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Antitumor Activity of 7-[2-(N-Isopropylamino)ethyl]-(20s)-camptothecin, CKD602, as a Potent DNA Topoisomerase I Inhibitor

  • Lee, Jun-Hee;Lee, Ju-Mong;Kim, Joon-Kyum;Ahn, Soon-Kil;Lee, Sang-Joon;Kim, Mie-Young;Jew, Sang-Sup;Park, Jae-Gab;Hong, Chung-Il
    • Archives of Pharmacal Research
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    • v.21 no.5
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    • pp.581-590
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    • 1998
  • We developed a novel water-soluble camptothecin analobue, CKD602, and evaluated the inhibition of topoisomerase I and the antitumor activities against mammalian tumor cells and human tumor xenografts. CKD602 was a nanomolar inhibitor of the topoisomerase I enzyme in the cleavable complex assay. CKD602 was found to be 3 times and slightly more potent than topotecan and camptothecin as inhibitors of topoisomerase, respecitively. In tumor cell cytotoxicity, CKD602 was more potent than topotecan in 14 out of 26 human cancer cell lines tested, while it was comparable to camptothecin. CKD602 was tested for the in vivo antitumor activity against the human tumor xenograft models. CKD602 was able to imduce regression of established HT-29, WIDR and CX-1 colon tumors, LX-1 lung tumor, MX-1 breast tumor and SKOV-3 ovarian tumor as much as 80, 94, 76, 67, 87% and 88%, respectively, with comparable body weight changes to those of topotecan. Also the therapeutic margin (R/Emax: maximum tolerance dose/$ED-{58}$) of CKD602 was significantly higher than that of topotecan by 4 times. Efficacy was determined at the maximal tolerated dose levels using schedule dependent i.p. administration in mice bearing L1210 leukemia. On a Q4dx4 (every 4 day for 4 doses) schedule, the maximum tolerated dose (MTD) was 25 mg/kg per administration, which caused great weight loss and lethality in <5% tumor bearing mouse. this schedule brought significant increase in life span (ILS), 212%, with 33% of long-term survivals. The ex vivo antitumor activity of CKD602 was compared with that of topotecan and the mean antitumor index (ATI) values recorded for CKD602 were significantly higher than that noted for topotecan. From these results, CKD602 warrants further clinical investigations as a potent inhibitor of topoisomerase I.

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The influence of adjacent tooth to the microbiology of implant sulcus (인접치아가 임플란트 치은연하 세균총의 분포에 미치는 영향)

  • Lee, Dong-Young;Lee, Man-Sub;Kwon, Young-Hyuk;Park, Joon-Bong;Herr, Yeek;Chung, Jong-Hyuk
    • Journal of Periodontal and Implant Science
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    • v.35 no.3
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    • pp.563-575
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    • 2005
  • The aim of present study is to evaluate the influence of adjacent tooth to the microbiology of clinically healthy implant. Control group included patients who had clinically healthy implant and tooth with healthy $periodontium(PD{\leq}3mm)$, test group was composed of patients who had clinically healthy implant and tooth with periodontal pocket(PD>3mm). The criteria of clinically health implant are no pain or discomfort, the restorative suprastructure provide satisfactory fit and function, and the tissue around the fixtures were firm and probing with standard periodontal probe with a rounded tip 0.5mm in diameter resulted in penetration of no more than 5mm when using a force of 0.5N at any location. 38 patients, partially edentulous subjects with endosseous root-form implants were selected. All subjects were medically healthy and had not taken systemic antibiotics and professional plaque control 3 months before sampling. Number of control group is 25(mean age $52{\pm}13$, 26 teeth, 34 implants) and test group is 13(mean age $60{\pm}13$, 13 teeth, 17 implants). All teeth and implants of each patient were examined probing depth(PD), bleeding on probing(BOP), and plaque index(PI), and samples of subgingival plaque were obtained at each site with sterile curet or fine paper points, then the plaque transferred to PBS. Obtained samples were examined for the presence of P. gingivalis, T. forsythensis, and T. denticola by the polymerase chain reaction(PCR). The relationship among clinical parameters and the colonizations by the 3 bacterial species from natural teeth and implants region were analyzed by student t-test. The results of this study were as follows: 1. PD was different in teeth between 2 groups(p<0.05), but the other parameters were not. 2. Statistically significant difference was not found in clinical parameters of implants between 2 groups. 3. All bacterial prevalences of teeth were higher in test group than in control group, and prevalence of T. forsythensis had statistically significant difference between 2 groups(p<0.05). 4. Prevalences of P. gingivalis and T. forsythensis are higher in test group than control group, and that of T. denticola is higher in control group than in test group. But there were no statistically significant differences between 2 groups. In conclusion, there is no statistically significant difference in prevalence of implant microbiology between 2 groups. But if the number of samples increased, it will be possible to find out statistical significance in prevalence of P. gingivalis. It seems that pocket of adjacent tooth influences prevalence of P. gingivalis. These results mean that improvement of the periodontal condition before implantation is very important.

