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Antitumor Activity of Arylacetylshikonin Analogues

  • Kim, Seon-Hee;Song, Gyu-Yong;Jin, Guang-Zhu;Ahn, Byung-Zun
    • Archives of Pharmacal Research
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    • v.19 no.5
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    • pp.416-422
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    • 1996
  • Twenty one phenylacetylshikonin analogues were synthesized from various subsitituted phenyl acetic acids and their cytotoxicity values against A549, K562 and L1210 cell lines and antitumor action in mice bearing S-180 cells were measured. All of phenylacetylshikonin analogues expressed a potent cytotoxicity $(ED_{50}, 0.1-1.80{\mu}g/ml)$ against L1210 and K562 cells. L1210 cells were the most sensitive to shikonin analogues among these cells. Except 4-methosyphenylacetylshikonin $(0.098 {\mu}g/ml)$, and a-acetoxyphenylacetylshikonin $(0.10 {\mu}g/ml)$, all other shikonin derivatives sshowed higher $ED_{50}$ values than phenylacetylshikonin $(0.13{\mu}g/ml)$, in L1210. In K562 cell, a-substitution of phenylacetylshikonin $(0.1{\mu}g/ml)$, while other subsitutions increased it slightly; 4-methoxyphenylacetylshikonin $(0.033{\mu}g/ml)$ showed a exceptionally good cytotoxicity against K562 cell. 4-Halogenation tended to decrease the cytotoxic effect on L1210 cells, while it enhanced the effect on K562; 4-bromophenylacetyl $$[ED_{50};(L1210)=1.76{\mu}g/ml, ;ED_{50};(K 562)=0.32 {\mu}g/ml]$$ and 4-chlorophenylacetyl shikonin $$[ED_{50};(L1210)=1.64 {\mu}g/ml, ;ED_{50};(K562)=0.32 {\mu}g/ml]$$. In contrast, A549 cells were much less sensitive to these shikonin analogues which showed $ED_{50}$ values of$1.5-1.35 {\mu}g/ml)$.Most of phenylacetylshikonin derivatives showed good antitumor activity in mice bearing S-180 cells. a-A-cetoxyphenylacetylshikonin and 4-dimethylaminophenylacetylshikonin showed highest T/C value (192-195%), implying that introduction of a-acetyl or of 4-dimethylamino group enhanced the antitumor activity as shown for 4-dimethylaminophenylacetylshikonin (T/C, 192%). It might be due to improvement of water solubility by dimethylamino group in the molecule.

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The Study of anti-inflammatory Mechanism with Cobra Venom on Astrocytes of Rats (뇌(腦) 성상세포(星狀細胞)를 대상으로 한 Cobrotoxin의 염증(炎症) 치료(治療) 기전(機轉) 연구(硏究))

