• Journal of Pharmaceutical Investigation
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• 제25권3호spc1호
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• pp.7-20
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• 1995

Taurine, a ${\beta}-amino$ acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine dose not cross the blood-brain barrier, we examined whether the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, plays a role in taurine transport in the central nervous system. The uptake of $[^3H]-taurine$ into ATP depleted choroid plexus from rabbit was substantially greater in the presence of an inwardly directed $Na^+$ gradient taurine accumulation was negligible. A transient in side-negative potential gradient enhanced the $Na^+-driven$ uptake of taurine into the tissue slices, suggesting that the transport process is electrogenic, $Na^+-driven$ taurine uptake was saturable with an estimated $V_{max}$ of $111\;{\pm}\;20.2\;nmole/g/15\;min$ and a $K_M\;of\;99.8{\pm}29.9\;{\mu}M$. The estimated coupling ratio of $Na^+$ and taurine was $1.80\;{\pm}\;0.122.$ $Na^+-dependent$ taurine uptake was significantly inhibited by ${\beta}-amino$ acids, but not by ${\alpha}-amino$ acids, indicating that the transporter is selective for ${\beta}-amino$ acids. Since it is known that the physiological concentration of taurine in the CSF is lower than that in the plasma, the active transport system we characterized may face the brush border (i.e., CSF facing) side of the choroid plexus and actively transport taurine out of the CSF. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to determine whether elimination kinetics of taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for upto 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005) indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e. g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of taurine was reduced (p<0.0l), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment. Collectively, our results demonstrate that taurine is transported in the choroid plexus via a $Na^+-dependent,saturable$ and apparently ${\beta}-amino$ acid selective mechanism. This process may be functionally relevant to taurine homeostasis in the brain.

• Journal of Korean Neurosurgical Society
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• 제29권6호
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• pp.754-762
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• 2000

Objectives : The surgical results of 80 patients with growth hormone(GH)-producing pituitary adenoma were analyzed retrospectively to evaluate the clinical manifestations and to determine which preoperative factors significantly influenced the surgical outcome. Patients and Methods : The patients consisted of 39 men and 41 women and the age of patients at the time of initial operation ranged from 17 to 67 years(mean age, 40.5 years) Between January 1990 and June 1996, 77 patients underwent transsphenoidal surgery and 3 patients underwent craniotomy for GH-producing pituitary adenoma at our institution. Preoperative administration of octreotide was performed in 18 patients. Surgical control was defined as a postoperative serum basal level of GH less than 5ng/ml. A logistic regression model was used for univariate and multivariate analysis. Probability value of less than 0.05 was considered as statistically significant. Results : The most common presenting symptom was acromegaly, followed by headache, visual disturbance, and fatigability. Visual symptoms were present in 39% of the patients. Diabetes mellitus was associated in 24 patients and hypertension in 12. Preoperative mean basal level of GH was 93.2ng/ml(range 72-500ng/ml) which was closely related with tumor size(p<0.05). Grade II by Hardy's classification was the most common radiological type. Preoperative octreotide treatment significantly reduced the level of GH(p<0.05), but not enough to induce endocrinological remission. One patient died of cerebral infarction after craniotomy. The most common surgical complication was transient diabetes insipidus. The symptom of the earliest improvement after surgery was paresthesia and tightness of the hand and foot, followed by headache and easy fatigability. The preoperative visual symptom was improved in all patients. The patients who had hypertension or DM experienced alleviated symptoms in 67% and 92%, respectively. The overall rate of endocrinological remission was 44%. By multivariate logistic regression analysis, the size of tumor, extrasellar extension, and extent of removal were significant prognostic factors for endocrinologial remission. Conclusion : Early detection of a small tumor without extrasellar extension followed by a complete resection is highly recommended in order to achieve endocrinological cure of GH-producing pituitary adenomas.