Does Market Competition Reduce Hospital Charges & LOS for the Degenerative Lumbar Spinal Disease?: A Two-point Cross Sectional Study (병원시장 경쟁이 퇴행성 요추질환 환자의 진료비 및 재원일수에 미치는 영향)

  • Lee, Joo Eun;Park, Eun-Cheol;Lee, Sang Gyu;Kim, Tae Hyun
    • Korea Journal of Hospital Management
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    • v.22 no.4
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    • pp.33-49
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    • 2017
  • Background: Health care utilizations and costs of the patients with degenerative lumbar spine disease in Korea increased dramatically. We analyzed whether hospital market competition is associated with charges and length of stay for patients with degenerative lumbar spine disease. Methods: We used Medical claims data of 2002 and 2010 from the nationwide representative sample of National Health Insurance Service of Korea. The study subjects were inpatients with degenerative lumbar spine disease (N=24,768) in 2002 and 2010. We employed a multilevel linear mixed model that included patient- and hospital-level variables in hierarchical data. Results: Higher hospital competition was associated with lower charges (${\beta}=57.5$, p<.0001 in 2002; ${\beta}=353.7$, p<.0001 in 2010) and shorter length of stay (${\beta}=0.3$, p<.0001 in 2002; ${\beta}=0.9$, p<.0001 in 2010) in both 2002 and 2010. Compared to 2002, the magnitude of such association became greater in 2010. However, subgroup analyses show that the influence of competition on charges and length of stay differed by hospital size. Conclusions: This study showed that hospital market structure (e.g., hospital competition) affects hospital efficiency (i.e., hospital charges and length of stay). It is necessary to continue to monitor how changing market structure influences hospital outcomes, including more detailed outcomes such as patient satisfaction.

Antioxidant and Anti-Inflammatory Effects of Kamisipjeondaebotang in RAW 264.7 Cells (가미십전대보탕의 RAW 264.7 세포에서 항산화 및 항염증 효과)

  • Myung, Jeong-Ho;Lee, Myung-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1271-1277
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    • 2017
  • As Kamisipjeondaebotang (KSD) extract is an herbal ingredient, safety is very important due to possible cell poisoning or heavy metal toxicity to organs when administered to humans or animals. Accordingly, this study examined the antioxidant and anti-inflammatory effects of KSD extract to confirm its medicinal safety by using RAW 264.7 cells after heavy metal screening, functional index test of the liver and kidney, and cell survival rate test. Heavy metals were not found in KSD extracts or were less than standard amounts. Liver function indices such as aspartate aminotransferase and alanine aminotransferase revealed low values and kidney function indices such as creatinine and blood urea nitrogen were not significantly different from the normal group. This proved the safety to the human. RAW 264.7 cells showed no poisoning compared to the control group in terms of survival rate. Regarding the antioxidant effect of KSD extract, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and 2,2'-azino-bis(3-ethylbenzothiazo-line-6-sulphonic acid) radical scavenging activity increased at concentrations over $10{\mu}g/mL$. The anti-inflammatory effect of KSD extract significantly decreased based on the amount of nitric oxide at concentrations of 10 and $100{\mu}g/mL$ compared to the control group. Expression of interleukin (IL)-$1{\beta}$ and IL-6 decreased in a concentration-dependent manner. There was no significant difference in tumor necrosis factor-${\alpha}$ level. Based on the results, KSD can be regarded as a safe antioxidant with anti-inflammatory effects for fracture treatment.

