Sample preparation for large-scale bioanalytical studies based on liquid chromatographic techniques.

Science.gov (United States)

Medvedovici, Andrei; Bacalum, Elena; David, Victor

2018-01-01

Quality of the analytical data obtained for large-scale and long term bioanalytical studies based on liquid chromatography depends on a number of experimental factors including the choice of sample preparation method. This review discusses this tedious part of bioanalytical studies, applied to large-scale samples and using liquid chromatography coupled with different detector types as core analytical technique. The main sample preparation methods included in this paper are protein precipitation, liquid-liquid extraction, solid-phase extraction, derivatization and their versions. They are discussed by analytical performances, fields of applications, advantages and disadvantages. The cited literature covers mainly the analytical achievements during the last decade, although several previous papers became more valuable in time and they are included in this review. Copyright © 2017 John Wiley & Sons, Ltd.

11th GCC Closed Forum: cumulative stability; matrix stability; immunogenicity assays; laboratory manuals; biosimilars; chiral methods; hybrid LBA/LCMS assays; fit-for-purpose validation; China Food and Drug Administration bioanalytical method validation.

Science.gov (United States)

Islam, Rafiq; Briscoe, Chad; Bower, Joseph; Cape, Stephanie; Arnold, Mark; Hayes, Roger; Warren, Mark; Karnik, Shane; Stouffer, Bruce; Xiao, Yi Qun; van der Strate, Barry; Sikkema, Daniel; Fang, Xinping; Tudoroniu, Ariana; Tayyem, Rabab; Brant, Ashley; Spriggs, Franklin; Barry, Colin; Khan, Masood; Keyhani, Anahita; Zimmer, Jennifer; Caturla, Maria Cruz; Couerbe, Philippe; Khadang, Ardeshir; Bourdage, James; Datin, Jim; Zemo, Jennifer; Hughes, Nicola; Fatmi, Saadya; Sheldon, Curtis; Fountain, Scott; Satterwhite, Christina; Colletti, Kelly; Vija, Jenifer; Yu, Mathilde; Stamatopoulos, John; Lin, Jenny; Wilfahrt, Jim; Dinan, Andrew; Ohorodnik, Susan; Hulse, James; Patel, Vimal; Garofolo, Wei; Savoie, Natasha; Brown, Michael; Papac, Damon; Buonarati, Mike; Hristopoulos, George; Beaver, Chris; Boudreau, Nadine; Williard, Clark; Liu, Yansheng; Ray, Gene; Warrino, Dominic; Xu, Allan; Green, Rachel; Hayward-Sewell, Joanne; Marcelletti, John; Sanchez, Christina; Kennedy, Michael; Charles, Jessica St; Bouhajib, Mohammed; Nehls, Corey; Tabler, Edward; Tu, Jing; Joyce, Philip; Iordachescu, Adriana; DuBey, Ira; Lindsay, John; Yamashita, Jim; Wells, Edward

2018-04-01

The 11th Global CRO Council Closed Forum was held in Universal City, CA, USA on 3 April 2017. Representatives from international CRO members offering bioanalytical services were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The second CRO-Pharma Scientific Interchange Meeting was held on 7 April 2017, which included Pharma representatives' sharing perspectives on the topics discussed earlier in the week with the CRO members. The issues discussed at the meetings included cumulative stability evaluations, matrix stability evaluations, the 2016 US FDA Immunogenicity Guidance and recent and unexpected FDA Form 483s on immunogenicity assays, the bioanalytical laboratory's role in writing PK sample collection instructions, biosimilars, CRO perspectives on the use of chiral versus achiral methods, hybrid LBA/LCMS assays, applications of fit-for-purpose validation and, at the Global CRO Council Closed Forum only, the status and trend of current regulated bioanalytical practice in China under CFDA's new BMV policy. Conclusions from discussions of these topics at both meetings are included in this report.

Statistical approach for selection of regression model during validation of bioanalytical method

Directory of Open Access Journals (Sweden)

Natalija Nakov

2014-06-01

Full Text Available The selection of an adequate regression model is the basis for obtaining accurate and reproducible results during the bionalytical method validation. Given the wide concentration range, frequently present in bioanalytical assays, heteroscedasticity of the data may be expected. Several weighted linear and quadratic regression models were evaluated during the selection of the adequate curve fit using nonparametric statistical tests: One sample rank test and Wilcoxon signed rank test for two independent groups of samples. The results obtained with One sample rank test could not give statistical justification for the selection of linear vs. quadratic regression models because slight differences between the error (presented through the relative residuals were obtained. Estimation of the significance of the differences in the RR was achieved using Wilcoxon signed rank test, where linear and quadratic regression models were treated as two independent groups. The application of this simple non-parametric statistical test provides statistical confirmation of the choice of an adequate regression model.

Development and Validation of a Bioanalytical Method for Direct ...

African Journals Online (AJOL)

Purpose: To develop and validate a user-friendly spiked plasma method for the extraction of diclofenac potassium that reduces the number of treatments with plasma sample, in order to minimize human error. Method: Instead of solvent evaporation technique, the spiked plasma sample was modified with H2SO4 and NaCl, ...

Improving productivity and profitability of a bioanalytical business through sales and operation planning.

Science.gov (United States)

Islam, Rafiqul

2013-07-01

Today's bioanalytical CROs face increasing global competition, highly variable demand, high fixed costs, pricing pressure, and increasing demand for quality and speed. Most bioanalytical laboratories have responded to these challenges by implementing automation and by implementing process improvement methodologies (e.g., Six Sigma). These solutions have not resulted in a significant improvement in productivity and profitability since none of them are able to predict the upturn or downturn in demand. High volatility of demand causes long lead times and high costs during peak demand and poor productivity during trough demand. Most bioanalytical laboratories lack the tools to align supply efficiently to meet changing demand. In this paper, sales and operation planning (S&OP) has been investigated as a tool to balance supply and demand. The S&OP process, when executed effectively, can be the single greatest determinant of profitability for a bioanalytical business.

Bioanalytical development and validation of liquid chromatographic–tandem mass spectrometric methods for the quantification of total and free cefazolin in human plasma and cord blood

Directory of Open Access Journals (Sweden)

Christopher A. Crutchfield

2015-04-01

Full Text Available Objectives: Cefazolin is a commonly prescribed β-lactam antibiotic for prophylaxis against skin infections following surgery, including caesarean sections. Assessment of maternal and neonatal exposure is important for correlating drug concentrations to clinical outcomes. Thus, bioanalytical methods for the quantification of both total and free cefazolin in maternal plasma and cord blood can assist in the comprehensive evaluation of cefazolin exposure. Design and methods: Specimen preparation for the measurement of total cefazolin was performed via protein precipitation with acetonitrile containing the internal standard cloxacillin. Ultrafiltration was used to isolate free cefazolin. Processed samples were analyzed on a Prelude SPLC system coupled to a TSQ triple quadrupole Vantage mass spectrometer. Methods were validated following FDA bioanalytical guidelines. Results: The analytical measuring ranges of these methods were 0.48–480 µg/mL and 0.048–48 µg/mL for total and free drug, respectively. Calibration curves were generated using 1/x2 weighted linear regression analysis. Total cefazolin demonstrated inter- and intra-assay precision of ≤20% at the LLOQ and ≤11.2% at other levels. Free cefazolin demonstrated inter- and intra-assay precision of ≤18.5% at the LLOQ and ≤12.6% at other levels, respectively. Accuracy (%DEV, carryover, matrix effects, recovery and stability studies were also acceptable based on FDA recommendations. Furthermore, it was demonstrated that samples prepared in cord blood can be accurately quantified from an adult plasma calibration curve, with recoveries ≤9.1% DIF and ≤11.9% DIF for total and free cefazolin, respectively. Conclusions: The described LC–MS/MS methods allow for the measurement of total and free cefazolin in both plasma and cord blood. Keywords: Mass spectrometry, Method validation, Cefazolin, Antibiotic, Ultrafiltration

Verification of Bioanalytical Method for Quantification of Exogenous Insulin (Insulin Aspart) by the Analyser Advia Centaur® XP.

Science.gov (United States)

Mihailov, Rossen; Stoeva, Dilyana; Pencheva, Blagovesta; Pentchev, Eugeni

2018-03-01

In a number of cases the monitoring of patients with type I diabetes mellitus requires measurement of the exogenous insulin levels. For the purpose of a clinical investigation of the efficacy of a medical device for application of exogenous insulin aspart, a verification of the method for measurement of this synthetic analogue of the hormone was needed. The information in the available medical literature for the measurement of the different exogenous insulin analogs is insufficient. Thus, verification was required to be in compliance with the active standards in Republic of Bulgaria. A manufactured method developed for ADVIA Centaur XP Immunoassay, Siemens Healthcare, was used which we verified using standard solutions and a patient serum pool by adding the appropriate quantity exogenous insulin aspart. The method was verified in accordance with the bioanalytical method verification criteria and regulatory requirements for using a standard method: CLIA chemiluminescence immunoassay ADVIA Centaur® XP. The following parameters are determined and monitored: intra-day precision and accuracy, inter-day precision and accuracy, limit of detection and lower limit of quantification, linearity, analytical recovery. The routine application of the method for measurement of immunoreactive insulin using the analyzer ADVIA Centaur® XP is directed to the measurement of endogenous insulin. The method is applicable for measuring different types of exogenous insulin, including insulin aspart.

Submission of scientifically sound and ethical manuscripts to peer-reviewed journals - a reviewer's personal perspective on bioanalytical publications.

Science.gov (United States)

Weng, Naidong

2012-11-01

In the pharmaceutical industry, bioanalysis is very dynamic and is probably one of the few fields of research covering the entire drug discovery, development and post-marketing process. Important decisions on drug safety can partially rely on bioanalytical data, which therefore can be subject to regulatory scrutiny. Bioanalytical scientists have historically contributed significant numbers of scientific manuscripts in many peer-reviewed analytical journals. All of these journals provide some high-level instructions, but they also leave sufficient flexibility for reviewers to perform independent critique and offer recommendations for each submitted manuscript. Reviewers play a pivotal role in the process of bioanalytical publication to ensure the publication of high-quality manuscripts in a timely fashion. Their efforts usually lead to improved manuscripts. However, it has to be a joint effort among authors, reviewers and editors to promote scientifically sound and ethically fair bioanalytical publications. Most of the submitted manuscripts were well written with only minor or moderate revisions required for further improvement. Nevertheless, there were small numbers of submitted manuscripts that did not meet the requirements for publications because of scientific or ethical deficiencies, which are discussed in this Letter to the Editor. Copyright © 2012 John Wiley & Sons, Ltd.

Real Time Analysis of Bioanalytes in Healthcare, Food, Zoology and Botany.

Science.gov (United States)

Wang, Tianqi; Ramnarayanan, Ashwin; Cheng, Huanyu

2017-12-21

The growing demand for real time analysis of bioanalytes has spurred development in the field of wearable technology to offer non-invasive data collection at a low cost. The manufacturing processes for creating these sensing systems vary significantly by the material used, the type of sensors needed and the subject of study as well. The methods predominantly involve stretchable electronic sensors to monitor targets and transmit data mainly through flexible wires or short-range wireless communication devices. Capable of conformal contact, the application of wearable technology goes beyond the healthcare to fields of food, zoology and botany. With a brief review of wearable technology and its applications to various fields, we believe this mini review would be of interest to the reader in broad fields of materials, sensor development and areas where wearable sensors can provide data that are not available elsewhere.

New practical algorithm for modelling analyte recovery in bioanalytical reversed phase and mixed-mode solid phase extraction

NARCIS (Netherlands)

Hendriks, G.; Uges, D. R. A.; Franke, J. P.

2008-01-01

Solid phase extraction (SPE) is a widely used method for sample cleanup and sample concentration in bioanalytical sample preparation. A few methods to model the retention behaviour on SPE cartridges have been described previously but they are either not applicable to ionised species or are not

Activity-Based Detection and Bioanalytical Confirmation of a Fatal Carfentanil Intoxication

Directory of Open Access Journals (Sweden)

Annelies Cannaert

2018-05-01

Full Text Available Carfentanil, one of the most potent opioids known, has recently been reported as a contaminant in street heroin in the United States and Europe, and is associated with an increased number of life-threatening emergency department admissions and deaths. Here, we report on the application of a novel in vitro opioid activity reporter assay and a sensitive bioanalytical assay in the context of a fatal carfentanil intoxication, revealing the highest carfentanil concentrations reported until now. A 21-year-old male was found dead at home with a note stating that he had taken carfentanil with suicidal intentions. A foil bag and plastic bag labeled “C.50” were found at the scene. These bags were similar to a sample obtained by the Belgian Early Warning System on Drugs from a German darknet shop and to those found in the context of a fatality in Norway. Blood, urine and vitreous, obtained during autopsy, were screened with a newly developed in vitro opioid activity reporter assay able to detect compounds based on their μ-opioid receptor activity rather than their chemical structure. All extracts showed strong opioid activity. Results were confirmed by a bioanalytical assay, which revealed extremely high concentrations for carfentanil and norcarfentanil. It should be noted that carfentanil concentrations are typically in pg/mL, but here they were 92 ng/mL in blood, 2.8 ng/mL in urine, and 23 ng/mL in vitreous. The blood and vitreous contained 0.532 and 0.300 ng/mL norcarfentanil, respectively. No norcarfentanil was detected in urine. This is the first report where a novel activity-based opioid screening assay was successfully deployed in a forensic case. Confirmation and quantification using a validated bioanalytical procedure revealed the, to our knowledge, highest carfentanil concentrations reported in humans so far.

