• Communications for Statistical Applications and Methods
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• v.27 no.6
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• pp.701-714
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• 2020

Quantitative high throughput screening (qHTS) assays are used to assess toxicity for many chemicals in a short period by collectively analyzing them at several concentrations. Data are routinely analyzed using nonlinear regression models; however, we propose a new method to analyze qHTS data using a nonlinear mixed effects model. qHTS data are generated by repeating the same experiment several times for each chemical; therefor, they can be viewed as if they are repeated measures data and hence analyzed using a nonlinear mixed effects model which accounts for both intra- and inter-individual variabilities. Furthermore, we apply a one-step approach incorporating robust estimation methods to estimate fixed effect parameters and the variance-covariance structure since outliers or influential observations are not uncommon in qHTS data. The toxicity of chemicals from a qHTS assay is classified based on the significance of a parameter related to the efficacy of the chemicals using the proposed method. We evaluate the performance of the proposed method in terms of power and false discovery rate using simulation studies comparing with one existing method. The proposed method is illustrated using a dataset obtained from the National Toxicology Program.

• Proceedings of the Materials Research Society of Korea Conference
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• 2008.05a
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• pp.6-6
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• 2008

• 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.

• KSBB Journal
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• v.22 no.6
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• pp.393-400
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• 2007

Analysis of protein interactions/functions in a microarray format has been of great potential in drug discovery, diagnostics, and cell biology, because it is amenable to large-scale and high-throughput biological assays in a rapid and economical way. In recent years, the protein microarray have broaden their utility towards the global analysis of protein interactions on a proteome scale, the functional activity analysis based on protein interactions and post-translational modifications (PTMs), and the discovery of biomarkers through profiling of protein expression between sample and reference pool. As a promising tool for proteomics, the protein microarray technology has advanced outstandingly over the past decade in terms of surface chemistry, acquisition of relevant proteins on a proteomic level, and detection methods. In this article, we briefly describe various techniques for development of protein microarray, and introduce developmental state of protein microarray and its applications.

• Molecules and Cells
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• v.23 no.3
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• pp.357-362
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• 2007

There is an increasing demand for high throughput (HTP) methods for gene analysis on a genome-wide scale. However, the current repertoire of HTP detection methodologies allows only a limited range of cellular phenotypes to be studied. We have constructed two HTP-optimized expression vectors generated from the red fluorescent reporter protein (RFP) gene. These vectors produce RFP-tagged target proteins in a multiple expression system using gateway cloning technology (GCT). The RFP tag was fused with the cloned genes, thereby allowing us localize the expressed proteins in mammalian cells. The effectiveness of the vectors was evaluated using an HTP-screening system. Sixty representative human C2 domains were tagged with RFP and overexpressed in HiB5 neuronal progenitor cells, and we studied in detail two C2 domains that promoted the neuronal differentiation of HiB5 cells. Our results show that the two vectors developed in this study are useful for functional gene analysis using an HTP-screening system on a genome-wide scale.

• Proceedings of the Korean Society for Technology of Plasticity Conference
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• 2004.05a
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• pp.259-264
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• 2004

The hot embossing process as a method for the fabrication of polymer is becoming increasingly important because of its simple process, low cost, high replication fidelity and relatively high throughput. In this paper, we carried out experimental studies and numerical simulations in order to understand the viscous flow of polymer film during hot embossing process. As the initial step of quantitating the hot embossing process, simple parametric studies for the embossing conditions have been carried out using high resolution masters which patterned by DRIE process. Under different embossing times and pressures, the viscous flow of PMMA films into micro/nano cavities has been investigated. Also, the viscous flow during the hot embossing process has been simulated by the continuum based FDM analysis considering micro/nano effect, such as surface tension and contact angle.

• The KIPS Transactions:PartC
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• v.13C no.2 s.105
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• pp.235-240
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• 2006

Stream Control Transmission Protocol (SCTP) provides the multi-homing feature, which allows each SCTP endpoint to use two or more IP addresses for data transmission. In this paper, the SCTP multi-homing feature is experimented and analyzed in terms of throughput over Linux platforms based on the NISTNET network emulator. We perform the experimental analysis of SCTP throughputs by SCTP multi-homing for the various network conditions: different packet loss rates, network bandwidths, and transmission delays. From the experimental results, it is shown that the SCTP multi-homing gives much better throughout gun over the SCTP single-homing case in the networks with a high packet loss rate. In the meantime, the other factors including network bandwidth and transmission delay do not seem to give a significant impact on the performance of the SCTP multi-homing.

• The Journal of the Korea Contents Association
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• v.9 no.7
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• pp.67-75
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• 2009

IEEE 802.11 WLAN(Wireless Local Area Network) standard is currently developing with increased wireless internet demand. Study trends of IEEE 802.11n for high throughput show two aspects, enhanced system throughput using aggregation among packets in MAC(Medium Access Control) layer, and better data rates adapting MIMO(Multiple-Input Multiple-Output) in PRY(Physical) layer. But, no one demonstrates IEEE 802.11n system performance results considering MAC and PRY connection. This paper adapts A-MPDU(Aggregation-MAC Protocol Data Unit) method in MAC layer and MIMO in PRY layer for IEEE 802.11n system. Consequently, Simulation results show enhanced throughput and data rates compared to existing system. Also, We use NS-2(Network Simulator-2) considering MAC and PRY connection for reality.

• Journal of Internet Computing and Services
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• v.8 no.1
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• pp.15-23
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• 2007

Wireless LAN (IEEE 802.11) uses traditional TCP for reliable data transmission, But it brings the unintentional packet loss which is not congestion loss caused by handoff, interference, and fading in wireless LAN. In wireless LAN, TCP experiences performance degradation because it consumes that the cause of packet loss is congestion, and it decrease the sending rate by activating congestion control algorithm. This paper analyzes that correlation of throughput and buffer size for wireless buffer tuning. We find MBT (Maximum Buffer Threshold) which does not increase the throughput through the analysis, For calculation of MBT, we experiment the throughput by using high volume music data which is creased by real-time performance of piano. The experiment results is shown that buffer tuing based on MBT shows 20.3%, 21.4%, and 45.4% throughput improvement under 5ms RTT, 10ms RTT, and 20ms RTT, respectively, comparing with the throughput of operation system default buffer size, In addition, we describe that The setting of TCP buffer size by exceeding MBT does not have an effect on the performance of TCP.

• Journal of the Institute of Electronics Engineers of Korea TC
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• v.46 no.5
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• pp.78-87
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• 2009

In the IEEE 802.16 Wireless MAN standard, the best effort service class is ranked on the lowest position in priority and is assisted by a MAC scheme based on reservation ALOHA. In such a MAC scheme, a collision among the requests is unavoidable so that the standard adopted a binary exponential back-off rule to arbitrate a collision. Aiming at improving throughput performance, we present two generic collision arbitration rules based on p-persistence rule, (identified as pristine and metamorphosed rules), as alternatives in a wireless MAN. For each of these rules, we then develop an analytical method to calculate an approximate value of saturated throughput. In comparison with simulation results, we confirm the high accuracy of the analytical method. Also, the pristine and metamorphosed rules are observed to exhibit higher saturated throughput compared with the binary exponential back-off rule.