Protective Effect of 3,5-Dicaffeoylquinic Acid Isolated from Ligularia fischeri against Oxidative Damage in HepG2 Cells (HepG2 세포에서 산화적 손상에 대한 곰취 유래 3,5-Dicaffeoylquinic Acid의 보호 효과)

  • Park, Sun-Young;Kim, Gur-Yoo;Jhoo, Jin-Woo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1286-1292
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    • 2017
  • This study was conducted to investigate the hepatoprotective effects of 3,5-dicaffeoylquinic acid (3,5-DCQA) isolated from Ligularia fischeri against hydrogen peroxide-induced oxidative stress in HepG2 cells. Antioxidative effects of 3,5-DCQA were determined by measuring antioxidant enzyme [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx)] expression levels against hydrogen peroxide-induced oxidative stress using real-time PCR analysis. 3,5-DCQA treatment significantly increased gene expression levels of SOD, CAT, and GPx in a dose-dependent manner ($10{\sim}30{\mu}g/mL$) in HepG2 cells. Hepatoprotective effects were analyzed by measuring glutamic oxaloacetic transaminase (GOT), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) activities using a biochemistry analyzer in hydrogen peroxide-treated HepG2 cells. 3,5-DCQA treatment significantly reduced GOT, LDH, and GGT activities in a dose-dependent manner ($10{\sim}30{\mu}g/mL$) against increased liver function index enzyme activities induced by hydrogen peroxide oxidative stress in HepG2 cells. The results reveal that 3,5-DCQA compound isolated from Ligularia fischeri can be useful for the development of an effective hepatoprotective agent.

Sensory Nerve Conduction Velocity of Median Proper Palmar Digital Nerve Recorded by Bar Electrode (막대전극을 이용하여 기록한 정중고유손바닥쪽 손가락신경의 감각신경전도속도)

  • Kwak, Kyo Ho;Lee, Dong Kuck
    • Annals of Clinical Neurophysiology
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    • v.2 no.1
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    • pp.21-26
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    • 2000
  • Background: There has been few electrophysiologic studies in median proper palmar digital nerve(PPDN). Bar electrode may be a useful tool to evaluate the pathophysiologic state of the distal peripheral nerves. Objectives : To evaluate sensory nerve conduction velocities(NCVs) of median PPDNs in normal controls and carpal tunnel syndrome(CTS) patients by bar electrode, and clarify the usefulness of the bar electrode. Methods : We checked NCV of each median PPDN of thumb(D1), index(D2) and middle finger(D3) in normal controls(68 hands) and CTS patients(95 hands) by bar electrode. The each mean NCV of both groups were compared to find the correlation between them. Results : The mean NCV of each median PPDN in control group were $38.7{\pm}4.2$(D1), $32.0{\pm}4.6$(D2), $34.2{\pm}4.4$(D3) m/sec, and in CTS group were $35.3{\pm}8.9$(D1), $20.2{\pm}5.2$(D2), $20.2{\pm}5.1$(D3) m/sec orderly. There were significant differences between mean NCV of each finger in control group(p=0.0001), but not between each left and right finger(p>0.05). The differences between each mean NCV of control and CTS were significant in all 3 fingers(p=0.0014, 0.0000, 0.0000). Conclusion : Bar electrode is a useful tool to evaluate the pathophysiologic state of the median PPDNs in normal controls and CTS patients.

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Dietary and Non-dietary Factors Related to Bone Mineral Density in Female College Students (여대생의 골밀도와 식이 및 비식이 요인들 간의 상관성)