  • Yoo, Jae-ryong;Song, Ho-sueb
    • Journal of Acupuncture Research
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    • v.22 no.3
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    • pp.155-167
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    • 2005
  • Objectives : The purpose of this study was to investigate the anti-inflammatory effect of Cobrotoxin on binding affinity of cobrotoxin with P50, $IKK{\alpa}$ and $IKK{\beta}$, activities of NF-${\kappa}B$, Cell viability of astrocyte, expressions of protein molecules of NF-${\kappa}B$ such as P50, P-$1{kappa}B$, $1{\kappa}B$ and iflammation related genes such as Cox-2, iNOS, cPLA2 in the SNP or LPS induced Inflammatory pathway of Rats' astrocytes. Methods : In this study, The expression of cytosolic phospholipase A2, Nitric oxcide, Cyclooxygenase-2 and inducible nitrogen oxide synthase was determined by western blotting with corresponding antibodies, and the generation of NF-${\kappa}B$ was assayed by EMSA method in astrocytes of rats. The Cell viability of astrocytes was determined by MTT assay, and Binding affinity of Cobrotoxin with P50, $IKK{\alpha}$ and $IKK{\beta}$ was assayed by Surface plasmon resonance analysis, and NF-${\kappa}B$ dependent luciferase activity was determined by luciferase analysis, and Uptake of cobrotoxin in astrocytes was identified by Confocal laser scanning microscope Results : 1. Compared with control, LPS-induced NF-${\kappa}B$ DNA binding activity was decreased significantly by 0.1, $0.5{\mu}g/m{\ell}$ of Cobrotoxin in Astrocyte. 2. Compared with control, LPS-induced NF-kB dependent luciferase expression was decreased significantly by 0.1, 0.5 and $1{\mu}g/m{\ell}$ of Cobrotoxin in Astrocyte. 3. Compared with control, SNP induced P50, $I{\kappa}B$ expressions in astrocyte were decreased significantly by 0.1, 0.5 and $1{\mu}g/m{\ell}$ of Cobrotoxin and P-$1{\kappa}B$ expression was decreased significantly by 0.5 and $1{\mu}g/m{\ell}$ of Cobrotoxin. 4. Compared with control, LPS induced P50, $1{\kappa}B$ expressions in astrocyte were decreased significantly by 0.5 and $1{\mu}g/m{\ell}$ of Cobrotoxin. 5. Compared with control, SNP induced Cox-2, iNOS, CPLA2 expressions in astrocyte were decreased significantly by $1{\mu}g/m{\ell}$ of Cobrotoxin. 6. Compared with control, LPS induced Cox-2, cPLA2 expressions in astrocyte were decreased significantly by 0.1, 0.5, $1{\mu}g/m{\ell}$ of Cobrotoxin and iNOS expression was decreased significantly by 0.5, $1{\mu}g/m{\ell}$ of Cobrotoxin. 7. Compared with $0.5{\mu}g/m{\ell}$ of Cobrotoxin, SNP-induced NF-${\kappa}B$ DNA bindins activity in astrocyte was increased significantly by Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 1mM and Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 5mM. 8. Compared with $0.5{\mu}g/m{\ell}$ of Cobrotoxin, LPS-induced NF-${\kappa}B$ DNA binding activity in astrocyte was increased significantly by Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 1mM, Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 5mM, Cobrotoxin $0.5{\mu}g/m{\ell}$with GSH 1mM and Cobrotoxin $0.5{\mu}g/m{\ell}$ with GSH 5mM 9. Compared with $0.1{\mu}g/m{\ell}$ of cobrotoxin, SNP induced P50 expressions in astrocyte were increased significantly by Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 1mM, Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 5mM Cobrotoxin $0.5{\mu}g/m{\ell}$ with GSH 1mM and Cobrotoxin $0.5{\mu}g/m{\ell}$ with GSH 5mM. 10. The uptake of the labeled cobrotoxin into the cells was shown under a confocal laser scanning microscope. cobrotoxin was uptaken into the membrane and nucleus of astrocytes. Conclusions : In summary, the present results demonstrate that cobrotoxin directly binds to sulfhydryl group of p50 and IKKS resulting In the reduction of translocation of p50 and IkB release, thereby inhibits activation of NF-${\kappa}B$, and suggest that pico to nanomolar range of cobrotoxin could inhibit the expression of genes in the NF-${\kappa}B$ signal pathway.

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Effects of Vinegar and Lactic Acid on the Survival of Pathogens Causing Food Poisoning of Sliced Raw Fish Meat (식초와 젖산이 생선회 식중독 유래 병원성 세균의 생존에 미치는 영향)

  • 김영만;김경희
    • Journal of Life Science
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    • v.12 no.6
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    • pp.669-675
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    • 2002
  • Introduction of sliced raw fish meat(SRFM) to fast food business has been considered seriously. However bacteria causing food poisoning should be controlled. Organic acids such as vinegar and lactic acid used in the sauce for SRFM were evaluated for their antibacterial activities. At low concentration levels of vinegar and lactic acid exerted strong antibacterial activities toward Vibriu sp.. In contrast, in case of Salmonella typhimurium and Escherichia coli O157:H7 low anitbacterial activities were observed even at relatively high concentrations. Minimum inhibitory concentrations(MIC) of vinegar for V. vulnificus, V. cholerae non-O1, V. parahaemolyticus, V. mimicus, S. typhimurium and E. coli O157:H7 were 16, 18, 16, 12, 26, and $20{\mu}\ell /m\ell, respertively. MIC of lactic acid for V. vilnificus, V. cholerae non-O1, V. parahaemolyticus, V. mimicus, S. typhimurium and E. coli O157:H7 were 20, 25, 25, 25, 40, and $35{\mu}\ell /m\ell, respectively. In case of vinegar bactericidal concentration upon 10 second contact for V. vulnificus, V. cholerae non-O1, V. parahaenolyticus, V. mimicus and E. coli O157:H7 were 8, 14, 10, 4, and 48%, respectively; however, even at 50% colony of S. typhimurium was observed. In case of lactic acid any colony was observed for V. vulnificus, V. cholerae non-O1, V. parahaemolyticus, V. mimicus, S. typhimurium and E. coli O157:H7 at the concentration of 2, 3, 4, 3, 14, and 17%, respectively. Vinegar and lactic acid of low concentration inhibited the growth of Vibrio sp., food poisoning pathogen in SRFM; in contrast, at high concentration these organic acids inhibited Salmonella sp. and Escherichia sp., food poisoning pathogen in other than SRFM.

