• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.191-199
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• 2000

Genomics is providing targets faster than we can validate them and combinatorial chemistry is providing new chemical entities faster than we can screen them. Historically, the drug discovery cascade has been established as a sequential process initiated with a potency screening against a selected biological target. In this sequential process, pharmacokinetics was often regarded as a low-throughput activity. Typically, limited pharmacokinetics studies would be conducted prior to acceptance of a compound for safety evaluation and, as a result, compounds often failed to reach a clinical testing due to unfavorable pharmacokinetic characteristics. A new paradigm in drug discovery has emerged in which the entire sample collection is rapidly screened using robotized high-throughput assays at the outset of the program. Higher-throughput pharmacokinetics (HTPK) is being achieved through introduction of new techniques, including automation for sample preparation and new experimental approaches. A number of in vitro and in vivo methods are being developed for the HTPK. In vitro studies, in which many cell lines are used to screen absorption and metabolism, are generally faster than in vivo screening, and, in this sense, in vitro screening is often considered as a real HTPK. Despite the elegance of the in vitro models, however, in vivo screenings are always essential for the final confirmation. Among these in vivo methods, cassette dosing technique, is believed the methods that is applicable in the screening of pharmacokinetics of many compounds at a time. The widespread use of liquid chromatography (LC) interfaced to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) allowed the feasibility of the cassette dosing technique. Another approach to increase the throughput of in vivo screening of pharmacokinetics is to reduce the number of sample analysis. Two common approaches are used for this purpose. First, samples from identical study designs but that contain different drug candidate can be pooled to produce single set of samples, thus, reducing sample to be analyzed. Second, for a single test compound, serial plasma samples can be pooled to produce a single composite sample for analysis. In this review, we validated the issue whether the second method can be applied to practical screening of in vivo pharmacokinetics using data from seven of our previous bioequivalence studies. For a given drug, equally spaced serial plasma samples were pooled to achieve a 'Pooled Concentration' for the drug. An area under the plasma drug concentration-time curve (AUC) was then calculated theoretically using the pooled concentration and the predicted AUC value was statistically compared with the traditionally calculated AUC value. The comparison revealed that the sample pooling method generated reasonably accurate AUC values when compared with those obtained by the traditional approach. It is especially noteworthy that the accuracy was obtained by the analysis of only one sample instead of analyses of a number of samples that necessitates a significant man-power and time. Thus, we propose the sample pooling method as an alternative to in vivo pharmacokinetic approach in the selection potential lead(s) from combinatorial libraries.

• Proceedings of the Korean Society for Emotion and Sensibility Conference
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• 2000.11a
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• pp.81-87
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• 2000

Beat-to-beat changes in heart period (heart period variability, HPV) are mediated by fluctuations in autonomic activity. Spectral analysis is used to quantify such fluctuations in the range of 0.15-0.40 Hz (high frequency, HF), which are influenced primarily by parasympathetic factors. These fluctuations are often referred to as RSA (respiratory sinus arrhythmia), the physiological phenomenon extracted by spectral analysis and other methods including histograms of heart rate ( HR), deviations of HR etc. Respiratory sinus arrhythmia indexing with peak-to-valley method suggested by Grossman et at., (1981) yields a simple range statistic and is quantified on breath-by-breath basis, thus being quite sensitive and less dependent on recording time as compared to spectral analysis. It is strongly recommended to use at least 1 min epoch to asses HF component of HPV and at least 2 min fer low frequency (LF) of HPV and even 5 min far valid clinical assessment. Peak-to-valley statistic is limited to RSA index only, but has its pragmatic advantages. Most important is possibility of its application far relatively small epoch analysis. We used short periods (20,30, 40 sec only) and off-line analysis of RSA using ECG and respiration curve this method of assessment and proved that this method is more practically effective. The RSA index was not so far dependent on respiration pattern differences and reflected actual vagal control of HR and were accompanied by low HR under some high stress conditions and in an aversive affective visual stimulation experiments. Another factor that might modulate cardiac chronotropic response is the interaction of sympathetic and parasympathetic inputs on sino-atrial (SA) node level, because responses to vagal influences are known to be proportional to ongoing sympathetic activity, that is so called accentuated antagonism. Since sympathetic outflow (increment of influences on SA) under negative emotions or stress was high in almost all physiological responses, vagal effects on HR could be therefore potentiated, leading to masking of output cardiac response seen in HPV, In the case of moderate sympathetic activation, on the other hand, autonomic interactions in cardiac control appear to be minimal. Thus RSA index appears to be an effective alternative method to assess and measure spectral HPV.

