• Title/Summary/Keyword: Screening Technique

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Evaluation of a Sample-Pooling Technique in Estimating Bioavailability of a Compound for High-Throughput Lead Optimazation (혈장 시료 풀링을 통한 신약 후보물질의 흡수율 고효율 검색기법의 평가)

  • Yi, In-Kyong;Kuh, Hyo-Jeong;Chung, Suk-Jae;Lee, Min-Haw;Shim, Chang-Koo
    • 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.

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High Throughput Screening for Searching a New Inhibitors of Acetolactate Synthase (Acetolactate synthase에 대한 고효율 활성 측정방법 및 신규 저해제 탐색)

  • Park, S.H.;Lee, K.H.;Choi, J.S.;Pyon, J.Y.;Cho, K.Y.;Hwang, I.T.
    • The Korean Journal of Pesticide Science
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    • v.5 no.3
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    • pp.41-46
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    • 2001
  • This study was conducted to develop a high throughput system for screening acetolactate synthase(ALS) inhibitors, and to detect basic mother molecules for developing new novel herbicide candidates. The high throughput screening (HTS) method using 96-well plate and microplate reader was developed. This method is 8 times more effective than basic technique in one cycle per person. Futhermore, considering for less than 1/10 volume of materials required for ALS test and enzyme kinetics with 16 times faster speed compared to those of former procedure, this HTS method has more than 100 times higher efficacy than basic system in a consecutive procedure. We discovered 11 new ALS inhibitors such as 2-oxoglutaric acid, aminooxyacetic acid, azelaic acid, citric acid, cyanuric fluoride, itaconic acid, malonic acid, niclosamide, oxalic acid, glyoxylic acid, and suramin from 107 commercial plant-specific inhibitors using this technique. We hope these results might be useful to discover lead compounds for developing new novel herbicide candidate.

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Benefits of Cervical Cancer Screening by Liquid-Based Cytology as Part of Routine Antenatal Assessment

  • Parkpinyo, Nichamon;Inthasorn, Perapong;Laiwejpithaya, Somsak;Punnarat, Tippawan
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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    • pp.4457-4461
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    • 2016
  • Purpose: To determine the prevalence of abnormal cervical cytology, as diagnosed using a liquid-based cytology technique, in pregnant women attending the Antenatal Care (ANC) clinic at Siriraj Hospital. Materials and Methods: This cross-sectional study included 655 first-visit pregnant women who attended ANC clinic at Siriraj Hospital during June to November 2015 study period. After receiving routine antenatal care, cervical cytology screening was performed with the Siriraj liquid-based cytology technique. All specimens were reviewed by a certified cytopathologist using Bethesda System 2001 criteria. Patients with abnormal PAP results characterized as epithelial cell abnormalities were referred to a gynecologic oncologist for further management according to ASCCP Guidelines 2012. Results: Mean age of participants was $28.9{\pm}6.2$ years. Prevalence of abnormal cervical cytology was 3.4% (95% CI: 2.0-4.7). Among this group, there were ASC-US, ASC-H, LSIL, HSIL for 12(1.8%), 2(0.3%), 7(1.1%) and 1(0.2%), respectively. In 633 specimens of the normal group, infection was identified in 158 specimens (24.1%) which were caused by Candida spp. and Trichomonas vaginalis. Regarding patient perception about the importance of cervical cancer screening, although most women perceived screening to be important, 54% of participants had never been screened for cervical cancer. Rate of loss to follow-up in the postpartum period was as high as 41.8%. Conclusions: Prevalence of abnormal cervical cytology in pregnant women attending the ANC clinic at Siriraj Hospital was 3.4%. Inclusion of cervical cancer screening as part of antenatal assessment can help to identify precancerous lesions or cervical cancers in patients who might otherwise not be screened, thereby facilitating early treatment and improved patient outcomes.

Development of Korean Intensive Care Delirium Screening Tool (KICDST) (중환자 섬망 선별도구 개발)

  • Nam, Ae-Ri-Na;Park, Jee-Won
    • Journal of Korean Academy of Nursing
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    • v.46 no.1
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    • pp.149-158
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    • 2016
  • Purpose: This study was done to develop of the Korean intensive care delirium screening tool (KICDST). Methods: The KICDST was developed in 5 steps: Configuration of conceptual frame, development of preliminary tool, pilot study, reliability and validity test, development of final KICDST. Reliability tests were done using degree of agreement between evaluators and internal consistency. For validity tests, CVI (Content Validity Index), ROC (Receiver Operating Characteristics) analysis, known group technique and factor analysis were used. Results: In the reliability test, the degree of agreement between evaluators showed .80~1.00 and the internal consistency was KR-20=.84. The CVI was .83~1.00. In ROC analysis, the AUC (Area Under the ROC Curve) was .98. Assessment score was 4 points. The values for sensitivity, specificity, correct classification rate, positive predictive value, and negative predictive value were found to be 95.0%, 93.7%, 94.4%, 95.0% and 93.7%, respectively. In the known group technique, the average delirium screening tool score of the non-delirium group was $1.25{\pm}0.99$ while that of delirium group was $5.07{\pm}1.89$ (t= - 16.33, p <.001). The factors were classified into 3 factors (cognitive change, symptom fluctuation, psychomotor retardation), which explained 67.4% of total variance. Conclusion: Findings show that the KICDST has high sensitivity and specificity. Therefore, this screening tool is recommended for early identification of delirium in intensive care patients.

