• Title/Summary/Keyword: PD-L1

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A Clinical Study on Childhood Hemolytic Anemia According to Etiological Classification (소아 용혈성 빈혈 환자에서 원인에 따른 임상적 분석)

  • Kwon, Hae-Sik;Kang, Jung-Chul;Won, Sung-Chul;Oh, Seung-Hwan;Lyu, Chuhl-Joo
    • Clinical and Experimental Pediatrics
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    • v.46 no.9
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    • pp.883-888
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    • 2003
  • Purpose : The etiology of hemolytic anemia can be classified as either cellular or extracellular defects of red blood cells. The aim of this study was to investigate the clinical and laboratory findings of hemolytic anemia concerning its etiological classification. Methods : Clinical and laboratory findings of the patients with hemolytic anemia treated from January 1987 to May 2002 at Severance Hospital were analyzed retrospectively. They were divided into two groups based on the types of red cell defects(group I : erythrocytic defect, group II : extraerythrocytic defect). Results : Twenty one cases were included in group I, thirty four cases in group II, and three cases were unclassified. In group I, nineteen cases(90.5%) were diagnosed as hereditary spherocytosis and were proved to have red cell membrane disorders while two cases(9.5%) were shown to have red cell enzyme deficiencies. In group II, thirteen cases(38.2%) were noted as autoimmune hemolytic anemia, eleven cases(32.4%) as traumatic or microangiopathic hemolytic anemia, four cases(11.8%) as drug induced hemolytic anemia, two cases(5.9%) were related with systemic lupus erythematosus and one case(2.9%) with malignancy. Hemoglobin at the time of diagnosis(7.5 g/dL vs. 6.2 g/dL, P<0.05) and the incidence of splenomegaly(85.7% vs. 18.2%, P<0.05) were higher in group I though blood urea nitrogen(9.0/0.4 mg/dL vs. 27.8/1.6 mg/dL, P<0.05) was higher in group II. Conclusion : Comparing the clinical features of pediatric hemolytic anemia, we concluded as following : In cases associated with extraerythrocytic defect, blood tests revealed significant initial lower hematocrit with higher level of BUN and Cr while cases with erythrocytic defect, splenomegaly were more common noted.

Regulation of tumor-associated macrophage (TAM) differentiation by NDRG2 expression in breast cancer cells

  • Lee, Soyeon;Lee, Aram;Lim, Jihyun;Lim, Jong-Seok
    • BMB Reports
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    • v.55 no.2
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    • pp.81-86
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    • 2022
  • Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

SB202190- and SB203580-Sensitive p38 Mitogen-Activated Protein Kinase Positively Regulates Heat Shock- and Amino Acid Analog-Induced Heat Shock Protein Expression

  • Kim, Sun-Hee;Han, Song-Iy;Oh, Su-Young;Seo, Myoung-Suk;Park, Hye-Gyeong;Kang, Ho-Sung
    • Biomedical Science Letters
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    • v.9 no.2
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    • pp.59-65
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    • 2003
  • When cells are exposed to proteotoxic stresses such as heat shock, amino acid analogs, and heavy metals, they increase the synthesis of the heat shock proteins (HSPs) by activating the heat shock transcription factor 1 (HSF1), whose activity is controlled via multiple steps including homotrimerization, nuclear translocation, DNA binding, and hyperphosphorylation. Under unstressed conditions, the HSF1 activity is repressed through its constitutive phosphorylation by glycogen synthase kinase 3$\beta$ (GSK3$\beta$), extracellular regulated kinase 1/2 (ERK1/2), and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). However, the protein kinase (s) responsible for HSF1 hyperphosphorylation and activation is not yet identified. In the present study, we observed that profile of p38 mitogen-activated protein kinase (p38MAPK) activation in response to heat shock was very similar to those of HSF1 hyperphosphorylation and nuclear translocation. Therefore, we investigated whether p38MAPK is involved in the heat shock-induced HSF1 activation and HSP expression. Here we show that the p38MAPK inhibitors, SB202190 and SB203580, but not other inhibitors including the MEK1/2 inhibitor PD98059 and the PI3-K inhibitor LY294002 and wortmannin, suppress HSF1 hyperphosphorylation in response to heat shock and L-azetidine 2-carboxylic acid (Azc), but not to heavy metals. Furthermore, heat shock-induced HSF1-DNA binding and HSP72 expression was specifically prevented by the p38MAPK inhibitors, but not by the MEK1/2 inhibitor and the PI3-K inhibitors. These results suggest that SB202190- and SB203580-sensitive p38MAPK may positively regulate HSP gene regulation in response to heat shock and amino acid analogs.

