• BMB Reports
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• 제49권2호
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• pp.71-72
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• 2016

Focal cortical dysplasia type II (FCDII) is a focal malformation of the developing cerebral cortex and the major cause of intractable epilepsy. However, since the molecular genetic etiology of FCD has remained enigmatic, the effective therapeutic target for this condition has remained poorly understood. Our recent study on FCD utilizing various deep sequencing platforms identified somatic mutations in MTOR (existing as low as 1% allelic frequency) only in the affected brain tissues. We observed that these mutations induced hyperactivation of the mTOR kinase. In addition, focal cortical expression of mutant MTOR using in utero electroporation in mice, recapitulated the neuropathological features of FCDII, such as migration defect, cytomegalic neuron and spontaneous seizures. Furthermore, seizures and dysmorphic neurons were rescued by the administration of mTOR inhibitor, rapamycin. This study provides the first evidence that brain somatic activating mutations in MTOR cause FCD, and suggests the potential drug target for intractable epilepsy in FCD patients.

• Toxicological Research
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• 제11권1호
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• pp.103-108
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• 1995

Rat renal proximal tubule suspension was prepared from adult male Sprague Dawley rat (250-300g) by mechanical (non-enzymatical) method and evaluated as a pontential model for mechanistic studies and early screening of nephrotoxicity, using anionic antibiotics (cephaloridine). Cephaloridine (CPL) produced an increase in LDH release into media. This release results from decrease a proximal tubule cell viability and subsequently increase the permeability of cell viability and subsequently increase the permeability of cell membrane. Since loss of intracellular potassium and ATP into media is the sign of disruption of cell membrane, especially basolateral membrane (BLM), CPL induced proximal tubule cell compromise also appear be associated with BLM, maybe $Na^+-K^+$ ATPase. Also seen was significant depression in brush border membrane (BBM) ALP activity and no significantly increase in BBM GGT activities. The inhibition of typical anion, PAH accumulation (especially, CPL 5 mM) and cation, TEA (especially, 4hours incubation) were seen dose dependently. This is because of CPL accumulation in renal proximal tubule and increase of cytotoxicity.

• Molecular & Cellular Toxicology
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• 제4권2호
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• pp.170-176
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• 2008

The quantitative structure-activity relationship (QSAR) of a set of 35 flavonoid compounds presenting antioxidant activity was established by means of Genetic Algorithm-Multiple Linear Regression (GA-MLR) technique. Four-parametric models for two sets of data, the 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity $(R^2=0.788,\;Q^2_{cv}=0.699\;and\;Q^2_{ext}=0.577)$ and scavenging activity of reactive oxgen species (ROS) induced by $H_2O_2 (R^=0.829,\;Q^2_{cv}=0.754\;and\;Q^2_{ext}=0.573)$ were obtained with low external predictive ability on a mass basis, respectively. Each model gave some different mechanistic aspects of the flavonoid compounds tested in terms of the radical scavenging activity. Topological charge, H-bonding complex and deprotonation processes were likely to be involved in the radical scavenging activity.

• 한국생산제조학회지
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• 제22권6호
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• pp.1003-1009
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• 2013

This paper presents a simple procedure to obtain the instantaneous cutting force constants needed to predict milling forces. Cutting force data measured in a series of slot milling tests were used to determine the cutting force constants at different feed rates. The values of the cutting force constants were determined directly at the tool rotation angle that maximized the uncut chip thickness. Then, the instantaneous cutting force constant was obtained as a function of the instantaneous uncut chip thickness. This approach can greatly enhance the accuracy of the mechanistic cutting force model for end milling. In addition, the influences of several cutting parameters on the cutting forces, such as the tool helix angle and axial depth of cut, were discussed.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.109-117
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• 2011

In this work, we have investigated the effect of polyoxyethylene alkyl ester nonionic surfactants on percutaneous permeation enhancement of a model drug, ketoprofen. We also investigated the mechanism involved in the enhancement using impedance and solubility measurement. Three groups of nonionic surfactants with different ethylene oxide content were studied. The permeation results showed that all surfactants enhanced the percutaneous absorption, irrespective of the molecular weight. The permeation results from PEG-45 monostearate (PEGMS45) were rather unexpected. Impedance and solubility results indicate that the mechanism involved in the enhancement of permeation by PEG-10 monooleate (PEGMO10) and PEGMS45 is rather different. The results from PEGMS45 suggest that it could be a potential candidate as a skin penetration enhancer with high molecular weight, which may poses less skin irritation and systemic side effect than the smaller surfactant molecules. Overall, this work provided some useful information on percutaneous transport enhancement and the mechanistic insights involved in skin permeation for these nonionic surfactants.