• 한국자기공명학회논문지
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• 제11권2호
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• pp.85-94
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• 2007

Vanilloid receptor I [transient receptor potential vanilloid subfamily member 1 (TRPV1), also known as VR1] is a non-selective cationic channel activated by noxious heat, vanilloids, and acid, thereby causing pain. VR1 possesses six transmembrane domain and N-and C-terminus cytosolic domains, and appears to be a homotetramer. We studied the structural properties of Cterminus of VR1 (VR1C) using CD and NMR spectroscopy. DPC micelles, with a zwitterionic surface, and SDS micelles, with a negatively charged surface, were used as a membrane mimetic model system. Both SDS and DPC micelles could increase the stability of helical structures and/or reduce the aggregation form of the VR1C. However, the structural changing mode of the VR1C induced by the SDS and DPC micelles was different. The changes according to the various pHs were also different in two micelles conditions. Because the net charges of the SDS and DPC micelles are negative and neutral, respectively, we anticipate that this difference might affect the structure of the VR1C by electrostatic interaction between the surface of the VR1C and phospholipids of the detergent micelles. Based on these similarity and dissimilarity of changing aspects of the VR1C, it is supposed that the VR1C probably has the real pI value near the pH 7. Generally, mild extracellular acidic pH ($6.5{\sim}6.8$) potentiates VRI channel activation by noxious heat and vanilloids, whereas acidic conditions directly activate the channel. The channel activation of the VRI might be related to the structural change of VR1C caused by pH (electrostatic interactions), especially near the pH 7. By measuring the $^1-^{15}N$ TROSY spectra of the VR1C, we could get more resolved and dispersed spectra at the low pH and/or detergent micelles conditions. We will try to do further NMR experiments in low pH with micelles conditions in order to get more information about the structure of VR1C.

• Tribology and Lubricants
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• 제36권2호
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• pp.105-115
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• 2020

This paper presents a numerical study on the rotordynamic analysis of a dual-spool turbofan engine in the context of blade defect events. The blades of an axial-type aeroengine are typically well aligned during the compressor and turbine stages. However, they are sometimes exposed to damage, partially or entirely, for several operational reasons, such as cracks due to foreign objects, burns from the combustion gas, and corrosion due to oxygen in the air. Herein, we designed a dual-spool rotor using the commercial 3D modeling software CATIA to simulate blade defects in the turbofan engine. We utilized the rotordynamic parameters to create two finite element Euler-Bernoulli beam models connected by means of an inter-rotor bearing. We then applied the unbalanced forces induced by the mass eccentricities of the blades to the following selected scenarios: 1) fully balanced, 2) crack in the low-pressure compressor (LPC) and high pressure compressor (HPC), 3) burn on the high-pressure turbine (HPT) and low pressure compressor, 4) corrosion of the LPC, and 5) corrosion of the HPC. Additionally, we obtained the transient and steady-state responses of the overall rotor nodes using the Runge-Kutta numerical integration method, and employed model reduction techniques such as component mode synthesis to enhance the computational efficiency of the process. The simulation results indicate that the high-vibration status of the rotor commences beyond 10,000 rpm, which is identified as the first critical speed of the lower speed rotor. Moreover, we monitored the unbalanced stages near the inter-rotor bearing, which prominently influences the overall rotordynamic status, and the corrosion of the HPC to prevent further instability. The high-speed range operation (>13,000 rpm) coupled with HPC/HPT blade defects possibly presents a rotor-case contact problem that can lead to catastrophic failure.

• 한국환경과학회지
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• 제14권2호
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• pp.221-230
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• 2005

Catalytic wet oxidation of trichloroethylene (TCE) in water has been conducted using $TiO_2-supported$ cobalt oxides at $36^{\circ}C$ with a weight hourly space velocity of $7,500\;h^{-1}.\;5\%\;CoO_x/TiO_2$, prepared by using an incipient wetness technique, might be the most promising catalyst for the wet oxidation although it exhibited a transient behavior in time on-stream activity. Not only could the bare support be inactive for the wet decomposition reaction, but no TCE removal also occurred by the process of adsorption on $TiO_2$ surface. The catalytic activity was independent of all particle sizes used, thereby representing no mass transfer limitation in intraparticle diffusion. XPS spectra of both fresh and used Co surfaces gave different surface spectral features for each $CoO_x,\;Co\;2P_{3/2}$ binding energy for Co species in the fresh catalyst appeared at 781.3 eV, which is very similar to the chemical states of $CoTiO_x$ such as $CO_2TiO_4\;and\;CoTiO_3$. The used catalyst exhibited a 780.3-eV main peak with a satellite structure at 795.8 eV. Based on XPS spectra of reference Co compound, the TCE-exposed Co surfaces could be assigned to be in the form of mainly $Co_3O_4$. XRD patterns for $5\%\;CoO_x/TiO_2$ catalyst indicated that the phase structure of Co species in the catalyst even before reaction is quite comparable to the diffraction lines of external $Co_3O_4$ standard. A model structure of $CoO_x$ present predominantly on titania surfaces would be $Co_3O_4$, encapsulated in thin-film $CoTiO_x$ species consisting of $Co_2TiO_4$ and $CoTiO_3$, which may be active for the decomposition of TCE in a flow of water.

