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.
Magazine of the Korean Society of Agricultural Engineers
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v.22
no.4
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pp.108-114
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1980
A deterministic conceptual erosion model which simulates detachment, entrainment, transport and deposition of eroded soil particles by rainfall impact and flowing water is presented. Both upland and channel phases of sediment yield are incorporated into the erosion model. The algorithms for the soil erosion and sedimentation processes including land and crop management effects are taken from the literature and then solved using a digital computer. The erosion model is used in conjunction with the modified Kentucky Watershed Model which simulates the hydrologic characteristics from watershed data. The two models are linked together by using the appropriate computer code. Calibrations for both the watershed and erosion model parameters are made by comparing the simulated results with actual field measurements in the Four Mile Creek watershed near Traer, Iowa using 1976 and 1977 water year data. Two water years, 1970 and 1978 are used as test years for model verification. There is good agreement between the mean daily simulated and recorded streamflow and between the simulated and recorded suspended sediment load except few partial differences. The following conclusions were drawn from the results after testing the watershed and erosion model. 1. The watershed and erosion model is a deterministic lumped parameter model, and is capable of simulating the daily mean streamflow and suspended sediment load within a 20 percent error, when the correct watershed and erosion parameters are supplied. 2. It is found that soil erosion is sensitive to errors in simulation of occurrence and intensity of precipitation and of overland flow. Therefore, representative precipitation data and a watershed model which provides an accurate simulation of soil moisture and resulting overland flow are essential for the accurate simulation of soil erosion and subsequent sediment transport prediction. 3. Erroneous prediction of snowmelt in terms of time and magnitute in conjunction with The frozen ground could be the reason for the poor simulation of streamflow as well as sediment yield in the snowmelt period. More elaborate and accurate snowmelt submodels will greatly improve accuracy. 4. Poor simulation results can be attributed to deficiencies in erosion model and to errors in the observed data such as the recorded daily streamflow and the sediment concentration. 5. Crop management and tillage operations are two major factors that have a great effect on soil erosion simulation. The erosion model attempts to evaluate the impact of crop management and tillage effects on sediment production. These effects on sediment yield appear to be somewhat equivalent to the effect of overland flow. 6. Application and testing of the watershed and erosion model on watersheds in a variety of regions with different soils and meteorological characteristics may be recommended to verify its general applicability and to detact the deficiencies of the model. Futhermore, by further modification and expansion with additional data, the watershed and erosion model developed through this study can be used as a planning tool for watershed management and for solving agricultural non-point pollution problems.
Objective: The present study aims to evaluate the visual reactions of users when they are playing games of different flow levels, and to explore the visual variables that can sensitively reflect the different flow levels. Background: The flow is defined as a psychological state where interface users feel their actions in a virtual setting identical to those in real environment. To measure the flow states of users, the questionnaire-based FSS(Flow State Scale) has mostly been used. However, this method is a qualitative test that has limits in terms of the accuracy of users' flow experiences. Therefore, more accurate methods to measure users' flow experiences are required. Method: Ten subjects participated in the experiment, where the independent variables were three games with different flow levels(puzzle games, dot drawing and coloring) and the time frame(the first and last 10 seconds in game playing), whereas the dependent variables included the pupil size and the frequency and duration of eye blinking. This study was a within-subject design. Each participant performed three types of games with different flow levels 3 times for each for 10 minutes, and their visual reactions to each game were measured. Results: The higher the flow cause the bigger pupil size(p<0.01) and the lower eye blinking frequency(p<0.1), indicating that different types of games lead to different flow levels. The pupil size during the last 10 seconds when the flow level was higher was bigger by 2.1% compared with that during the first 10 seconds in game playing(p<0.1), and the eye blinking frequency decreased by 12%(p<0.01). Conclusion: It was found out that the pupil size and the frequency and duration of eye blinking were psychophysiological indices for evaluating users' flow experiences, which could quantify the flow states users go through. The psychophysiological variables capable of measuring diverse aspects of the flow need diversifying to be applicable to precise measurement of the flow. Application: These studies are warranted for both quantitative analysis of flow levels and qualitative improvement of cyber leisure in line with development of healthy games.
Journal of the Institute of Electronics and Information Engineers
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v.52
no.6
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pp.126-134
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2015
A sleep disorder is being recognized as one of the major health issues related to high levels of stress. At the same time, interests about quality of sleep are rapidly increasing. However, diagnosing sleep disorder is not a simple task because patients should undergo polysomnography test, which requires a long time and high cost. To solve this problem, an accelerometer embedded wrist-worn device is being considered as a simple and low cost solution. However, conventional methods determine a state of user to "sleep" or "wake" according to whether values of individual section's accelerometer data exceed a certain threshold or not. As a result, a high miss-classification rate is observed due to user's intermittent movements while sleeping and tiny movements while awake. In this paper, we propose a novel method that resolves the above problems by employing a dynamic classifier which evaluates a similarity between the neighboring data scores obtained from SVM classifier. A performance of the proposed method is evaluated using 50 data sets and its superiority is verified by achieving 88.9% accuracy, 88.9% sensitivity, and 88.5% specificity.
Crack widths play an important role in the serviceability limit state. When crack widths are controlled sufficiently, the reinforcement corrosion can be reduced using only existing concrete cover thickness due to low permeability in the region of finely distributed hair-cracks. Thus, the knowledge about the tensile crack opening is essential in designing more durable concrete structures. Therefore, numerous researches related to the topic have been performed. Nevertheless accurate measurement of a crack width is not a simple task due to several reasons such as unknown potential crack formation location and crack opening damaging strain gages. In order to overcome these difficulties and measure precise crack widths, a displacement measurement system was developed using digital image correlation. Accuracy calibration tests gave an average measurement error of 0.069 pixels and a standard deviation of 0.050 pixels. Direct tensile test was performed using ultra high performance concrete specimens. Crack widths at both notched and unnotched locations were measured and compared with clip-in gages at various loading steps to obtain crack opening profile. Tensile deformation characteristics of concrete were well visualized using displacement vectors and full-field displacement contour maps. The proposed technique made it possible to measure crack widths at arbitrary locations, which is difficult with conventional gages such as clip-in gages or displacement transducers.
