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Expression of Hypoxia-inducible Factor-$1{\alpha}$ in Non-small Cell Lung Cancer: Relationship to Prognosis and Tumor Biomarkers (비소세포 폐암에서 HIF-$1{\alpha}$의 발현: 예후 및 종양표지자와의 관련성)

  • Cho, Sung-Rae;Byun, Joung-Hun;Kim, Jong-In;Lee, Bong-Geun;Chun, Bong-Kwon
    • Journal of Chest Surgery
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    • v.39 no.11 s.268
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    • pp.828-837
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    • 2006
  • Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

Effect of Estrus Cycle on the Neclear Development of Preantral Follicle Oocytes in Canine (개 발정주기가 미성숙난자의 핵발달에 미치는 영향)

  • 최정림;조성균;공일근
    • Korean Journal of Animal Reproduction
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    • v.25 no.2
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    • pp.93-100
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    • 2001
  • This study was conducted to evaluate the nuclear development of preantral follicle oocytes in dog following collecting from different estrus ovaries and oocyte diameter. To do this, ovaries were collected from Sunchon livestock station by ovarioectomy and then transported to laboratory in 3$0^{\circ}C$ saline within 2 h. All of the ovaries were washed three times with saline supplemented with 100 IU Penicillin and 100 $\mu\textrm{g}$/$m\ell$ Streptomycin and then sliced with blade in 100 mm dish. All of the oocytes collected were classified the oocyte size such as over 110 ${\mu}{\textrm}{m}$ or under 110 ${\mu}{\textrm}{m}$ and the estrus status. To induce the nuclear development, oocytes were cultured in TCM199 $\alpha$-MEM supplemented with 10% FCS, 0.1 $\mu\textrm{g}$/$m\ell$ sodium pyruvate, 100 ng/$m\ell$ FSH, 100 ng/$m\ell$ EGF, 1% ITS, 100 IU/$m\ell$ penicillin, 100 $\mu\textrm{g}$/$m\ell$ streptomycin at 38.5$^{\circ}C$, 5% $CO_2$ incubator for 72 h. After culture, all of the oocytes were stained in 1% orcein following fixed in 45% Acetic acid for 48 h. The oocyte recovery rates of over 110 ${\mu}{\textrm}{m}$ from estrus ovary (63.6%) were significantly higher rather than that in anestrus status (51.5%). Oocyte recovery rate per ovary of over 110 ${\mu}{\textrm}{m}$ in estrus status ovary (22.6/63.8%) was also significantly higher rather than that in anestrus status ovary (8.2/51.6%). Nuclear development to MI of over 110 ${\mu}{\textrm}{m}$ in estrus ovary (24.3%) was significantly higher rather than those in under 110 ${\mu}{\textrm}{m}$ or over and under 110 ${\mu}{\textrm}{m}$ in anestrus (2.5, 6.8 and 0.0%), respectively (P < 0.05). Nuclear development to AT and MII of over 110 ${\mu}{\textrm}{m}$ in estrus was more developed in other groups. Nuclear development to MI in TCM199 (21.8%) was significantly higher than in $\alpha$-MEM (10.0%). Altho $\mu\textrm{g}$h the development rate to AT was significantly different between TCM199 (7.3%) and $\alpha$-MEM (1.1%), but to MII was not different between TCM199 (0.9%) and $\alpha$-MEM (1.1%). The results indicated that over 110 ${\mu}{\textrm}{m}$ oocytes was could be recovery from estrus status ovary, bigger oocytes were more developed to MI, AT or MII in TCM199.

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The Optimal TDN Levels of Concentrates and Slaughter Age in Hanwoo Steers (거세한우에 있어서 배합사료의 적정 TDN 수준과 도축 월령)