• 대한치과마취과학회지
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• 제14권3호
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• pp.157-165
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• 2014

Background: Incisional site of surgical operation become transient ischemic state and then occur reoxygenation due to vasodilatation by inflammatory reaction, the productive reactive oxygen species (ROS) give rise to many physiologic results. Apoptosis have major role on elimination of inflammatory cell and formation of granulation tissue in normal wound healing process. Remifentanil can prevent the inflammatory response and can suppress inducible nitric oxide synthase expression in a septic mouse model. After cardiopulmonary bypass for coronary artery surgery, remifentanil can also inhibit the release of biomarkers of myocardial damage. Here we investigated whether remifentanil pretreatment has cellular protective effect against hypoxia-reoxygenation in HaCaT human keratinocytes, if so, the role of apoptosis and autophagy on this phenomenon. Methods: The HaCaT human keratinocytes were exposed to various concentrations of remifentanil (0.01, 0.05, 0.1, 0.5 and 1 ng/ml) for 2 h before hypoxia (RPC/HR group). These cells were cultured under 1% oxygen tension for 24h at $37^{\circ}C$. After hypoxia, to simulate reoxygenation and recovery, the cells were reoxygenated for 12 h at $37^{\circ}C$. 3-MA/RPC/HR group was treated 3-methyladenine (3-MA), autophagy inhibitor for 1h before remifentanil treatment. Cell viability was measured using a quantitative colorimetric assay with thiazolyl blue tetrazoliumbromide (MTT, amresco), showing the mitochondrial activity of living cells. To investigate whether the occurrence of autophagy and apoptosis, we used fluorescence microscopy and Western blot analysis. Results: The viability against hypoxia-reoxygenation injury in remifentanil preconditioning keratinocytes were increased, and these cells were showed stimulated expression of autophagy 3-MA suppressed the induction of autophagy effectively and the protective effects on apoptosis. Atg5, Beclin-1, LC3-II and p62 were elevated in RPC/HR group. But they were decreased when autophagy was suppressed by 3-MA. Conclusions: Remifentanil preconditioning showed the protective effect in human keratinocytes, and we concluded that autophagy may take the major role in the recovery of wound from hypoxia-reoxygenation injury. We suggest that further research is needed about the cell protective effects of autophagy.

• 한국지반공학회논문집
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• 제32권8호
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• pp.5-14
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• 2016

싱크홀 발생의 주요 원인인 하수관거 배면의 공동 탐지를 위해 비파괴검사 방법 중 하나인 충격반향법을 적용한 실내 모형 실험을 수행하였다. 콘크리트 하수관의 모의를 위해 얇은 두께의 콘크리트 평판 시험체를 제작하였고 주변지반은 모래로 조성하였으며 공동의 모사를 위해 스티로폼 박스를 모래에 매립하였다. 콘크리트 판 배면이 공동인 경우와 완전히 모래에 밀착된 경우로 나누어 실험이 진행되었으며 일정한 타격 강도의 유지를 위해 새롭게 제작된 타격 장치를 사용하여 획득 자료의 신뢰성을 높였다. 측정된 반사파는 고속 푸리에 변환과 국소 푸리에 변환을 사용하여 주파수 특성 및 시간 특성을 분석하였다. 그 결과, 푸리에 스펙트럼의 형상으로는 공동의 유무를 판별할 수 없는 것으로 나타났다. 본 연구에서는 공진 시간이라고 명한 새로운 지표를 제안하였다. 이는 공진 주파수가 일정 강도를 초과하는 지속 시간으로 정의하였다. 공진 시간은 공동의 유무를 효과적으로 예측하는 것으로 나타났다. 나아가 공동유무를 구분할 수 있는 공진 시간을 제시하였다. 실제 현장 조건에서의 검증과 보다 광범위한 적용성의 확보를 위해 다양한 지반 조건에 대한 추가 실험과 실제 하수관에 대한 현장 실험 등을 진행할 예정이다.

