• Title/Summary/Keyword: K-Ras

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Analysis of Serum proteom before and after Intravenous Injection of wild ginseng herbal acupuncture (자연산 산삼 증류약침의 혈맥주입 전.후 혈장의 Proteom 분석)

  • Kang, Tae-Sik;Lee, Sun-Gu;Kwon, Ki-Rok
    • Journal of Pharmacopuncture
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    • v.7 no.3
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    • pp.5-25
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    • 2004
  • Objectives : To observe changes in the serum proteins before and after intravenous injection of wild ginseng herbal acupuncture. Methods : Blood was collected before and after the administration of wild ginseng herbal acupuncture and only the serum was centrifuged. Then differences in the spots on the scanned image after running 2-Dimensionl electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of wild ginseng herbal acupuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 803, 1505, 2205, 3105, 7104, 9001 spots, with more than one-time increase were 1101, 1302, 2013, 3009, 3010, 4002, 4009, 6706, 7103, 8006, 8101, and spots with decrease were 205, 801, 3205, 5202, 6105. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1101 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAP1 protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein L1, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as Transferrin, 9001 as(Alpha-Oxy, Beta-(C112g)deoxy) T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d, which acts against microbes and pathogenic organisms, and Antitrypsin(803), which is secreted with inflammatory response in the lungs, were increased by more than 200% after the administration of herbal acupuncture. 5. Immunoglobulin lambda chain(3105), Alpha-Oxy, Beta-(C112g)deoxy T-State Human Hemoglobin(9001), and human hemoglobin(9003) were increased by more than two-times after the administration of herbal acupuncture. 6. Proapolipoprotein(2013, 3010) and apolipoprotein(7104), key components of the HDL-cholesterol which plays an important role in preventing arteriosclerosis, were increased after the administration of herbal acupuncture. 7. Vitamin D binding protein(DBP, 2403), protecting the lung at the time of inflammatory response, was increased after the administration of herbal acupuncture. 8. Transthyretin(TTR, 3205), which is the main protein causing familial aimyloid polyneuropathy(FAP), was decreased after the administration of herbal acupuncture. 9. Ras-related protein Ral-A(4002) that controls phospholipid metabolism, cytoskeletal formation, and membrane traffic, was increased after the administration of herbal acupuncture. 10. Testis-specific protein Y(8006), which takes part in determination of the gender, was increased by more than two-times after the administration of herbal acupuncture. 11. Transferrin(8101), T-State Human Hemoblobin(9001), and Human Hemoblobin(9003) which balances the iron level in the body, were increased after the administration of herbal acupuncture. Conousion : Above results support the notion that intravenous injection of cultivated wild ginseng herbal acupuncture induce changes in serum proteins and this research can be a pioneer work in finding biomarkers.

Differential Roles of Vascular Endothelial Growth Factor Receptor-1 and Receptor-2 in Angiogenesis

  • Shibuya, Masabumi
    • BMB Reports
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    • v.39 no.5
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    • pp.469-478
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    • 2006
  • Vascular endothelial growth factor (VEGF)-A, a major regulator for angiogenesis, binds and activates two tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). These receptors regulate physiological as well as pathological angiogenesis. VEGFR2 has strong tyrosine kinase activity, and transduces the major signals for angiogenesis. However, unlike other representative tyrosine kinase receptors which use the Ras pathway, VEGFR2 mostly uses the Phospholipase-$C{\gamma}$-Protein kinase-C pathway to activate MAP-kinase and DNA synthesis. VEGFR2 is a direct signal transducer for pathological angiogenesis including cancer and diabetic retinopathy, thus, VEGFR2 itself and the signaling appear to be critical targets for the suppression of these diseases. VEGFR1 plays dual role, a negative role in angiogenesis in the embryo most likely by trapping VEGF-A, and a positive role in adulthood in a tyrosine kinase-dependent manner. VEGFR1 is expressed not only in endothelial cells but also in macrophage-lineage cells, and promotes tumor growth, metastasis, and inflammation. Furthermore, a soluble form of VEGFR1 was found to be present at abnormally high levels in the serum of preeclampsia patients, and induces proteinurea and renal dysfunction. Therefore, VEGFR1 is also an important target in the treatment of human diseases. Recently, the VEGFR2-specific ligand VEGF-E (Orf-VEGF) was extensively characterized. Interestingly, the activation of VEGFR2 via VEGF-E in vivo results in a strong angiogenic response in mice with minor side effects such as inflammation compared with VEGF-A, suggesting VEGF-E to be a novel material for pro-angiogenic therapy.

