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      • KCI등재

        뉴질랜드 흰 토끼를 이용한 추간판의 퇴행성 변화 모델 형성

        소광영,최용수,윤대현,류지훈,Brian Johnstone,Jung U Yoo 대한척추외과학회 2011 대한척추외과학회지 Vol.18 No.4

        Study Design: An experimental animal study. Objectives: To create a more appropriate disc degeneration model which shows how Interleukin 1α may induce the activation of metalloproteinases within the nucleus pulposus. Summary of Literature Review: There are few disc degeneration models wherein there is activation of metalloproteinases within the nucleus pulposus without structural destruction of the intervertebral disc. Materials and Methods: Three consecutive intervertebral discs in New Zealand White Rabbits were exposed. Each disc was injected with 0.1ml of saline (Saline group), 0.1ml of 1μg/ml (IL-1 group), 0.1ml of 10μg/ml (IL-10 group) of IL-1α through a 30-gauge needle. The lumbar spine was harvested 12 weeks after operation. We then analyzed radiographic findings and histological changes. Results: There was no difference in the radiological disc height index among the three groups; 0.071 in saline group, 0.045 in IL-1 group and 0.058 in IL-10 group (p=0.194). The histological cellularity of the nucleus pulposus revealed a decrease in the number of cells (p=0.0001,1.42 in saline group vs. 3.00 in IL-10 group; p=0.001, 2.00 in IL-1 group and 3.00 in IL-10). The histological matrix of the nucleus pulposus was 1.42 in saline group and 2.42 in IL-10(p=0.007), which meant that there had been condensation of the extracellular nucleus pulposus matrix. Conclusions: The results of this study demonstrate that interleukin-1α may contribute to degradation of the nucleus pulposus. This is useful for future study into the effects of the cytokine inhibitor on matrix regeneration and cellularity in the nucleus pulposus in intervertebral disc disease. 뉴질랜드 흰 토끼를 이용한 추간판의 퇴행성 변화 모델 형성소광영 • 최용수 • 윤대현 • 류지훈 • Brian Johnstone*, Jung U Yoo*광주기독병원 정형외과, Oregon Health and Science University*연구계획: 실험 동물 연구목적: 섬유 연골의 퇴행성 변화가 추간판 세포에서 생성된 matrix metalloproteinases의 활성에 따른 보고를 근거하여 토끼의 추간판에 수핵내metalloproteinase를 활성화하기 위한 Interleukin 1α를 기계적 손상 없이 주사하여 추간판의 퇴행성 변화를 생성하고자 하였다. 선행문헌의 요약: 추간판의 퇴행성 변화에 대한 병태 생리를 밝히기 위해 다양한 분야에서 접근하고 있다. 그러나 추간판의 구조적 이상 없이 추간판의자연 경과에 따른 병태 생리를 설명하는 동물 실험 모델은 아직 드물다. 대상 및 방법: 뉴질랜드 흰 토끼를 전방 복부 도달법으로 세 개의 연속된 추간판을 노출 시킨 후 상위 추간판에 생리 식염수 0.1ml(식염수군), 중간 추간판에 Interleukin 1α의 1μg/ml 농도 0.1ml(IL-1군), 하위 추간판에 Interleukin 1α의 10μg/ml 농도 0.1ml(IL-10군)를 추간판의 기계적 손상을 방지하기 위해 30게이지 주사침을 이용하여 중앙에서 주사하였다. 주사 후 12주에 방사선학적 및 조직학적 변화를 조사하였다. 결과: 12주째 방사선학적 추간판 높이지수는 식염수군 0.071, IL-1군 0.045, IL-10군 0.058로 추간판 높이 변화에 차이가 없었다(p=0.194). 조직학적 수핵내 세포는 식염수군 평균 1.42, IL-1군 2.00, IL-10군 3.00의 결과로 식염수군과 IL-10군(p=0.001), IL-1군과 IL-10군(p=0.0001)의 두 군간에 유의한 차이를 보였다. 조직학적 수핵내 조성은 식염수군 평균 1.42, IL-1군 2.00, IL-10군 2.42의 결과로 식염수군과 IL-10군(p=0.007) 군의 비교에서만 차이를 보였다. 조직학적 수핵의 변화 결과는 IL-10군이 수핵내 세포 및 조성의 퇴행성 변화를 유발함을 알 수 있었다. 결론: 토끼의 추간판에서 Interleukin 1α가 수핵의 세포와 기질변화에 관여함을 시사하였다. 토끼 모델을 이용한 퇴행성 추간판 모델 형성은 사이토카인차단제 등의 수핵에서 기질 재생이나 세포 활성을 확인하는 추간판 질환의 실험을 위해 유용하게 적용될 수 있으리라 사료된다.