  • Kim, K.H.;Lee, J.H.;Oh, Y.G.;Kang, S.W.;Lee, S.C.;Park, W.Y.;Ko, Y.D.
    • Journal of Animal Science and Technology
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    • v.47 no.5
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    • pp.731-744
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    • 2005
  • Ninety Hanwoo steers(initial BW=167.2$\pm$13.4kg) were used to determine the effect of energy concentrations in concentrates and slaughter age on performance, carcass characteristics. Steers were allotted by BW to one of eighteen pens. Eighteen pens were randomly allotted to a low(70-70-71-72% for the growing, the early, the middle or the late fattening periods), medium(70-71-72-73%) or high(70-72- 73-74%) TDN level of concentrates. Five steers for each treatment of energy level were slaughtered every one month from 26 month of age to 31 month of age. Concentrates was fed restrictedly to achieve a predicted gain of 0.7-0.9kg from growing stage to middle fattening stage. All steers were fed orchard grass(Dactylis glomerata L.) hay as roughage during the growing period, fed rice straw gradually substituted for orchard grass hay during the early fattening period, and fed rice straw only thereafter. Overall body weight and feed intake were not affected by TDN levels of concentrates. Average daily gain for all treatments was higher than 0.9kg/d during the 19-21 month of age and decrease thereafter, but sustained above 0.7kg/d. Mean concentrates intake for all treatments was 1.0-1.3% of live BW during the growing period and 1.5% during the early fattening. Thereafter, it decreased up to 1.4% during the middle fattening and 1.0% during late fattening period. Delay of slaughter end point resulted in a gradual increase of rib-eye area, back fat thickness and marbling score, especially after slaughter age of 29 month there was significant increases(P<0.05). The appearance rate of 1+ and 1 grade related to the slaughter ages was 100% at 29, 30 and 31 months of age, whereas those at 26, 27 and 28 months were 93, 86 and 80%, respectively. Dressing rate was significantly(P<0.05) increased and rate of retailed cut weight significantly(P<0.05) decreased when slaughter age increased. In economic analysis, there was pronounced increase in net income up to 32-46% after slaughter age of 29 months. Under the conditions of this study, high TDN intake is not necessarily required for high quality Hanwoo meat production and slaughter age of 29 month might be the optimum for Hanwoo steers.

Studies on Molecular Plasticity of Bergmann Glia following Purkinje Cell Degeneration (조롱박신경세포의 변성에 따른 버그만아교세포의 면역조직학적 연구)

  • Yoon, Chul-Jong;Cho, Sa-Sun;Lee, Ha-Kyu;Park, Min-Chul
    • Applied Microscopy
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    • v.35 no.3
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    • pp.165-176
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    • 2005
  • Studies on molecular plasticity of Bermann glia (BG) after harmaline-induced Purkinje cell (PC) degeneration in the rat cerebellum. The intimate structural relationship between BG and PC, evidenced by the sheathing of the PC dendrites by veil-like process from the BG has been suggestive of the close functional relationship between these two cell types. However, little is known about metabolic couplings between these cells. This study designed to investigate molecular plasticity of BG in the rat cerebellum in which PCs were chemically ablated by harmaline treatment. Immunohistochemical examination reveals that harmaline induced PC degeneration causes a marked glial reaction in the cerebellum with activated BG and microglia aligned in parasagittal stripes within the vermis. In these strips, activated BG were associated with upregulaion of metallotheionein, while GLAST and was down regulated, as compared with nearby intact area where both BG are in contact with PCs. The data from this study demonstrate that BG can change their phenotypic expression when BG loose their contact with PCs. It is conceivable that activated BG may upregulate structural proteins, metallothionein expression to use for their proliferation and hypertrophy; metallothionein expression to cope with oxidative stress induced by PC degeneration and microglial activation. On the contrary, BG may down regulated expression of GLAST because sustained loss of contact with PCs would eliminate the necessity for the cellular machinery involved glutamate metabolism. In conclusion, BG might respond man to death of PCs by undergoing a change in metabolic state. It seems possible that signaling molecules released from PCs regulates the phenotype expression of BG. Also ultrastructures in the organelles of normal PC and BG are distinguished by mitochondrial appearance, and distributed vesicles at the synaptic area in the cytoplasm.

Radium Isotope Ratio as a Tracer for Estimating the Influence of Changjiang Outflow to the Northern Part of the East China Sea (라듐 동위원소 방사능비를 추적자로 사용한 동중국해 북부 해역에서 장강 유출수의 영향 추정)

  • Kim, Kee-Hyun;Kim, Seung-Soo
    • Journal of the Korean Society for Marine Environment & Energy
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    • v.12 no.3
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    • pp.133-142
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    • 2009
  • In order to understand the present environmental condition and future impingement of Changjiang(Yangtze River) outflow upon the adjacent seas after the scheduled completion of the Sanxia (Three Gorges) Dam in 2009, we tried to estimate the mixing ratios among surface waters of three end-members: Changjiang Water (CW), Kuroshio Water (KW), and East China Sea Water (ECSW) using $^{228}Ra/^{226}Ra$ activity ratio and salinity as tracers. Water samples were collected from 32 stations in November 2005 (R/V Tamgu 3), from 20 stations in July 2006 (R/V Ocean 2000) and from 17 stations in August 2006 (R/V Ieodo) in the northern part of the East China Sea. Radium isotopes in ~300 liters of surface seawater were extracted onboard by filtering through manganese impregnated acrylic fibers and following coprecipitation as $Ba(Ra)SO_4$. Activities of radium isotopes were determined by a high purity germanium detector. Results show that the fraction of CW was in the range of 1-23% in the study area, while KW was in the range of 0-30 % and ECSW 58-100 %. The eastward plume of Changjiang outflow, commonly observed in satellite images during summer and also displayed by the eastward-decreasing CW fraction in this study, could be attributed to Ekman transport caused by the SE monsoon prevailing in this region during summer. Results of this study showed that in the drought season, there was a little or no fraction of CW in the study area. Concentration of dissolved inorganic nitrogen (DIN) showed strong positive relationship with the fraction of CW, suggesting Changjiang as the major source of nitrogen. The mixing curve of DIN indicates the removal of nitrate by biological uptake during the mixing of CW with ambient seawater in the study area.