• Korean Journal of Applied Biomechanics
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• v.19 no.4
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• pp.655-661
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• 2009

This study investigated the effects of different types of shouting actions on the strength of the human body. Both H-reflex and MVIC measures of the rectus femoris muscle were used to investigate effects on impact force and motor performance, in order to find optimum shouting methods. The H-reflex of the soleus muscle gave an electric stimulus to the curve of the knee that contains the tibial nerves. Surface electromyelography was used to collect muscle activity the amplitude increased 28% at action with shouting and 29% at the one immediately after short-time shouting than the one without shouting was. To assess the myoelectric activity of the rectus femoris, a surface electrode was attached to the right side of the lower extremity and to increase 10% and 1% depending upon shouting type. The findings were as follows. Shouting affected not only motor efficiency (H-reflex), but also the amplitude of MVIC, with a positive effect on increased muscle strength. Further comprehensive studies are needed to investigate the many variables of increased muscle strength for general purposes, for instance, shouting and breathing, brain waves, and so on.

• Korean Journal of Clinical Pharmacy
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• v.24 no.4
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• pp.231-239
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• 2014

Background and objective: Pravastatin has been shown to have favorable risk-benefit profile when it is administered to hypercholesterolemic subjects to prevent cardiovascular events. However, subjects with impaired OATP1B1 activity may be more susceptible to pravastatin-induced muscle toxicity than subjects with normal OATP1B1 activity. A systematic review was conducted to evaluate the effect of SLCO1B1 genetic polymorphism on pharmacokinetics of pravastatin. Method: Medline$^{(R)}$ and Embase$^{(R)}$ were searched for relevant studies until July 2013. The search terms used were pravastatin AND (SLCO1B1 OR OATP1B1 OR LST1 OR SLC21A6) AND (gene OR $genetic^*$ OR $genomic^*$ OR $pharmacogenet^*$ OR $pharmacogenom^*$ OR $polymorph^*$). Results: A meta-analysis of the area under the concentration-time curve (AUC) of pravastatin in $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ was conducted. Five studies met all the inclusion criteria and methodological requirements. There was no statistically significant difference in the AUC value between $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ (p=0.728). However, $SLCO1B1^*15$ participants exhibited significantly higher AUC values than $SLCO1B1^*1b/^*1b$ carriers (p<0.001). In case of $SLCO1B1^*15^*15$ carriers, they had significantly higher AUC value than $SLCO1B1^*1a/^*1a$ subjects (p=0.002). Lastly, compared with to the subjects of $SLCO1B1^*1a/^*1a$, the carriers of heterozygous $SLCO1B1^*15$ increased the AUC value of pravastatin statistically significantly in Asian population (p=0.014). Conclusion: The present meta-analysis suggests that subjects with $SLCO1B1^*15$ are associated with increased AUC of pravastatin.

• Korean Journal of Veterinary Research
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• v.51 no.4
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• pp.253-257
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• 2011

Amikacin is a semisynthetic derivative of kanamycin and primarily active against aerobic Gram-negative-pathogens with limited activity against Gram-positive bacteria. Meager study was reported on pharmacokinetic data on multi-days administration of amikacin. Hence, pharmacokinetics study was done in five clinically healthy goats (n = 5), after intravenous bolus injection of amikacin sulfate at the dose rate of 10 mg/kg body weight daily for three consecutive days. The amikacin concentrations in plasma and pharmacokinetics-parameters were analyzed by using microbiological assay technique and noncompartmental open-model, respectively. The mean peak plasma concentrations (Mean ${\pm}$ SD) of amikacin at time zero ($Cp^{0}$) was $114.19{\pm}20.78$ and $128.67{\pm}14.37{\mu}g/mL$, on day 1st and 3rd, respectively. The mean elimination half-life ($t_{1/2}ke$) was $1.00{\pm}0.28h$ on day 1st and $1.22{\pm}0.29h$ on day 3rd. Mean of area under concentration-time curve ($AUC_{0{\rightarrow}{\infty}}$) was $158.26{\pm}60.10$ and $159.70{\pm}22.74{\mu}g.h/mL$, on day 1st and 3rd respectively. The total body clearance ($Cl_{B}$) and volume of distribution at steady state (Vdss) on day 1st and 3rd were $Cl_{B}=0.07{\pm}0.02$ and $0.06{\pm}0.01L/h.kg$ and $Vdss=0.10{\pm}0.03$ and $0.11{\pm}0.05L/kg$, respectively. No-significant difference was noted in both drug-plasma concentration and pharmacokinetics-parameters, respectively. Amikacin concentration in plasma was found higher up-to 4 h and 6 h onward on down-ward trends favour to reduce toxicity. Which also support the pharmacokinetic-pharmacodynamic way of dosing of aminoglycosides and hence, amikacin may be administered 10 mg/kg intravenously daily to treat principally Gram-negative pathogens and limitedly Gram-positive-pathogens.

