• Journal of Microbiology and Biotechnology
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• 제27권11호
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• pp.2044-2051
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• 2017

The main pathological hallmark of Alzheimer's disease is the deposition of amyloid-beta ($A{\beta}$) peptides in the brain. $A{\beta}$ has been widely used to mimic several aspects of Alzheimer's disease. However, several characteristics of amyloid-induced Alzheimer's disease pathology are not well established, especially in mice. The present study aimed to develop a new Alzheimer's disease model by investigating how $A{\beta}$ can be effectively aggregated using prokaryotes and eukaryotes. To express the $A{\beta}42$ complex in HEK293 cells, we cloned the $A{\beta}42$ region in a tandem repeat and incorporated the resulting construct into a eukaryotic expression vector. Following transfection into HEK293 cells via lipofection, cell viability assay and western blotting analysis revealed that exogenous $A{\beta}42$ can induce cell death and apoptosis. In addition, recombinant His-tagged $A{\beta}42$ was successfully expressed in Escherichia coli BL21 (DE3) and not only readily formed $A{\beta}$ complexes, but also inhibited the proliferation of SH-SY5Y cells and E. coli. For in vivo testing, recombinant His-tagged $A{\beta}42$ solution ($3{\mu}g/{\mu}l$ in $1{\times}PBS$ containing $1mM\;Ni^{2+}$) was injected stereotaxically into the left and right lateral ventricles of the brains of C57BL/6J mice (n = 8). Control mice were injected with $1{\times}PBS$ containing $1mM\;Ni^{2+}$ following the same procedure. Ten days after the sample injection, the Morris water maze test confirmed that exogenous $A{\beta}$ caused an increase in memory loss. These findings demonstrated that $Ni^{2+}$ is capable of complexing the 50-kDa amyloid and that intracerebroventricular injection of $A{\beta}42$ can lead to cognitive impairment, thereby providing improved Alzheimer's disease models.

• 대한핵의학회지
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• 제29권3호
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• pp.328-331
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• 1995

$^{99m}Tc$ labeled PnAO(propylene amine oxime) derivatives have been widely studied as brain perfusion agents. We synthesized and characterized a PnAO derivative, (RR/SS/ meso)-4,8-diaza-3,9-dimethylundecane-2, 10-dione bisoxime(PRODD). Proton-NMR spectroscopy and thin layer chromatography(silica gel) were performed for its characterization. PRODD was labeled with $^{99m}Tc$ using stannous chloride as reducing agent. The labeling efficiency was determined to be about 85%. Brain uptakes of $4.16{\pm}0.42$ %ID/g and $3.24{\pm}0.13$ %ID/g were found after 10min and 30min after intravenous injection. Brain-to-blood ratios were 1.17 and 0.75 at 10 and 30 minutes, which were lower than 1.3 and 1.9 of the ratios with commercial ${\pm}$-HMPAO. Autoradiographs of rat brain sections showed the gray matter to white matter ratios of $1.13{\pm}0.10$ at 30 min after intravenous injection, which was lower than $1.94{\pm}0.19$ of commercial $^{99m}Tc$-HMPAO. With the above findings, we concluded that the lipophilic $^{99m}Tc$-PRODD complex was able to cross the blood-brain barrier, however the complex showed lower uptake than $^{99m}Tc$-HMPAO in mouse or rat brains. We could suggest possibility that PRODD could be used as another $^{99m}Tc$ chelator.

• 한국동물학회지
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• 제31권1호
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• pp.35-48
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• 1988