WEAKLY DENSE IDEALS IN PRIVALOV SPACES OF HOLOMORPHIC FUNCTIONS

  • Mestrovic, Romeo;Pavicevic, Zarko
    • Journal of the Korean Mathematical Society
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    • v.48 no.2
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    • pp.397-420
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    • 2011
  • In this paper we study the structure of closed weakly dense ideals in Privalov spaces $N^p$ (1 < p < $\infty$) of holomorphic functions on the disk $\mathbb{D}$ : |z| < 1. The space $N^p$ with the topology given by Stoll's metric [21] becomes an F-algebra. N. Mochizuki [16] proved that a closed ideal in $N^p$ is a principal ideal generated by an inner function. Consequently, a closed subspace E of $N^p$ is invariant under multiplication by z if and only if it has the form $IN^p$ for some inner function I. We prove that if $\cal{M}$ is a closed ideal in $N^p$ that is dense in the weak topology of $N^p$, then $\cal{M}$ is generated by a singular inner function. On the other hand, if $S_{\mu}$ is a singular inner function whose associated singular measure $\mu$ has the modulus of continuity $O(t^{(p-1)/p})$, then we prove that the ideal $S_{\mu}N^p$ is weakly dense in $N^p$. Consequently, for such singular inner function $S_{\mu}$, the quotient space $N^p/S_{\mu}N^p$ is an F-space with trivial dual, and hence $N^p$ does not have the separation property.

ON SOME MEASURE RELATED WITH POISSON INTEGRAL ON THE UNIT BALL

  • Yang, Gye Tak;Choi, Ki Seong
    • Journal of the Chungcheong Mathematical Society
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    • v.22 no.1
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    • pp.89-99
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    • 2009
  • Let $\mu$ be a finite positive Borel measure on the unit ball $B{\subset}\mathbb{C}^n$ and $\nu$ be the Euclidean volume measure such that ${\nu}(B)=1$. For the unit sphere $S=\{z:{\mid}z{\mid}=1\}$, $\sigma$ is the rotation-invariant measure on S such that ${\sigma}(S)=1$. Let $\mathcal{P}[f]$ be the invariant Poisson integral of f. We will show that there is a constant M > 0 such that $\int_B{\mid}{\mathcal{P}}[f](z){\mid}^{p}d{\mu}(z){\leq}M\;{\int}_B{\mid}{\mathcal{P}}[f](z)^pd{\nu}(z)$ for all $f{\in}L^p({\sigma})$ if and only if ${\parallel}{\mu}{\parallel_r}\;=\;sup_{z{\in}B}\;\frac{\mu(E(z,r))}{\nu(E(z,r))}\;<\;\infty$.

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Identification of Infectious Fungus in the Artificial Cultivation Rooms of Paecilomyces tenuipes (눈꽃동충하초 재배상 내에 발생된 오염균의 동정)

  • 남성희;정이연;홍인표;지상덕;장승종;한명세
    • Journal of Sericultural and Entomological Science
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    • v.45 no.2
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    • pp.108-111
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    • 2003
  • A infectious fungus (J131) recently isolated from artificial cultivation farms of Paecilomyces tenuipes is known to cause a great yield loss and deterioration of products. In this study, its occurrence and characterization were made. The isolate (J131) was identified as Paecilomyces farinosus (Holm ex S. F. Gray) Brown & Smith. Colonies of the isolate on PDA grew moderately fast, attaining a diameter of 19mm within 14 days at 24${\pm}$1$^{\circ}C$. Vegetative hyphae are smooth-walled and hyaline. Conidiophores mainly arose from the submerged mycelium, usually measuring 1.3-1.5$\mu\textrm{m}$ wide and consisted of verticillate branches with whorls of 2 to 4 phialides. Phialides of 3.8-5.8${\times}$1.5-1.8 $\mu\textrm{m}$, with a swollen basal portion tapered into a distinct neck of about 0.6-0.8 $\mu\textrm{m}$ wide. Conidia arisen from the phialides, were ellipsoidal to fusiform, smooth-walled, hyaline, 1.8-2.4${\times}$1.1-1.4$\mu\textrm{m}$. .When silkworm larvae were injected with concentration of 1${\times}$10$\^$8/ conidia/$m\ell$ of infectious fungus J131, infection rate was 41.3% and synnemata formation rate was 23.6%. Black spots were appeared on the surface of silkworm larvae in 5-9 days after injection. The surface of larvae was covered with hyphae which were gradually turned into yellow from white color during the incubation period of 3-4 days. 1 to several 4-6mm long synnemata of yellow or orange color were formed on the surface. The matured synnemata were ramified from its end and produced much conidia of white color.