Multifunctional Nanomaterials Utilizing Hybridization Chain Reaction for Molecular Diagnostics and Bioanalytical Applications

Science.gov (United States)

Rana, Md. Muhit

DNA nanotechnology has shown great promise in molecular diagnostic, bioanalytical and biomedical applications. The great challenge of detecting target analytes, biomarkers and small molecules, in molecular diagnostics is low yield sensitivity. To address this challenge, different nanomaterials have been used for a long time and to date there is no such cost-effective bioanalytical technique which can detect these target biomarkers (DNA, RNA, circulating DNA/miRNA) or environmental heavy metal ions (Hg2+ and Ag+) in a cost-effective and efficient manner. Herein, we initially discuss two possible bioanalytical detection methods- a) colorimetric and b) fluorometric assays which are very popular nowadays due to their distinctive spectroscopic properties. Finally, we report the promising colorimetric assay using a novel DNA based amplification strategy know as hybridization chain reaction (HCR) for potential application in the visual detection of low copies of biomarkers (miRNAs as little as 20 femtomole in an RNA pool and cell extracts in seven different combinations and Ebola virus DNA as low as 400 attomoles in liquid biopsy mimics in sixteen different combinations), environmental and biological heavy metal ions (mercury and silver concentrations as low as 10 pM in water, soil and urine samples) and also successfully applied to a molecular logic gate operation to distinguish OR and AND logic gates. No results showed any false-positive or false-negative information. On the other hand, we also discuss the future possibilities of HCR amplification technology, which is very promising for fluorometric bioanalysis. The HCR based nanoprobe technology has numerous remarkable advantages over other methods. It is re-programmable, simple, inexpensive, easy to assemble and operate and can be performed with visual and spectroscopic read-outs upon recognition of the target analytes. This rapid, specific and sensitive approach for biomarkers and heavy metal ion detection generates

Luminescent lanthanide reporters: new concepts for use in bioanalytical applications

International Nuclear Information System (INIS)

Vuojola, Johanna; Soukka, Tero

2014-01-01

Lanthanides represent the chemical elements from lanthanum to lutetium. They intrinsically exhibit some very exciting photophysical properties, which can be further enhanced by incorporating the lanthanide ion into organic or inorganic sensitizing structures. A very popular approach is to conjugate the lanthanide ion to an organic chromophore structure forming lanthanide chelates. Another approach, which has quickly gained interest, is to incorporate the lanthanide ions into nanoparticle structures, thus attaining improved specific activity and a large surface area for biomolecule immobilization. Lanthanide-based reporters, when properly shielded from the quenching effects of water, usually express strong luminescence emission, multiple narrow emission lines covering a wide wavelength range, and exceptionally long excited state lifetimes enabling time-gated luminescence detection. Because of these properties, lanthanide-based reporters have found widespread applications in various fields of life. This review focuses on the field of bioanalytical applications. Luminescent lanthanide reporters and assay formats utilizing these reporters pave the way for increasingly sensitive, simple, and easily automated bioanalytical applications. (topical review)

Impact of the implementation of a well-designed electronic laboratory notebook on bioanalytical laboratory function.

Science.gov (United States)

Zeng, Jianing; Hillman, Mark; Arnold, Mark

2011-07-01

This paper shares experiences of the Bristol-Myers Squibb Company during the design, validation and implementation of an electronic laboratory notebook (ELN) into the GLP/regulated bioanalytical analysis area, as well as addresses the impact on bioanalytical laboratory functions with the implementation of the electronic notebook. Some of the key points covered are: knowledge management - the project-based electronic notebook takes full advantage of the available technology that focuses on data organization and sharing so that scientific data generated by individual scientists became department knowledge; bioanalytical workflows in the ELN - the custom-built workflows that include data entry templates, validated calculation processes, integration with laboratory information management systems/laboratory instruments, and reporting capability improve the data quality and overall workflow efficiency; regulatory compliance - carefully designed notebook reviewing processes, cross referencing of distributed information, audit trail and software validation reduce compliance risks. By taking into consideration both data generation and project documentation needs, a well-designed ELN can deliver significant improvements in laboratory efficiency, work productivity, and regulatory compliance.

An overview of the China Bioanalytical Forum: interview with Daniel Tang.

Science.gov (United States)

Tang, Daniel

2017-02-01

Daniel Tang talks to Sankeetha Nadarajah, Commissioning Editor (Bioanalysis), regarding the China Bioanalysis Forum (CBF), in which Daniel was one of the co-founders and remains as its co-chair. Daniel is currently the CEO of UP Pharma, a biologics focused bioanalytical CRO in China.

Multifunctional Fluorescent-Magnetic Polymeric Colloidal Particles: Preparations and Bioanalytical Applications.

Science.gov (United States)

Kaewsaneha, Chariya; Tangboriboonrat, Pramuan; Polpanich, Duangporn; Elaissari, Abdelhamid

2015-10-28

Fluorescent-magnetic particles (FMPs) play important roles in modern materials, especially as nanoscale devices in the biomedical field. The interesting features of FMPs are attributed to their dual detection ability, i.e., fluorescent and magnetic modes. Functionalization of FMPs can be performed using several types of polymers, allowing their use in various applications. The synergistic potentials for unique multifunctional, multilevel targeting nanoscale devices as well as combination therapies make them particularly attractive for biomedical applications. However, the synthesis of FMPs is challenging and must be further developed. In this review article, we summarized the most recent representative works on polymer-based FMP systems that have been applied particularly in the bioanalytical field.

Surface-enhanced Raman spectroscopy bioanalytical, biomolecular and medical applications

CERN Document Server

Procházka, Marek

2016-01-01

This book gives an overview of recent developments in RS and SERS for sensing and biosensing considering also limitations, possibilities and prospects of this technique. Raman scattering (RS) is a widely used vibrational technique providing highly specific molecular spectral patterns. A severe limitation for the application of this spectroscopic technique lies in the low cross section of RS. Surface-enhanced Raman scattering (SERS) spectroscopy overcomes this problem by 6-11 orders of magnitude enhancement compared with the standard RS for molecules in the close vicinity of certain rough metal surfaces. Thus, SERS combines molecular fingerprint specificity with potential single-molecule sensitivity. Due to the recent development of new SERS-active substrates, labeling and derivatization chemistry as well as new instrumentations, SERS became a very promising tool for many varied applications, including bioanalytical studies and sensing. Both intrinsic and extrinsic SERS biosensing schemes have been employed to...

A novel liquid chromatography/tandem mass spectrometry (LC-MS/MS) based bioanalytical method for quantification of ethyl esters of Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) and its application in pharmacokinetic study.

Science.gov (United States)

Viswanathan, Sekarbabu; Verma, P R P; Ganesan, Muniyandithevar; Manivannan, Jeganathan

2017-07-15

Omega-3 fatty acids are clinically useful and the two marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are prevalent in fish and fish oils. Omega-3 fatty acid formulations should undergo a rigorous regulatory step in order to obtain United States Food and Drug Administration (USFDA) approval as prescription drug. In connection with that, despite quantifying EPA and DHA fatty acids, there is a need for quantifying the level of ethyl esters of them in biological samples. In this study, we make use of reverse phase high performance liquid chromatography coupled with mass spectrometry (RP-HPLC-MS)technique for the method development. Here, we have developed a novel multiple reaction monitoring method along with optimized parameters for quantification of EPA and DHA as ethyl esters. Additionally, we attempted to validate the bio-analytical method by conducting the sensitivity, selectivity, precision accuracy batch, carryover test and matrix stability experiments. Furthermore, we also implemented our validated method for evaluation of pharmacokinetics of omega fatty acid ethyl ester formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Green approaches in sample preparation of bioanalytical samples prior to chromatographic analysis.

Science.gov (United States)

Filippou, Olga; Bitas, Dimitrios; Samanidou, Victoria

2017-02-01

Sample preparation is considered to be the most challenging step of the analytical procedure, since it has an effect on the whole analytical methodology, therefore it contributes significantly to the greenness or lack of it of the entire process. The elimination of the sample treatment steps, pursuing at the same time the reduction of the amount of the sample, strong reductions in consumption of hazardous reagents and energy also maximizing safety for operators and environment, the avoidance of the use of big amount of organic solvents, form the basis for greening sample preparation and analytical methods. In the last decade, the development and utilization of greener and sustainable microextraction techniques is an alternative to classical sample preparation procedures. In this review, the main green microextraction techniques (solid phase microextraction, stir bar sorptive extraction, hollow-fiber liquid phase microextraction, dispersive liquid - liquid microextraction, etc.) will be presented, with special attention to bioanalytical applications of these environment-friendly sample preparation techniques which comply with the green analytical chemistry principles. Copyright © 2016 Elsevier B.V. All rights reserved.

Transgene traceability in transgenic mice: a bioanalytical approach for potential gene-doping analysis.

Science.gov (United States)

Bogani, Patrizia; Spiriti, Maria Michela; Lazzarano, Stefano; Arcangeli, Annarosa; Buiatti, Marcello; Minunni, Maria

2011-11-01

The World Anti-Doping Agency fears the use of gene doping to enhance athletic performances. Thus, a bioanalytical approach based on end point PCR for detecting markers' of transgenesis traceability was developed. A few sequences from two different vectors using an animal model were selected and traced in different tissues and at different times. In particular, enhanced green fluorescent protein gene and a construct-specific new marker were targeted in the analysis. To make the developed detection approach open to future routine doping analysis, matrices such as urine and tears as well blood were also tested. This study will have impact in evaluating the vector transgenes traceability for the detection of a gene doping event by non-invasive sampling.

pH adjustment of human blood plasma prior to bioanalytical sample preparation

NARCIS (Netherlands)

Hendriks, G.; Uges, D. R. A.; Franke, J. P.

2008-01-01

pH adjustment in bioanalytical sample preparation concerning ionisable compounds is one of the most common sample treatments. This is often done by mixing an aliquot of the sample with a proper buffer adjusted to the proposed pH. The pH of the resulting mixture however, does not necessarily have to

Recent development in software and automation tools for high-throughput discovery bioanalysis.

Science.gov (United States)

Shou, Wilson Z; Zhang, Jun

2012-05-01

Bioanalysis with LC-MS/MS has been established as the method of choice for quantitative determination of drug candidates in biological matrices in drug discovery and development. The LC-MS/MS bioanalytical support for drug discovery, especially for early discovery, often requires high-throughput (HT) analysis of large numbers of samples (hundreds to thousands per day) generated from many structurally diverse compounds (tens to hundreds per day) with a very quick turnaround time, in order to provide important activity and liability data to move discovery projects forward. Another important consideration for discovery bioanalysis is its fit-for-purpose quality requirement depending on the particular experiments being conducted at this stage, and it is usually not as stringent as those required in bioanalysis supporting drug development. These aforementioned attributes of HT discovery bioanalysis made it an ideal candidate for using software and automation tools to eliminate manual steps, remove bottlenecks, improve efficiency and reduce turnaround time while maintaining adequate quality. In this article we will review various recent developments that facilitate automation of individual bioanalytical procedures, such as sample preparation, MS/MS method development, sample analysis and data review, as well as fully integrated software tools that manage the entire bioanalytical workflow in HT discovery bioanalysis. In addition, software tools supporting the emerging high-resolution accurate MS bioanalytical approach are also discussed.

Integrated quantitative and qualitative workflow for in vivo bioanalytical support in drug discovery using hybrid Q-TOF-MS.

Science.gov (United States)

Ranasinghe, Asoka; Ramanathan, Ragu; Jemal, Mohammed; D'Arienzo, Celia J; Humphreys, W Griffith; Olah, Timothy V

2012-03-01

UHPLC coupled with orthogonal acceleration hybrid quadrupole-TOF (Q-TOF)-MS is an emerging technique offering new strategies for the efficient screening of new chemical entities and related molecules at the early discovery stage within the pharmaceutical industry. In the first part of this article, we examine the main instrumental parameters that are critical for the integration of UHPLC-Q-TOF technology to existing bioanalytical workflows, in order to provide simultaneous quantitative and qualitative bioanalysis of samples generated following in vivo studies. Three modern Q-TOF mass spectrometers, including Bruker maXis™, Agilent 6540 and Sciex TripleTOF™ 5600, all interfaced with UHPLC systems, are evaluated in the second part of the article. The scope of this work is to demonstrate the potential of Q-TOF for the analysis of typical small molecules, therapeutic peptides (molecular weight <6000 Da), and enzymatically (i.e., trypsin, chymotrypsin and pepsin) cleaved peptides from larger proteins. This work focuses mainly on full-scan TOF data obtained under ESI conditions, the major mode of TOF operation in discovery bioanalytical research, where the compounds are selected based on their pharmacokinetic/pharmacodynamic behaviors using animal models prior to selecting a few desirable candidates for further development. Finally, important emerging TOF technologies that could potentially benefit bioanalytical research in the semi-quantification of metabolites without synthesized standards are discussed. Particularly, the utility of captive spray ionization coupled with TripleTOF 5600 was evaluated for improving sensitivity and providing normalized MS response for drugs and their metabolites. The workflow proposed compromises neither the efficiency, nor the quality of pharmacokinetic data in support of early drug discovery programs.

Laboratory automation of high-quality and efficient ligand-binding assays for biotherapeutic drug development.

Science.gov (United States)

Wang, Jin; Patel, Vimal; Burns, Daniel; Laycock, John; Pandya, Kinnari; Tsoi, Jennifer; DeSilva, Binodh; Ma, Mark; Lee, Jean

2013-07-01

Regulated bioanalytical laboratories that run ligand-binding assays in support of biotherapeutics development face ever-increasing demand to support more projects with increased efficiency. Laboratory automation is a tool that has the potential to improve both quality and efficiency in a bioanalytical laboratory. The success of laboratory automation requires thoughtful evaluation of program needs and fit-for-purpose strategies, followed by pragmatic implementation plans and continuous user support. In this article, we present the development of fit-for-purpose automation of total walk-away and flexible modular modes. We shared the sustaining experience of vendor collaboration and team work to educate, promote and track the use of automation. The implementation of laboratory automation improves assay performance, data quality, process efficiency and method transfer to CRO in a regulated bioanalytical laboratory environment.

Applicability of bioanalysis of multiple analytes in drug discovery and development: review of select case studies including assay development considerations.

Science.gov (United States)

Srinivas, Nuggehally R

2006-05-01

The development of sound bioanalytical method(s) is of paramount importance during the process of drug discovery and development culminating in a marketing approval. Although the bioanalytical procedure(s) originally developed during the discovery stage may not necessarily be fit to support the drug development scenario, they may be suitably modified and validated, as deemed necessary. Several reviews have appeared over the years describing analytical approaches including various techniques, detection systems, automation tools that are available for an effective separation, enhanced selectivity and sensitivity for quantitation of many analytes. The intention of this review is to cover various key areas where analytical method development becomes necessary during different stages of drug discovery research and development process. The key areas covered in this article with relevant case studies include: (a) simultaneous assay for parent compound and metabolites that are purported to display pharmacological activity; (b) bioanalytical procedures for determination of multiple drugs in combating a disease; (c) analytical measurement of chirality aspects in the pharmacokinetics, metabolism and biotransformation investigations; (d) drug monitoring for therapeutic benefits and/or occupational hazard; (e) analysis of drugs from complex and/or less frequently used matrices; (f) analytical determination during in vitro experiments (metabolism and permeability related) and in situ intestinal perfusion experiments; (g) determination of a major metabolite as a surrogate for the parent molecule; (h) analytical approaches for universal determination of CYP450 probe substrates and metabolites; (i) analytical applicability to prodrug evaluations-simultaneous determination of prodrug, parent and metabolites; (j) quantitative determination of parent compound and/or phase II metabolite(s) via direct or indirect approaches; (k) applicability in analysis of multiple compounds in select

Relationship of Ambient Atmosphere and Biological Aerosol Responses from a Fielded Pyrolysis-Gas Chromatography-Ion Mobility Spectrometry Bioanalytical Detector

National Research Council Canada - National Science Library

Snyder, A

2003-01-01

.... A pyrolysis-gas chromatography-ion mobility spectrometry stand-alone bioaerosol system was interfaced to an aerosol concentrator to collect ambient background aerosols and produce bioanalytical...