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Fermentation Characteristics and Increased Functionality of Doenjang Prepared with Bamboo Salt (죽염 된장의 발효 특성 및 기능성 증진 효과)

  • Jeong, Min-Woo;Jeong, Ji-Kang;Kim, Sin-Jeong;Park, Kun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.12
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    • pp.1915-1923
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    • 2013
  • The aim of this study is carried out to evaluate the fermentation characteristics and increased functionality when doenjang was prepared with bamboo salts. Grain type mejus were fermented with mixed starter cultures of Aspergillus oryzae, Bacillus subtilis, and Lactococcus lactis. These mejus were mixed with different kinds of salts-purified salt (PD), sea salt (SD), one-time baked bamboo salt ($1{\times}BD$), three-time baked bamboo salt ($3{\times}BD$), and nine-time baked bamboo salt ($9{\times}BD$)- when doenjangs were prepared. For doenjang fermentation period of 8 weeks at $37^{\circ}C$, the fermentation characteristics of all the groups were compared. The amino type nitrogen content and enzyme activities (protease and ${\alpha}$-amylase) in the samples were significantly increased. In DPPH radical scavenging activities and hydroxyl radical scavenging activities, $9{\times}BD$ (47% and 69%) showed the highest scavenging activities compared to PD (40% and 49%), SD (42% and 57%), $1{\times}BD$ (42% and 64%) and $3{\times}BD$ (45% and 65%) (P<0.05). The anticancer effects of doenjang in HT-29 cancer cells indicated all the groups, especially doenjang prepared with bamboo salts were higher than the others (P<0.05). Apoptosis related genes of Bax and Bcl-2, as well as inflammation related genes of iNOS and COX-2 were regulated by the treatment of doenjangs in HT-29 cancer cells. SD, $1{\times}BD$, $3{\times}BD$, and $9{\times}BD$ increased the expression level of Bax and decreased the expression level of Bcl-2, iNOS, and COX-2. These results suggest that sea salt and bamboo salt especially bamboo salt could improve fermentation characteristics and functionality of doenjang and play an important role in regulating apoptosis and inflammation related genes in cancer cells.

Brief low [Mg2+]o-induced Ca2+ spikes inhibit subsequent prolonged exposure-induced excitotoxicity in cultured rat hippocampal neurons

  • Kim, Hee Jung;Yang, Ji Seon;Yoon, Shin Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.1
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    • pp.101-109
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    • 2016
  • Reducing $[Mg^{2+}]_o$ to 0.1 mM can evoke repetitive $[Ca^{2+}]_i$ spikes and seizure activity, which induces neuronal cell death in a process called excitotoxicity. We examined the issue of whether cultured rat hippocampal neurons preconditioned by a brief exposure to 0.1 mM $[Mg^{2+}]_o$ are rendered resistant to excitotoxicity induced by a subsequent prolonged exposure and whether $Ca^{2+}$ spikes are involved in this process. Preconditioning by an exposure to 0.1 mM $[Mg^{2+}]_o$ for 5 min inhibited significantly subsequent 24 h exposure-induced cell death 24 h later (tolerance). Such tolerance was prevented by both the NMDA receptor antagonist D-AP5 and the L-type $Ca^{2+}$ channel antagonist nimodipine, which blocked 0.1 mM $[Mg^{2+}]_o$-induced $[Ca^{2+}]_i$ spikes. The AMPA receptor antagonist NBQX significantly inhibited both the tolerance and the $[Ca^{2+}]_i$ spikes. The intracellular $Ca^{2+}$ chelator BAPTA-AM significantly prevented the tolerance. The nonspecific PKC inhibitor staurosporin inhibited the tolerance without affecting the $[Ca^{2+}]_i$ spikes. While $G{\ddot{o}}6976$, a specific inhibitor of $PKC{\alpha}$ had no effect on the tolerance, both the $PKC{\varepsilon}$ translocation inhibitor and the $PKC{\zeta}$ pseudosubstrate inhibitor significantly inhibited the tolerance without affecting the $[Ca^{2+}]_i$ spikes. Furthermore, JAK-2 inhibitor AG490, MAPK kinase inhibitor PD98059, and CaMKII inhibitor KN-62 inhibited the tolerance, but PI-3 kinase inhibitor LY294,002 did not. The protein synthesis inhibitor cycloheximide significantly inhibited the tolerance. Collectively, these results suggest that low $[Mg^{2+}]_o$ preconditioning induced excitotoxic tolerance was directly or indirectly mediated through the $[Ca^{2+}]_i$ spike-induced activation of $PKC{\varepsilon}$ and $PKC{\xi}$, JAK-2, MAPK kinase, CaMKII and the de novo synthesis of proteins.