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Complex Terrain and Ecological Heterogeneity (TERRECO): Evaluating Ecosystem Services in Production Versus water Quantity/quality in Mountainous Landscapes (산지복잡지형과 생태적 비균질성: 산지경관의 생산성과 수자원/수질에 관한 생태계 서비스 평가)

  • Kang, Sin-Kyu;Tenhunen, John
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.12 no.4
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    • pp.307-316
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    • 2010
  • Complex terrain refers to irregular surface properties of the earth that influence gradients in climate, lateral transfer of materials, landscape distribution in soils properties, habitat selection of organisms, and via human preferences, the patterning in development of land use. Complex terrain of mountainous areas represents ca. 20% of the Earth's terrestrial surface; and such regions provide fresh water to at least half of humankind. Most major river systems originate in such terrain, and their resources are often associated with socio-economic competition and political disputes. The goals of the TERRECO-IRTG focus on building a bridge between ecosystem understanding in complex terrain and spatial assessments of ecosystem performance with respect to derived ecosystem services. More specifically, a coordinated assessment framework will be developed from landscape to regional scale applications to quantify trade-offs and will be applied to determine how shifts in climate and land use in complex terrain influence naturally derived ecosystem services. Within the scope of TERRECO, the abiotic and biotic studies of water yield and quality, production and biodiversity, soil processing of materials and trace gas emissions in complex terrain are merged. There is a need to quantitatively understand 1) the ecosystem services derived in regions of complex terrain, 2) the process regulation occurred to maintain those services, and 3) the sensitivities defining thresholds critical in stability of these systems. The TERRECO-IRTG is dedicated to joint study of ecosystems in complex terrain from landscape to regional scales. Our objectives are to reveal the spatial patterns in driving variables of essential ecosystem processes involved in ecosystem services of complex terrain region and hence, to evaluate the resulting ecosystem services, and further to provide new tools for understanding and managing such areas.

Determination of Carazolol and Azaperone in Livestock and Fishery Products Using Liquid Chromatography-tandem Mass Spectrometry (축수산물에서 LC-MS/MS를 이용한 카라졸롤 및 아자페론 분석)

  • Choi, Soo Yeon;Kang, Hui-Seung;Kim, Joohye;Cheon, So-Young;Jeong, Jiyoon;Cho, Byung-Hoon;Lee, Kang-Bong
    • Journal of Food Hygiene and Safety
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    • v.33 no.3
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    • pp.176-184
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    • 2018
  • The aim of the present work was to develop simultaneous methods of quantification of carazolol, azaperone, and azaperol residues in livestock and fishery products using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Samples were extracted from beef, pork, chicken, egg, milk and shrimp using acetonitrile (ACN); while flat fish and eel were extracted using 80% ACN. For purification, ACN saturated n-hexane was used to remove fat composition. The standard calibration curves showed good linearity as correlation coefficients; $r^2$ was > 0.99. Average recoveries expressed were within the range of 67.9-105% for samples fortified at three different levels ($0.5{\times}MRL$, $1{\times}MRL$ and $2{\times}MRL$). The correlation coefficient expressed as precision was within the range of 0.55-7.93%. The limit of quantification (LOQ) was 0.0002-0.002 mg/kg. The proposed analytical method showed high accuracy and acceptable sensitivity based on Codex guideline requirements (CAC/GL71-2009). This method can be used to analyze the residue of carazolol, azaperone, and azaperol in livestock and fishery products.

JSAP1 Interacts with Kinesin Light Chain 1 through Conserved Binding Segments (JSAP1과 Kinesin Light Chain 1의 결합 및 결합부위 규명)

  • Kim, Sang-Jin;Lee, Chul-Hee;Park, Hye-Young;Yea, Sung-Su;Jang, Won-Hee;Lee, Sang-Kyeong;Park, Yeong-Hong;Cha, Ok-Soo;Moon, Il-Soo;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.17 no.7 s.87
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    • pp.889-895
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    • 2007
  • A conventional kinesin, KIF5/kinesin-I, is composed of two kinesin heavy chains (KHCs) and two kinesin light chains (KLCs) and binds directly to microtubules. KIF5 motor mediates the transport of various membranous organelles, but the mechanism how they recognize and bind to a specific cargo has not yet been completely elucidated. Here, we used the yeast two-hybrid system to identify the neuronal protein(s) that interacts with the tetratricopeptide repeats (TRP) of KLCI and found a specific interaction with JNK/stress-activated protein kinase-associated protein 1 (JSAP1/JIPP3). The yeast two-hybrid assay demonstrated that the TRP 1,2 domain-containing region of KLCI mediated binding to the leucine zipper domain of JSAP1. JSAP1 also bound to the TRP region of lac2 but not to neuronal KIF5A, KIF5C and ubiquitous KIF5B in the yeast two-hybrid assay. In addition, these proteins showed specific interactions in the GST pull-down assay and by co-immunoprecipitation. KLCI and KIF5B interacted with GST-ISAP1 fusion proteins, but not with GST alone. An antibody to JSAPI specifically co-immunoprecipitated KIF5s associated with JSAP1 from mouse brain extracts. These results suggest that JSAP1, as KLC1 receptor, is involved in the KIF5 mediated transport.