• 한국정밀공학회:학술대회논문집
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• 한국정밀공학회 1996년도 추계학술대회 논문집
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• pp.31-35
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• 1996

The cross section of the circular rod type workpiece to be cut in the band saw machine is variable at every moment in the sawing process. When the cutting feed rate is fixed to the constant speed, the cutting edges of the band saw teeth are also variabl eat any moment, so this causes the wear of the land saw teeth and the deterioration of the quality in the surface roughness. In this study, to work out this kind of problem basically, the mean cutting force of a tooth in the band saw was estimated by using the workpiece which was smaller than the interval of each tooth, i.e. band saw pitch, in the thickness. Then the static cutting forces were predicted by appling the mean cutting forces referred above to the mechanistic cutting force model which were analyzed through the geometric profile of a band saw tooth.

• Toxicological Research
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• 제8권2호
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• pp.317-329
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• 1992

Fifty chemicals are currently classified as human carcinogens based on epidemiologic and animal data. Humans are daily exposed to them from various sources of exposure via inhalation, dermal contact and oral ingestion. To reduce cancer risk to man, these human carcinogens should be appropriately regulated and monitored environmentally or biologically for routine human cancer risk assessment. A number of mathematical risk assessment models have been introduced, but any realistic and relevant model system is not available for humans. A mechanistic process for human cancer risk assessment was comprehensively reviewed and problems were also discussed. Here, a new conceptual approach using epidemiology and biological human monitoring was suggested for the most relevant method to study human cancer risk assessment.

• 한국지반공학회:학술대회논문집
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• 한국지반공학회 2009년도 춘계 학술발표회
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• pp.11-16
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• 2009

Better understanding of in-situ mechanical behavior of pavement foundations is very important to predict long-term effects on the system performance of transport infrastructure. In order to do that, resilient stiffness characterization of geomaterals is needed to properly adopt such mechanistic analysis under both traffic and environmental loadings. In this paper, in situ monitoring data from KHC test road was used to analyze the non-linearity of stress conditions under traffic and moisture loadings. Then, the predicted non-linear response using finite element method with a selected constitutive model of foundation geomaterials are verified with the field data.

• Nuclear Engineering and Technology
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• 제46권2호
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• pp.159-168
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• 2014

In order to advance understanding of the breakaway swelling behavior of U-Mo/Al dispersion fuel under a high-power irradiation condition, the effects of fuel-matrix interaction on the fuel performance of U-Mo/Al dispersion fuel were investigated. Fission gas release into large interfacial pores between interaction layers and the Al matrix was analyzed using both mechanistic models and observations of the post-irradiation examination results of U-Mo dispersion fuels. Using the model predictions, advantageous fuel design parameters are recommended to prevent breakaway swelling.

• Bulletin of the Korean Chemical Society
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• 제21권9호
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• pp.860-866
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• 2000

Hydrocarbostyril, which is a key intermediate in our new synthetic route to 6-nitroquipazine, can be prepared from 1-indanone oxime by Beckmann rearrangement. We have optimized the reaction by using a Lewis acid, aluminum chloride,in the yield of 91% instead of common acids such as polyphosphoric acid,and sulfuric acid used in conventional Beckmann rearrangement (20% in the literature, 10% in our experiment).The optimized condition is established by usingthree equivalents of aluminum chloride in CH2Cl2 at -40 $^{\circ}C$ - room tempera-turefor 40 min. We have applied this condition to other 1-indanone derivatives, such as 4-methyl-, 4-methoxy-, 4-nitro and 6-nitro-1-indanones. The mechanism ofthis BR has been proposed on the basis of the effect of tem-perature and substituenton product ratio, with the aid of PM3 calculation for a model system.