• Journal of the Korean Geographical Society
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• v.39 no.6 s.105
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• pp.922-932
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• 2004

This paper uses the diary entitled Kieo, which was kept by Ryu Hyeong-eop for 38 years, to analyze the active space of small-scale Yangban landlords. Ryu lived during the period spanning from the end of the Taehan Empire through the colonial era. The researcher classified the contents of Kieo into different sections which were divided according to different stages of the writer's life, his objectives, destinations, and periods, and based on the writer's life-cycle, strived to recreate his spatial activities. As a result, researcher was able to ascertain that Ryu's spatial activities gradually increased, and that his active space also continuously expanded. Ryu's active space during his youth was narrow and centered around certain specific places. However, this active space gradually increased as time went by. It was during the middle stages of his life that the volume of his spatial activities was the heaviest. In addition, the objectives of his outings also became more diversified over time. This change was originated in the larger changes in his roles within the family and community, as well as by the changes in the periodic situation. Moreover, the regional sphere of Ryu's outings, including his day and over nights trips, allowed the researcher to form a better understanding of the daily living area of the Yangban.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.418-427
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• 2003

Objects: $^{99m}-lactosylated$ human serum albumin (LSA) is a newly synthesized radiopharmaceutical that binds to asialoglycoprotein receptors, which are specifically presented on the hepatocyte membrane. Hepatic uptake and blood clearance of LSA were evaluated in rat with acute hepatic injury induced by dimethylnitrosamine (DMN) and results were compared with corresponding findings of liver enzyme profile and these of histologic changes. Materials and Methods: DMN (27 mg/kg) was injected intraperitoneally in Sprague-Dawley rat to induce acute hepatic injury. At 3(DMN-3), 8(DMN-8), and 21 (DMN-21) days after injection of DMN, LSA injected intravenously, and dynamic images of the liver and heart were recorded for 30 minutes. Time-activity curves of the heart and liver were generated from regions of interest drawn over liver and heart area. Degree of hepatic uptake and blood clearance of LSA were evaluated with visual interpretation and semiquantitative analysis using parameters (receptor index : LHL3 and index of blood clearance : HH3), analysis of time-activity curve was also performed with curve fitting using Prism program. Results: Visual assessment of LSA images revealed decreased hepatic uptake in DMN treated rat, compared to control group. In semiquantitative analysis, LHL3 was significantly lower in DMN treated rat group than control rat group (DMN-3: 0.842, DMN-8: 0.898, DMN-21: 0.91, Control: 0.96, p<0.05), whereas HH3 was significantly higher than control rat group (DMN-3: 0.731,.DMN-8: 0.654, DMN-21: 0.604, Control: 0.473, p<0.05). AST and ALT were significantly higher in DMN-3 group than those of control group. Centrilobular necrosis and infiltration of inflammatory cells were most prominent in DMN-3 group, and were decreased over time. Conclusion: The degree of hepatic uptake of LSA was inversely correlated with liver transaminase and degree of histologic liver injury in rat with acute hepatic injury.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.4
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• pp.603-607
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• 2003

To investigate the alcohol metabolizing system in liver of rats drunken 10% ethanol with Monascus pigment extract (MPE), Sprague-Dawley male rats weighing about 250 g have been drunken 10% ethanol containing 1, 2.5 and 5% Monascus pigment extract for a month. Three groups of rats drunken 10% ethanol with MPE gained somewhat less body weight than normal group, but the changes of body weight was not significantly different among the former groups. All groups drunken MPE supplemented alcohol had no remarkable changes in liver function on the basis of liver weight/body weight, the serum levels of alanine aminotransferase and xanthine oxidase activity. 10% alcohol drunken animals (control group) showed significantly increased activity of hepatic alcohol dehydrogenase (ADH) by 87% compared with normal group and the animals drunken 1%, 2.5% and 5% MPE showed respectively 34%, 29% and 21% increased activity of hepatic ADH, whileas Km value of ADH in 1, 2.5 and 5% MPE group decreased by 40%, 30% and 19% respectively compared with the control, but Vmax showed no significant changes among MPE groups. In case of aldehyde dehydrogenase (ALDH), 1% MPE group showed significantly increased activity by 32% and 2.5% or 5% MPE group showed increasing tendency compared with control, and Km value in three experimental groups declined by 27% and no particular changes were found among those. Furthermore, Vmax value in 1, 2.5 and 5% MEP group increased by 88,56 and 22% respectively with the control. In the aspect of the area under the curve of a ethanol concentration versus time (AUC) profile obtained after administration of 10% alcohol with 1 or 5% MPE, the decreasing rate of AUC to the control was 18% in 1% MPE treated rats whereas 10% in 5% MPE group.