Implications of differences in bioanalytical regulations between Canada, USA and South America.

Science.gov (United States)

Arnold, Mark E

2011-02-01

To complete globally, pharmaceutical companies desire to use bioanalytical data and reports as a single version for all filings; not revising for specific countries or regions. Historically, this meant following the US FDA and International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidance/guidelines; finding them sufficient to achieve global acceptance. However, a growing challenge of the past decade has been additional country-specific and regional regulations that have been released. The differences between the bioanalytical regulations among countries have been recognized as a challenge to the pharmaceutical industry and its CRO partners. Harmonization of the regulations at a global level has been the subject of a number of recent articles and editorials, and the topic has been vigorously discussed at several conferences over the past year. Since all have been in agreement about the need to harmonize regulations, this article will not focus on harmonization but rather it will provide a comparison of the USA/Canadian regulations versus those of South America, in particular Brazil, noting the additional work needed to achieve compliance with country-specific regulations. All countries discussed have specific guidance or regulations on clinical bioequivalence studies, and due to the higher standards for these studies, the regulations for bioequivalence studies will be used as the basis for comparison in the article.

A Simple HPLC Bioanalytical Method for the Determination of ...

African Journals Online (AJOL)

Purpose: To develop a simple, accurate, and precise high performance chromatography (HPLC) method with spectrophotometric detection for the determination of doxorubicin hydrochloride in rat plasma. Methods: Doxorubicin hydrochloride and daunorubicin hydrochloride (internal standard, IS) were separated on a C18 ...

Validação em métodos cromatográficos para análises de pequenas moléculas em matrizes biológicas Chromatographic methods validation for analysis of small molecules in biological matrices

OpenAIRE

Neila Maria Cassiano; Juliana Cristina Barreiro; Lúcia Regina Rocha Martins; Regina Vincenzi Oliveira; Quezia Bezerra Cass

2009-01-01

Chromatographic methods are commonly used for analysis of small molecules in different biological matrices. An important step to be considered upon a bioanalytical method's development is the capacity to yield reliable and reproducible results. This review discusses validation procedures adopted by different governmental agencies, such as Food and Drug Administration (USA), European Union (EU) and Agência Nacional de Vigilância Sanitária (BR) for quantification of small molecules by bioanalyt...

Surface Modification of Photoresist SU-8 for Low Autofluorescence and Bioanalytical Applications

DEFF Research Database (Denmark)

Cao, Cuong; Birtwell, Sam W.; Høgberg, Jonas

2011-01-01

This paper reports a surface modification of epoxy-based negative photoresist SU-8 for reducing its autofluorescence while enhancing its biofunctionality. By covalently depositing a thin layer of 20 nm Au nanoparticles (AuNPs) onto the SU-8 surface, we found that the AuNPs-coated SU-8 surface...... is much less fluorescent than the untreated SU-8. Moreover, DNA probes can easily be immobilized on the Au surface and are thermally stable over a wide range of temperature. These improvements will benefit bioanalytical applications such as DNA hybridization and solid-phase PCR (SP-PCR)....

Label-Free Bioanalyte Detection from Nanometer to Micrometer Dimensions—Molecular Imprinting and QCMs †

Directory of Open Access Journals (Sweden)

Adnan Mujahid

2018-06-01

Full Text Available Modern diagnostic tools and immunoassay protocols urges direct analyte recognition based on its intrinsic behavior without using any labeling indicator. This not only improves the detection reliability, but also reduces sample preparation time and complexity involved during labeling step. Label-free biosensor devices are capable of monitoring analyte physiochemical properties such as binding sensitivity and selectivity, affinity constants and other dynamics of molecular recognition. The interface of a typical biosensor could range from natural antibodies to synthetic receptors for example molecular imprinted polymers (MIPs. The foremost advantages of using MIPs are their high binding selectivity comparable to natural antibodies, straightforward synthesis in short time, high thermal/chemical stability and compatibility with different transducers. Quartz crystal microbalance (QCM resonators are leading acoustic devices that are extensively used for mass-sensitive measurements. Highlight features of QCM devices include low cost fabrication, room temperature operation, and most importantly ability to monitor extremely low mass shifts, thus potentially a universal transducer. The combination of MIPs with quartz QCM has turned out as a prominent sensing system for label-free recognition of diverse bioanalytes. In this article, we shall encompass the potential applications of MIP-QCM sensors exclusively label-free recognition of bacteria and virus species as representative micro and nanosized bioanalytes.

Bioanalytical system for detection of cancer cells with photoluminescent ZnO nanorods

Science.gov (United States)

Viter, R.; Jekabsons, K.; Kalnina, Z.; Poletaev, N.; Hsu, S. H.; Riekstina, U.

2016-11-01

Using photoluminescent ZnO nanorods and carbohydrate marker SSEA-4, a novel cancer cell recognition system was developed. Immobilization of SSEA-4 antibodies (αSSEA-4) on ZnO nanorods was performed in buffer solution (pH = 7.1) over 2 h. The cancer cell line probes were fixed on the glass slide. One hundred microliters of ZnO-αSSEA-4 conjugates were deposited on the cell probe and exposed for 30 min. After washing photoluminescence spectra were recorded. Based on the developed methodology, ZnO-αSSEA-4 probes were tested on patient-derived breast and colorectal carcinoma cells. Our data clearly show that the carbohydrate SSEA-4 molecule is expressed on cancer cell lines and patient-derived cancer cells. Moreover, SSEA-4 targeted ZnO nanorods bind to the patient-derived cancer cells with high selectivity and the photoluminescence signal increased tremendously compared to the signal from the control samples. Furthermore, the photoluminescence intensity increase correlated with the extent of malignancy in the target cell population. A novel portable bioanalytical system, based on optical ZnO nanorods and fiber optic detection system was developed. We propose that carbohydrate SSEA-4 specific ZnO nanorods could be used for the development of cancer diagnostic biosensors and for targeted therapy.

Comparison of two-concentration with multi-concentration linear regressions: Retrospective data analysis of multiple regulated LC-MS bioanalytical projects.

Science.gov (United States)

Musuku, Adrien; Tan, Aimin; Awaiye, Kayode; Trabelsi, Fethi

2013-09-01

Linear calibration is usually performed using eight to ten calibration concentration levels in regulated LC-MS bioanalysis because a minimum of six are specified in regulatory guidelines. However, we have previously reported that two-concentration linear calibration is as reliable as or even better than using multiple concentrations. The purpose of this research is to compare two-concentration with multiple-concentration linear calibration through retrospective data analysis of multiple bioanalytical projects that were conducted in an independent regulated bioanalytical laboratory. A total of 12 bioanalytical projects were randomly selected: two validations and two studies for each of the three most commonly used types of sample extraction methods (protein precipitation, liquid-liquid extraction, solid-phase extraction). When the existing data were retrospectively linearly regressed using only the lowest and the highest concentration levels, no extra batch failure/QC rejection was observed and the differences in accuracy and precision between the original multi-concentration regression and the new two-concentration linear regression are negligible. Specifically, the differences in overall mean apparent bias (square root of mean individual bias squares) are within the ranges of -0.3% to 0.7% and 0.1-0.7% for the validations and studies, respectively. The differences in mean QC concentrations are within the ranges of -0.6% to 1.8% and -0.8% to 2.5% for the validations and studies, respectively. The differences in %CV are within the ranges of -0.7% to 0.9% and -0.3% to 0.6% for the validations and studies, respectively. The average differences in study sample concentrations are within the range of -0.8% to 2.3%. With two-concentration linear regression, an average of 13% of time and cost could have been saved for each batch together with 53% of saving in the lead-in for each project (the preparation of working standard solutions, spiking, and aliquoting). Furthermore

Biological methods used to assess surface water quality

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Szczerbiñska Natalia

2015-12-01

Full Text Available In accordance with the guidelines of the Water Framework Directive 2000/60 (WFD, both ecological and chemical statuses determine the assessment of surface waters. The profile of ecological status is based on the analysis of various biological components, and physicochemical and hydromorphological indicators complement this assessment. The aim of this article is to present the biological methods used in the assessment of water status with a special focus on bioassay, as well as to provide a review of methods of monitoring water status. Biological test methods include both biomonitoring and bioanalytics. Water biomonitoring is used to assess and forecast the status of water. These studies aim to collect data on water pollution and forecast its impact. Biomonitoring uses organisms which are characterized by particular vulnerability to contaminants. Bioindicator organisms are algae, fungi, bacteria, larval invertebrates, cyanobacteria, macroinvertebrates, and fish. Bioanalytics is based on the receptors of contaminants that can be biologically active substances. In bioanalytics, biosensors such as viruses, bacteria, antibodies, enzymes, and biotests are used to assess degrees of pollution.

Validação em métodos cromatográficos para análises de pequenas moléculas em matrizes biológicas Chromatographic methods validation for analysis of small molecules in biological matrices

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Neila Maria Cassiano

2009-01-01

Full Text Available Chromatographic methods are commonly used for analysis of small molecules in different biological matrices. An important step to be considered upon a bioanalytical method's development is the capacity to yield reliable and reproducible results. This review discusses validation procedures adopted by different governmental agencies, such as Food and Drug Administration (USA, European Union (EU and Agência Nacional de Vigilância Sanitária (BR for quantification of small molecules by bioanalytical chromatographic methods. The main parameters addressed in this review are: selectivity, linearity, precision, accuracy, quantification and detection limits, recovery, dilution integrity, stability and robustness. Also, the acceptance criterions are clearly specified.

A new high-performance liquid chromatography-tandem mass spectrometry method for the determination of paclitaxel and 6α-hydroxy-paclitaxel in human plasma: Development, validation and application in a clinical pharmacokinetic study.

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Bianca Posocco

Full Text Available Paclitaxel belongs to the taxanes family and it is used, alone or in multidrug regimens, for the therapy of several solid tumours, such as breast-, lung-, head and neck-, and ovarian cancer. Standard dosing of chemotherapy does not take into account the many inter-patient differences that make drug exposure highly variable, thus leading to the insurgence of severe toxicity. This is particularly true for paclitaxel considering that a relationship between haematological toxicity and plasma exposure was found. Therefore, in order to treat patients with the correct dose of paclitaxel, improving the overall benefit-risk ratio, Therapeutic Drug Monitoring is necessary. In order to quantify paclitaxel and its main metabolite, 6α-hydroxy-paclitaxel, in patients' plasma, we developed a new, sensitive and specific HPLC-MS/MS method applicable to all paclitaxel dosages used in clinical routine. The developed method used a small volume of plasma sample and is based on quick protein precipitation. The chromatographic separation of the analytes was achieved with a SunFire™ C18 column (3.5 μM, 92 Å, 2,1 x 150 mm; the mobile phases were 0.1% formic acid/bidistilled water and 0.1% formic acid/acetonitrile. The electrospray ionization source worked in positive ion mode and the mass spectrometer operated in selected reaction monitoring mode. Our bioanalytical method was successfully validated according to the FDA-EMA guidelines on bioanalytical method validation. The calibration curves resulted linear (R2 ≥0.9948 over the concentration ranges (1-10000 ng/mL for paclitaxel and 1-1000 ng/mL for 6α-hydroxy-paclitaxel and were characterized by a good accuracy and precision. The intra- and inter-day precision and accuracy were determined on three quality control concentrations for paclitaxel and 6α-hydroxy-paclitaxel and resulted respectively <9.9% and within 91.1-114.8%. In addition, to further verify the assay reproducibility, we tested this method by re

Development and Validation of Liquid Chromatography- Mass ...

African Journals Online (AJOL)

HP

Method: A novel liquid chromatography–tandem mass spectrometry method for the quantitative determination of naproxen in human K2-EDTA plasma in negative ion mode was employed ..... Practice and Applications of Bio-analytical Method.

Bioanalytical method development and validation for determination of metoprolol tartarate and hydrochlorothiazide using HPTLC in human plasma

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Ambadas Ranganath Rote

2013-12-01

Full Text Available A simple, sensitive, rapid and economic chromatographic method has been developed for determination of metoprolol tartarate and hydrochlorothiazide in human plasma using paracetamol as an internal standard. The analytical technique used for method development was high-performance thin-layer chromatography. HPTLC Camag with precoated silica gel Plate 60F254 (20 cm×10 cm at 250 µm thicknesses (E. Merck, Darmstadt, Germany was used as the stationary phase. The mobile phase used consisted of chloroform: methanol: ammonia (9:1:0.5v/v/v. Densitometric analysis was carried out at a wavelength of 239 nm. The rf values for hydrochlorothiazide, paracetamol and metoprolol tartarate were 0.13±0.04, 0.28±0.05, 0.48±0.04, respectively. Plasma samples were extracted by protein precipitation with methanol. Concentration ranges of 200, 400, 600, 800, 1000, 1200 ng/mL and 2000, 4000, 6000, 8000, 10000, 12000 ng/mL of hydrochlorothiazide and metoprolol tartarate, respectively, were used with plasma for the calibration curves. The percent recovery of metoprolol tartarate and hydrochlorothiazide was found to be 77.30 and 77.02 %, respectively. The stability of metoprolol tartarate and hydrochlorothiazide in plasma were confirmed during three freeze-thaw cycles (-20 ºC on a bench for 24 hours and post-preparatively for 48 hours. The proposed method was validated statistically and proved suitable for determination of metoprolol tartarate and hydrochlorothiazide in human plasma.