Surface Mass Imaging Technique for Nano-Surface Analysis

  • Lee, Tae Geol
    • Proceedings of the Korean Vacuum Society Conference
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    • 2013.02a
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    • pp.113-114
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    • 2013
  • Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging is a powerful technique for producing chemical images of small biomolecules (ex. metabolites, lipids, peptides) "as received" because of its high molecular specificity, high surface sensitivity, and submicron spatial resolution. In addition, matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) imaging is an essential technique for producing chemical images of large biomolecules (ex. genes and proteins). For this talk, we will show that label-free mass imaging technique can be a platform technology for biomedical studies such as early detection/diagnostics, accurate histologic diagnosis, prediction of clinical outcome, stem cell therapy, biosensors, nanomedicine and drug screening [1-7].

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Wave Screening Effectiveness of Infilled Trenches (방진벽의 표면가 산란효과)

  • 이종세
    • Proceedings of the Earthquake Engineering Society of Korea Conference
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    • 1997.04a
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    • pp.152-159
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    • 1997
  • An analytical method is developed to study the propagation of surface waves across infilled trenches. The Green's function technique is used to estimate the reflection and transmission coefficients of Rayleigh waves across a semi-infinite plate inserted between two homogeneous quarter-spaces. After validating the method against experimental data, influence of the material contrast and the angle of incidence on the screening effectiveness of an infilled trench is examined.

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Korean Immigrant Women's Meanings of Breast, Breast Cancer, and Breast Cancer Screenings

  • Suh Eun-Young Eunice
    • Journal of Korean Academy of Nursing
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    • v.36 no.4
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    • pp.604-611
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    • 2006
  • Purpose. Koreans are one of the fastest growing Asian populations in the U.S. since 1960s. In Korean immigrant women (KIW), breast cancer was reported as the most frequently diagnosed cancer. However, their screening rates for breast cancer are lower than national guidelines; it is assumed that underlying cultural schemas of breast, breast cancer, and its screening modalities exist and need to be studied. This study was aimed to investigate cultural meanings of breast, breast cancer, and breast cancer screenings in KIW. Methods. Using cultural models theory from cognitive anthropology, naturalistic qualitative methodology was utilized. Three focus group interviews with fifteen KIW were conducted. Thematic analysis with constant comparison technique was performed eliciting units of meaning, categories, and themes. Results. The cultural schema of the meaning of breast is 'mother who is breast-feeding her baby,' with two themes of 'balance in size,' and 'shyness.' Regarding breast cancer, three themes, i.e., 'indifference,' 'fear,' and 'uncertainty' are emerged. 'Lack of information about screening modalities' is the overarching schema with reference to breast cancer screenings. Conclusions. The findings of this study demonstrate unique cultural models of KIW related to breast cancer and its screenings, which are critical to understand and penetrate their barriers to breast cancer screening.

Application of digital polymerase chain reaction technology for noninvasive prenatal test

  • Lee, Seung Yong;Hwang, Seung Yong
    • Journal of Genetic Medicine
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    • v.12 no.2
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    • pp.72-78
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    • 2015
  • Recently, noninvasive prenatal test (NIPT) has been adopted as a primary screening tool for fetal chromosomal aneuploidy. The principle of NIPT lies in isolating the fetal fraction of cell-free DNA in maternal plasma and analyzing it with bioinformatic tools to measure the amount of gene from the target chromosome, such as chromosomes 21, 18, and 13. NIPT will contribute to decreasing the need for unnecessary invasive procedures, including amniocentesis and chorionic villi sampling, for confirming fetal aneuploidy because of its higher positive predictive value than that of the conventional prenatal screening method. However, its greater cost than that of the current antenatal screening protocol may be an obstacle to the adoption of this innovative technique in clinical practice. Digital polymerase chain reaction (dPCR) is a novel approach for detecting and quantifying nucleic acid. dPCR provides real-time diagnostic advantages with higher sensitivity, accuracy, and absolute quantification than conventional quantitative PCR. Since the groundbreaking discovery that fetal cell-free nucleic acid exists in maternal plasma was reported, dPCR has been used for the quantification of fetal DNA and for screening for fetal aneuploidy. It has been suggested that dPCR will decrease the cost by targeting specific sequences in the target chromosome, and dPCR-based noninvasive testing will facilitate progress toward the implementation of a noninvasive approach for screening for trisomy 21, 18, and 13. In this review, we highlight the principle of dPCR and discuss its future implications in clinical practice.

Diagnostic aids for the detection of oral cancer (구강암의 간편 진단 기법)

  • Bang, Kang-Mi;Kim, Soung-Min;Myoung, Hoon;Kim, Myung-Jin;Lee, Jong-Ho
    • The Journal of the Korean dental association
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    • v.49 no.3
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    • pp.146-152
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    • 2011
  • Historically, the screening of patients for signs of oral cancer and precancerous lesions has relied upon the conventional oral examination. A variety of commercial diagnostic aids and adjunctive techniques are developed to potentially assist in the screening of healthy patients for evidence of occult cancerous change. This paper is reviewing the literature associated with current oral cancer screening aids such as spectroscopy, chemoiluminescence, exfoliative cytopathology, vital staining and saliva as a diagnostic tool. Despite the increased public awareness of oral cancer, no technique or technology to date has provided definitive evidence to suggest that it improves the sensitivity or specificity of oral cancer screening beyond clinical oral examination alone.