Hydrologic and Hydraulic Analysis in Sumjin River Basin under Climate Change (기후변화에 따른 섬진강 유역 내 수리.수문학적 변화 평가)

  • Kim, Yon-Soo;Kim, Soo-Jun;Kim, Duck-Gil;Kim, Duck-Hwan;Kim, Hung-Soo
    • Proceedings of the Korea Water Resources Association Conference
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    • 2012.05a
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    • pp.611-611
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    • 2012
  • 지구온난화에 따른 기후변화로 인해 자연재해는 빈번히 발생하고 있으며, 그 피해규모는 증가하고 있는 추세로 나타나고 있다. 이로 인하여, 최근 빈발하는 집중호우에 의한 자연재해는 생명과 재산에 직접적인 피해를 입히게 된다. 따라서, 기후변화에 따른 강수량 특성이 반영된 홍수량 및 홍수위 산정은 미래 기후변화가 유역에 미치는 영향을 파악하고, 이 치수 계획수립 등의 수자원 계획에 있어 중요하다고 할 수 있다. 본 연구에서는 미래 기후변화가 섬진강 유역의 수리 수문학적 변화에 미치는 영향을 평가하고자 국가하천인 섬진강(송정수위표~섬진강댐 하류)을 포함한 섬진강 유역의 중하류부에 위치한 요천(섬진강 합류점~이백교), 보성강(섬진강합류점~주암댐 하류) 구간을 모의대상으로 선정하고 모형을 구성하였다. 기상청에서 제공하는 KMA-RCM 기후자료를 바탕으로 목표기간(목표I :1979~2008년, 목표 II:2011~2040년, 목표 III:2041~2070년, 목표 IV:2071~2100년)에 따라 HEC-HMS를 이용하여 홍수량을 산정하였고, 이를 HEC-RAS에 적용하여 기후변화에 따른 홍수위 변화를 대상 유역의 유역출구점인 송정 수위관측소를 기준으로 산정 및 검토하였다. 산정된 결과를 섬진강 유역의 기 수립된 계획과 비교 검토를 하였으며, 목표기간별 홍수량 및 홍수위 변화양상을 제시하였다. 본 연구결과는 기후변화 시나리오를 고려한 목표기간별 수공시설물의 방재기준 개선 방안 및 재설정 기준 마련에 있어 기초자료로 활용할 수 있을 것으로 판단된다.

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Analysis of Inundation Area in the Agricultural Land under Climate Change through Coupled Modeling for Upstream and Downstream (상·하류 연계 모의를 통한 기후변화에 따른 농경지 침수면적 변화 분석)

  • Park, Seongjae;Kwak, Jihye;Kim, Jihye;Kim, Seokhyeon;Lee, Hyunji;Kim, Sinae;Kang, Moon Seong
    • Journal of The Korean Society of Agricultural Engineers
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    • v.66 no.1
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    • pp.49-66
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    • 2024
  • Extreme rainfall will become intense due to climate change, increasing inundation risk to agricultural land. Hydrological and hydraulic simulations for the entire watershed were conducted to analyze the impact of climate change. Rainfall data was collected based on past weather observation and SSP (Shared Socio-economic Pathway)5-8.5 climate change scenarios. Simulation for flood volume, reservoir operation, river level, and inundation of agricultural land was conducted through K-HAS (KRC Hydraulics & Hydrology Analysis System) and HEC-RAS (Hydrologic Engineering Center - River Analysis System). Various scenarios were selected, encompassing different periods of rainfall data, including the observed period (1973-2022), near-term future (2021-2050), mid-term future (2051-2080), and long-term future (2081-2100), in addition to probabilistic precipitation events with return periods of 20 years and 100 years. The inundation area of the Aho-Buin district was visualized through GIS (Geographic Information System) based on the results of the flooding analysis. The probabilistic precipitation of climate change scenarios was calculated higher than that of past observations, which affected the increase in reservoir inflow, river level, inundation time, and inundation area. The inundation area and inundation time were higher in the 100-year frequency. Inundation risk was high in the order of long-term future, near-term future, mid-term future, and observed period. It was also shown that the Aho and Buin districts were vulnerable to inundation. These results are expected to be used as fundamental data for assessing the risk of flooding for agricultural land and downstream watersheds under climate change, guiding drainage improvement projects, and making flood risk maps.