Testosterone과 cyclic AMP(cAMP)가 부정소에 미치는 영향을 조사하기 위하여 흰쥐의 복강내로 testosterone 및 cAMP를 투여하여 acid phosphatase(ACP),alkaline phosphatase(ALP), lactate dehydrogenase(LDH)의 활성도를 측정하였으며 상피세포내 미세구조의 변화를 전자현미경으로 관찰하였다. 그 결과 거세한 실험군에서 ACP활성도는 거세 후 3일째까지 감소하기 시작하였으며 ALP활성도는 5일째,LDH활성도는 7일째부터 각각 감소하였다. 또한 거세 후 14일째 부터 testosterone을 7일간 투여한 경우 ACP와 ALP의 활성도는 5일간 계속 투여하였을 때,LDH의 활성도는 7일간 계속 투여하였을 때만 각각 유의성있게 증가하였다. cAMP 및 cAMP-theophyllin을 투여한 경우 LDH 및 ACP의 활성도가 증가하였으나 그 증가폭은 큰 의미가 없었다. ALP의 활성도는 두 가지의 경우에서 모두 증가를 나타내었다. 미세구조를 관찰한 결과는 거세한 실험군에서 골지체가 점차 변형되어 층상구조가 없어지며 미토콘드리아도 파괴되었고 상당수 존재하던 부동모 (stereocilia)도 파괴되었다. 이 경우 testosterone투여시 파괴되었던 고리지체, 미토콘드리아 및 부동모가 회복되었고 cAMP 및 cAMP-theophyllin 을 투여하였을 때는 골지체 및 여러 세포기관들이 대조군과 같은 수준으로 회복되었으나 부동모는 거세군과 같은 수준으로 관찰되었다. 이상의 결과는 부정소액에서 정자성숙시 나타나는 효소활성도 증가와 유사하게 나타났는데, 이것은 정자↔부정소액↔부정소 상피세포 와 같은 상호작용을 통하여 정자성숙이 이루어지며 이는 상피세포에서 합성된 물질이 부정소내 강으로 방출된다는 것을 의미하며 cAMP를 처리하였을 경우 효소활성도 증가 및 여러 세포소기관의 회복 등 testosterone과 유사한 작용을 나타내는 것은 cAMP가 웅성호르몬 작용시 화확적으로 전달자로 작용할 수 있다는 가능성을 나타내는 것으로 생각된다.

• 대한약리학회지
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• 제22권2호
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• pp.105-114
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• 1986

본 실험실에서는 민간요법으로 말라리아와 성병등의 치료제로 사용되어온 회양목(Buxus microphylla var. koreana Nakai)에서 steroid성 alkaloid인 cyclobuxine D와 nonalkaloid인 buxuletin을 분리하였다. Buxuletin의 가토에 있어서 이뇨작용에 대해서는 본 실험실에서 보고한바 있으며 cyclobuxine D의 약리작용에 대한 보고는 지금까지 전무한 상태이다. 본 실험에서는 새로운 항부정맥 약물의 밭견의 일환으로 cyclobuxine D의 적출 개구리 심장에 대한 작용과 마취시킨 흰쥐의 ECG와 심박동수에 대한 작용을 관찰하였다. Cyclobuxine D는 적출 개구리 심장에 대해 용량의존적 심근 수축력 감소를 나타냈으며 흰쥐에 있어서 현저한 심박동수 감소를 나타냈다. Cyclobuxine D는 흰쥐의 ECG에 있어서 PR interval과 P ${\alpha}T$ interval을 연장시키며, QRS complex와 PR interval의 심박동수에 대한 보상치인 PRc에 대해서는 고용량에서는 연장시키나 그 작용이 현저하지 않다. 이 결과로 보아 cyclobuxine D는 흰쥐의 ECG에서 A-V conduction과 ventricular depolarization에 주로 관여하는 것으로 사료 되며 이는 기존의 antiarrhythmic drugs과 비교해 볼 때 quinidine sulfate와 유사성이 있다고 추정된다.

• Genomics & Informatics
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• 제10권1호
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• pp.40-43
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• 2012

Recent genomewide association studies of large samples have identified genes that are associated with blood pressure. The Global Blood Pressure Genetics (Global BPgen) and Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortiums identified 14 loci that govern blood pressure on a genomewide significance level, one of which is $CASZ1$ confirmed in both Europeans and Asians. $CASZ1$ is a zinc finger transcription factor that controls apoptosis and cell fate and suppresses neuroblastoma tumor growth by reprogramming gene expression, like a tumor suppressor. To validate the function of $CASZ1$ in blood pressure, we decreased $Casz1$ mRNA levels in mice by siRNA. $Casz1$ siRNA reduced mRNA levels by 59% in a mouse cell line. A polyethylenimine-mixed siRNA complex was injected into mouse tail veins, reducing $Casz1$ mRNA expression to 45% in the kidney. However, blood pressure in the treated mice was unaffected, despite a 55% reduction in $Casz1$ mRNA levels in the kidney on multiple siRNA injections daily. Even though $Casz1$ siRNA-treated mice did not experience any significant change in blood pressure, our study demonstrates the value of $in$ $vivo$ siRNA injection in analyzing the function of candidate genes identified by genomewide association studies.

