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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제29권4호
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pp.59-72
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1987
Although long-term runoff analysis is important as much as flood analysis in the design of water works, the technological level of the former is relatively lower than that of the latter. In this respect, the precise estimation model for the volume of successive runoff should he developed as soon as possible. Up to now, in Korea, Gajiyama's formula has been widely used in long-term runoff analysis, which has many problems in applying in real situation. On the other hand, in flood analysis, unit hydrograph method has been exclusively used. Therefore, this study aims at trying to apply unit hydrograph method in long-term runoff analysis for the betterment of its estimation. Four test catchment areas were selected ; Maesan area in Namlum river as a representative area of Han river system, Cheongju area in Musim river as one of Geum river system, Hwasun area in Hwasun river as one of Yongsan river system, and Supyung area in Geum river as one of Nakdong river system. In the analysis of unit hydrograph, seperation of effective rainfall was carried out firstly. Considering that effective rainfall and moisture condition of catchrnent area are inside and outside of a phenomenon respectively and the latter is not considered in the analysis, Initial base flow(qb)was selected as an index of moisture condition. At the same time, basic equation(Eq.7) was established, in which qb can take a role as a parameter in relating between cumulative rainfall(P) and cumulative loss of rainfall(Ld). Based on the above equation, computer program for estimation model of qbwas seperately developed according to the range of qb, Developed model was applied to measured hydrographs and hyetographs for total 10 years in 4 test areas and effective rainfall was estimated. Estimation precision of model was checked as shown in Tab- 6 and Fig.8. In the next stage, based on the estimated effective rainfall(R) and runoff(Qd), a runoff distribution ratio was calculated for each teat area using by computerised least square method and used in making unit hydrographs in each test area. Significance of induced hydrographs was tested by checking the relative errors between estimated and measured runoff volume(Tab-9, 10). According to the results, runoff estimation error by unit hydrograph itself was merely 2 or 3 %, but other 2 or 3 % of error proved to be transferred error in the seperation of effective rainfall. In this study, special attentioning point is that, in spite of different river systems and forest conditions of test areas, standardized unit hydrographs for them have very similar curve shape, which can be explained by having similar catchinent characteristics such as stream length, catchinent area, slope, and vegetation intensity. That fact should be treated as important factor ingeneralization of unit hydrograph method.
We have examined the applicability of f-k analysis to the GPR direct wave measurement for water content to characterize vadose zone condition. When the vadose zone consists of a dry surface layer over wet substratum, we obtained f-k spectra where most of the energy is bounded by the air and dry soil velocities. In this case, dry soil velocity was successfully estimated by using high frequency data. On the other hands, when wet soil overlies dry substratum, the f-k spectra show a contrasting response where most of the energy travels with the velocity bounded by dry and wet soil velocities. In this case, the radar waves are trapped and guided within wet soil layer, exhibiting velocity dispersion. By adopting modal propagation theory, we could formulae a simple inversion code to find two layer's dielectric constants as well as layer thickness. By inverting the velocity dispersion curve obtained from f-k spectra of synthetic modeling data, we could obtain good estimates of dielectric constants of each layer as well as first layer thickness. Moreover, we could obtain more accurate results by including the higher mode data. We expect this method will be useful to get the quantitative property of real subsurface when the field condition is similar.
Background: MicroRNAs (miRNAs) have demonstrated their potential as biomarkers for lung cancer diagnosis. In recent years, miRNAs have been found in body fluids such as serum, plasma, urine and saliva. Circulating miRNAs are highly stable and resistant to RNase activity along with, extreme pH and temperatures in serum and plasma. In this study, we investigated serum miRNA profiles that can be used as a diagnostic biomarker of non-small cell lung cancer (NSCLC). Methods: We compared the expression profile of miRNAs in the plasma of patients diagnosed with lung cancer using an miRNA microarray. The data from this assay were validated by quantitative real-time PCR (qRT-PCR). Results: Six miRNAs were overexpressed and three miRNAs were underexpressed in both tissue and serum from squamous cell carcinoma (SCC) patients. Sixteen miRNAs were overexpressed and twenty two miRNAs were underexpressed in both tissue and serum from adenocarcinoma (AC) patients. Of the four miRNAs chosen for qRT-PCR analysis, the expression of miR-23a was consistent with microarray results from AC patients. Receiver operating characteristic (ROC) curve analyses were done and revealed that the level of serum miR-23a was a potential marker for discriminating AC patients from chronic obstructive pulmonary disease (COPD) patients. Conclusion: Although a small number of patients were examined, the results from our study suggest that serum miR-23a can be used in the diagnosis of AC.
Journal of the Korean Institute of Intelligent Systems
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제20권5호
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pp.722-727
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2010
This paper is presented to study simplification of face image using cubic spline interpolation for a business card with 2D barcode. People often forget business card's owner because business cards don't be included a face picture generally. To solve such problem, many applications have be developed through mobile devices, Internet and so on. But they couldn't caught up with value of existing business card mad by paper. Hence, some methods which can put information on business card using 1D or 2D barcode had suggested. but they couldn't include information like face image or company logo image which have too much data. Therefore, we study the simplification method of face image to encode from a face image to 2D barcode. The simplification method using spline curves defined by feature points which we dotted on face, ears, hair, eyebrows, nose, lips, neck, etc.. on a face area. for experiment, we see real face image and simplified face image made by proposed method after we automatically extract face watch through camera. In experimental results, data of simplified face image was reduced as small as it can be expressed by 2D barcode, and confirmed that it can effectively express features.
Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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한국해양정보통신학회 2006년도 춘계종합학술대회
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pp.957-960
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2006
In this paper, we studied the location estimation algorithm of a spatial 3 dimension which extend the location estimation algorithm of a plane 2 dimension in 2.45GHz band RTLS(Real time location system). We used TDOA scheme which need not a time of transmission information of the tag and estimated 3 dimension coordinates. Also, estimated intersection of hyperbolic curve to X, Y coordinate of the tag at 2D coordinates searching area, $300m\times300m$ and LOS propagation environments. And, we estimated Z coordinate ultimately using X, Y coordinate. The location estimation algorithm of a spatial 3 dimension satisfies the RTLS specification requirement, 3m radius accuracy. From the result, we confirm that the location of tag which similar to actual coordinate in the case to an ideal received offset. However, we verified that the location of tag which escapes from a radius 3m within error range when received offset increased. Therefore, as the future work we are consider enhanced location accuracy of a spatial 3 dimension in RTLS system which using the decrease scheme of reader offset or the discriminate scheme of the estimation location.
Jo, Won-Beom;Kim, Yong-Seok;Choe, Jae-Seong;Kim, Sang-Yeop;Kim, Jin-Guk
Journal of Korean Society of Transportation
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제28권5호
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pp.141-153
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2010
The study is about the development of operating speed prediction models aimed for an evaluation of design consistency of four lane rural roads. The main differences of this study relative to previous research are the method of data collection and classification of road alignments. The previous studies collected speed data at several points in the horizontal curve and approaching tangent. This method of collection is based on the assumption that acceleration and deceleration only occurs at horizontal tangents and the speed is kept constant at horizontal curves. However, this assumption leads to an unreliable speed estimation, so drivers' behavior is not well represented. Contrary to the previous approach, speed data were collected with one and data analysis using a speed profile is made for data selection before building final models. A total of six speed prediction models were made according to the combination of horizontal and vertical alignments. The study predicts that the speed data analysis and selection for model building employed in this study can improve the prediction accuracy of models and be useful to analyze drivers' speed behavior in a more detailed way. Furthermore, it is expected that the operating speed prediction models can help complement the current design-speed-based guidelines, so more benefits to drivers as real road users, rather than engineers or decision makers, can be achieved.
Contact area and pressure are important factors which directly influence a life of knee implants. Since implant's mechanical functions should be experimentally evaluated for clinical use, many studies using a knee simulator and a pressure sensor system have been conducted. However it has not been reported that the contact pressure's distribution of a knee implant motion was estimated in real-time during a gate cycle. Therefore. the objective of this study was to analyze the contact pressure distribution for the motion of a joint using the knee simulator and I-scan sensor system. For this purpose, we developed a force-controlled dynamic knee simulator to evaluate the mechanical performance of artificial knee joint. This simulator includes a function of a soft tissue and has a 4-degree-of-freedom to represent an axial compressive load and a flexion angle. As axial compressive force and a flexion angle of the femoral component can be controlled by PC program. The pressure is also measured from I-scan system and simulator to visualize the pressure distribution on the joint contact surfaces under loading condition during walking cycle. The compressive loading curve was the major cause for the contact pressure distribution and its center move in a cycle as to a flexion angie. In conclusion, this system can be used to evaluate to the geometric interaction of femoral and tibial design due to a measured mechanical function such as a contact pressure, contact area and a motion of a loading center.
Journal of the Korea institute for structural maintenance and inspection
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제10권3호
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pp.165-175
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2006
To analyze the deformation and failure of slopes, generally, two types of model, Polynomial model and Growth model, are applied. These two models are focused on the behavior of the slope by time. Therefore, this research is more focused on predicting of slope failure than analyzing the slope behavior by time. Generally, Growth model is used to analyze the soil slope, to the contrary, Polynomial model is used for rock slope. However, 3-degree polynomial($y=ax^3+bx^2+cx+d$) is suggested to combine two models in this research. The main trait of this model is having an asymptote. The fields to adopt this model are Gosujae Danyang(soil slope) and Youngduk slope(rock slope), which are the cut-slope near national road. Data from Gosujae are shown the failure traits of soil slope, to the contrary, those of Youngduk slope are shown the traits of rock slope. From the real-time monitoring data of the slope, 3-degree polynomial is proved as excellent system to analyze the failure and behavior of slope. In case of Polynomial model, even if the order of polynomials is increased, the $R^2$ value and shape of the curve-fitted graph is almost the same.
Purpose: Breast cancer is the most commonly occurring cancer among women worldwide, and therefore, improved approaches for its early detection are urgently needed. As microRNAs (miRNAs) are increasingly recognized as critical regulators in tumorigenesis and possess excellent stability in plasma, this study focused on using miRNAs to develop a method for identifying noninvasive biomarkers. Methods: To discover critical candidates, differential expression analysis was performed on tissue-originated miRNA profiles of 409 early breast cancer patients and 87 healthy controls from The Cancer Genome Atlas database. We selected candidates from the differentially expressed miRNAs and then evaluated every possible molecular signature formed by the candidates. The best signature was validated in independent serum samples from 113 early breast cancer patients and 47 healthy controls using reverse transcription quantitative real-time polymerase chain reaction. Results: The miRNA candidates in our method were revealed to be associated with breast cancer according to previous studies and showed potential as useful biomarkers. When validated in independent serum samples, the area under curve of the final miRNA signature (miR-21-3p, miR-21-5p, and miR-99a-5p) was 0.895. Diagnostic sensitivity and specificity were 97.9% and 73.5%, respectively. Conclusion: The present study established a novel and effective method to identify biomarkers for early breast cancer. And the method, is also suitable for other cancer types. Furthermore, a combination of three miRNAs was identified as a prospective biomarker for breast cancer early detection.
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