  • Lim, Ji-Hye;Bae, Hyun-Sook;Lee, Seung-Min;Ahn, Hong-Seok
    • Korean Journal of Community Nutrition
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    • v.13 no.3
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    • pp.418-425
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    • 2008
  • The purpose of this study was to investigate correlations between bone mineral density (BMD) and dietary and non-dietary factors in female college students. The BMD of the subjects (n = 38) was measured using DEXA (Dual Energy X-ray Absorptiometry) at lumbar spine and three femoral sites including femoral neck, ward's triangle, and femoral trochanter. Three-day 24-hour dietary recall data were collected from each subject to assess consumption levels of nutrients and food groups. The mean (${\pm}SD$) values of age, age of menarche, height, weight, body mass index (BMI), waist-to-hip ratio (WHR), fat mass, and % body fat of the subjects were 21.34 (${\pm}1.73$) years, 13.1 (${\pm}1.2$) years, 161.3 (${\pm}5.0$) cm, 53.7 (${\pm}7.2$) kg, 20.6 (${\pm}2.6$) $kg/m^2$, 0.80 (${\pm}0.04$), 15.4 (${\pm}4.4$) kg, and 28.2 (${\pm}4.7$), respectively. The BMD values of lumbar spine, femoral neck, ward's triangle, and femoral trochanter as T-value were $1.150{\pm}0.13\;g/cm^2$, $0.932{\pm}0.11\;g/cm^2$, $0.850{\pm}0.13\;g/cm^2$, and $0.721{\pm}0.10\;g/cm^2$, respectively. The daily mean energy intake of the subjects was 1660.6 kcal. The intake levels of carbohydrate, calcium, iron, vitamin C, and folic acid were lower than the KDRIs, while those of fat, phosphorus, sodium, vitamin A, and vitamin $B_6$ were higher than the KDRIs. Significantly negative correlation were detected between consumption of fat and oils and the BMD of all sites measured (p < 0.05). Potato and starch intake was negatively correlated to the BMD of femoral neck and word's triangle (p < 0.05). The intake of cereals was found to be negatively correlated to the BMD of ward's triangle (p v 0.05). There was also negative correlation of intake of soybeans and products with the BMD of lumbar spine (p < 0.05). Weight and muscle mass were positively correlated to the BMD of both lumbar spine and femurs (p < 0.01). Significantly positive correlations between BMI, and fat mass and the BMD of lumbar spine were observed (p < 0.001). Additionally fat mass was positively correlated to the BMD of femoral neck. WHR and % body fat were positively correlated to the BMD of lumbar spine (p < 0.05). Negative correlation was found between a serum calcium level and the BMD of femoral neck (p < 0.05). In summary non-dietary factors generally showed significant correlations with the BMD of lumbar spine, while several dietary factors showed significant correlations with the BMD of femurs.

Sex Determination in Somatic and Embryonic Cells of the Pig by FISH and PCR (FISH와 PCR에 의한 돼지 체세포 및 배아세포의 성 판정)

  • Chung, Y.;Jeon, J.T.;Kim, K.D.;Lee, S.H.;Hong, K.C.
    • Korean Journal of Animal Reproduction
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    • v.20 no.3
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    • pp.323-331
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    • 1996
  • Predetermination of sex in mammalian species has many aspects of application including the prenatal diagnoses of genetic disorders in humans and sex-selected breeding programs in the animal industry. Embryos sexing can be carried out using the polymerase chain reaction (PCR) to amplify specific sequences present in the sex chromosomes, or by fluorescent in situ hybridization (FISH) of specific probes to the X and Y chromosomes. A 3.3 kb porcine male-specific DNA fragment (pEM39) was cloned previously in our laboratory. In this study, FISH and PCR methods were employed to examine if the pEM39 can be used a sex-specific DNA probes Porcine ovaries were obtained from a local slaughter house and oocytes collected. All oocytes were subjected to in vitro maturation followed by 1n vitro fertilization. Parthenogenetically activated embryos were served as a negative control. Embryonic samples were collected at the 2-cell stages and PCR was performed to analyze DNA. Among 10 embryos examined, four embryos were identified as males and six were females. The cloned male-specific DNA fragment showed male-specificity for the cells in the liver tissue and the porcine early embryos by FISH. It was also demonstrated that the cloned male-specific DNA is localized on the hetero chromatic region of the long arm in the Y chrom-osome (Yq) as shown by the FISH and karyotyping. The results suggest that the cloned male-specific DNA fragment may be useful for predetermination of sex with a few embryonic cells. The porcine male-specific sequence can be a reliable index for embryo sexing by PCR.

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Soil Condition and Vegetation Structure in Acer mono for. rubripes Stand in Geoje, Gyeongnam Province (경남 거제지역 붉은고로쇠나무림의 토양특성과 식생구조)

  • Moon Hyun Shik;Roh Il;Kim Jong Kab;Kwon SuDeok
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.6 no.4
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    • pp.265-271
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    • 2004
  • This study was carried out to furnish basic information on the habitat through soil condition and vegetation structure of an Acer mono for. rubripes stand in Geoje, Gyeongnam Province. Soil pH of the A. mono for. rubripes stand was 5.17. The contents of organic matter, total N and available P205 were 8.7%,0.38%, 15.7ppm, respectively. A. mono for. rubripes, Meliosma oldhamii, Zelkova serrata, Styrax japonica, Sapium japonicum, Lindera erythrocarpa and Euonymus oxyphyllus appeared in all layers. The importance values of A. mono for. rubripes, Z. serrata and Quercus serrata in the upper layer were high, S. japonicum and M. myriantha were high in the middle layer and lower layer, respectively. Species diversity and evenness ranged from 0.931 of the middle layer to 1.638 of the lower layer, and from 0.706 of the upper layer to 0.959 of the lower layer, respectively. The study results provide basic information on soil condition and vegetation structure of the Acer mono for. rubripes stand native to Geoje, Korea.