Development and validation of a high throughput LC–MS/MS method for simultaneous quantitation of pioglitazone and telmisartan in rat plasma and its application to a pharmacokinetic study

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Pinaki Sengupta

2017-12-01

Full Text Available Management of cardiovascular risk factors in diabetes demands special attention due to their co-existence. Pioglitazone (PIO and telmisartan (TLM combination can be beneficial in effective control of cardiovascular complication in diabetes. In this research, we developed and validated a high throughput LC–MS/MS method for simultaneous quantitation of PIO and TLM in rat plasma. This developed method is more sensitive and can quantitate the analytes in relatively shorter period of time compared to the previously reported methods for their individual quantification. Moreover, till date, there is no bioanalytical method available to simultaneously quantitate PIO and TLM in a single run. The method was validated according to the USFDA guidelines for bioanalytical method validation. A linear response of the analytes was observed over the range of 0.005–10 µg/mL with satisfactory precision and accuracy. Accuracy at four quality control levels was within 94.27%–106.10%. The intra- and inter-day precision ranged from 2.32%–10.14 and 5.02%–8.12%, respectively. The method was reproducible and sensitive enough to quantitate PIO and TLM in rat plasma samples of a preclinical pharmacokinetic study. Due to the potential of PIO-TLM combination to be therapeutically explored, this method is expected to have significant usefulness in future. Keywords: LC–MS/MS, Rat plasma, Pharmacokinetic applicability, Telmisartan, Pioglitazone, Pharmacokinetic application

BIOANALYTICAL STANDARDIZING FOR SEROLOGICAL DIAGNOSTIC MEDICAL DEVICES

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A. Yu. Galkin

2015-04-01

Full Text Available In article we analyzed national and international regulations concerning the quality and safety of medical devices for in vitro diagnostics. We discussed the possibility of a partial application of the recommendations of the State Pharmacopoeia of Ukraine to this type of product. The main guiding regulatory documents establishing requirements for quality and safety tools for the serological diagnosis products are The technical regulation on medical devices for the diagnosis in vitro, DSTU ISO 13485 “Medical devices. Quality management system. Regulatory requirements”, and DSTU ISO/IEC 17025 “General requirements for the competence of testing and calibration laboratories”. Similar requirements of the State Pharmacopoeia of Ukraine which are used for drug standardization can not be directly applied to the medical devises for in vitro diagnostics due to a number of features, namely, the serological diagnosis products pre-designed to determine the unknown concentration of a particular analyte in a biological material, the diagnostic kits has to include the control samples (internal standard systems that need to be calibrated. It was determined following parameters of bioanalytical standardization and validation characterization for of qualitative (semi quantitative test-kits for serological diagnosis: precision (convergence, intralaboratory precision and reproducibility, diagnostic and analytical specificity, diagnostic sensitivity. It’s necessary to inspect additional parameters for quantitative test-kits such as accuracy (precision, linearity, analytical sensitivity and range.

Critical role of bioanalytical strategies in investigation of clinical PK observations, a Phase I case study

Science.gov (United States)

Peng, Kun; Xu, Keyang; Liu, Luna; Hendricks, Robert; Delarosa, Reginald; Erickson, Rich; Budha, Nageshwar; Leabman, Maya; Song, An; Kaur, Surinder; Fischer, Saloumeh K

2014-01-01

RG7652 is a human immunoglobulin 1 (IgG1) monoclonal antibody (mAb) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and is designed for the treatment of hypercholesterolemia. A target-binding enzyme-linked immunosorbent assay (ELISA) was developed to measure RG7652 levels in human serum in a Phase I study. Although target-binding assay formats are generally used to quantify free therapeutic, the actual therapeutic species being measured are affected by assay conditions, such as sample dilution and incubation time, and levels of soluble target in the samples. Therefore, in the presence of high concentrations of circulating target, the choice of reagents and assay conditions can have a significant effect on the observed pharmacokinetic (PK) profiles. Phase I RG7652 PK analysis using the ELISA data resulted in a nonlinear dose normalized exposure. An investigation was conducted to characterize the ELISA to determine whether the assay format and reagents may have contributed to the PK observation. In addition, to confirm the ELISA results, a second orthogonal method, liquid chromatography tandem mass spectrometry (LC-MS/MS) using a signature peptide as surrogate, was developed and implemented. A subset of PK samples, randomly selected from half of the subjects in the 6 single ascending dose (SAD) cohorts in the Phase I clinical study, was analyzed with the LC-MS/MS assay, and the data were found to be comparable to the ELISA data. This paper illustrates the importance of reagent characterization, as well as the benefits of using an orthogonal approach to eliminate bioanalytical contributions when encountering unexpected observations. PMID:25484037

The international validation of bio- and chemical-anlaytical screening methods for dioxins and dioxin-like PCBs: the DIFFERENCE project rounds 1 and 2

NARCIS (Netherlands)

Loco, van J.; Leeuwen, van S.P.J.; Roos, P.; Carbonnelle, S.; Boer, de J.; Goeyens, L.; Beernaert, H.

2004-01-01

The European research project DIFFERENCE is focussed on the development, optimisation and validation of screening methods for dioxin analysis, including bio-analytical and chemical techniques (CALUX, GC-LRMS/MS, GC x GC-ECD) and on the optimisation and validation of new extraction and clean-up

Development and Validation of a Bioanalytical Method for Direct ...

African Journals Online (AJOL)

Erah

2011-01-16

Jan 16, 2011 ... acetonitrile in water (v/v) as mobile phase containing ammonium acetate and triethylamine (TEA), at a .... The pH of the mobile ..... and Application to a Human Pharmacokinetic ... (Thesis), Rhodes University, Grahamstown,.

Going paperless: implementing an electronic laboratory notebook in a bioanalytical laboratory.

Science.gov (United States)

Beato, Brian; Pisek, April; White, Jessica; Grever, Timothy; Engel, Brian; Pugh, Michael; Schneider, Michael; Carel, Barbara; Branstrator, Laurel; Shoup, Ronald

2011-07-01

AIT Bioscience, a bioanalytical CRO, implemented a highly configurable, Oracle-based electronic laboratory notebook (ELN) from IDBS called E-WorkBook Suite (EWBS). This ELN provides a high degree of connectivity with other databases, including Watson LIMS. Significant planning and training, along with considerable design effort and template validation for dozens of laboratory workflows were required prior to EWBS being viable for either R&D or regulated work. Once implemented, EWBS greatly reduced the need for traditional quality review upon experiment completion. Numerous real-time error checks occur automatically when conducting EWBS experiments, preventing the majority of laboratory errors by pointing them out while there is still time to correct any issues. Auditing and reviewing EWBS data are very efficient, because all data are forever securely (and even remotely) accessible, provided a reviewer has appropriate credentials. Use of EWBS significantly increases both data quality and laboratory efficiency.

Enzyme-Based Logic Gates and Networks with Output Signals Analyzed by Various Methods.

Science.gov (United States)

Katz, Evgeny

2017-07-05

The paper overviews various methods that are used for the analysis of output signals generated by enzyme-based logic systems. The considered methods include optical techniques (optical absorbance, fluorescence spectroscopy, surface plasmon resonance), electrochemical techniques (cyclic voltammetry, potentiometry, impedance spectroscopy, conductivity measurements, use of field effect transistor devices, pH measurements), and various mechanoelectronic methods (using atomic force microscope, quartz crystal microbalance). Although each of the methods is well known for various bioanalytical applications, their use in combination with the biomolecular logic systems is rather new and sometimes not trivial. Many of the discussed methods have been combined with the use of signal-responsive materials to transduce and amplify biomolecular signals generated by the logic operations. Interfacing of biocomputing logic systems with electronics and "smart" signal-responsive materials allows logic operations be extended to actuation functions; for example, stimulating molecular release and switchable features of bioelectronic devices, such as biofuel cells. The purpose of this review article is to emphasize the broad variability of the bioanalytical systems applied for signal transduction in biocomputing processes. All bioanalytical systems discussed in the article are exemplified with specific logic gates and multi-gate networks realized with enzyme-based biocatalytic cascades. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bioanalytical methods for food allergy diagnosis, allergen detection and new allergen discovery.

Science.gov (United States)

Gasilova, Natalia; Girault, Hubert H

2015-01-01

For effective monitoring and prevention of the food allergy, one of the emerging health problems nowadays, existing diagnostic procedures and allergen detection techniques are constantly improved. Meanwhile, new methods are also developed, and more and more putative allergens are discovered. This review describes traditional methods and summarizes recent advances in the fast evolving field of the in vitro food allergy diagnosis, allergen detection in food products and discovery of the new allergenic molecules. A special attention is paid to the new diagnostic methods under laboratory development like various immuno- and aptamer-based assays, including immunoaffinity capillary electrophoresis. The latter technique shows the importance of MS application not only for the allergen detection but also for the allergy diagnosis.

Development and validation of a high performance liquid chromatography quantification method of levo-tetrahydropalmatine and its metabolites in plasma and brain tissues: application to a pharmacokinetic study.

Science.gov (United States)

Abdallah, Inas A; Huang, Peng; Liu, Jing; Lee, David Y; Liu-Chen, Lee-Yuan; Hassan, Hazem E

2017-04-01

Levo-tetrahydropalmatine (l-THP) is an alkaloid isolated from Chinese medicinal herbs of the Corydalis and Stephania genera. It has been used in China for more than 40 years mainly as an analgesic with sedative/hypnotic effects. Despite its extensive use, its metabolism has not been quantitatively studied, nor there a sensitive reliable bioanalytical method for its quantification simultaneously with its metabolites. As such, the objective of this study was to develop and validate a sensitive and selective HPLC method for simultaneous quantification of l-THP and its desmethyl metabolites l-corydalmine (l-CD) and l-corypalmine (l-CP) in rat plasma and brain tissues. Rat plasma and brain samples were processed by liquid-liquid extraction using ethyl acetate. Chromatographic separation was achieved on a reversed-phase Symmetry® C 18 column (4.6 × 150 mm, 5 μm) at 25°C. The mobile phase consisted of acetonitrile-methanol-10 mm ammonium phosphate (pH 3) (10:30:60, v/v) and was used at a flow rate of 0.8 mL/min. The column eluent was monitored at excitation and emission wavelengths of 230 and 315 nm, respectively. The calibration curves were linear over the concentration range of 1-10,000 ng/mL. The intra- and interday reproducibility studies demonstrated accuracy and precision within the acceptance criteria of bioanalytical guidelines. The validated HPLC method was successfully applied to analyze samples from a pharmacokinetic study of l-THP in rats. Taken together, the developed method can be applied for bioanalysis of l-THP and its metabolites in rodents and potentially can be transferred for bioanalysis of human samples. Copyright © 2016 John Wiley & Sons, Ltd.

Avoiding the pitfalls when quantifying thyroid hormones and their metabolites using mass spectrometric methods: The role of quality assurance.

Science.gov (United States)

Richards, Keith; Rijntjes, Eddy; Rathmann, Daniel; Köhrle, Josef

2017-12-15

This short review aims to assess the application of basic quality assurance (QA) principles in published thyroid hormone bioanalytical methods using mass spectrometry (MS). The use of tandem MS, in particular linked to liquid chromatography has become an essential bioanalytical tool for the thyroid hormone research community. Although basic research laboratories do not usually work within the constraints of a quality management system and regulated environment, all of the reviewed publications, to a lesser or greater extent, document the application of QA principles to the MS methods described. After a brief description of the history of MS in thyroid hormone analysis, the article reviews the application of QA to published bioanalytical methods from the perspective of selectivity, accuracy, precision, recovery, instrument calibration, matrix effects, sensitivity and sample stability. During the last decade the emphasis has shifted from developing methods for the determination of L-thyroxine (T 4 ) and 3,3',5-triiodo-L-thyronine (T 3 ), present in blood serum/plasma in the 1-100 nM concentration range, to metabolites such as 3-iodo-L-thyronamine (3-T 1 AM), 3,5-diiodo-L-thyronine (3,5-T 2 ) and 3,3'-diiodo-L-thyronine (3,3'-T 2 ). These metabolites seem likely to be present in the low pM concentrations; consequently, QA parameters such as selectivity and sensitivity become more critical. The authors conclude that improvements, particularly in the areas of analyte selectivity, matrix effect measurement/documentation and analyte recovery would be beneficial. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and validation of HPLC analytical method for quantitative determination of metronidazole in human plasma

International Nuclear Information System (INIS)

Safdar, K.A.; Shyum, S.B.; Usman, S.

2016-01-01

The objective of the present study was to develop a simple, rapid and sensitive reversed-phase high performance liquid chromatographic (RP-HPLC) analytical method with UV detection system for the quantitative determination of metronidazole in human plasma. The chromatographic separation was performed by using C18 RP column (250mm X 4.6mm, 5 meu m) as stationary phase and 0.01M potassium dihydrogen phosphate buffered at pH 3.0 and acetonitrile (83:17, v/v) as mobile phase at flow rate of 1.0 ml/min. The UV detection was carried out at 320nm. The method was validated as per the US FDA guideline for bioanalytical method validation and was found to be selective without interferences from mobile phase components, impurities and biological matrix. The method found to be linear over the concentration range of 0.2812 meu g/ml to 18.0 meu g/ml (r2 = 0.9987) with adequate level of accuracy and precision. The samples were found to be stable under various recommended laboratory and storage conditions. Therefore, the method can be used with adequate level of confidence and assurance for bioavailability, bioequivalence and other pharmacokinetic studies of metronidazole in human. (author)

Perspectives on bioanalytical mass spectrometry and automation in drug discovery.

Science.gov (United States)

Janiszewski, John S; Liston, Theodore E; Cole, Mark J

2008-11-01

The use of high speed synthesis technologies has resulted in a steady increase in the number of new chemical entities active in the drug discovery research stream. Large organizations can have thousands of chemical entities in various stages of testing and evaluation across numerous projects on a weekly basis. Qualitative and quantitative measurements made using LC/MS are integrated throughout this process from early stage lead generation through candidate nomination. Nearly all analytical processes and procedures in modern research organizations are automated to some degree. This includes both hardware and software automation. In this review we discuss bioanalytical mass spectrometry and automation as components of the analytical chemistry infrastructure in pharma. Analytical chemists are presented as members of distinct groups with similar skillsets that build automated systems, manage test compounds, assays and reagents, and deliver data to project teams. The ADME-screening process in drug discovery is used as a model to highlight the relationships between analytical tasks in drug discovery. Emerging software and process automation tools are described that can potentially address gaps and link analytical chemistry related tasks. The role of analytical chemists and groups in modern 'industrialized' drug discovery is also discussed.

Update of Standard Practices for New Method Validation in Forensic Toxicology.

Science.gov (United States)

Wille, Sarah M R; Coucke, Wim; De Baere, Thierry; Peters, Frank T

2017-01-01

International agreement concerning validation guidelines is important to obtain quality forensic bioanalytical research and routine applications as it all starts with the reporting of reliable analytical data. Standards for fundamental validation parameters are provided in guidelines as those from the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), the German speaking Gesellschaft fur Toxikologie und Forensische Chemie (GTFCH) and the Scientific Working Group of Forensic Toxicology (SWGTOX). These validation parameters include selectivity, matrix effects, method limits, calibration, accuracy and stability, as well as other parameters such as carryover, dilution integrity and incurred sample reanalysis. It is, however, not easy for laboratories to implement these guidelines into practice as these international guidelines remain nonbinding protocols, that depend on the applied analytical technique, and that need to be updated according the analyst's method requirements and the application type. In this manuscript, a review of the current guidelines and literature concerning bioanalytical validation parameters in a forensic context is given and discussed. In addition, suggestions for the experimental set-up, the pros and cons of statistical approaches and adequate acceptance criteria for the validation of bioanalytical applications are given. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Bioanalytical methods for food allergy diagnosis, allergen detection and new allergen discovery

OpenAIRE

Gasilova, Natalia; Girault, Hubert H

2015-01-01

For effective monitoring and prevention of the food allergy, one of the emerging health problems nowadays, existing diagnostic procedures and allergen detection techniques are constantly improved. Meanwhile, new methods are also developed, and more and more putative allergens are discovered. This review describes traditional methods and summarizes recent advances in the fast evolving field of the in vitro food allergy diagnosis, allergen detection in food products and discovery of the new all...