      • SCIESCOPUSKCI등재

        Effects of Expander Conditioning of Corn- and Sorghum-Based Diets on Pellet Quality and Performance in Finishing Pigs and Lactating Sows

        Johnston, S.L.,Hancock, J.D.,Hines, R.H.,Kennedy, G.A.,Traylor, S.L.,Chae, B.J.,Han, In K. Asian Australasian Association of Animal Productio 1999 Animal Bioscience Vol.12 No.4

        Two experiments were conducted to determine the effects of conditioning (conventional vs expander) corn- and sorghum-based diets on production traits for lactating sows and finishing pigs. In Exp. 1, one hundred sixty-eight sows (parity 1-4, PIC line C15) were fed the corn or sorghum grain diets as a meal, standard (steam) conditioned pellets, or expanded pellets to give a $2{\times}3$ factorial arrangement of treatments. Pellet durability index (PDD was similar for the sorghum- vs corn-based diets, but increased when diets were expanded pellets for both corn- and sorghum-based diets. The corn-based meal diet supported 3.3% greater litter weight gain than the sorghum-based meal diet (44.0 kg vs 42.8 kg). However, the advantage for the corn-based diet disappeared with expander processing (ie., sows fed the sorghum-based diet responded more to diets processed with the alternative processing technology). Sow weight change during lactation was similar (p>0.15) among treatments, although average daily feed intake tended to be greater (p<0.09) for the sows fed sorghum. For Exp. 2, a total of 71 barrows (average initial weight of 58.0 kg) were used in a growth assay to determine the effects of feeding com- and sorghum-based diets, as meal or pellets, after processing with a conventional steam conditioner or an expander (high-shear) conditioner. PDI was not different for the sorghum- vs corn-based diets, but increased from 84 to 95% with expander conditioning compared to conventional steam conditioning. Rate and efficiency of gain, and carcass leanness were similar for pigs fed sorghum and corn (p>0.15). Efficiency of gain was greater (p<0.04) for pigs fed the pelleted (356 g/kg) diets compared to those given the meal (348 g/kg) diets. However, efficiencies of gain were similar (p>0.11) for pigs fed the conventional- and expander-conditioned diets. Pelleting increased (p<0.01) the incidence and severity of stomach lesions regardless of grain type. In conclusion, corn-based meal diet resulted in a greater litter weight gain than the sorghum-based meal diet. However, that advantage disappeared when the diets were expanded and pelleted. Finishing pigs fed pelleted diets were more efficient than those fed meal diets.

      • KCI등재후보
      • SCISCIESCOPUS

        Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breas

        Johnston, Stephen R. D.,Hegg, Roberto,Im, Seock-Ah Grune & Stratton 2018 Journal of clinical oncology Vol.36 No.8

        <P>PurposeHuman epidermal growth factor receptor 2 (HER2) targeting plus endocrine therapy (ET) improved clinical benefit in HER2-positive, hormone receptor (HR)-positive metastatic breast cancer (MBC) versus ET alone. Dual HER2 blockade enhances clinical benefit versus single HER2 blockade. The ALTERNATIVE study evaluated the efficacy and safety of dual HER2 blockade plus aromatase inhibitor (AI) in postmenopausal women with HER2-positive/HR-positive MBC who received prior ET and prior neo(adjuvant)/first-line trastuzumab (TRAS) plus chemotherapy.MethodsPatients were randomly assigned (1:1:1) to receive lapatinib (LAP) + TRAS + AI, TRAS + AI, or LAP + AI. Patients for whom chemotherapy was intended were excluded. The primary end point was progression-free survival (PFS; investigator assessed) with LAP + TRAS + AI versus TRAS + AI. Secondary end points were PFS (comparison of other arms), overall survival, overall response rate, clinical benefit rate, and safety.ResultsThree hundred fifty-five patients were included in this analysis: LAP + TRAS + AI (n = 120), TRAS + AI (n = 117), and LAP + AI (n = 118). Baseline characteristics were balanced. The study met its primary end point; superior PFS was observed with LAP + TRAS + AI versus TRAS + AI (median PFS, 11 v 5.7 months; hazard ratio, 0.62; 95% CI, 0.45 to 0.88; P = .0064). Consistent PFS benefit was observed in predefined subgroups. Overall response rate, clinical benefit rate, and overall survival also favored LAP + TRAS + AI. The median PFS with LAP + AI versus TRAS + AI was 8.3 versus 5.7 months (hazard ratio, 0.71; 95% CI, 0.51 to 0.98; P = .0361). Common adverse events (AEs; 15%) with LAP + TRAS + AI, TRAS + AI, and LAP + AI were diarrhea (69%, 9%, and 51%, respectively), rash (36%, 2%, and 28%, respectively), nausea (22%, 9%, and 22%, respectively), and paronychia (30%, 0%, and 15%, respectively), mostly grade 1 or 2. Serious AEs were reported similarly across the three groups, and AEs leading to discontinuation were lower with LAP + TRAS + AI.ConclusionDual HER2 blockade with LAP + TRAS + AI showed superior PFS benefit versus TRAS + AI in patients with HER2-positive/HR-positive MBC. This combination offers an effective and safe chemotherapy-sparing alternative treatment regimen for this patient population. (C) 2017 by American Society of Clinical Oncology</P>

      • SCISCIESCOPUS

        A Robust Optimization Approach to Backup Network Design With Random Failures

        Johnston, Matthew,Hyang-Won Lee,Modiano, Eytan IEEE 2015 IEEE/ACM transactions on networking Vol.23 No.4

        <P>This paper presents a scheme in which a dedicated backup network is designed to provide protection from random link failures. Upon a link failure in the primary network, traffic is rerouted through a preplanned path in the backup network. We introduce a novel approach for dealing with random link failures, in which probabilistic survivability guarantees are provided to limit capacity over provisioning. We show that the optimal backup routing strategy in this respect depends on the reliability of the primary network. Specifically, as primary links become less likely to fail, the optimal backup networks employ more resource sharing among backup paths. We apply results from the field of robust optimization to formulate an ILP for the design and capacity provisioning of these backup networks. We then propose a simulated annealing heuristic to solve this problem for large-scale networks and present simulation results that verify our analysis and approach.</P>

      • SSCISCOPUSKCI등재

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