• 한국항공우주학회지
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• 제32권8호
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• pp.138-144
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• 2004

우주환경에서 운용되는 위성은 상호 유기적으로 연결된 다양한 전자장비에서 방출하는 전도성/복사성 에너지 결함에 의해 다양한 노이즈를 발생하게 되는데, 이러한 노이즈는 위성 시스템과 탑재체의 전자기적인 영향에 의하여 주요 기능에 중대한 결함을 유발시킬 수 있다 이에 위생 시스템은 개발 단계에서부터 전자파환경에 대한 영향을 최소화하기 위한 시스템 설계 검증이 요구된다. 위성 시스템에서 검증하여야 하는 전자파환경시험은 위성으로부터 방출되는 전도성/복사성 노이즈 레벨측정과 이러한 노이즈환경에서 위성의 정상운용을 검증하는 감응성 시험이 있다. 다목적실용위성 2호의 전도성 전자파환경에서의 시스템 설계 검증은 PCU가 전원을 각 유닛에 분배하는 그 과정에서 전원선에서 방출하는 전도성 방출특성을 측정하여 시스템에서 통제하는 전자파 규격에 적합한지를 검증하고, 이러한 방출 레벨로부터 6dB 시스템 안전성마진을 고려한 레벨의 전도성 노이즈를 전원선에 인가하여 시스템의 성능을 검증하는 것이다. 본 논문에서는 다목적실용위성 2호의 전도성 특성을 검증하기 위해 ETB에서 수행한 시스템 검증결과 및 노이즈 요소 분석을 제시하였으며, 노이즈요소 분석 결과는 FM EMC 시험에 반영될 것이다.

• BMB Reports
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• 제53권9호
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• pp.484-489
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• 2020

Epilepsy is a neurological disorder characterized by unpredictable seizures, which are bursts of electrical activity that temporarily affect the brain. Cereblon (CRBN), a DCAFs (DDB1 and CUL4-associated factors), is a well-established protein associated with human mental retardation. Being a substrate receptor of the cullin-RING E3 ubiquitin ligase (CRL) 4 complex, CRBN mediates ubiquitination of several substrates and conducts multiple biological processes. In the central nervous system, the large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel, which is the substrate of CRBN, is an important regulator of epilepsy. Despite the functional role and importance of CRBN in the brain, direct injection of pentylenetetrazole (PTZ) to induce seizures in CRBN knock-out mice has not been challenged. In this study, we investigated the effect of PTZ in CRBN knock-out mice. Here, we demonstrate that, compared with WT mice, CRBN knock-out mice do not show the intensification of seizures by PTZ induction. Moreover, electroencephalography recordings were also performed in the brains of both WT and CRBN knockout mice to identify the absence of significant differences in the pattern of seizure activities. Consistently, immunoblot analysis for validating the protein level of the CRL4 complex containing CRBN (CRL4^Crbn) in the mouse brain was carried out. Taken together, we found that the deficiency of CRBN does not affect PTZ-induced seizure.

• 한국분말야금학회:학술대회논문집
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• 한국분말야금학회 1997년도 추계학술강연 및 발표대회 강연 및 발표논문 초록집
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• pp.7-7
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• 1997