Development and validation of a bioanalytical LC-MS method for the quantification of GHRP-6 in human plasma.

Science.gov (United States)

Gil, Jeovanis; Cabrales, Ania; Reyes, Osvaldo; Morera, Vivian; Betancourt, Lázaro; Sánchez, Aniel; García, Gerardo; Moya, Galina; Padrón, Gabriel; Besada, Vladimir; González, Luis Javier

2012-02-23

Growth hormone-releasing peptide 6 (GHRP-6, His-(DTrp)-Ala-Trp-(DPhe)-Lys-NH₂, MW=872.44 Da) is a potent growth hormone secretagogue that exhibits a cytoprotective effect, maintaining tissue viability during acute ischemia/reperfusion episodes in different organs like small bowel, liver and kidneys. In the present work a quantitative method to analyze GHRP-6 in human plasma was developed and fully validated following FDA guidelines. The method uses an internal standard (IS) of GHRP-6 with ¹³C-labeled Alanine for quantification. Sample processing includes a precipitation step with cold acetone to remove the most abundant plasma proteins, recovering the GHRP-6 peptide with a high yield. Quantification was achieved by LC-MS in positive full scan mode in a Q-Tof mass spectrometer. The sensitivity of the method was evaluated, establishing the lower limit of quantification at 5 ng/mL and a range for the calibration curve from 5 ng/mL to 50 ng/mL. A dilution integrity test was performed to analyze samples at higher concentration of GHRP-6. The validation process involved five calibration curves and the analysis of quality control samples to determine accuracy and precision. The calibration curves showed R² higher than 0.988. The stability of the analyte and its internal standard (IS) was demonstrated in all conditions the samples would experience in a real time analyses. This method was applied to the quantification of GHRP-6 in plasma from nine healthy volunteers participating in a phase I clinical trial. Copyright © 2011 Elsevier B.V. All rights reserved.

Application of Quality by Design Approach to Bioanalysis: Development of a Method for Elvitegravir Quantification in Human Plasma.

Science.gov (United States)

Baldelli, Sara; Marrubini, Giorgio; Cattaneo, Dario; Clementi, Emilio; Cerea, Matteo

2017-10-01

The application of Quality by Design (QbD) principles in clinical laboratories can help to develop an analytical method through a systematic approach, providing a significant advance over the traditional heuristic and empirical methodology. In this work, we applied for the first time the QbD concept in the development of a method for drug quantification in human plasma using elvitegravir as the test molecule. The goal of the study was to develop a fast and inexpensive quantification method, with precision and accuracy as requested by the European Medicines Agency guidelines on bioanalytical method validation. The method was divided into operative units, and for each unit critical variables affecting the results were identified. A risk analysis was performed to select critical process parameters that should be introduced in the design of experiments (DoEs). Different DoEs were used depending on the phase of advancement of the study. Protein precipitation and high-performance liquid chromatography-tandem mass spectrometry were selected as the techniques to be investigated. For every operative unit (sample preparation, chromatographic conditions, and detector settings), a model based on factors affecting the responses was developed and optimized. The obtained method was validated and clinically applied with success. To the best of our knowledge, this is the first investigation thoroughly addressing the application of QbD to the analysis of a drug in a biological matrix applied in a clinical laboratory. The extensive optimization process generated a robust method compliant with its intended use. The performance of the method is continuously monitored using control charts.

The development and validation of an UHPLC-MS/MS method for the rapid quantification of the antiretroviral agent dapivirine in human plasma.

Science.gov (United States)

Seserko, Lauren A; Emory, Joshua F; Hendrix, Craig W; Marzinke, Mark A

2013-11-01

Dapivirine is a non-nucleoside reverse transcriptase inhibitor designed to prevent HIV-1 viral replication and subsequent propagation. A sensitive method is required to quantify plasma concentrations to assess drug efficacy. Dapivirine-spiked plasma was combined with acetonitrile containing deuterated IS and was processed for analysis. The method has an analytical measuring range from 20 to 10,000 pg/ml. For the LLOQ, low, mid and high QCs, intra- and inter-assay precision (%CV) ranged from 5.58 to 13.89% and 5.23 to 13.36%, respectively, and intra- and inter-day accuracy (% deviation) ranged from -5.61 to 0.75% and -4.30 to 6.24%, respectively. A robust and sensitive LC-MS/MS assay for the high-throughput quantification of the antiretroviral drug dapivirine in human plasma was developed and validated following bioanalytical validation guidelines. The assay meets criteria for the analysis of samples from large research trials.

Validação de métodos cromatográficos para a determinação de resíduos de medicamentos veterinários em alimentos Validation of chromatographic methods for the determination of residues of veterinary drugs in foods

OpenAIRE

Jonas Augusto Rizzato Paschoal; Susanne Rath; Flavia Pereira da Silva Airoldi; Felix G. R. Reyes

2008-01-01

Different agencies that supply validation guidelines worldwide establish almost the same parameters to be evaluated in the validation process of bioanalytical methods. However, they recommend different procedures, as well as establish different acceptance criteria. The present review delineates and discusses the stages involved in the validation procedures of bioanalytical methods designed for determining veterinary residues in food, explaining the main differences in the guidelines establish...

A generic template for automated bioanalytical ligand-binding assays using modular robotic scripts in support of discovery biotherapeutic programs.

Science.gov (United States)

Duo, Jia; Dong, Huijin; DeSilva, Binodh; Zhang, Yan J

2013-07-01

Sample dilution and reagent pipetting are time-consuming steps in ligand-binding assays (LBAs). Traditional automation-assisted LBAs use assay-specific scripts that require labor-intensive script writing and user training. Five major script modules were developed on Tecan Freedom EVO liquid handling software to facilitate the automated sample preparation and LBA procedure: sample dilution, sample minimum required dilution, standard/QC minimum required dilution, standard/QC/sample addition, and reagent addition. The modular design of automation scripts allowed the users to assemble an automated assay with minimal script modification. The application of the template was demonstrated in three LBAs to support discovery biotherapeutic programs. The results demonstrated that the modular scripts provided the flexibility in adapting to various LBA formats and the significant time saving in script writing and scientist training. Data generated by the automated process were comparable to those by manual process while the bioanalytical productivity was significantly improved using the modular robotic scripts.

Strategies for the design of bright upconversion nanoparticles for bioanalytical applications

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Wiesholler, Lisa M.; Hirsch, Thomas

2018-06-01

In recent years upconversion nanoparticles (UCNPs) received great attention because of their outstanding optical properties. Especially in bioanalytical applications this class of materials can overcome limitations of common probes like high background fluorescence or blinking. Nevertheless, the requirements for UCNPs to be applicable in biological samples, e.g. small size, water-dispersibility, excitation at low power density are in contradiction with the demand of high brightness. Therefore, a lot of attention is payed to the enhancement of the upconversion luminescence. This review discuss the recent trends and strategies to boost the brightness of UCNPs, classified in three main directions: a) improving the efficiency of energy absorption by the sensitizer via coupling to plasmonic or photonic structures or via attachment of ligands for light harvesting; b) minimizing non-radiative deactivation by variations in the architecture of UCNPs; and c) changing the excitation wavelength to get bright particles at low excitation power density for applications in aqueous systems. These strategies are critically reviewed including current limitations as well as future perspectives for the design of efficient UCNPs especially for sensing application in biological samples or cells.

On the performance of bioanalytical fluorescence correlation spectroscopy measurements in a multiparameter photon-counting microscope

Energy Technology Data Exchange (ETDEWEB)

Mazouchi, Amir; Liu Baoxu; Bahram, Abdullah [Department of Physics, Institute for Optical Sciences, University of Toronto, Toronto (Canada); Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Rd. N., Mississauga, ON, L5L 1C6 (Canada); Gradinaru, Claudiu C., E-mail: claudiu.gradinaru@utoronto.ca [Department of Physics, Institute for Optical Sciences, University of Toronto, Toronto (Canada); Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Rd. N., Mississauga, ON, L5L 1C6 (Canada)

2011-02-28

Fluorescence correlation spectroscopy (FCS) data acquisition and analysis routines were developed and implemented in a home-built, multiparameter photon-counting microscope. Laser excitation conditions were investigated for two representative fluorescent probes, Rhodamine110 and enhanced green fluorescent protein (EGFP). Reliable local concentrations and diffusion constants were obtained by fitting measured FCS curves, provided that the excitation intensity did not exceed 20% of the saturation level for each fluorophore. Accurate results were obtained from FCS measurements for sample concentrations varying from pM to {mu}M range, as well as for conditions of high background signals. These experimental constraints were found to be determined by characteristics of the detection system and by the saturation behavior of the fluorescent probes. These factors actually limit the average number of photons that can be collected from a single fluorophore passing through the detection volume. The versatility of our setup and the data analysis capabilities were tested by measuring the mobility of EGFP in the nucleus of Drosophila cells under conditions of high concentration and molecular crowding. As a bioanalytical application, we studied by FCS the binding affinity of a novel peptide-based drug to the cancer-regulating STAT3 protein and corroborated the results with fluorescence polarization analysis derived from the same photon data.

The development and validation of an UHPLC–MS/MS method for the rapid quantification of the antiretroviral agent dapivirine in human plasma

Science.gov (United States)

Seserko, Lauren A; Emory, Joshua F; Hendrix, Craig W; Marzinke, Mark A

2014-01-01

Background Dapivirine is a non-nucleoside reverse transcriptase inhibitor designed to prevent HIV-1 viral replication and subsequent propagation. A sensitive method is required to quantify plasma concentrations to assess drug efficacy. Results Dapivirine-spiked plasma was combined with acetonitrile containing deuterated IS and was processed for analysis. The method has an analytical measuring range from 20 to 10,000 pg/ml. For the LLOQ, low, mid and high QCs, intra- and inter-assay precision (%CV) ranged from 5.58 to 13.89% and 5.23 to 13.36%, respectively, and intra- and inter-day accuracy (% deviation) ranged from -5.61 to 0.75% and -4.30 to 6.24%, respectively. Conclusion A robust and sensitive LC–MS/MS assay for the high-throughput quantification of the antiretroviral drug dapivirine in human plasma was developed and validated following bioanalytical validation guidelines. The assay meets criteria for the analysis of samples from large research trials. PMID:24256358

The BioSentinel Bioanalytical Microsystem: Characterizing DNA Radiation Damage in Living Organisms Beyond Earth Orbit

Science.gov (United States)

Ricco, A. J.; Hanel, R.; Bhattacharya, S.; Boone, T.; Tan, M.; Mousavi, A.; Rademacher, A.; Schooley, A.; Klamm, B.; Benton, J.;

Validação em métodos cromatográficos para análises de pequenas moléculas em matrizes biológicas

OpenAIRE

Cassiano,Neila Maria; Barreiro,Juliana Cristina; Martins,Lúcia Regina Rocha; Oliveira,Regina Vincenzi; Cass,Quezia Bezerra

2009-01-01

Chromatographic methods are commonly used for analysis of small molecules in different biological matrices. An important step to be considered upon a bioanalytical method's development is the capacity to yield reliable and reproducible results. This review discusses validation procedures adopted by different governmental agencies, such as Food and Drug Administration (USA), European Union (EU) and Agência Nacional de Vigilância Sanitária (BR) for quantification of small molecules by bioanalyt...

Synthesis, Characterization and Utility of Carbon Nanotube Based Hybrid Sensors in Bioanalytical Applications

Science.gov (United States)

Badhulika, Sushmee

The detection of gaseous analytes and biological molecules is of prime importance in the fields of environmental pollution control, food and water - safety and analysis; and medical diagnostics. This necessitates the development of advanced and improved technology that is reliable, inexpensive and suitable for high volume production. The conventional sensors are often thin film based which lack sensitivity due to the phenomena of current shunting across the charge depleted region when an analyte binds with them. One dimensional (1-D) nanostructures provide a better alternative for sensing applications by eliminating the issue of current shunting due to their 1-D geometries and facilitating device miniaturization and low power operations. Carbon nanotubes (CNTs) are 1-D nanostructures that possess small size, high mechanical strength, high electrical and thermal conductivity and high specific area that have resulted in their wide spread applications in sensor technology. To overcome the issue of low sensitivity of pristine CNTs and to widen their scope, hybrid devices have been fabricated that combine the synergistic properties of CNTs along with materials like metals and conducting polymers (CPs). CPs exhibit electronic, magnetic and optical properties of metals and semiconductors while retaining the processing advantages of polymers. Their high chemical sensitivity, room temperature operation and tunable charge transport properties has made them ideal for use as transducing elements in chemical sensors. In this dissertation, various CNT based hybrid devices such as CNT-conducting polymer and graphene-CNT-metal nanoparticles based sensors have been developed and demonstrated towards bioanalytical applications such as detection of volatile organic compounds (VOCs) and saccharides. Electrochemical polymerization enabled the synthesis of CPs and metal nanoparticles in a simple, cost effective and controlled way on the surface of CNT based platforms thus resulting in

Validation and implementation of liquid chromatographic-mass spectrometric (LC-MS) methods for the quantification of tenofovir prodrugs.

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Hummert, Pamela; Parsons, Teresa L; Ensign, Laura M; Hoang, Thuy; Marzinke, Mark A

2018-04-15

The nucleotide reverse transcriptase inhibitor tenofovir (TFV) is widely administered in a disoproxil prodrug form (tenofovir disoproxil fumarate, TDF) for HIV management and prevention. Recently, novel prodrugs tenofovir alafenamide fumarate (TAF) and hexadecyloxypropyl tenofovir (CMX157) have been pursued for HIV treatment while minimizing adverse effects associated with systemic TFV exposure. Dynamic and sensitive bioanalytical tools are required to characterize the pharmacokinetics of these prodrugs in systemic circulation. Two parallel methods have been developed, one to combinatorially quantify TAF and TFV, and a second method for CMX157 quantification, in plasma. K 2 EDTA plasma was spiked with TAF and TFV, or CMX157. Following the addition of isotopically labeled internal standards and sample extraction via solid phase extraction (TAF and TFV) or protein precipitation (CMX157), samples were subjected to liquid chromatographic-tandem mass spectrometric (LC-MS/MS) analysis. For TAF and TFV, separation occurred using a Zorbax Eclipse Plus C18 Narrow Bore RR, 2.1 × 50 mm, 3.5 μm column and analytes were detected on an API5000 mass analyzer; CMX157 was separated using a Kinetex C8, 2.1 × 50 mm, 2.6 μm column and quantified using an API4500 mass spectrometer. Methods were validated according to FDA Bioanalytical Method Validation guidelines. Analytical methods: were optimized for the multiplexed monitoring of TAF and TFV, and CMX157 in plasma. The lower limits of quantification (LLOQs) for TAF, TFV, and CMX157 were 0.03, 1.0, and 0.25 ng/mL, respectively. Calibration curves were generated via weighted linear regression of standards. Intra- and inter-assay precision and accuracy studies demonstrated %CVs ≤ 14.4% and %DEVs ≤ ± 7.95%, respectively. Stability and matrix effects studies were also performed. All results were acceptable and in accordance with the recommended guidelines for bioanalytical methods. Assays were also

Bioanalytical assessment of adaptive stress responses in drinking water: A predictive tool to differentiate between micropollutants and disinfection by-products.

