARγ의 target 유전자인 LPL, A-FABP 및 Glut4 단백질의 발현을 농도 의존적으로 억제하였다. 따라서 꾸지뽕 신초 정단잎(CTL0) 추출물은 항비만 효과가 우수한 소재로서 활용가치가 높을 것으로 사료된다.

Crystal Structure and Spectroscopic Properties of Cyclic Dipeptide: A Racemic Mixture of cyclo(ᴅ-Prolyl-ʟ-Tyrosyl) and cyclo(ʟ-Prolyl-ᴅ-Tyrosyl)

  • Hong, Yong Pyo;Lee, Sung-Hong;Choi, Jong-Ha;Kashima, Ayana;Nakamura, Go;Suzuki, Takayoshi
    • Bulletin of the Korean Chemical Society
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    • 제35권8호
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    • pp.2299-2303
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    • 2014
  • Two diastereoisomers of cyclo(Pro-Tyr) have been synthesized simultaneously. The crystal structures and conformations of both cyclo($\small{L}$-Pro-$\small{L}$-Tyr) and a racemic mixture of cyclo($\small{D}$-Pro-$\small{L}$-Tyr) and cyclo($\small{L}$-Pro-$\small{D}$-Tyr), abbreviated as rac-cyclo($\small{D}$-Pro-$\small{L}$-Tyr/$\small{L}$-Pro-$\small{D}$-Tyr), have been determined by a single-crystal X-ray diffraction study at low temperature. The crystals of rac-cyclo($\small{D}$-Pro-$\small{L}$-Tyr/$\small{L}$-Pro-$\small{D}$-Tyr) belong to orthorhombic space group $Pna2_1$ with a = 10.755 (1), b = 12.699 (1), c = 9.600 (1) ${\AA}$ and Z = 4. The tyrosine side chain is folded towards the diketopiperazine (DKP) ring. The DKP ring adopts a twist boat conformation with pseudo symmetry $C_{2v}$. The pyrrolidine ring has an envelope conformation with the N5, C4, C7 and C8 atoms in a plane. The crystal of rac-cyclo($\small{D}$-Pro-$\small{L}$-Tyr/$\small{L}$-Pro-$\small{D}$-Tyr) is stabilized by hydrogen bonds between amide N2-H2 and carbonyl oxygen O2 in the neighbor. The hydroxyl group of tyrosine residue is also hydrogen bonded to the oxygen of the carbonyl group of the DKP ring in the next molecule. The spectroscopic properties of both isomers are also described.

Novel Discovery of LINE-1 in a Korean Individual by a Target Enrichment Method

  • Shin, Wonseok;Mun, Seyoung;Kim, Junse;Lee, Wooseok;Park, Dong-Guk;Choi, Seungkyu;Lee, Tae Yoon;Cha, Seunghee;Han, Kyudong
    • Molecules and Cells
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    • 제42권1호
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    • pp.87-95
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    • 2019
  • Long interspersed element-1 (LINE-1 or L1) is an autonomous retrotransposon, which is capable of inserting into a new region of genome. Previous studies have reported that these elements lead to genomic variations and altered functions by affecting gene expression and genetic networks. Mounting evidence strongly indicates that genetic diseases or various cancers can occur as a result of retrotransposition events that involve L1s. Therefore, the development of methodologies to study the structural variations and interpersonal insertion polymorphisms by L1 element-associated changes in an individual genome is invaluable. In this study, we applied a systematic approach to identify human-specific L1s (i.e., L1Hs) through the bioinformatics analysis of high-throughput next-generation sequencing data. We identified 525 candidates that could be inferred to carry non-reference L1Hs in a Korean individual genome (KPGP9). Among them, we randomly selected 40 candidates and validated that approximately 92.5% of non-reference L1Hs were inserted into a KPGP9 genome. In addition, unlike conventional methods, our relatively simple and expedited approach was highly reproducible in confirming the L1 insertions. Taken together, our findings strongly support that the identification of non-reference L1Hs by our novel target enrichment method demonstrates its future application to genomic variation studies on the risk of cancer and genetic disorders.