The concentration of serum amyloid A and haptoglobin of pigs infected with Aujeszky′s disease virus (오제스키병에 감염된 돼지의 serum amyloid A와 haptoglobin의 농도 변화)

  • 오윤택;조정곤
    • Korean Journal of Veterinary Service
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    • v.25 no.1
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    • pp.45-52
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    • 2002
  • The acute phase serum protein response is a well-known general indicator of inflammation, trauma or other pathological conditions and its relevance for the monitoring of the health status of domestic animals is being increasingly realized. The changes in serum protein composition which occur after tissue damage represent a part of the systemic response of the injured animals which is mediated by pro-inflammatory cytokines such as TNF-$\alpha$, IL-6 and IL-1. These responses play a vital role in containing the tissue damage and enhancing the processes of repair and resolution. From a clinical perspective, the assay of acute phase proteins can provide a method for detecting inflammation. In animals, the most sensitive acute phase proteins are haptoglogin, serum amyloid A and at-acid glycoprotein in response to inflammatory condition. The aim of this study was to assess the diagnostic value of the concentrations of serum amyloid A(SAA) and haptoglobin(HP) in serum of pigs infected with Aujeszky's disease virus(ADV). Fifty pigs infected with ADV and 5 normal pigs were used in this experiment. The mean serum concentration of Shh of pigs infected with ADV was 96.8 $\pm$ 7.1 $\mu\textrm{g}$/㎖(range, 36.0∼187.5 $\mu\textrm{g}$/㎖) and that of normal pigs was 42.9$\pm$3.3 $\mu\textrm{g}$/㎖(range, 17.3∼127.8 $\mu\textrm{g}$/㎖). The mean serum concentration of HP of pigs infected with ADV was 1,164.4 $\pm$ 96.9 $\mu\textrm{g}$/㎖ (range, 790.2∼l,769.2 $\mu\textrm{g}$/㎖) and that of normal pigs was 675.4 $\pm$ 56.3 $\mu\textrm{g}$/㎖ (range, 650.0-690.4 $\mu\textrm{g}$/㎖). The mean concentrations of SAA and HP in serum of pigs infected with ADV compared with those of normal pigs showed approximately a two-fold. It was concluded that the concentrations of Shh and HP in serum may proved to be diagnostic marker of Aujeszky's disease.

Effects of varying CO2, Nutrient and Light Irradiance Levels on the Growth of Ulva australis at Germling, Juvenile, and Adult Stages (해수의 CO2와 영양염 농도 및 조도가 구멍갈파래(Ulva australis) 배아, 유엽과 성체의 생장에 미치는 영향)