Inhibitory Effect of Glycoprotein Isolated from Cudrania tricuspidata Bureau on Histamine Release and COX-2 Activity in RBL-2H3 Cells (RBL-2H3 세포에 있어서 꾸지뽕 당단백질에 의한 히스타민 방출 및 COX-2 활성 억제 효과)

  • Oh, Phil-Sun;Lee, Hye-Jin;Lim, Kye-Taek
    • Korean Journal of Food Science and Technology
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    • v.41 no.4
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    • pp.405-412
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    • 2009
  • The purpose of this study was to determine the inhibitory effect of a glycoprotein isolated from Cudrania tricuspidata Bureau (CTB glycoprotein, 75 kDa) on immunoglobulin E (IgE)-induced allergic inflammation in RBL-2H3 cells. This experiment evaluated the production of intracellular reactive oxygen species (ROS), the activities of mitogenactivated protein kinase (MAPK), transcription factor (c-jun), and cyclooxygenase (COX)-2, and histamine release in cells. The results showed that the CTB glycoprotein inhibited histamine release and COX-2 expression induced by IgE in the cells. The CTB glycoprotein also had suppressive effects on the expressions of ERK1/2, p38 MAPK, c-jun, and the production of intracellular ROS in IgE-treated RBL-2H3 cells. The activities of c-jun and COX-2 were collectively blocked by ERK1/2 inhibitor (PD98059) and p38 MAPK inhibitor (SKF86002), respectively. Hence, we speculate that CTB glycoprotein might be a component with potential use in the preparation of health supplements for the prevention of allergic diseases.

UHV Materials (초고진공계재료)

  • 박동수
    • Proceedings of the Korean Vacuum Society Conference
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    • 1998.02a
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    • pp.24-24
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    • 1998
  • 반도체장비를 포함하는 초고진공장비의 園훌化가 급속히 그리고 절실히 요구되고 있는 것이 현실정이다. 當面해서 실현할 국산진공장비의 대상은 廣範圍하다. 즉, 각종 진공 pump ( (rotary, dry, diffusion, cryo, ion, turbo melecular pump), 진공 chamber, 진공 line, gate valve 를 위 시 한 진공 V머ve, flange, gasket, fl않d야lU, mainpulater 퉁 진공 部品이 다. 진공계 의 핵심 은 適切하고 優良한 진공재료의 선태파 사용이다. 진공장비는 사용자가 원하는 진공도를 원하 는 시간 동안 륨空度를 유지해 주어야 한다. 진공재료 선태의 기준사항은:(1) 기체의 透過성 (2) 薰했훌 (3) 혔體放出특성 - -outgassing과 degassing- (4) 機械的 량훌度 (5) 온도 의존성 (6) 化學톡성 (7) 加I성 및 鎔接 성 (8) 課電특성 (9) 磁氣특성 (10) 高速함子 및 放射線 특성 (11) 經濟성 및 調達생 둥이 다. 우량한 초고진공계재료는 풍부하게 개발되어 왔고, 또 新材料들이 개발되고 있다. 여기에서는 주로 초고진공 내지는 극고진공계의 構造材料, 機能材料, 部品材料 일반파 몇가지 신재료의 특 성에 관해서 記述한다. M Mild SteeHSAE, 1112, 1010, 1020, 1022, etc)., S Stainless SteeHAlSI, 304, 304L, 310, 316, 321, 347): 구조재료, chamber, fl하1ges A Aluminum과 Alloys (1060, 1100, 2014, 4032, 6(뻐1): 구조재료, chamber, flanges, gaskets A AI, Al 떠loy는 SS에 代替하는 역 할올 시 작하고 있다. C Copper, Copper Alloys(C11$\alpha$)0, C26800, C61400, Cl7200): 내장인자, gasket, cryopanel, tubing T Titanium, Ziriconium, Haf띠um 및 Alloys: 특히 Ti은 10n pump 용 getter material 이 외 에 U UHV,XHV용 chamber계로서 관심올 끌고 있다. N Nickel, Nickel Alloys (200, 204, 211, monel, nichrome): 부식 방지 , 전자장치 , 자기 장치 귀 금속(Ag, Au, Pt, Pd, Rh, Ir, Os, Ru): 보조부품, gasket, filament, coating, thermocouple, 접 합부위 T TiC, SiC, zrC, HfC, TaC 둥의 탄화물과, BN, TiN, AlN 동의 질화물, 붕화물이 둥장하고 었 다. 유리: Soda Lime, Borosilicate, Potash Soda Lead: View Port, Chamber envelope C Ceramics: AlZ03, BeO, MgO, zrOz, SiOz, MgOzSiOz, 3Alz032SiOz, Z$textsc{k}$hSiOz S상N4: e electrical, thermal insulators, crucibles, boats, single crystals, sepctr려 windows 저자는 최근 저자들이 발견한 Zr-Ti-Cu-Ni-Be amorphous alloys coated cham뾰r가 radiation p proof로 이용될 수 있는 사실을 점검하고 었다 .. Z.Y. Hua 들은 Cs3Sb를 새로운 photocathode 재료로 보고하고 있다.