During sintering of very porous green bodies, as obtained by compaction of hard powders - such as tungsten carbide or ceramics - or by injection moulding, important shrinkage occurs. Due to heterogeneous green density field, gravity effects, friction on the support, thermal gradients, etc., this shrinkage is often non-uniform, which' may induce significant shape changes. As the ratio of compact dimension to powder size is very high, the mechanics of continuum is relevant to model such phenomena. Thus numerical techniques, such as the finite element method can be used to simulate the sintering process and predict the final shape of the sintered part. Such type of simulation has much been developed in the last decade firstly for hot isostatic pressing and next for die compaction. Finite element modelling has been recently applied to free sintering. The simulation of sintering should be based on constitutive equations describing the thermo-mechanical behaviour of the material under any state of stress and any temperature which may arise within the sintering body. These equations can be drawn either from experimental data or from micromechanical models. The experiments usually consist in free sintering and sinter-forging tests. Indeed applying more complex loading conditions at high temperature under controlled atmosphere is delicate. Micromechanical models describe the constitutive behaviour of aggregates of spheres from the deformation of two-sphere contact either by viscous flow or grain boundary diffusion. Such models are not able to describe complex microstructure and mechanisms as observed in real materials but they can give some basic information on the formulation of constitutive equations. Practically both experimental and theoretical approaches can be coupled to identify the constitutive equations. Such procedure has been performed for modelling the sintering of compacts obtained by die pressing of a mixture of tungsten carbide and cobalt powders. The constitutive behaviour of this material during sintering has been described by a linear viscous constitutive model, whose functions have been fitted from results of free sintering and sinter-forging experiments. This model has next been introduced in ABAQUS finite element code to simulate the sintering of heterogeneous green compacts of various geometries at constant temperature. Examples of simulations are shown and compared with experiments.

• 산업경영시스템학회지
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• 제40권1호
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• pp.35-40
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• 2017

A most important progress in civilization was the introduction of mass production. One of main methods for mass production is die-casting molds. Due to the high velocity of the liquid metal, aluminum die-casting is so complex where flow momentum is critical matter in the mold filling process. Actually in complex parts, it is almost impossible to calculate the exact mold filling performance with using experimental knowledge. To manufacture the lightweight automobile bodies, aluminum die-castings play a definitive role in the automotive part industry. Due to this condition in the design procedure, the simulation is becoming more important. Simulation can make a casting system optimal and also elevate the casting quality with less experiment. The most advantage of using simulation programs is the time and cost saving of the casting layout design. For a die casting mold, generally, the casting layout design should be considered based on the relation among injection system, casting condition, gate system, and cooling system. Also, the extent or the location of product defects was differentiated according to the various relations of the above conditions. In this research, in order to optimize the casting layout design of an automotive Oil Pan_BR2E, Computer Aided Engineering (CAE) simulation was performed with three layout designs by using the simulation software (AnyCasting). The simulation results were analyzed and compared carefully in order to apply them into the production die-casting mold. During the filling process with three models, internal porosities caused by air entrapments were predicted and also compared with the modification of the gate system and overflows. With the solidification analysis, internal porosities occurring during the solidification process were predicted and also compared with the modified gate system.

• 대한기계학회논문집B
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• 제21권9호
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• pp.1149-1164
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• 1997

In this study, the applicability of the RNG k-.epsilon. model to the analysis of the complex flows is studied. The governing equations based on a non-orthogonal coordinate formulation with Cartesian velocity components are used and discretized by the finite volume method with non-staggered variable arrangements. The predicted results using the RNG k-.epsilon. model of three complex flows, i.e., the flow over a backward-facing step and a blunt flat plate, the flow around a 2D model car are compared to these from the standard k-.epsilon. model and experimental data. That of the unsteady axisymmetric turbulent flow within a cylinder of reciprocating model engine including port/valve assembly and the spray characteristics within a chamber of direct injection model engine are compared to these from the standard k-.epsilon. model and experimental data. The results of reattachment length, separated eddy size, average surface pressure distribution using the RNG k-.epsilon. model show more reasonable trends comparing with the experimental data than those using the modified k-.epsilon. model. Although the predicted rms velocity using the modified k-.epsilon. model is lower considerably than the experimental data in incylinder flow with poppet valve, predicted axial and radial velocity distributions at the valve exit and in-cylinder region show good agreements with the experimental data. The spray tip penetration predicted using the RNG k-.epsilon. model is more close to the experimental data than that using the modified k-.epsilon. model. The application of the RNG k-.epsilon. model seems to have some potential for the simulations of the unsteady turbulent flow within a port/valve-cylinder assembly and the spray characteristics over the modified k-.epsilon. model.