Science.gov (United States)

Hebert, Armelle; Feliers, Cedric; Lecarpentier, Caroline; Neale, Peta A; Schlichting, Rita; Thibert, Sylvie; Escher, Beate I

2018-04-01

Drinking water can contain low levels of micropollutants, as well as disinfection by-products (DBPs) that form from the reaction of disinfectants with organic and inorganic matter in water. Due to the complex mixture of trace chemicals in drinking water, targeted chemical analysis alone is not sufficient for monitoring. The current study aimed to apply in vitro bioassays indicative of adaptive stress responses to monitor the toxicological profiles and the formation of DBPs in three drinking water distribution systems in France. Bioanalysis was complemented with chemical analysis of forty DBPs. All water samples were active in the oxidative stress response assay, but only after considerable sample enrichment. As both micropollutants in source water and DBPs formed during treatment can contribute to the effect, the bioanalytical equivalent concentration (BEQ) approach was applied for the first time to determine the contribution of DBPs, with DBPs found to contribute between 17 and 58% of the oxidative stress response. Further, the BEQ approach was also used to assess the contribution of volatile DBPs to the observed effect, with detected volatile DBPs found to have only a minor contribution as compared to the measured effects of the non-volatile chemicals enriched by solid-phase extraction. The observed effects in the distribution systems were below any level of concern, quantifiable only at high enrichment and not different from bottled mineral water. Integrating bioanalytical tools and the BEQ mixture model for monitoring drinking water quality is an additional assurance that chemical monitoring is not overlooking any unknown chemicals or transformation products and can help to ensure chemically safe drinking water. Copyright © 2017. Published by Elsevier Ltd.

Bioanalysis of antibody-drug conjugates: American Association of Pharmaceutical Scientists Antibody-Drug Conjugate Working Group position paper.

Science.gov (United States)

Gorovits, Boris; Alley, Stephen C; Bilic, Sanela; Booth, Brian; Kaur, Surinder; Oldfield, Phillip; Purushothama, Shobha; Rao, Chetana; Shord, Stacy; Siguenza, Patricia

2013-05-01

Antibody-drug conjugates (ADCs) typically consist of a cytotoxic drug covalently bound to an antibody by a linker. These conjugates have the potential to substantially improve efficacy and reduce toxicity compared with cytotoxic small-molecule drugs. Since ADCs are generally complex heterogeneous mixtures of multiple species, these novel therapeutic products present unique bioanalytical challenges. The growing number of ADCs being developed across the industry suggests the need for alignment of the bioanalytical methods or approaches used to assess the multiple species and facilitate consistent interpretation of the bioanalytical data. With limited clinical data, the current strategies that can be used to provide insight into the relationship between the multiple species and the observed clinical safety and efficacy are still evolving. Considerations of the bioanalytical strategies for ADCs based on the current industry practices that take into account the complexity and heterogeneity of ADCs are discussed.

cp-R, an interface the R programming language for clinical laboratory method comparisons.

Science.gov (United States)

Holmes, Daniel T

2015-02-01

Clinical scientists frequently need to compare two different bioanalytical methods as part of assay validation/monitoring. As a matter necessity, regression methods for quantitative comparison in clinical chemistry, hematology and other clinical laboratory disciplines must allow for error in both the x and y variables. Traditionally the methods popularized by 1) Deming and 2) Passing and Bablok have been recommended. While commercial tools exist, no simple open source tool is available. The purpose of this work was to develop and entirely open-source GUI-driven program for bioanalytical method comparisons capable of performing these regression methods and able to produce highly customized graphical output. The GUI is written in python and PyQt4 with R scripts performing regression and graphical functions. The program can be run from source code or as a pre-compiled binary executable. The software performs three forms of regression and offers weighting where applicable. Confidence bands of the regression are calculated using bootstrapping for Deming and Passing Bablok methods. Users can customize regression plots according to the tools available in R and can produced output in any of: jpg, png, tiff, bmp at any desired resolution or ps and pdf vector formats. Bland Altman plots and some regression diagnostic plots are also generated. Correctness of regression parameter estimates was confirmed against existing R packages. The program allows for rapid and highly customizable graphical output capable of conforming to the publication requirements of any clinical chemistry journal. Quick method comparisons can also be performed and cut and paste into spreadsheet or word processing applications. We present a simple and intuitive open source tool for quantitative method comparison in a clinical laboratory environment. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Rapid methods for dioxin and dioxin-like PCBs in food and feedingstuffs. State of the art

Energy Technology Data Exchange (ETDEWEB)

Behnisch, P.A. [eurofins-GfA, Muenster (Germany); Hoogenboom, R. [RIKILT-Institute of Food Safety, Wageningen (Netherlands)

2004-09-15

The increasing number of local dioxin crises since 2002 becoming more and more apparent due to stricter controls of feed and food in the European Union and the globally increasing number of countries applying similar guidelines make it necessary to establish reliable, time and cost-effective screening methods for the dioxin intake through nutritional pathways. Five years after the last overview presentation about all kinds of different bio-analytical detection methods (BDMs) and the establishment of quality guidelines for screening methods, time has come to include as well the improvements in the chemical methods to speed up the analysis. This review gives an overview about the state-of-the-art improvements and gives a future outlook for both methods, chemical and bio-analytical approach for rapid analyses of dioxins and dioxin-like compounds. Now several new ways of improvement are currently in the pipeline of research and testing, such as PCR, proteomic biomarkers and in case of the clean-up ASE11, PowerPrep and different detection methods as well as different other ways of indicators for dioxins (e.g. correlations to fatty acids).

Bioanalytical methods for determination of tamoxifen and its phase I metabolites: A review

International Nuclear Information System (INIS)

Teunissen, S.F.; Rosing, H.; Schinkel, A.H.; Schellens, J.H.M.; Beijnen, J.H.

2010-01-01

The selective estrogen receptor modulator tamoxifen is used in the treatment of early and advanced breast cancer and in selected cases for breast cancer prevention in high-risk subjects. The cytochrome P450 enzyme system and flavin-containing monooxygenase are responsible for the extensive metabolism of tamoxifen into several phase I metabolites that vary in toxicity and potencies towards estrogen receptor (ER) alpha and ER beta. An extensive overview of publications on the determination of tamoxifen and its phase I metabolites in biological samples is presented. In these publications techniques were used such as capillary electrophoresis, liquid, gas and thin layer chromatography coupled with various detection techniques (mass spectrometry, ultraviolet or fluorescence detection, liquid scintillation counting and nuclear magnetic resonance spectroscopy). A trend is seen towards the use of liquid chromatography coupled to mass spectrometry (LC-MS). State-of-the-art LC-MS equipment allowed for identification of unknown metabolites and quantification of known metabolites reaching lower limit of quantification levels in the sub pg mL -1 range. Although tamoxifen is also metabolized into phase II metabolites, the number of publications reporting on phase II metabolism of tamoxifen is scarce. Therefore the focus of this review is on phase I metabolites of tamoxifen. We conclude that in the past decades tamoxifen metabolism has been studied extensively and numerous metabolites have been identified. Assays have been developed for both the identification and quantification of tamoxifen and its metabolites in an array of biological samples. This review can be used as a resource for method transfer and development of analytical methods used to support pharmacokinetic and pharmacodynamic studies of tamoxifen and its phase I metabolites.

Simple and Selective HPLC-UV/Vis Bioanalytical Method to Determine Aluminum Phthalocyanine Chloride in Skin Permeation Studies

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Thaiene Avila Reis

2018-01-01

Full Text Available Considering the feasibility of the aluminum phthalocyanine chloride (AlPcCl application in the topical photodynamic therapy of cutaneous tumors and the lack of HPLC methods capable of supporting skin permeation experiments using this compound, the aim of this study was to obtain a simple and selective chromatographic method for AlPcCl determination in skin matrices. A HPLC-UV/Vis method was developed using a normal-phase column operating at 30°C, an isocratic mobile phase of methanol : phosphoric acid (0.01 M at 1.5 mL/min, and detection at 670 nm. The method exhibited (i selectivity against various contaminants found in the different skin layers, (ii high drug extraction capacity from the hair follicle (>70% and remaining skin (>80%, and (iii low limits of detection and of quantification (0.03 and 0.09 μg/mL, resp.. The method was also linear in the range from 0.1 to 5.0 µg/mL (r = 0.9994 and demonstrated robustness with regard to experimental chromatographic parameters according to a factorial design. Lastly, the developed method was successfully tested in in vitro skin permeation studies of AlPcCl, proving its effectiveness in the development of pharmaceutical delivery systems containing this drug for topical photodynamic therapy of skin cancers.

Development and Validation of HPLC Method for Determination of Crocetin, a constituent of Saffron, in Human Serum Samples

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Amir Hooshang Mohammadpour

2013-01-01

Full Text Available Objective(s:The present study reports the development and validation of a sensitive and rapid extraction method beside high performance liquid chromatographic method for the determination of crocetin in human serum. Materials and Methods:The HPLC method was carried out by using a C18 reversed-phase column and a mobile phase composed of methanol/water/acetic acid (85:14.5:0.5 v/v/v at the flow rate of 0.8 ml/min. The UV detector was set at 423 nm and 13-cis retinoic acid was used as the internal standard. Serum samples were pretreated with solid-phase extraction using Bond Elut C18 (200mg cartridges or with direct precipitation using acetonitrile. Results:The calibration curves were linear over the range of 0.05-1.25 µg/ml for direct precipitation method and 0.5-5 µg/ml for solid-phase extraction. The mean recoveries of crocetin over a concentration range of 0.05-5 µg/ml serum for direct precipitation method and 0.5-5 µg/ml for solid-phase extraction were above 70 % and 60 %, respectively. The intraday coefficients of variation were 0.37- 2.6% for direct precipitation method and 0.64 - 5.43% for solid-phase extraction. The inter day coefficients of variation were 1.69 – 6.03% for direct precipitation method and 5.13-12.74% for solid-phase extraction, respectively. The lower limit of quantification for crocetin was 0.05 µg/ml for direct precipitation method and 0.5 µg/ml for solid-phase extraction. Conclusion: The validated direct precipitation method for HPLC satisfied all of the criteria that were necessary for a bioanalytical method and could reliably quantitate crocetin in human serum for future clinical pharmacokinetic study

Rapid and label-free bioanalytical method of alpha fetoprotein detection using LSPR chip

Science.gov (United States)

Kim, Dongjoo; Kim, Jinwoon; Kwak, Cheol Hwan; Heo, Nam Su; Oh, Seo Yeong; Lee, Hoomin; Lee, Go-Woon; Vilian, A. T. Ezhil; Han, Young-Kyu; Kim, Woo-Sik; Kim, Gi-bum; Kwon, Soonjo; Huh, Yun Suk

2017-07-01

Alpha fetoprotein (AFP) is a cancer marker, particularly for hepatocellular carcinoma. Normal levels of AFP are less than 20 ng/mL; however, its levels can reach more than 400 ng/mL in patients with HCC. Enzyme linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) have been employed for clinical diagnosis of AFP; however, these methods are time consuming and labor intensive. In this study, we developed a localized surface plasmon resonance (LSPR) based biosensor for simple and rapid detection of AFP. This biosensor consists of a UV-Vis spectrometer, a cuvette cell, and a biosensor chip nanopatterned with gold nanoparticles (AuNPs). In our LSPR biosensor, binding of AFP to the surface of the sensor chip led to an increasing magnitude of the LSPR signals, which was measured by an ultraviolet-visible (UV-Vis) spectrometer. Our LSPR biosensor showed sufficient detectability of AFP at concentrations of 1 ng/mL to 1 μg/mL. Moreover, the overall procedure for detection of AFP was completed within 20 min. This biosensor could also be utilized for a point of care test (POCT) by employing a portable UV-Vis spectrometer. Owing to the simplicity and rapidity of the detection process, our LSPR biosensor is expected to replace traditional diagnostic methods for the early detection of diseases.

Rapid Determination of Isomeric Benzoylpaeoniflorin and Benzoylalbiflorin in Rat Plasma by LC-MS/MS Method

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Chuanqi Zhou

2017-01-01

Full Text Available Benzoylpaeoniflorin (BP is a potential therapeutic agent against oxidative stress related Alzheimer’s disease. In this study, a more rapid, selective, and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS method was developed to determine BP in rat plasma distinguishing with a monoterpene isomer, benzoylalbiflorin (BA. The method showed a linear response from 1 to 1000 ng/mL (r>0.9950. The precision of the interday and intraday ranged from 2.03 to 12.48% and the accuracy values ranged from −8.00 to 10.33%. Each running of the method could be finished in 4 minutes. The LC-MS/MS method was validated for specificity, linearity, precision, accuracy, recovery, and stability and was found to be acceptable for bioanalytical application. Finally, this fully validated method was successfully applied to a pharmacokinetic study in rats following oral administration.

Bioanalytical method development and validation for the determination of glycine in human cerebrospinal fluid by ion-pair reversed-phase liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Jiang, Jian; James, Christopher A; Wong, Philip

2016-09-05

A LC-MS/MS method has been developed and validated for the determination of glycine in human cerebrospinal fluid (CSF). The validated method used artificial cerebrospinal fluid as a surrogate matrix for calibration standards. The calibration curve range for the assay was 100-10,000ng/mL and (13)C2, (15)N-glycine was used as an internal standard (IS). Pre-validation experiments were performed to demonstrate parallelism with surrogate matrix and standard addition methods. The mean endogenous glycine concentration in a pooled human CSF determined on three days by using artificial CSF as a surrogate matrix and the method of standard addition was found to be 748±30.6 and 768±18.1ng/mL, respectively. A percentage difference of -2.6% indicated that artificial CSF could be used as a surrogate calibration matrix for the determination of glycine in human CSF. Quality control (QC) samples, except the lower limit of quantitation (LLOQ) QC and low QC samples, were prepared by spiking glycine into aliquots of pooled human CSF sample. The low QC sample was prepared from a separate pooled human CSF sample containing low endogenous glycine concentrations, while the LLOQ QC sample was prepared in artificial CSF. Standard addition was used extensively to evaluate matrix effects during validation. The validated method was used to determine the endogenous glycine concentrations in human CSF samples. Incurred sample reanalysis demonstrated reproducibility of the method. Copyright © 2016 Elsevier B.V. All rights reserved.