The Effect of Excess Dietary Vitamin A on Vitamin K-dependent Carboxylation in Rat Liver Microsomes (비타민 A 과량 섭취가 흰쥐의 간 Microsome의 비타민 K-dependent Carboxylation에 미치는 영향)

  • Lilha Lee
    • Journal of Nutrition and Health
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    • v.25 no.6
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    • pp.492-500
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    • 1992
  • The rate of vitamin K-dependent carboxylation of endogenous liver microsomal proteins and an exogenous peptide substrate for carboxylase were measured to test the effects of excess vitamin A on vitamin K function in rats. In vitro vitamin A incubation in normal rat microsomes of vitamin K-sufficient ras did not influence the carboxylation rates of either endogenous prothrombin precursors or a peptide substrate added, Similarly vitamin A incubation in micro-somes from control and excess vitamin A-fed rats that were on vitamin K-free diet did not change the rate significantly within the respectively groups ; however the rates of endogenous protein carboxylation from excess vitamin A-fed rats tended to be increased by the in vitro vitamin A addition compared to that of control rats. Excess vitamin A-fed rats had 2- to 3- fold higher carboxylase activites of endogenous protein carboxylation either with or without the invitro vitamin A incubation than did control rats. In an in vivo study carboxyalase activites with an added exogenous peptide substrate were not influenced by excess intake of vitamin excess vitamin A-fed rats than for control rats. Carboxylase activites tended to be increased amounts of vitamin A on endogenous protein carboxylation appeareed as early as one week post-initiation of the diet. The results of this study indicate that excess vitamin A produces toxic effect rapidly and that excess dietary vitamin A increase the rate of carboxylation of endogenous protein mainly prothrombin precursors which is an indication of vitamin K defi-ciency.

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Influence of Blockade of Sympathetic Nervous System, Renin-Angiotensin System, and Vasopressin System on Basal Blood Pressure Levels and on Pressor Response to Norepinephrine, Angiotensin II, and Vasopressin (교감신경계, Renin-Angiotensin계, Vasopressin계의 차단이 혈압 및 Norepinephrine, Angiotensin II 및 Vasopressin의 승압효과에 미치는 영향)

  • Chung, Haeng-Nam
    • The Korean Journal of Pharmacology
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    • v.28 no.1
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    • pp.61-74
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    • 1992
  • Influence of the blockade of the three major pressor systems-sympathetic nervous system (SNS), renin-angiotensin system (RAS) and vasopressin system-on the pressor responsiveness to norepinephrine (NE), angiotensin II (AII), and vasopressin (VP) as well as on basal blood pressure (BP) levels was investigated in urethane-anesthetized rabbits. To block the SNS and RAS, chlorisondamine (CS) and pirenzepine (PZ), sympathetic ganglionic blockers, and enalapril (ENAL), an inhibitor of angiotensin converting enzyme, respectively were used. And for suppressing the VP system bremazocine (BREM), a kappa opiate receptor agonist shown to suppress plasma levels of VP, was employed. Each of CS (0.4 mg/kg), ENAL (2 mg/kg), and BREM (0.25 mg/kg) produced almost same levels of steady hypotensive state. The hypotensive effect of BREM was significantly attenuated by desmopressin, a synthetic VP-like analogue, suggesting the hypotension being at least in part due to suppression of plasma levels of VP. CS, ENAL and BREM elicited further fall of the BP which had been lowered by ENAL or BREM, CS or BREM, and CS or ENAL, respectively. The hypotension produced by both CS and PZ together with either of ENAL or BREM was more marked than that produced by the three drugs other than CS. CS potentiated the pressor response not only to NE but to AII and VP. The pressor effect of AII was increased by ENAL and BREM, too. The pressor response to VP was also enhanced by BREM. Blockade of ${\alpha}-adrenergic$ receptors with phentolamine or phenoxybenzamine potentiated the pressor response to AII and that to VP. The results on basal BP levels indicate that the three major pressor systems are all participating in control of BP, but SNS has the greatest potential for supporting BP. The finding that blockade of one of the pressor systems induced enhanced pressor responsiveness to the pressor hormone of that particular system as well as to the pressor hormone(s) of the other systems(s) provides evidence for important interactions among the three major pressor systems.