• Journal of Intelligence and Information Systems
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• v.21 no.4
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• pp.17-35
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• 2015

Demand forecasting is the activity of estimating the quantity of a product or service that consumers will purchase for a certain period of time. Developing precise forecasting models are considered important since corporates can make strategic decisions on new markets based on future demand estimated by the models. Many studies have developed market growth curve models, such as Bass, Logistic, Gompertz models, which estimate future demand when a market is in its early stage. Among the models, Bass model, which explains the demand from two types of adopters, innovators and imitators, has been widely used in forecasting. Such models require sufficient demand observations to ensure qualified results. In the beginning of a new market, however, observations are not sufficient for the models to precisely estimate the market's future demand. For this reason, as an alternative, demands guessed from those of most adjacent markets are often used as references in such cases. Reference markets can be those whose products are developed with the same categorical technologies. A market's demand may be expected to have the similar pattern with that of a reference market in case the adoption pattern of a product in the market is determined mainly by the technology related to the product. However, such processes may not always ensure pleasing results because the similarity between markets depends on intuition and/or experience. There are two major drawbacks that human experts cannot effectively handle in this approach. One is the abundance of candidate reference markets to consider, and the other is the difficulty in calculating the similarity between markets. First, there can be too many markets to consider in selecting reference markets. Mostly, markets in the same category in an industrial hierarchy can be reference markets because they are usually based on the similar technologies. However, markets can be classified into different categories even if they are based on the same generic technologies. Therefore, markets in other categories also need to be considered as potential candidates. Next, even domain experts cannot consistently calculate the similarity between markets with their own qualitative standards. The inconsistency implies missing adjacent reference markets, which may lead to the imprecise estimation of future demand. Even though there are no missing reference markets, the new market's parameters can be hardly estimated from the reference markets without quantitative standards. For this reason, this study proposes a case-based expert system that helps experts overcome the drawbacks in discovering referential markets. First, this study proposes the use of Euclidean distance measure to calculate the similarity between markets. Based on their similarities, markets are grouped into clusters. Then, missing markets with the characteristics of the cluster are searched for. Potential candidate reference markets are extracted and recommended to users. After the iteration of these steps, definite reference markets are determined according to the user's selection among those candidates. Then, finally, the new market's parameters are estimated from the reference markets. For this procedure, two techniques are used in the model. One is clustering data mining technique, and the other content-based filtering of recommender systems. The proposed system implemented with those techniques can determine the most adjacent markets based on whether a user accepts candidate markets. Experiments were conducted to validate the usefulness of the system with five ICT experts involved. In the experiments, the experts were given the list of 16 ICT markets whose parameters to be estimated. For each of the markets, the experts estimated its parameters of growth curve models with intuition at first, and then with the system. The comparison of the experiments results show that the estimated parameters are closer when they use the system in comparison with the results when they guessed them without the system.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.12
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• pp.1903-1907
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• 2010

Drying curves for raw Alaska pollack seemed to follow typical food dehydration process with a very short initial settling down period. It was evident that there are some differences in drying rates between each part of fish body showing the highest drying rate for fish head followed by that for fish skin and that for flesh, presumably because of differences in water holding capacity of the components of each part. Specifically, the drying curve of fish flesh revealed that a boundary layer, thereby, a time period, existed which showed a big difference in moisture content and/or water activity as drying proceeds. The boundary layer in fish flesh with high moisture content between the layer contributes to reduce drying rate mainly as a consequence of protein aggregation resulting in hardening of fish flesh. The first boundary layer in this work appeared to show within several hours after initiation of drying. For Hwangtae, a naturally cyclic freeze-thaw dried and aged Alaska pollack which was popular in Korea, manufacturing process, it is clear that periodic moistening of boundary layer in fish flesh prohibits hardening fish flesh in boundary layer and enables steady moisture diffusion from inside of the fish flesh to surface of the fish body.