Paraquat 투여 생쥐 간에서 홍삼 추출물이 항산화효소 활성과 지질과산화에 미치는 항산화 효과 (Antioxidant Effects of Korean Red Ginseng Components on the Antioxidant Enzymes Activity and Lipid Peroxidation in the Liver of Mouse Treated with Paraquat)

  • 이화재;김동윤;장재철
    • Journal of Ginseng Research
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    • 제23권3호
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    • pp.182-189
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    • 1999
  • 본 연구에서 홍삼의 항산화 효과를 알아보기 위하여 생쥐에 홍삼의 총사포닌 분획, 수용성 추출물, 알코올 추출물, 지용성 분획과 ascorbic acid를 투여(200mg/kg/0.1ml)한 후 paraquat(PQ) 100mg/kg을 복강투여 하였을 때 활성산소 라디칼의 생성을 촉진시킨 후 간에서 $H_2O_2$ 함량, SOD, catalase, GP의 량을 측정한 결과 총사포닌 투여군을 제외한 홍삼추출물 투여 후 PQ투여군 치가 PQ 단독 처리군에 비하여 $H_2O_2$ 생성량이 유의성(p<0.01) 있게 감소 억제되었다. 한편 항산화효소의 활성은 PQ단독 처리군에 비하여 SOD는 홍삼추출물 투여 모든 군에서 유의성있는 증가를 하였고, catalase는 수용성 추출물과 지용성 분획 투여군에서 증가하였으며, CP는 지용성 분획에서 유의성(p<0.01)있는 증가를 보였다. 그리고 지질과산화에서 PQ처리는 지질과산화 경향 MDA량이 증가되는 것을 볼 수 있었고, 홍삼추출물 투여는 PQ단독 처리군에 비하여 지질과산화 경향에서 MDA량은 억제되는 경향을 보였다.

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Mitochondrially Targeted Bcl-2 and Bcl-XL Chimeras Elicit Different Apoptotic Responses

  • Liu, Sen;Pereira, Natasha Ann;Teo, Joong Jiat;Miller, Peter;Shah, Priya;Song, Zhiwei
    • Molecules and Cells
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    • 제24권3호
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    • pp.378-387
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    • 2007
  • The Bcl-2 family of proteins interacts at the mitochondria to regulate apoptosis. However, the anti-apoptotic Bcl-2 and $Bcl-X_L$ are not completely localized to the mitochondria. In an attempt to generate Bcl-2 and $Bcl-X_L$ chimeras that are constitutively localized to the mitochondria, we substituted their C-terminal transmembrane tail or both the C-terminal transmembrane tail and the adjacent loop with the equivalent regions from Bak or Bax mutant (BaxS184V) as these regions determine the mitochondrial localization of Bak and Bax. The effects of these substitutions on subcellular localization and their activities were assessed following expression in HeLa and CHO K1 cells. The substitution of the C-terminal tail or the C-terminal tail and the adjacent loop of Bcl-2 with the equivalent regions from Bak or the Bax mutant resulted in its association with the mitochondria. This change in subcellular localization of Bcl-2 chimeras triggered cells to undergo apoptotic-like cell death. The localization of this Bcl-2 chimera to the mitochondria may be associated with the disruption of mitochondrial membrane potential. Unlike Bcl-2, the loop structure adjacent to the C-terminal tail in $Bcl-X_L$ is crucial for its localization. To localize the $Bcl-X_L$ chimeras to the mitochondria, the loop structure next to the C-terminal tail in $Bcl-X_L$ protein must remain intact and cannot be substituted by the loop from Bax or Bak. The chimeric $Bcl-X_L$ with both its C-terminal tail and the loop structure replaced by the equivalent regions of Bak or Bax mutant localized throughout the entire cytosol. The $Bcl-X_L$ chimeras that are targeted to the mitochondria and the wild type $Bcl-X_L$ provided same protection against cell death under several death inducing conditions.