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Mitochondrial Cytochrome b Sequence Variations and Population Structure of Siberian Chipmunk (Tamias sibiricus) in Northeastern Asia and Population Substructure in South Korea

  • Lee, Mu-Yeong;Lissovsky, Andrey A.;Park, Sun-Kyung;Obolenskaya, Ekaterina V.;Dokuchaev, Nikolay E.;Zhang, Ya-Ping;Yu, Li;Kim, Young-Jun;Voloshina, Inna;Myslenkov, Alexander;Choi, Tae-Young;Min, Mi-Sook;Lee, Hang
    • Molecules and Cells
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    • v.26 no.6
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    • pp.566-575
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    • 2008
  • Twenty-five chipmunk species occur in the world, of which only the Siberian chipmunk, Tamias sibiricus, inhabits Asia. To investigate mitochondrial cytochrome b sequence variations and population structure of the Siberian chipmunk in northeastern Asia, we examined mitochondrial cytochrome b sequences (1140 bp) from 3 countries. Analyses of 41 individuals from South Korea and 33 individuals from Russia and northeast China resulted in 37 haplotypes and 27 haplotypes, respectively. There were no shared haplotypes between South Korea and Russia - northeast China. Phylogenetic trees and network analysis showed 2 major maternal lineages for haplotypes, referred to as the S and R lineages. Haplotype grouping in each cluster was nearly coincident with its geographic affinity. In particular, 3 distinct groups were found that mostly clustered in the northern, central and southern parts of South Korea. Nucleotide diversity of the S lineage was twice that of lineage R. The divergence between S and R lineages was estimated to be 2.98-0.98 Myr. During the ice age, there may have been at least 2 refuges in South Korea and Russia - northeast China. The sequence variation between the S and R lineages was 11.3% (K2P), which is indicative of specific recognition in rodents. These results suggest that T. sibiricus from South Korea could be considered a separate species. However, additional information, such as details of distribution, nuclear genes data or morphology, is required to strengthen this hypothesis.

Common Docking Domain Mutation E322K of the ERK2 Gene is Infrequent in Oral Squamous Cell Carcinomas

  • Valiathan, Gopalakrishnan Mohan;Thenumgal, Siji Jacob;Jayaraman, Bhaskar;Palaniyandi, Arunmozhi;Ramkumar, Hemalatha;Jayakumar, Keerthivasan;Bhaskaran, Sajeev;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6155-6157
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    • 2012
  • Background: Mutations in the MAPK (Mitogen Activated Protein Kinase) signaling pathway - EGFR/Ras/RAF/MEK have been associated with the development of several carcinomas. ERK2, a downstream target of the MAPK pathway and a founding member of the MAPK family is activated by cellular signals emanating at the cell membrane. Activated ERK2 translocates into the nucleus to transactivate genes that promote cell proliferation. MKP - a dual specific phosphatase - interacts with activated ERK2 via the common docking (CD) domain of the later to inactivate (dephosphorylate) and effectively terminate further cell proliferation. A constitutively active form of ERK2 carrying a single point mutation - E322K in its CD domain, was earlier reported by our laboratory. In the present study, we investigated the prevalence of this CD domain E322K mutation in 88 well differentiated OSCC tissue samples. Materials and Method: Genomic DNA specimens isolated from 88 oral squamous cell carcinoma tissue samples were amplified with primers flanking the CD domain of the ERK2 gene. Subsequently, PCR amplicons were gel purified and subjected to direct sequencing to screen for mutations. Results: Direct sequencing of eighty eight OSCC samples identified an E322K CD domain mutation in only one (1.1%) OSCC sample. Conclusions: Our result indicates that mutation in the CD domain of ERK2 is rare in OSCC patients, which suggests the role of genetic alterations in other mitogenic genes in the development of carcinoma in the rest of the patients. Nevertheless, the finding is clinically significant, as the relatively rare prevalence of the E322K mutation in OSCC suggests that ERK2, being a common end point signal in the multi-hierarchical mitogen activated signaling pathway may be explored as a viable drug target in the treatment of OSCC.