Variations of Fish Community and Fish Density on Artificial Reefs (인공어초어장의 어류 군집상과 어획량 변동)

  • LEE Jeong-Woo;KANG Young-Shil
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.27 no.5
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    • pp.535-548
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    • 1994
  • Community structures and fish densit were investigated on three different types of artificial reefs, dice, turtle artificial reef and tubes, constructed in the Korean waters. Variations of fish fauna according to type of artificial reef and the proper artificial reef in each area for optimizing harvest were discussed. Fish were captured by trammel gill net during May, June, September and November, 1988 and both identified and counted. Fourty-five fish species were found in the artificial reefs. Of these, Sebastes spp., Hexagrammos otakii, Pleuronectidae, Navodon modestus and Stephanolepis cirrhifer showed high occurrence-frequency. The dominant species groups were coastal settlement, demersal or rock fishes such as Pleuronectidae, Rajiformes, Stephanolepis cirrhifer, Navodon modestus, Hexagrammos otakii and Sebastes spp. in all of the Artificial reefs except the oceanic area of southern waters. Scomber japonicus was predominant in the oceanic area of southern waters. Composition of demersal, rock and pelagic fishes were different depending on the types of artificial reef. Dice artificial reefs were occupied by rock fish, on the other hand turtle artificial reefs were dominated by dermersal fish. Fish density was high at the dice artificial reef in all survey areas except the middle area of Eastern waters, with high fish density evident in the Tube artificial reef. Fish community structures were remarkably different between Dice and Turtle artificial reefs. The Tube artificial reef showed intermediate characteristics between the above two types of artificial reefs. The coastal areas of Southern waters and the middle and southern areas of Western waters revealed similar fish fauna. Results from the oceanic areas of Southern waters were well associated with the middle and southern areas of Eastern waters.

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Early Changes after Death of Plaice, Paralichthys olivaceus Muscle -4. Effect of Killing Methods on Rigor Index and Breaking Strength of Muscle- (넙치(Paralichthys olivaceus)육의 사후 조기 변화 -4. 치사 방법이 육의 사후 경직도와 파괴 강도에 미치는 영향-)

  • CHO Young-Je;LEE Nam-Geoul;KIM Yuck-Yong;KIM Jae-Hyun;CHOI Young-Joon;KIM Geon-Bae;LEE Keun-Woo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.27 no.1
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    • pp.41-46
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    • 1994
  • This study was undertaken to clarify the effect of killing methods on physical and rheological changes of plaice, Paralichthys olivaceus muscle at early period after death. Plaices killed by the four different methods(1. spiking at the brain instantly. 2. drowning in air. 3. dipping in 1,000ppm ethylaminobenzoate dissolved sea water as an anesthetic. 4. electrifying in sea water.) were stored at $5^{\circ}C$, and the rigor-index and breaking strength through storage were monitored. The longest onset time of rigor-mortis and full rigor was in the samples killed by dipping in sea water with dissolved anesthetic among all samples, where rigor-mortis began at 20hrs after killing and maximum tension was attained after 56hrs. However, in the cases of plaice electrified in sea water or drowned in air, the onset of rigor-mortis began just after killing and maximum tensions were attained after 9hrs and 13hrs, respectively. The level of breaking strength in the muscle of fish killed by spiking the brain instantly was $950.30{\pm}50.23g$, immediately after killing. The value and time reached around the maximum breaking strength for each of the samples were $1,230.60{\pm}30.32g$ and Ohr (immediately after killing) for samples killed by electrifying in sea water, $1,235.83{\pm}35.37g$ and 2.5hrs for drowning samples, $1,186.29{\pm}55.90g$ and 10hrs for spiking samples, and $1,189.67{\pm}50.32g$ and 15hrs for samples dipped in anesthetic, respectively. From the results above, it could be concluded that electrification in sea water is the most effective method in accelerating rigor-mortis and shortening times of reaching the maximum breaking strength of fresh plaice flesh of all the killing methods at early periods after death, whereas dipping in sea water treated with anesthetic was the most effective way in delaying those changes.

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