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An experimental study of the strength and internal structure of solder joint of fixed partial denture (가공의치(架工義齒) 납착부(蠟着部)의 강도(强度)와 내부구조(內部構造)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Park, Sang-Nam;Kay, Kee-Sung
    • The Journal of Korean Academy of Prosthodontics
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    • v.23 no.1
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    • pp.39-59
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    • 1985
  • The purpose of this study was to investigate how gap distances of 0.13mm, 0.15mm, 0.20mm, and 0.30mm affects solder joint strength from gold alloys and nickel-chromium base alloys and to examine the composition of solder gold, the solder joint of gold alloys and nickel-chromium base alloys. The tensile test specimens were prepared in the split stainless steel mold with a half dumbbell shape 2.5mm in diameter and l2mm in length. 6 pairs of specimens of each gap distance group of gold alloys and nickel-chromium base alloys were made and 48 pairs of all specimens were soldered with solder gold of 666 fineness. All soldered specimens were machined to a uniform diameter and then a tensile load was applied at a cross-head speed of 0.10mm/min using Instron Universal Testing Machine, Model 1115. The fractured specimens at solder gold of solder joint fracture with each gap distance of 0.13mm, 0.15mm, 0.20mm, and 0.30mm were examined under the Scanning Electron Microscope, JSM-35c and the composition of solder gold, the solder joint of gold alloys and nickel-chromium base alloys was analyzed by Electron Probe Micro Analyzer. The results of this study were obtained as follows: 1. In case of soldering of gold alloys, the tensile strength between gold alloys showed $37.33{\pm}2.52kg/mm^2$ at 0.13, $39.14{\pm}3.35kg/mm^2$ at 0.15mm, $43.76{\pm}2.97kg/mm^2$ at 0.20mm, and $49.18{\pm}4.60kg/mm^2$ at 0.30mm. There was statistically significant difference at each gap distance, and so the greater increase of gap distance showed the greater tensile strength. 2. In case of soldering of nickel-chromium base alloys, the tensile strength between nickel-chromium base alloys showed $34.84{\pm}4.26kg/mm^2$ at 0.13mm, $37.25{\pm}2.49kg/mm^2$ at 0.15mm, $42.91{\pm}4.32kg/mm^2$ at 0.20mm, and $46.93{\pm}4.21kg/mm^2$ at 0.30mm. There was not statistically significant difference only between 0.13mm and 0.15mm and bet ween 0.20 mm and 0.30mm, but generally the greater increase of gap distance showed the greater tensile strength. 3. The greater increase of gap distance shoed less porosities in solder gold at solder joint fracture. 4. In solder gold Au, Cu, Ag, Zn, and Sn were composed and Au and Cu were mostly distributed uniformly. 5. In solder joints of solder gold and gold alloys Au, Cu, Ag, Zn, and Sn were composed in solder gold and Au, Cu, Ag, Pt, and Pd were composed in gold alloys. Au and Cu of solder gold and gold alloys were mostly distributed uniformly and the diffusion of other elements except Pt and Pd around the solder joint was not almost found. In solder joints of solder gold and nickel-chromium base alloys Au, Cu, Ag, Zn, and Sn were composed in solder gold and Ni, Cr, and Al were composed in nickel-chromium base alloys. Au and Cu of solder gold and Ni and Cr of nickel-chromium base alloys were mostly distributed uniformly and the diffusion of other elements except Cr around the solder joint was not almost found.