• BMB Reports
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• 제46권11호
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• pp.561-566
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• 2013

We examined the ways in which fenobam could promote not only the transduction of PEP-1-FK506BP into cells and tissues but also the neuroprotective effect of PEP-1-FK506BP against ischemic damage. Fenobam strongly enhanced the protective effect of PEP-1-FK506BP against $H_2O_2$-induced toxicity and DNA fragmentation in C6 cells. In addition, combinational treatment of fenobam with PEP-1-FK506BP significantly inhibited the activation of Akt and MAPK induced by $H_2O_2$, compared to treatment with PEP-1-FK506BP alone. Interestingly, our results showed that fenobam significantly increased the transduction of PEP-1-FK506BP into both C6 cells and the hippocampus of gerbil brains. Subsequently, a transient ischemic gerbil model study demonstrated that fenobam pretreatment led to the increased neuroprotection of PEP-1-FK506BP in the CA1 region of the hippocampus. Therefore, these results suggest that fenobam can be a useful agent to enhance the transduction of therapeutic PEP-1-fusion proteins into cells and tissues, thereby promoting their neuroprotective effects.

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2002년도 국제심포지엄
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• pp.97-97
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• 2002

Human eryhropoietin (EPO) is acidic glycoprotein hormone that plays key role in hematopoiesis by facilitating differentiation of erythrocyte and formation of hemoglobin (Hb) and is used for the treatment of anemia. Human EPO is consist of 166 amino acids which is modified by three N-glycosylations (24, 38, 83) and single O-glycosylation (126). N-glycosylation is reported to be related to the cellular secretion and activity of EPO. In this study, we examined effects of mutagenesis in glycosylation site of recombinat hEPO for the cellular secretion during production from cultured CHO cell. We produced rhEpo which was cloned by PCR from human liver cDNA (TaKaRa) in cultured CHO cell. Using supernatant of the culture, ELISA assay and western analysis were performed. To estimate biological activity, 20IU of rhuEpo was subcutaneously injected into four ICR mice. After 8 days, HCT level was increased average 13 per cent, RBC was increased ca. 2${\times}$10$\^$6//${\mu}\ell$. In disease model Rat (anemia c-kit, WSRC-WS/WS), HCT was increased ca. 12%, RBC was increased ca. 1.6${\times}$10$\^$6//${\mu}\ell$. These results suggests that rhEpo we produced has biological activity. To remove glycosylation site by substituting 24, 38, 83, and 126th asparagine (or serine) with glutamic acid, overlapping -extension site-directed mutagenesis was performed. To add novel glycosylation sites, 69, 105th leucine was mutated to asparagine. Mutant EPO construct was transfected into CHO cell. Supernatant of the cell culture was analyzed using ELISA assay with monoclonal anti-EPO antibody (Medac, Germany). Since, several reports for mutagenesis of glycosylation sites showed case-by-case results, we examined both transient expression and stable expression. Addition of novel glycosylation sites resulted no secretion while deletion mutants had little effect except some double deletion mutants (24/83 and 38/83) and triple mutant. We suggest that not single but combination of glycosyl group affect secretion of EPO.

• 한국지하수토양환경학회지:지하수토양환경
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• 제14권6호
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• pp.1-18
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• 2009

한국 부산광역시 수영구 지역 해안 대수층 내의 밀도 의존적 지하수 유동 및 염분 이동에 대한 도시화의 영향을 효과적으로 모사하고 정량적으로 평가하기 위하여 하나의 범용 다차원 수리동역학적 분산 수치 모델을 이용한 일련의 삼차원 수치 모델링이 수행되었다. 먼저 모든 도시화 요소들을 고려한 수치 모델링 보정을 통해 확립된 연구 지역해안 대수층의 지층 물성을 가지고, 도시화 요소들을 모두 고려하지 않은 도시화 이전의 지하수 유동과 염분 이동에 대한 정상 상태 수치 모델링을 수행하였다. 그 다음에 도시화 요소들을 개별적으로 그리고 통합적으로 고려한 도시화 이후의 지하수 유동 및 염분 이동에 대한 비정상 상태 수치 모델링을 수행하였다. 그리고 두 수치 모델링 결과를 서로 비교하고 분석하였다. 수치 모델링 결과는 해안 대수층 내의 밀도 의존적 지하수 유동 및 염분 이동 그리고 해수 침투가 이러한 도시화 요소들에 의해 크게 그리고 광범위하게 영향을 받음을 보여준다. 특히 이러한 도시화 요소들은 해안 대수층 내의 총지하수량 및 총염분량의 변화를 초래한다. 그러나 각 도시화 요소의 그러한 영향은 공간적으로 균일하지 않고 국부적으로 차별적이다.