건강한 Thoroughbred 신생망아지의 혈액상 (The Reference Values on Hematologic Parameters in Clinically Normal Thoroughbred Neonatal Foals)

  • 양재혁;윤영민;이경갑;임윤규
    • 한국임상수의학회지
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    • 제28권4호
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    • pp.365-368
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    • 2011
  • Next to performing an expert physical examination, a blood sample submitted for a complete blood count is the most basic tool available to owners or veterinary practitioners. Reference values of complete blood count were determined at 6 different ages in 114 Thoroughbred foals during the second month of life. Hematologic results were as follows: RBC 8.2-10.5 ($10^6/{\mu}l$), Hb 10.9-13.3 (g/dl), HCT 28.2-35.2 (%), MCV 30.7-35.8 (fL), MCH 11.9-13.5 (pg), MCHC 37.9-40.5 (g/dl), RDW 24.5-25.7 (%), PLT 146.3-256.4 ($10^3/{\mu}l$), MPV 6.7-8.3(fL), total WBC 8.1-12.5 ($10^3/{\mu}l$), basophils 0.0 ($10^3/{\mu}l$), eosinophils 0.0-0.3 ($10^3/{\mu}l$), neutrophils 2.4-8.6 ($10^3/{\mu}l$), lymphocytes 1.8-2.9 ($10^3/{\mu}l$) and monocytes 0.0-1.4 ($10^3/{\mu}l$). The results of this study serve as reference ranges for Thoroughbred neonatal foals populations and can be useful for health control, regular examination and pre-sale soundness examination.

Status of Oxidative Stress and Antioxidant Levels in Smokers with Breast Cancer from Western Nepal

  • Nagamma, T.;Baxi, Jalaj;Singh, P.P.
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권21호
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    • pp.9467-9470
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    • 2014
  • Background: Research indicates that oxidative stress induced by smoking plays a role in breast cancer. In view of these reports, we aimed to study th relationship between smoking and oxidative stress in breast cancer patients from the western region of Nepal. Materials and Methods: The study included a control group of 42 females (non-smoking healthy women) and a test group sudivided into Group I consisting of 46 female breast cancer patients who were smokers and Group II consisting of 42 non-smoking breast cancer patients. Detailed history of the patients was collected with the help of pre-test proforma. Plasma levels of malondialdehyde (MDA), total antioxidant activity (TAA) which represents total dietary antioxidants, vitamin C and ${\alpha}$- tocopherol were estimated by standard methods. Statistical analysis was done using SPSS version 16. Results: The plasma MDA, TAA, vitamin C and ${\alpha}$- tocopherol were $1{\pm}1.4nmol/ml$, $918{\pm}207{\mu}mol/L$, $1{\pm}0.24mg/dL$ and $0.94{\pm}0.31mg/dL$ in controls, $5{\pm}1.2nmol/ml$, $458{\pm}166{\mu}mol/L$, $0.64{\pm}0.32mg/dL$ and $0.5{\pm}0.3mg/dL$ in Group-I and $2.56{\pm}1.2nmol/ml$, $663{\pm}178{\mu}mol/L$, $0.78{\pm}0.2mg/dL$ and $0.77{\pm}0.2mg/dL$ in Group- II, respectively. Vitamin C, ${\alpha}$- tocopherol and TAA (p=0.001) were significantly reduced whereas MDA (p=0.001) was significantly raised in Group-I when compared to controls and Group-II. Conclusions: We observed a significant rise in oxidative stress and low levels of antioxidants in breast cancer patients with smoking habit. It is well known that free radicals facilitate the progression of breast cancer, possibly increasing the risk of progression to the next stage.