This paper introduces the modified VaR which takes into account the asymmetry and fat-tails of financial asset distribution, and then compares its out-of-sample forecast performance with traditional VaR model such as historical simulation model and Riskmetrics. The empirical tests using stock indices of 6 countries showed that the modified VaR has the best forecast accuracy. At the test of independence, Riskmetrics and GARCH model showed best performances, but the independence was not rejected for the modified VaR. The Monte Carlo simulation using skew t distribution again proved the best forecast performance of the modified VaR. One of many advantages of the modified VaR is that it is appropriate for measuring VaR of the portfolio, because it can reflect not only the linear relationship but also the nonlinear relationship between individual assets of the portfolio through coskewness and cokurtosis. The empirical analysis about decomposing VaR of the portfolio of 6 stock indices confirmed that the component VaR is very useful for the re-allocation of component assets to achieve higher Sharpe ratio and the active risk management.
Journal of the Korean Data and Information Science Society
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v.26
no.6
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pp.1397-1407
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2015
Individual phenotype is mostly influenced by genetic factors as well as the effects of environmental factors. Therefore, adjustment of environmental factors are needed in order to see more clearly the effects of genetic factors that we are interested in gene screening study related to Hanwoo's economic trait. The purpose of this study is to propose new statistical model that was adjusted environmental factor and identify adjustment effect in a superior gene marker screening study for producing high quality Hanwoo. First, statistical model including both genetic factor and environmental factor establishes and adjusted value of economic trait find by removing effect of environmental factor such as age, breeding farm. Finally, we identify superior gene marker combination and compare accuracy by applying MDR to data of before and after adjustment. Economic trait is used C18:1, SFA, MUFA, MS, CWT, BFT and SNP marker is used 6 markers of LPL that were identified as more excellent SNP marker than the others among 49 markers through fatty acid composition and economic trait performance test.
Journal of The Korean Association For Science Education
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v.31
no.6
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pp.887-900
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2011
Teachers use explanations to communicate important scientific ideas to students. Consequently, all biology teachers should be evaluated to determine how effective they are at constructing and communicating biological explanations. Open response questions are required to detect pre-service biology teachers' abilities to communicate robust and accurate scientific explanations. Nevertheless, multiple-choice questions are typically preferred by educators because of the common drawbacks of using open-response instruments, such as scoring time, inter-rater scoring disagreements, and delayed feedback to test takers. This study aims to measure pre-service biology teachers' competence in building scientific explanations and to investigate how accurately multiple-choice questions predict the results of open-response questions. One hundred twenty four pre-service biology teachers participated in the study and were administered 20 multiple-choice items and three open-response items designed to measure the accuracy and quality of their explanations of evolutionary change. The results demonstrated that pre-service teachers displayed higher competence when tested with multiple choice items than when tested with open response items. Moreover, scores derived from multiple-choice items poorly predicted the scores derived from open-response items. Multiple-choice items were also found to be poor measures of the consistency, purity and abundance of conceptual elements in teachers' evolutionary explanations. Additionally, many teachers held mixed-models composed of both scientific and naive ideas, which were difficult to detect using multiple-choice formats. Overall, the study indicates that multiple-choice formats are poorly suited to measuring several aspects of biology teachers' knowledge of evolution, including their ability to generate scientific explanations. This study suggests that open-response items should be used in teacher education programs to assess pre-service teachers' explanatory competency prior to being permitted to teach science to children.
The beam size and the antenna efficiency of TRAO 14m radio telescope were measured at 86.2, 98.0 and 115.2 GHz. The beam size was determined by deconvolving the azimuthal scanning data of the Venus. To test the accuracy of our deconvolution method, the beam size at 86.2 GHz was compared with that determined from the mapping data of SiO maser line and we found no difference between them. With above beam sizes, antenna efficiencies were calculated from the continuum measurements of Venus, Jupiter and Moon. The beam efficiencies at these frequencies are appeared to be 0.49, 0.45 and 0.41, respectively. On the other hand, we also suggest that an automatic focus setting can be adopted for TRAO radio telescope based on the gradual change of best focus with elevation.
This study was conducted to develop an on-line monitoring system for a forest hydrological environment and its meteorological condition, such as temperature, wind direction and speed, rainfall and water level on V-notch, electrical conductivity(EC), potential of hydrogen(PH) by the motor drive sensor unit and measurement with a single-chip microprocessor as controller. These results are summarized as follows ; 1. The monitoring system consists of a signal process unit, motor drive sensor unit, radio modem unit and power supply. 2. The motor drive sensor unit protects the sensor from swift current or freezing and can constantly maintain fixed water level during measurements. 3. This monitoring system can transfer the data by radio modem. Additionally, this system can monitor hydrological conditions in real time. 4. The hardware was made of several modules with an independent CPU. They can be mounted, removed, repaired and added to. Their function can be changed and expanded. 5. These are the result of an accuracy test, the values of temperature, EC and pH measured within an error range of ${\pm}0.2^{\circ}C$, ${\pm}1{\mu}S$ and ${\pm}0.1pH$ respectively. 6. This monitoring system proved to be able to measure various factors for a forest hydrological environment in various experimental stations.
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