• Proceedings of the Korean Society for Technology of Plasticity Conference
• /
• 2005.05a
• /
• pp.428-431
• /
• 2005

This paper describes the process design for hot forging of bearing hub. Forging processes of bearing hub are simulated using the rigid-plastic finite element method. In the process called closed die forging without flash, the design of blocker geometry is of critical importance. Forging processes designs are take advantage of computer aided Process planning and experts. But that is difficult to predict metal flow line. So the preform is designed by the expert, and modified through predict metal flow line by CAE. This paper is to approach preform design considered defect such as metal flow and unfitting etc. at the finisher process.

• Korean Journal of Veterinary Service
• /
• v.31 no.4
• /
• pp.457-463
• /
• 2008

The sex steroid hormone estradiol-$17{\beta}(E_2)$ mediate their biological effects on development, differentiation and maintenance of reproductive tract and other target tissue through gene regulation by nuclear steroid receptors. Although the importance of $E_2$ in many physiological process has been reported, but little is known about the effects of $E_2$ on primary cultured chicken hepatocyte. therefore, in the present study, we have examined the effect of $E_2$ on cell proliferation and it's related signal cascades. $E_2$ increase $[^3H]$-thymidine incorporation in time-(${\leq}8hr$) and dose-($10^{-10}M$)dependent manner and treatment of $E_2$ increased the phosphorylation of p44/43 MAPKs(p44/42 mitogen-activated protein kinase) and JNK(c-Jun N-terminal kinase) in a time dependent manner. In addition, PD98059(p44/42 blocker, $10^{-5}M$), SP600125(JNK blocker, $10^{-6}M$) blocked the estrogen-induced increase in $[^3H]$-thymidine incorporation. In conclusion, $E_2$ stimulates the proliferation of primary cultured chicken hepatocytes and this action is mediated by p44/42 MAPKs and JNK signal transduction pathway.

• International Journal of Oral Biology
• /
• v.40 no.4
• /
• pp.211-216
• /
• 2015

Nitric Oxide (NO) is an important signaling molecule in the nociceptive process. Our previous study suggested that high concentrations of sodium nitroprusside (SNP), a NO donor, induce a membrane hyperpolarization and outward current through large conductances calcium-activated potassium ($BK_{ca}$) channels in substantia gelatinosa (SG) neurons. In this study, patch clamp recording in spinal slices was used to investigate the sources of $Ca^{2+}$ that induces $Ca^{2+}$-activated potassium currents. Application of SNP induced a membrane hyperpolarization, which was significantly inhibited by hemoglobin and 2-(4-carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (c-PTIO), NO scavengers. SNP-induced hyperpolarization was decreased in the presence of charybdotoxin, a selective $BK_{Ca}$ channel blocker. In addition, SNP-induced response was significantly blocked by pretreatment of thapsigargin which can remove $Ca^{2+}$ in endoplasmic reticulum, and decreased by pretreatment of dentrolene, a ryanodine receptors (RyR) blocker. These data suggested that NO induces a membrane hyperpolarization through $BK_{ca}$ channels, which are activated by intracellular $Ca^{2+}$ increase via activation of RyR of $Ca^{2+}$ stores.

• Biomolecules & Therapeutics
• /
• v.26 no.5
• /
• pp.458-463
• /
• 2018

The phosphorylation of JNK is known to induce insulin resistance in insulin target tissues. The inhibition of JNK-JIP1 interaction, which interferes JNK phosphorylation, becomes a potential target for drug development of type 2 diabetes. To discover the inhibitors of JNK-JIP1 interaction, we screened out 30 candidates from 4320 compound library with In Cell Interaction Trap method. The candidates were further confirmed and narrowed down to five compounds using the FRET method in a model cell. Among those five compounds, Acebutolol showed notable inhibition of JNK phosphorylation and elevation of glucose uptake in diabetic models of adipocyte and liver cell. Structural computation showed that the binding affinity of Acebutolol on the JNK-JIP1 interaction site was comparable to the known inhibitor, BI-78D3. Our results suggest that Acebutolol, an FDA-approved beta blocker for hypertension therapy, could have a new repurposed effect on type 2 diabetes elevating glucose uptake process by inhibiting JNK-JIP1 interaction.

• Journal of the Korean Chemical Society
• /
• v.59 no.6
• /
• pp.488-492
• /
• 2015

In this study, the effective preparation method of (S)-(+)-pranidipine, the active component of antihypertensive drug as a calcium channel blocker, was developed using optical resolution. The racemic monocarboxylic acid 5 obtained by the hydrolysis of (±)-pranidipine was mixed with optically active quinidine to form salts, and the insoluble diastereomeric salt was collected and successive treatment with base and acid furnished (R)-(-)-carboxylic acid 7. (S)-(+)-Pranidipine was prepared by esterification of this acid with cinnamyl alcohol, and the analysis by chiral HPLC showed 100% enantiomeric excess (ee). This process would be industrially very useful to prepare chiral (S)-(+)-pranidipine, since the use of strong base and anhydrous solvents, and ultra-low temperature condition were excluded in this process.

• Transactions of Materials Processing
• /
• v.9 no.4
• /
• pp.348-355
• /
• 2000

The backward tracing scheme(BWT) of the finite element method has been extended lot the design of sheet blank in three-dimensional deformation. Originally the scheme was developed for preform design in bulk forming, and applied to several forming processes successfully. Its key concept is to trace backward from the final desirable configuration to an intermediate preform or initial blocker. A program for initial blank design in sheet forming which contains the capabilities of forward loading simulation by the finite element method and backward tracing simulation, has been developed and proved the effectiveness by applying to a square cup stamping process. In the blank design of square cup stamping, the backward tracing program can produce an optimum blank configuration which forms a sound net-shape cup product without machining after forming. For the confirmation of the analytic result derived from the backward tracing simulations as well as forward loading simulations, a series of experiment were carried out. The experiments include the first trial sheet forming process with a rectangular blank, an improved process with a modified blank preform and the final process with an optimum blank resulted from the backward tracing scheme. The experiments show that the backward tracing scheme has been implemented successfully in blank design of sheet metal forming.