The Clinical and Pathologic Features according to Expression of Acyl Protein Thioesterase-1 (APT1) in Stage I Non-small Cell Lung Cancer (제1기 비소세포폐암에서 APT1 발현의 임상적 의미)

  • Shin, Jung-Ar;Lee, Chang-Ryul;Byun, Min-Kwang;Chang, Yoon-Soo;Kim, Se-Kyu;Chang, Joon;Ahn, Chul-Min;Kim, Hyung-Jung
    • Tuberculosis and Respiratory Diseases
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    • v.68 no.4
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    • pp.212-217
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    • 2010
  • Background: Acyl protein thioesterase-1 (APT1) is a cytosolic protein that may function in the depalmitoylation of numerous proteins, including the Ras family. However, the clinical role of depalmitoyl thioesterase in human cancer is not known. We evaluated the APT1 expression in lung cancer tissue and its clinicopathological findings according APT1 expression pattern. Methods: APT1 expression was examined by immunohistochemistry in the tumor tissue from 79 patients, who had undergone curative surgical removal of the primary lesion; all patients had been diagnosed with stage I non-small cell lung cancer between 1993 and 2004, at Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. Results: The APT1 expression was seen in 50 out of 79 (63.3%) cases. The positive APT1 expression was significantly related with histologic subtype and T stage, but was not influenced by differentiation. The positive APT1 expression was not significantly related to patient age, gender, or smoking history. The median follow-up duration was 10.0 years; the 5-year survival rate was 71.0%. The positive APT1 expression group showed significantly worse overall survival and worse disease-free survival without statistical significance. Conclusion: We conclude that positive APT1 expression in stage I lung cancer after surgery is closely associated with overall survival. To evaluate APT1 as a prognostic marker in lung cancer, comprehensive studies on advanced stage cases are needed.

Genome-based Gene Expression Analysis of EGCG-mediated Cell Transformation Suppression Effect in Mouse Cell line Balb/c 3T3 A31-1-1 (마우스세포주 Balb/c 3T3 A31-1-1에서 Epigallocatechin gallate(EGCG)의 세포암화 억제효과에 대한 유전자발현 해석)

  • Jung, Ki-Kyung;Suh, Soo-Kyung;Kim, Tae-Gyun;Park, Moon-Suk;Lee, Woo-Sun;Park, Sue-Nie;Kim, Seung-Hee;Jung, Hai-Kwan
    • Environmental Mutagens and Carcinogens
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    • v.26 no.4
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    • pp.125-132
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    • 2006
  • Previous studies showed that epigallocatechin gallate(EGCG) have substantial effects of suppressing the N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-initiated cell transformation process on the bases of foci formation frequency and loss of anchorage dependency. In this study we tried to clarify the molecular mechanism of suppressing the cell transformation process. Mouse cell line balb/c 3T3 A31-1-1 was exposed 2 days to MNNG followed by 15 days 12-O-tetradecanoylphorbol-13-acetate(TPA) treatment for our transformation process. EGCG was added after the time point of 24 hours exposure to TPA and incubated for 19 days. 2029 genes were selected in our transformation process that showed fold change value of 1.5 or more in the microarray gene expression analysis covering the mouse full genome. These genes were found to be involved mainly in the cell cycle pathway, focal adhesion, adherens junction, TGE-$\beta$ signaling, apoptosis, lysine degradation, insulin signaling, ECM-receptor interaction. Among the genes, we focused on the 631 genes(FC>0.5) reciprocally affected by EGCG treatment. Our study suggest that EGCG down-regulate the gene expressions of up stream signaling factors such as nemo like kinase with MAPK activity and PI3-Kinase, Ras GTPase and down stream factors such as cyclin D1, D2, H, T2, cdk6.

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