The role of calmodulin in regulating calcium-permeable PKD2L1 channel activity

  • Park, Eunice Yon June;Baik, Julia Young;Kwak, Misun;So, Insuk
    • The Korean Journal of Physiology and Pharmacology
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    • 제23권3호
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    • pp.219-227
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    • 2019
  • Polycystic kidney disease 2-like-1 (PKD2L1), polycystin-L or transient receptor potential polycystin 3 (TRPP3) is a TRP superfamily member. It is a calcium-permeable non-selective cation channel that regulates intracellular calcium concentration and thereby calcium signaling. Although the calmodulin (CaM) inhibitor, calmidazolium, is an activator of the PKD2L1 channel, the activating mechanism remains unclear. The purpose of this study is to clarify whether CaM takes part in the regulation of the PKD2L1 channel, and if so, how. With patch clamp techniques, we observed the current amplitudes of PKD2L1 significantly reduced when co-expressed with CaM and $CaM{\triangle}N$. This result suggests that the N-lobe of CaM carries a more crucial role in regulating PKD2L1 and guides us into our next question on the different functions of two lobes of CaM. We also identified the predicted CaM binding site, and generated deletion and truncation mutants. The mutants showed significant reduction in currents losing PKD2L1 current-voltage curve, suggesting that the C-terminal region from 590 to 600 is crucial for maintaining the functionality of the PKD2L1 channel. With PKD2L1608Stop mutant showing increased current amplitudes, we further examined the functional importance of EF-hand domain. Along with co-expression of CaM, ${\triangle}EF$-hand mutant also showed significant changes in current amplitudes and potentiation time. Our findings suggest that there is a constitutive inhibition of EF-hand and binding of CaM C-lobe on the channel in low calcium concentration. At higher calcium concentration, calcium ions occupy the N-lobe as well as the EF-hand domain, allowing the two to compete to bind to the channel.

Engineering of Biosynthesis Pathway and NADPH Supply for Improved L-5-Methyltetrahydrofolate Production by Lactococcus lactis

  • Lu, Chuanchuan;Liu, Yanfeng;Li, Jianghua;Liu, Long;Du, Guocheng
    • Journal of Microbiology and Biotechnology
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    • 제31권1호
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    • pp.154-162
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    • 2021
  • L-5-methyltetrahydrofolate (5-MTHF) is one of the biological active forms of folate, which is widely used as a nutraceutical. However, low yield and serious pollution associated with the chemical synthesis of 5-MTHF hampers its sustainable supply. In this study, 5-MTHF production was improved by engineering the 5-MTHF biosynthesis pathway and NADPH supply in Lactococcus lactis for developing a green and sustainable biosynthesis approach. Specifically, overexpressing the key rate-limiting enzyme methylenetetrahydrofolate reductase led to intracellular 5-MTHF accumulation, reaching 18 ㎍/l. Next, 5-MTHF synthesis was further enhanced by combinatorial overexpression of 5-MTHF synthesis pathway enzymes with methylenetetrahydrofolate reductase, resulting in 1.7-fold enhancement. The folate supply pathway was strengthened by expressing folE encoding GTP cyclohydrolase I, which increased 5-MTHF production 2.4-fold to 72 ㎍/l. Furthermore, glucose-6-phosphate dehydrogenase was overexpressed to improve the redox cofactor NADPH supply for 5-MTHF biosynthesis, which led to a 60% increase in intracellular NADPH and a 35% increase in 5-MTHF production (97 ㎍/l). To reduce formation of the by-product 5-formyltetrahydrofolate, overexpression of 5-formyltetrahydrofolate cyclo-ligase converted 5-formyltetrahydrofolate to 5,10-methyltetrahydrofolate, which enhanced the 5-MTHF titer to 132 ㎍/l. Finally, combinatorial addition of folate precursors to the fermentation medium boosted 5-MTHF production, reaching 300 ㎍/l. To the best of our knowledge, this titer is the highest achieved by L. lactis. This study lays the foundation for further engineering of L. lactis for efficient 5-MTHF biosynthesis.