  • Jeon, Da Vine;Na, Yeon Ju;Yu, Ok Hwan;Choi, Han Gil
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.48 no.1
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    • pp.96-103
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    • 2015
  • The effects of $CO_2$ concentration, nutrient levels, and irradiance on the growth of germlings and juveniles, and on the photosynthesis of adults were examined in a green tide alga, Ulva australis. We used a factorial experimental design with two $CO_2$ concentrations (380 and 750 ppm), two nutrient levels (control and PES medium), and two irradiance levels (50 and $100{\mu}mol$ photons $m^{-2}s^{-1}$). Germlings grew best ($664.15{\pm}61.45{\mu}m$ in length) under conditions of 750 ppm, PES, and $100{\mu}mol$ photons $m^{-2}s^{-1}$ after 10 days in culture. Relative growth rates (RGR) of the juveniles were greatest (4.41% $day^{-1}$) under conditions of 750 ppm, PES, and $50{\mu}mol$ photons $m^{-2}s^{-1}$ after 5 days in culture. Photosynthetic efficiency ($F_v/F_m$) of the adult discs was $0.73{\pm}0.05$ before the experiment and reached a maximum ($0.83{\pm}0.01$) under conditions of 750 ppm, control, and $50{\mu}mol$ photons $m^{-2}s^{-1}$ after 5 days in culture. Growth (germlings and juveniles) and photosynthesis (adult discs) of Ulva australis increased when $CO_2$ levels were 750 ppm. Additionally, the optimal irradiance for growth and photosynthesis differed among stages, wherein germlings grew best at $100{\mu}mol$ photons $m^{-2}s^{-1}$, juveniles grew best at $50{\mu}mol$ photons $m^{-2}s^{-1}$, and adults photosynthesized most at $50{\mu}mol$ photons $m^{-2}s^{-1}$. The performance of Ulva australis at all examined life stages was enhanced under the PES nutrient treatment. In conclusion, the physiological responses of U. australis to varying $CO_2$, nutrient, and irradiance levels differed slightly among life stages. However, growth and photosynthesis always increased with elevated $CO_2$ and nutrient concentrations. These results indicate that U. australis green tide blooms might occur more frequently in coastal areas if $CO_2$ and nutrient concentrations increase.

FISH Karyotype Analysis of Seven Rose Cultivars (주요 장미 7품종의 FISH 핵형분석)

  • Hwang, Yoon-Jung;Han, Tae Ho;Martin, Cathie;Lim, Ki-Byung
    • Horticultural Science & Technology
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    • v.30 no.5
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    • pp.568-572
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    • 2012
  • Determination of ploidy level for the mother plant is prerequisite for effective breeding. The study was carried out to determine the ploidy level in 7 different plant materials by FISH karyotype analysis. Among the seven plant varieties analyzed, all exhibit tetraploid (2n = 4x = 28) based on the results observed in chromosome analysis. Four signals of 45S rDNAs were detected on the terminal region of the short arm of chromosome 7. The length of somatic metaphase chromosomes ranges from 1.67 to $2.67{\mu}m$ in 'Alexandra', 1.40 to $2.04{\mu}m$ in 'Freud', 1.64 to 2.24 in 'Little Silver', 1.69 to $2.26{\mu}m$ in 'Teresa', 1.70 to $2.65{\mu}m$ in 'Tineke', 1.35 to $2.08{\mu}m$ in 'Vital', 1.39 to $2.04{\mu}m$ in 'Yellow Mimi'. Total length of the chromosome ranges from $11.23{\mu}m$ in 'Freud' as minimum to $15.05{\mu}m$ in 'Alexandra' as maximum. The karyotypes were composed of metacentric, submetacentric, and subtelocentric chromosome but there is no subtelocentric chromosome.

Fabrication of the Optical Fiber-Photodiode Array Module Using Si v-groove (실리콘 v-groove를 이용한 광섬유-광검출기 어레이 모듈 제작)

  • 정종민;지윤규;박찬용;유지범;박경현;김홍만
    • Journal of the Korean Institute of Telematics and Electronics A
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    • v.31A no.6
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    • pp.88-97
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    • 1994
  • We describe the design, fabrication, and performance of the optical fiber-photodiode 1$\times$12 arry module using mesa-type InS10.53T GaS10.47TAS/INP 1$\times$12 PIN photodiode array. We fabricated the PIN PD array for high-speed optical fiber parallel data link optimizing quantum efficiency, operating speed sensitivity from the PIN-FET structure, and electrical AC crosstalk. For each element of the array, the diameter of the photodetective area is 80 $\mu$m, the diameter of the p-metal pad is 90 $\mu$m, and the photodiode seperation is 250 $\mu$m to use Si v-groove. Ground conductor line is placed around diodes and p-metal pads are formed in zigzag to reduce Ac capacitance coupling between array elements. The dark current (IS1dT) is I nA and the capacitance(CS1pDT) is 0.9 pF at -5 V. No signifcant variations of IS1dT and CPD from element to element in the array were observed. We calulated the coupling efficiency for 10/125 SMF and 50/125 GI MMF, and measured the responsivity of the PD array at the wavelength is 1.55 $\mu$ m. Responsivities are 0.93 A/W for SMF and 0.96 A/W for MMF. The optical fiber-PD array module is useful in numerous high speed digital and analog photonic system applications.

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