Development and validation of a highly sensitive LC-ESI-MS/MS method for estimation of IIIM-MCD-211, a novel nitrofuranyl methyl piperazine derivative with potential activity against tuberculosis: Application to drug development.

Science.gov (United States)

Magotra, Asmita; Sharma, Anjna; Gupta, Ajai Prakash; Wazir, Priya; Sharma, Shweta; Singh, Parvinder Pal; Tikoo, Manoj Kumar; Vishwakarma, Ram A; Singh, Gurdarshan; Nandi, Utpal

2017-08-15

In the present study, a simple, sensitive, specific and rapid liquid chromatography (LC) tandem mass spectrometry (MS/MS) method was developed and validated according to the Food and Drug Administration (FDA) guidelines for estimation of IIIM-MCD-211 (a potent oral candidate with promising action against tuberculosis) in mice plasma using carbamazepine as internal standard (IS). Bioanalytical method consisted of one step protein precipitation for sample preparation followed by quantitation in LC-MS/MS using positive electrospray ionization technique (ESI) operating in multiple reaction monitoring (MRM) mode. Elution was achieved in gradient mode on High Resolution Chromolith RP-18e column with mobile phase comprised of acetonitrile and 0.1% (v/v) formic acid in water at the flow rate of 0.4mL/min. Precursor to product ion transitions (m/z 344.5/218.4 and m/z 237.3/194.2) were used to measure analyte and IS, respectively. All validation parameters were well within the limit of acceptance criteria. The method was successfully applied to assess the pharmacokinetics of the candidate in mice following oral (10mg/kg) and intravenous (IV; 2.5mg/kg) administration. It was also effectively used to quantitate metabolic stability of the compound in mouse liver microsomes (MLM) and human liver microsomes (HLM) followed by its in-vitro-in-vivo extrapolation. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomimetic Receptors for Bioanalyte Detection by Quartz Crystal Microbalances — From Molecules to Cells

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Usman Latif

2014-12-01

Full Text Available A universal label-free detection of bioanalytes can be performed with biomimetic quartz crystal microbalance (QCM coatings prepared by imprinting strategies. Bulk imprinting was used to detect the endocrine disrupting chemicals (EDCs known as estradiols. The estrogen 17β-estradiol is one of the most potent EDCs, even at very low concentrations. A highly sensitive, selective and robust QCM sensor was fabricated for real time monitoring of 17β-estradiol in water samples by using molecular imprinted polyurethane. Optimization of porogen (pyrene and cross-linker (phloroglucinol levels leads to improved sensitivity, selectivity and response time of the estradiol sensor. Surface imprinting of polyurethane as sensor coating also allowed us to generate interaction sites for the selective recognition of bacteria, even in a very complex mixture of interfering compounds, while they were growing from their spores in nutrient solution. A double molecular imprinting approach was followed to transfer the geometrical features of natural bacteria onto the synthetic polymer to generate biomimetic bacteria. The use of biomimetic bacteria as template makes it possible to prepare multiple sensor coatings with similar sensitivity and selectivity. Thus, cell typing, e.g., differentiation of bacteria strains, bacteria growth profile and extent of their nutrition, can be monitored by biomimetic mass sensors. Obviously, this leads to controlled cell growth in bioreactors.

A validated bioanalytical HPLC method for pharmacokinetic evaluation of 2-deoxyglucose in human plasma.

Science.gov (United States)

Gounder, Murugesan K; Lin, Hongxia; Stein, Mark; Goodin, Susan; Bertino, Joseph R; Kong, Ah-Ng Tony; DiPaola, Robert S

2012-05-01

2-Deoxyglucose (2-DG), an analog of glucose, is widely used to interfere with glycolysis in tumor cells and studied as a therapeutic approach in clinical trials. To evaluate the pharmacokinetics of 2-DG, we describe the development and validation of a sensitive HPLC fluorescent method for the quantitation of 2-DG in plasma. Plasma samples were deproteinized with methanol and the supernatant was dried at 45°C. The residues were dissolved in methanolic sodium acetate-boric acid solution. 2-DG and other monosaccharides were derivatized to 2-aminobenzoic acid derivatives in a single step in the presence of sodium cyanoborohydride at 80°C for 45 min. The analytes were separated on a YMC ODS C₁₈ reversed-phase column using gradient elution. The excitation and emission wavelengths were set at 360 and 425 nm. The 2-DG calibration curves were linear over the range of 0.63-300 µg/mL with a limit of detection of 0.5 µg/mL. The assay provided satisfactory intra-day and inter-day precision with RSD less than 9.8%, and the accuracy ranged from 86.8 to 110.0%. The HPLC method is reproducible and suitable for the quantitation of 2-DG in plasma. The method was successfully applied to characterize the pharmacokinetics profile of 2-DG in patients with advanced solid tumors. Copyright © 2011 John Wiley & Sons, Ltd.

Bioanalysis, metabolism & clinical pharmacology of antiretroviral drugs

NARCIS (Netherlands)

Heine, R. ter

2009-01-01

The aims of all studies described in this thesis were to develop new bioanalytical and more patient friendly methods for studying the clinical pharmacology of antiretroviral drugs and to ultimately improve antiretroviral treatment.

Development and Validation of a Bioanalytical Method for Quantification of 2,6-Bis-(4-hydroxy-3-methoxybenzylidene-cyclohexanone (BHMC in Rat Plasma

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Yu Zhao Lee

2012-12-01

Full Text Available A sensitive and accurate high performance liquid chromatography with ultraviolet/visible light detection (HPLC-UV/VIS method for the quantification of 2,6-bis-(4-hydroxy-3-methoxybenzylidene-cyclohexanone (BHMC in rat plasma was developed and validated. BHMC and the internal standard, harmaline, were extracted from plasma samples by a simple liquid–liquid extraction using 95% ethyl acetate and 5% methanol. Plasma concentration of BHMC and internal standard were analyzed by reversed phase chromatography using a C18 column (150 × 4.6 mm I.D., particle size 5 µm and elution with a gradient mobile phase of water and methanol at a flow rate of 1.0 mL/min. Detection of BHMC and internal standard was done at a wavelength of 380 nm. The limit of quantification was 0.02 µg/mL. The calibration curves was linear (R2 > 0.999 over the concentration range of 0.02–2.5 µg/mL. Intra- and inter-day precision were less than 2% coefficient of variation. The validated method was then applied to a pharmacokinetic study in rats by intravenous administration of BHMC at a single dose of 10 mg/kg. Pharmacokinetic parameters such as half-life, maximum plasma concentration, volume of distribution, clearance and elimination rate constant for BHMC were calculated.

Development and validation of bioanalytical UHPLC-UV method for simultaneous analysis of unchanged fenofibrate and its metabolite fenofibric acid in rat plasma: Application to pharmacokinetics

Directory of Open Access Journals (Sweden)

Rayan G. Alamri

2017-01-01

Full Text Available A simple, precise, selective and fast ultra-high performance liquid chromatography (UHPLC-UV method has been developed and validated for the simultaneous determination of a lipid regulating agent fenofibrate and its metabolite fenofibric acid in rat plasma. The chromatographic separation was carried out on a reversed-phase Acquity® BEH C18 column using methanol–water (65:35, v/v as the mobile phase. The isocratic flow was 0.3 ml/min with rapid run time of 2.5 min and UV detection was at 284 nm. The method was validated over a concentration range of 100–10000 ng/ml (r2 ⩾ 0.9993. The selectivity, specificity, recovery, accuracy and precision were validated for determination of fenofibrate/fenofibric acid in rat plasma. The lower limits of detection and quantitation of the method were 30 and 90 ng/ml for fenofibrate and 40 and 100 ng/ml for fenofibric acid, respectively. The within and between-day coefficients of variation were less than 5%. The validated method has been successfully applied to measure the plasma concentrations in pharmacokinetics study of fenofibrate in an animal model to illustrate the scope and application of the method.

Development of a new ultra-high performance liquid chromatography - tandem mass spectrometry method for determination of ambroxol hydrochloride in serum with pharmacokinetic application

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Vujović Maja M.

2016-01-01

Full Text Available Ambroxol hydrochloride is an expectorant agent, successfully applied in mucolytic therapy for acute and chronic bronchopulmonary diseases. The drug regulates not only mucus secretion but also showed antioxidant, anti-inflammatory and local anesthetic properties. To supplement the pharmacokinetic and toxicological studies of ambroxol, a rapid ultra-high performance liquid chromatography-tandem mass spectrometry method for the quantitation of ambroxol in rabbit serum was developed. A validation of the method was performed as per the ICH guidelines for the validation of bioanalytical methods. The chromatographic separation was achieved in a submicron Kinetex RP - C18 - column (2.1 mm x 50 mm, 1.3μm using the no buffer mobile phase. The ESI mass spectrometry in the MRM mode was used with a typical transitions m/z 378.9→263.8 for ambroxol and m/z 455.2→165.0 for IS. Linearity was determined with an average coefficient of determination >0.999 over the dynamic range from 0.5 - 200 ng/mL with LOD and LOQ of 0.25 ng/mL and 0.5 ng/mL, respectively. The results of the intra- and inter-day precision and accuracy determined in different days were all found to be within the acceptable limits ±15%. The present method was successfully applied to pharmacokinetic study in the rabbits after a single oral dose administration. [Projekat Ministarstva nauke Republike Srbije, br. 175045

Acceptability criteria for linear dependence in validating UV-spectrophotometric methods of quantitative determination in forensic and toxicological analysis

Directory of Open Access Journals (Sweden)

L. Yu. Klimenko

2014-08-01

Full Text Available Introduction. This article is the result of authors’ research in the field of development of the approaches to validation of quantitative determination methods for purposes of forensic and toxicological analysis and devoted to the problem of acceptability criteria formation for validation parameter «linearity/calibration model». The aim of research. The purpose of this paper is to analyse the present approaches to acceptability estimation of the calibration model chosen for method description according to the requirements of the international guidances, to form the own approaches to acceptability estimation of the linear dependence when carrying out the validation of UV-spectrophotometric methods of quantitative determination for forensic and toxicological analysis. Materials and methods. UV-spectrophotometric method of doxylamine quantitative determination in blood. Results. The approaches to acceptability estimation of calibration models when carrying out the validation of bioanalytical methods is stated in international papers, namely «Guidance for Industry: Bioanalytical method validation» (U.S. FDA, 2001, «Standard Practices for Method Validation in Forensic Toxicology» (SWGTOX, 2012, «Guidance for the Validation of Analytical Methodology and Calibration of Equipment used for Testing of Illicit Drugs in Seized Materials and Biological Specimens» (UNODC, 2009 and «Guideline on validation of bioanalytical methods» (ЕМА, 2011 have been analysed. It has been suggested to be guided by domestic developments in the field of validation of analysis methods for medicines and, particularly, by the approaches to validation methods in the variant of the calibration curve method for forming the acceptability criteria of the obtained linear dependences when carrying out the validation of UV-spectrophotometric methods of quantitative determination for forensic and toxicological analysis. The choice of the method of calibration curve is

Ask the experts: automation: part I.

Science.gov (United States)

Allinson, John L; Blick, Kenneth E; Cohen, Lucinda; Higton, David; Li, Ming

2013-08-01

Bioanalysis invited a selection of leading researchers to express their views on automation in the bioanalytical laboratory. The topics discussed include the challenges that the modern bioanalyst faces when integrating automation into existing drug-development processes, the impact of automation and how they envision the modern bioanalytical laboratory changing in the near future. Their enlightening responses provide a valuable insight into the impact of automation and the future of the constantly evolving bioanalytical laboratory.

A critical review of microextraction by packed sorbent as a sample preparation approach in drug bioanalysis.

Science.gov (United States)

Alves, Gilberto; Rodrigues, Márcio; Fortuna, Ana; Falcão, Amílcar; Queiroz, João

2013-06-01

Sample preparation is widely accepted as the most labor-intensive and error-prone part of the bioanalytical process. The recent advances in this field have been focused on the miniaturization and integration of sample preparation online with analytical instrumentation, in order to reduce laboratory workload and increase analytical performance. From this perspective, microextraction by packed sorbent (MEPS) has emerged in the last few years as a powerful sample preparation approach suitable to be easily automated with liquid and gas chromatographic systems applied in a variety of bioanalytical areas (pharmaceutical, clinical, toxicological, environmental and food research). This paper aims to provide an overview and a critical discussion of recent bioanalytical methods reported in literature based on MEPS, with special emphasis on those developed for the quantification of therapeutic drugs and/or metabolites in biological samples. The advantages and some limitations of MEPS, as well as its comparison with other extraction techniques, are also addressed herein.

High-throughput screening assay used in pharmacognosy: Selection, optimization and validation of methods of enzymatic inhibition by UV-visible spectrophotometry

Directory of Open Access Journals (Sweden)

Graciela Granados-Guzmán

2014-02-01

Full Text Available In research laboratories of both organic synthesis and extraction of natural products, every day a lot of products that can potentially introduce some biological activity are obtained. Therefore it is necessary to have in vitro assays, which provide reliable information for further evaluation in in vivo systems. From this point of view, in recent years has intensified the use of high-throughput screening assays. Such trials should be optimized and validated for accurate and precise results, i.e. reliable. The present review addresses the steps needed to develop and validate bioanalytical methods, emphasizing UV-Visible spectrophotometry as detection system. Particularly focuses on the selection of the method, the optimization to determine the best experimental conditions, validation, implementation of optimized and validated method to real samples, and finally maintenance and possible transfer it to a new laboratory.

Development of a Supercritical Fluid Chromatography-Tandem Mass Spectrometry Method for the Determination of Azacitidine in Rat Plasma and Its Application to a Bioavailability Study

Directory of Open Access Journals (Sweden)

Dongpo Li

2013-12-01

Full Text Available Azacitidine is widely used for the treatment of myelodysplastic syndromes (MDS and acute myelogenous leukaemia (AML. The analysis of azacitidine in biological samples is subject to interference by endogenous compounds. Previously reported high-performance liquid chromatography/tandem mass spectrometric (HPLC-MS/MS bioanalytical assays for azacitidine suffer from expensive sample preparation procedures or from long separation times to achieve the required selectivity. Herein, supercritical fluid chromatography with tandem mass spectrometry (SFC-MS/MS was explored as a more promising technique for the selective analysis of structure-like or chiral drugs in biological matrices. In this study, a simple, rapid and specific SFC/MS/MS analytical method was developed for the determination of azacitidine levels in rat plasma. Azacitidine was completely separated from the endogenous compounds on an ACQUITY UPLC™ BEH C18 column (100 mm × 3.0 mm, 1.7 μm; Waters Corp., Milford, MA, USA using isocratic elution with CO2/methanol as the mobile phase. The single-run analysis time was as short as 3.5 min. The sample preparation for protein removal was accomplished using a simple methanol precipitation method. The lower limit of quantification (LLOQ of azacitidine was 20 ng/mL. The intra-day and inter-day precisions were less than 15%, and the relative error (RE was within ±15% for the medium- and high-concentration quality control (QC samples and within ±20% for the low-concentration QC samples. Finally, the developed method was successfully applied to a pharmacokinetic study in rats following the intravenous administration of azacitidine.