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Development and Verification of a Simultaneous Analytical Method for Whole Blood Metals and Metalloids for Biomonitoring Programs (바이오모니터링 프로그램을 위한 혈중 금속류 동시분석법 개발 및 확인 평가)

  • Cha, Sangwon;Oh, Eunha;Oh, Selim;Han, Sang Beom;Im, Hosub
    • Journal of Environmental Health Sciences
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    • v.47 no.1
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    • pp.64-77
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    • 2021
  • Objective: Biological monitoring of trace elements in human blood samples has become an important indicator of the health environment. The purpose of this study was to detect and evaluate multiple metal items in blood samples based on ICP-MS, to perform comparative evaluation with the existing analysis method, and to develop and verify a new method. Methods: 100 μL of whole blood from 80 healthy subjects was used to analyze ten metals (Sb, tAs, Cd, Pb, Mn, Hg, Mo, Ni, Se, Tl) using ICP-MS. Verification of the analysis method included calculation of linearity, accuracy, precision and detection limits. In addition, a comparative test with the conventional graphite furnace atomic absorption spectroscopy (GF-AAS) method was performed. In the case of Pb, Cd, and Hg in whole blood, cross-analysis between Pb, Cd, and Hg analysis methods was performed to confirm the difference between the existing method and the new method (ICP-MS). Results: The coefficient of determination (R2) was 0.999 or higher in seven items and 0.995 or higher in three items. The Pb result showed that Pearson's correlation coefficient was very high at 0.983, and the intraclass correlation coefficient was 0.966. The Cd result showed that Pearson's correlation coefficient was 0.917 between the existing method and the new analysis concentration value. Its intraclass correlation coefficient was 0.960, and there was no significant difference between the two groups. Hg had a low correlation at 0.687, and the intraclass correlation coefficient was 0.761, which was lower than that of Pb and Cd. The intra-day and inter-day accuracy of Pd and Cd were satisfactory, but Hg did not meet the criteria for both accuracy and precision when compared with the conventional analysis method. Conclusion: This study can be meaningful in that it proposes a more efficient and feasible analysis method by verifying a blood heavy metal concentration experiment using multiple simultaneous analyses. All samples were processed and analyzed using the new ICP-MS. It was confirmed that the agreement between the two methods was very high, with the agreement between the current and new methods being 0.769 to 0.998. This study proposes an efficient simultaneous methodology capable of analyzing multiple elements with small samples. In the future, studies of various applications and the reliability of ICP-MS analysis methods are required, and research on the verification of accurate, precise, and continuous analysis methods is required.

A Study on Long-term Variations of BOD and COD as Indicators of Organic Matter Pollution in the Han River (한강 본류에서 유기물 오염도 지표인 BOD와 COD에 대한 장기변동 특성)

  • Cho, Hyun-Seok;Kim, Kwang-Rae;Lim, Gyu-Chul;Bae, Kyung-Seok;Lee, Min-Hwan
    • Korean Journal of Ecology and Environment
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    • v.45 no.4
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    • pp.474-481
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    • 2012
  • This study was performed to investigate the degree of long-term pollution at the mainstream of the Han River by comparing the concentration of BOD and COD from 1975 to 2011. The long-term annual average BOD and COD concentration at the mainstream of the Han River showed an increasing trend as it flowed downstream from Paldang Dam to Gayang. The concentration of BOD ($r^2$=0.646) and COD ($r^2$=0.260) showed a consistent decreasing trend for 37 years. In the case of Paldang Dam, BOD has maintained a decreasing trend, whereas the COD value showed an increasing trend after the 1990s. Therefore, a control of non-biodegradable materials in areas around Paldang Dam is required. The result of the seasonal variations of BOD and COD is as follows: spring>winter>summer and fall (p<0.001). The time series analysis revealed a strong correlation for every 12-month period. Also, the amount of water discharge at Paldang Dam has to be systematically controlled because the amount of water discharge from the dam influences the water quality at the mainstream of the Han River.