• Transactions of Materials Processing
• /
• v.13 no.7
• /
• pp.635-641
• /
• 2004

Today the specific outputs of modern supercharger DI diesel engine for passenger cars reach values exceeding 50kw/1. By development of the articulated piston, specific output of up to 70kw/1 are sought. In doing so, peak cylinder pressure increases from the current 14-16MPa to 18-20MPa. The Articulated piston was composed Al cast skirt part and steel forged crown part. We have the target fer the design of forging process and die of the steel forged crown part. The design parameters of the forging process of the piston were obtained by the forging industry experiences and our experimental data and analysis result of finite element simulation. Especially, the design parameter of preform in blocker die was decided by finite element simulation using numerical package DEFROM3D. And also we can verify the design parameter by conducting visio-plasticity test using plasticine material. When we compared the results of analysis and experiment, a metal flow and load curve showed good agreement. Through this research, we could design optimal preform shape of articulated piston for this supercharged DI diesel engine.

• Journal of Chest Surgery
• /
• v.22 no.6
• /
• pp.901-913
• /
• 1989

This study was investigated under the postulation that activation of intracellular calcium- calmodulin complex during ischemia-reperfusion leads to myocardial injury. The protective effects of calcium channel blocker, diltiazem and calmodulin inhibitors, trifluoperazine, flunarizine and calmidazolium from ischemic injury in rat hearts were observed by using Langendorff apparatus when the antagonists were infused for 3 min in the beginning of ischemia. Thereby, an increase in resting tension developed during 30-min ischemia was analyzed with regard to [1] the degree of cardiac functional recovery following 60-min reperfusion, [2] changes in biochemical variables evoked during 30-min ischemia. The results obtained were as follows: l. In the ischemic group, the resting tension was increased by 4.1*0.2 g at 30-min ischemia. However, the increase in resting tension was markedly reduced not only by pretreatment with diltiazem [3.3 p M] but also with calmodulin inhibitors, trifluoperazine [3.3 p M], flunarizine [0.5 p M] and calmidazolium [0.5 p M], respectively. 2. Recovery of myocardial contractility, +dF /dt and coronary flow were much reduced when evoked by reperfusion in the ischemic group. These variables were significantly improved either by pretreatment with diltiazem or with calmodulin inhibitors. 3. The resting tension increment evoked during ischemia was significantly inversely correlated with the degree of cardiac function recovered during reperfusion. 4. Following 30-min ischemia, the production of malondialdehyde and release of lysosomal enzyme were much increased in association with a decrease in creatine kinase activity. 5. The increases in malondialdehyde production and release of free lysosomal enzyme were suppressed by pretreatment with calmodulin inhibitors as well as diltiazem. Likewise, the decrease of creatine kinase activities was prevented by these calcium antagonists. With these results, it is indicated that a increase in resting tension observed during ischemia has an inverse relationship to the cardiac function recovered following reperfusion, and further, the later may be significantly dependent on the degree of biochemical alterations occurred during ischemia such as decrease in creatine kinase activity, increased production of malondialdehyde and increased release of free lysosomal enzyme. Thus it is concluded that calmodulin plays a pivotal role in the process of ischemic injury.

• Analytical Science and Technology
• /
• v.33 no.2
• /
• pp.59-67
• /
• 2020

Nadolol is a β-blocker drug, which effectively manages hypertension and angina pectoris. Its chemical structure allows the formation of four possible stereoisomers. A coupled column high-performance liquid chromatographic (HPLC) system with UV and fluorescence detection was investigated for simultaneously determining four nadolol enantiomers in human plasma. The plasma samples were prepared using a convenient liquid-liquid extraction process and passed through HPLC. Nadolol was initially separated from the endogenous compounds or other impurities in human plasma on a Phenomenex silica column, and its enantiomers were resolved and determined on a Chirapak AD-H column. The developed HPLC method achieved an effective chiral separation and significantly eliminated endogenous compound interference. This optimal HPLC method was validated following FDA guidelines. The results showed good selectivity, linearity, accuracy (90.50 % - 105.27 %), and precision (RSDs < 9.52 %) for each enantiomer. This method was also successfully applied to determine nadolol enantiomers in the plasma samples of a healthy male volunteer (after orally administering 80 mg racemic nadolol), proving its suitability for nadolol stereoselective pharmacokinetic studies.

• Journal of Korea Society of Industrial Information Systems
• /
• v.21 no.1
• /
• pp.43-50
• /
• 2016

In this paper, new automatic LC calibrator is proposed for realizing a passive LC filter with almost constant frequency characteristic regardless of the PVT variations. The SAW-less GPS RX front-end is implemented using a 65nm CMOS process using the proposed LC calibrator. Also, new dual-mode low noise amplifier (LNA) structure is proposed to generate the RF signal required for the LC calibrator. The characteristics of the implemented GPS RX front-end show the voltage gain of about 42.5 dB, noise figure of below 1.35 dB, the blocker input P1dB of -24 dBm in case of the worst blocker signal at 1710 MHz frequency, while it consumes 7 mA current at 1.2 V power supply voltage.