KMSCR: A system for managing knowledge assets of an IT consulting firm (IT 컨설팅 회사의 지적 자산 관리를 위한 지식관리시스템)

  • 김수연;황현석;서의호
    • Proceedings of the Korea Inteligent Information System Society Conference
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    • 2001.06a
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    • pp.233-239
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    • 2001
  • 최근 대부분의 회사들은 업무를 수행하는데 필요한 지식과 노하우를 공유하고 재사용하기 위하여 지적 자산 관리의 중요성을 인식하고 있다. 특히 고도로 지식 집약적인 업종이라 할 수 있는 IT컨설팅 회사에서는 지적 자산의 관리가 다른 어떤 회사에서보다 큰 중요성을 가지게 된다. 컨설팅 회사에 있어서 검증이 완료된 지적 자산의 공유 및 지능적이면서도 신속한 검색은 컨설팅 서비스의 품질과 고객 만족에 직결되는 중요한 요소이다. 따라서 대부분의 컨설팅 회사들은 자사의 지식 자산을 관리하기 위하여 많은 노력을 기울이고 있다. 본 논문의 목적은 IT 컨설팅 회사예서 관리되는 다양한 형태의 지적 자산들을 중앙 관리하여 설친 고객 사이트에 흩어져 프로젝트를 수행하는 컨설턴트들이 공유할 수 있도록 함으로써 컨설팅 서비스의 생산성과 품질들 높이고자 하는데 있다 이를 위하여 건설팅 회사에서 관리되는 모든 지적 자산의 재고를 조사하여 모델링하고 이를 쉽게 저장하고 검색할 수 있는 시스템 아키텍처를 제안한다. 제안된 아키텍처를 NT 기반에서 Index server를 이용하여 시스템으로 구현하였다 (KMSCR: A Knowledge Management System for managing Consulting Resources). KMSCR에서는 컨설턴트가 찾고자 하는 검색어를 입력하면 다양한 포맷의 (.doc, .ppt, xls, .rtf, .txt, .html 등과 같은) 결과물을 관련성이 높은 순서대로 출력해 줌으로써 컨설팅 리소스를 효과적으로 재사용할 수 있도록 도와 준다. 또한 검색 시에는 미리 등록된 키워드 뿐 아니라 본문 내의 텍스트 검색까지 가능하게 함으로써 컨설팅 리소스에 대한 보다 효과적이고 효율적인 검색을 가능하게 한다.간을 성능 평가 인자로 하여 수행하였다. 논문에서 제한된 방법을 적용한 개선된 RICH-DP을 모의 실험을 통하여 분석한 결과 기존의 제한된 RICH-DP는 실시간 서비스에 대한 처리율이 낮아지며 서비스 시간이 보장되지 못했다. 따라서 실시간 서비스에 대한 새로운 제안된 기법을 제안하고 성능 평가한 결과 기존의 RICH-DP보다 성능이 향상됨을 확인 할 수 있었다.(actual world)에서 가상 관성 세계(possible inertia would)로 변화시켜서, 완수동사의 종결점(ending point)을 현실세계에서 가상의 미래 세계로 움직이는 역할을 한다. 결과적으로, IMP는 완수동사의 닫힌 완료 관점을 현실세계에서는 열린 미완료 관점으로 변환시키되, 가상 관성 세계에서는 그대로 닫힌 관점으로 유지 시키는 효과를 가진다. 한국어와 영어의 관점 변환 구문의 차이는 각 언어의 지속부사구의 어휘 목록의 전제(presupposition)의 차이로 설명된다. 본 논문은 영어의 지속부사구는 논항의 하위간격This paper will describe the application based on this approach developed by the authors in the FLEX EXPRIT IV n$^{\circ}$EP29158 in the Work-package "Knowledge Extraction & Data mining"where the information captured from digital newspapers is extracted and reused in tourist information context.terpolation performance of CNN was relatively

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