Development of SPME-LC-MS method for screening of eight beta-blockers and bronchodilators in plasma and urine samples.

Science.gov (United States)

Goryński, Krzysztof; Kiedrowicz, Alicja; Bojko, Barbara

2016-08-05

The current work describes the development and validation of a simple, efficient, and fast method using solid phase microextraction coupled to liquid chromatography-tandem mass spectrometry (SPME-LC-MS/MS) for the concomitant measurement of eight beta-blockers and bronchodilators in plasma and urine. The presented assay enables quantitative determination of acebutolol, atenolol, fenoterol, nadolol, pindolol, procaterol, sotalol, and timolol. In this work, samples were prepared on a high-throughput platform using the 96-well plate format of the thin film solid phase microextraction (TFME) system, and a biocompatible extraction phase made of hydrophilic-lipophilic balance particles. Analytes were separated on a pentafluorophenyl column (100mm×2.1mm, 3μm) by gradient elution using an UPLC Nexera coupled with an LCMS-8060 mass spectrometer. The mobile phase consisted of water-acetonitrile (0.1% formic acid) at a flow rate of 0.4mLmin(-1). The linearity of the method was checked within therapeutic blood-plasma concentrations, and shown to adequately reflect typically expected concentrations of future study samples. Post-extraction addition experiments showed that the matrix effect ranged in plasma from 98% for procaterol to 115% for nadolol, and in urine, from 85% for nadolol and pindolol to 119% for atenolol. The method was successfully validated using Food and Drug Administration (FDA) guidelines, and met all acceptance criteria for bioanalytical assays at five concentration levels for all selected drugs. The final protocol can be successfully applied for monitoring concentrations of the selected drugs in both plasma and urine matrices obtained from patients or athletes. Copyright © 2016 Elsevier B.V. All rights reserved.

Organophosphorus insecticides: Toxic effects and bioanalytical tests for evaluating toxicity during degradation processes

Directory of Open Access Journals (Sweden)

Čolović Mirjana B.

2013-01-01

Full Text Available Organophosphorus insecticides have been the most applied group of insecticides for the last two decades. Their main toxic effects are related to irreversible inactivation of acetylcholinesterase (AChE. Actually, they covalently bind to serine OH group in the enzyme active site forming phosphorylated enzyme that cannot hydrolyze acetylcholine. Organophosphorus insecticides in the environment undergo the natural degradation pathway including mainly homogeneous and heterogeneous hydrolysis (especially at high pH generating non-inhibiting products. Additionally, thio organophosphates are easily oxidized by naturally present oxidants and UV light, forming more toxic and stable oxons. Thus, oxidative degradation procedures, generally referred as advanced oxidation processes (AOP, have been applied for their efficient removal from contaminated waters. The most applied bioassays to monitor the organophosphate toxicity i.e. the detoxification degree during AOP are Vibrio fischeri and AChE bioassays. Vibrio fischeri toxicity test exploits bioluminescence as the measure of luciferase activity of this marine bacterium, whereas AChE bioassay is based on AChE activity inhibition. Both bioanalytical techniques are rapid (several minutes, simple, sensitive and reproducible. Vibrio fischeri test seems to be a versatile indicator of toxic compounds generated in AOP for organophosphorus insecticides degradation. However, detection of neurotoxic AChE inhibitors, which can be formed in AOP of some organophosphates, requires AChE bioassays. Therefore, AChE toxicity test is more appropriate for monitoring the degradation processes of thio organophosphates, because more toxic oxo organophosphates might be formed and overlooked by Vibrio fischeri bioluminescence inhibition. In addition, during organophosphates removal by AOP, compounds with strong genotoxic potential may be formed, which cannot be detected by standard toxicity tests. For this reason, determination of

A Multi-Region Magnetoimpedance-Based Bio-Analytical System for Ultrasensitive Simultaneous Determination of Cardiac Biomarkers Myoglobin and C-Reactive Protein.

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Yang, Zhen; Wang, Huanhuan; Guo, Pengfei; Ding, Yuanyuan; Lei, Chong; Luo, Yongsong

2018-06-01

Cardiac biomarkers (CBs) are substances that appear in the blood when the heart is damaged or stressed. Measurements of the level of CBs can be used in course of diagnostics or monitoring the state of the health of group risk persons. A multi-region bio-analytical system (MRBAS) based on magnetoimpedance (MI) changes was proposed for ultrasensitive simultaneous detection of CBs myoglobin (Mb) and C-reactive protein (CRP). The microfluidic device was designed and developed using standard microfabrication techniques for their usage in different regions, which were pre-modified with specific antibody for specified detection. Mb and CRP antigens labels attached to commercial Dynabeads with selected concentrations were trapped in different detection regions. The MI response of the triple sensitive element was carefully evaluated in initial state and in the presence of biomarkers. The results showed that the MI-based bio-sensing system had high selectivity and sensitivity for detection of CBs. Compared with the control region, ultrasensitive detections of CRP and Mb were accomplished with the detection limits of 1.0 pg/mL and 0.1 pg/mL, respectively. The linear detection range contained low concentration detection area and high concentration detection area, which were 1 pg/mL⁻10 ng/mL, 10⁻100 ng/mL for CRP, and 0.1 pg/mL⁻1 ng/mL, 1 n/mL⁻80 ng/mL for Mb. The measurement technique presented here provides a new methodology for multi-target biomolecules rapid testing.

Addressing the need for biomarker liquid chromatography/mass spectrometry assays: a protocol for effective method development for the bioanalysis of endogenous compounds in cerebrospinal fluid.

Science.gov (United States)

Benitex, Yulia; McNaney, Colleen A; Luchetti, David; Schaeffer, Eric; Olah, Timothy V; Morgan, Daniel G; Drexler, Dieter M

2013-08-30

Research on disorders of the central nervous system (CNS) has shown that an imbalance in the levels of specific endogenous neurotransmitters may underlie certain CNS diseases. These alterations in neurotransmitter levels may provide insight into pathophysiology, but can also serve as disease and pharmacodynamic biomarkers. To measure these potential biomarkers in vivo, the relevant sample matrix is cerebrospinal fluid (CSF), which is in equilibrium with the brain's interstitial fluid and circulates through the ventricular system of the brain and spinal cord. Accurate analysis of these potential biomarkers can be challenging due to low CSF sample volume, low analyte levels, and potential interferences from other endogenous compounds. A protocol has been established for effective method development of bioanalytical assays for endogenous compounds in CSF. Database searches and standard-addition experiments are employed to qualify sample preparation and specificity of the detection thus evaluating accuracy and precision. This protocol was applied to the study of the histaminergic neurotransmitter system and the analysis of histamine and its metabolite 1-methylhistamine in rat CSF. The protocol resulted in a specific and sensitive novel method utilizing pre-column derivatization ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS), which is also capable of separating an endogenous interfering compound, identified as taurine, from the analytes of interest. Copyright © 2013 John Wiley & Sons, Ltd.

A liquid chromatography with tandem mass spectrometry method for simultaneous determination of UTL-5g and its metabolites in human plasma.

Science.gov (United States)

Shaw, Jiajiu; Wiegand, Richard; Wu, Jianmei; Bao, Xun; Valeriote, Frederick; Li, Jing

2015-06-01

UTL-5g is a novel small-molecule TNF-α inhibitor under investigation as both a chemoprotective and radioprotective agent. Animal studies showed that pretreatment of UTL-5g protected kidney, liver, and platelets from cisplatin-induced toxicity. In addition, UTL-5g reduced liver and lung injuries induced by radiation in vivo. Although a number of preclinical studies have been conducted, a validated bioanalytical method for UTL-5g in human plasma has not been published. In this work, a sensitive and reproducible reverse-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assay was developed and validated for the determination of UTL-5g and its metabolites, 5-methylisoxazole-3-carboxylic acid (ISOX) and 2,4-dichloroaniline (DCA), in human plasma. The method involves a simple methanol precipitation step followed by injection of the supernatant onto a Waters 2695 HPLC system coupled with a Waters Quattro Micro™ triple quadrupole mass spectrometer. Chromatographic separation was accomplished using a Waters Nova-Pak C18 column maintained at 30°C, running at gradient mode with mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in methanol at a flow rate of 0.2mL/min. The analytes were monitored under positive electrospray ionization (ESI). Quantitation of these compounds in plasma was linear from 0.05 to 10μM. The lower limit of quantitation (LLOQ) was 0.05, 0.1, and 0.2μM for UTL-5g, ISOX and DCA, respectively. The accuracy and intra-and inter-day precisions were within the generally accepted criteria for bioanalytical method (5g and its metabolites, ISOX and DCA. Copyright © 2015 Elsevier B.V. All rights reserved.

Cooperative method development

DEFF Research Database (Denmark)

Dittrich, Yvonne; Rönkkö, Kari; Eriksson, Jeanette

2008-01-01

The development of methods tools and process improvements is best to be based on the understanding of the development practice to be supported. Qualitative research has been proposed as a method for understanding the social and cooperative aspects of software development. However, qualitative...... research is not easily combined with the improvement orientation of an engineering discipline. During the last 6 years, we have applied an approach we call `cooperative method development', which combines qualitative social science fieldwork, with problem-oriented method, technique and process improvement....... The action research based approach focusing on shop floor software development practices allows an understanding of how contextual contingencies influence the deployment and applicability of methods, processes and techniques. This article summarizes the experiences and discusses the further development...

Determination of flutamide and two major metabolites using HPLC-DAD and HPTLC methods.

Science.gov (United States)

Abdelwahab, Nada S; Elshemy, Heba A H; Farid, Nehal F

2018-01-25

Flutamide is a potential antineoplastic drug classified as an anti-androgen. It is a therapy for men with advanced prostate cancer, administered orally after which it undergoes extensively first pass metabolism in the liver with the production of several metabolites. These metabolites are predominantly excreted in urine. One of the important metabolites in plasma is 4-nitro-3-(trifluoromethyl)phenylamine (Flu-1), while the main metabolite in urine is 2-amino-5-nitro-4-(trifluoromethyl)phenol (Flu-3). In this work the two metabolites, Flu-1 and Flu-3, have been synthesized, and then structural confirmation has been carried out by HNMR analysis. Efforts were exerted to develop chromatographic methods for resolving Flutamide and its metabolites with the use of acceptable solvents without affecting the efficiency of the methods. The drug along with its metabolites were quantitatively analyzed in pure form, human urine, and plasma samples using two chromatographic methods, HPTLC and HPLC-DAD methods. FDA guidelines for bio-analytical method validation were followed and USP recommendations were used for analytical method validation. Interference from excipients has been tested by application of the methods to pharmaceutical tablets. No significant difference was found between the proposed methods and the official one when they were statistically compared at p value of 0.05%.

LC-MS/MS method for the determination of clodronate in human plasma.

Science.gov (United States)

Hasan, Mahmoud; Schumacher, Gitta; Seekamp, Anne; Taedken, Tobias; Siegmund, Werner; Oswald, Stefan

2014-11-01

Clodronate belongs to the class of bisphosphonates which are used for the treatment of bone disorders. Due to its high polarity it has a low and highly variable oral bioavailability which results in low plasma concentrations and requires sensitive bioanalytical methods to characterize its pharmacokinetics in human. Here, we describe for the first time the development and validation of a LC-MS/MS assay for the quantification of clodronate in human plasma. The bisphosphonate was isolated from the biological matrix by protein precipitation using perchloric acid (10%), and derivatized with trimethylorthoacetate prior sample clean-up with liquid-liquid extraction using methyl tert-butyl ether. The chromatography was performed using an isocratic elution with ammonium acetate 5mM (85% v/v, pH 3.8) and acetonitrile (15% v/v) as mobile phase with a flow rate of 300μl/min on a reversed-phase column (Supelco Ascentis(®), C18) temporized at 50°C. The mass spectrometric detection was done using the API4000 triple quadruple mass spectrometer monitoring the mass/charge transitions 301.0/145 for clodronate and 305.2/137.1 for the internal standard etidronate. The analytical range was set to 5-800ng/ml, allowing an evaluation of the plasma concentration-time profiles of clodronate for approximately 7-8 half-life (∼24h). The method was validated according to current FDA/EMA guidelines on bioanalytical method validation with respect to specificity, linearity, intra- and inter-day accuracy and precision, matrix effect, recovery as well as stability. The precision of the assay was 0.6-6.9% and 0.6-8.1% for the intra-day and inter-day variability, respectively. The intra-day and inter-day accuracy (error) was 0.6-8.8% and 2.2-4.5%. The recovery of the analyte was low (2-3%) but reproducible over the entire validation range and sufficient to monitor the target concentrations in human plasma. The drug was shown to be stable in plasma at room temperature for at least 3h (96.0±6%) and

Cardiotoxicity evaluation using human embryonic stem cells and induced pluripotent stem cell-derived cardiomyocytes.

Science.gov (United States)

Zhao, Qi; Wang, Xijie; Wang, Shuyan; Song, Zheng; Wang, Jiaxian; Ma, Jing

2017-03-09

Cardiotoxicity remains an important concern in drug discovery. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have become an attractive platform to evaluate cardiotoxicity. However, the consistency between human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in prediction of cardiotoxicity has yet to be elucidated. Here we screened the toxicities of four representative drugs (E-4031, isoprenaline, quinidine, and haloperidol) using both hESC-CMs and hiPSC-CMs, combined with an impedance-based bioanalytical method. It showed that both hESC-CMs and hiPSC-CMs can recapitulate cardiotoxicity and identify the effects of well-characterized compounds. The combined platform of hPSC-CMs and an impedance-based bioanalytical method could improve preclinical cardiotoxicity screening, holding great potential for increasing drug development accuracy.

Development of probes for bioanalytic applications of the surface-enhanced Raman scattering; Entwicklung neuer Sonden fuer bioanalytische Anwendungen der oberflaechenverstaerkten Raman-Streuung

Energy Technology Data Exchange (ETDEWEB)

Matschulat, Andrea Isabel

2011-07-01

identification could be a promising method for SERS-multiplexing in analytical applications. Multivariate methods such as Principal Components Analysis (PCA) and Hierarchical Cluster Analysis (HCA) were as well applied for discrimination and imaging of the reporter signatures. With the help of multivariate imaging methods based on cluster analysis, it could be for the first time demonstrated that such methods provided a fast identification of various SERS hybrid probes inside the biological matrix, this was demonstrated using living 3T3 cells. Further, in a duplex imaging approach, the probes fulfill the requirements for the sensitive detection of both the specific reporter signatures and intrinsic information coming from eukaryotic cells. The results of cluster methods and principal components approaches for discrimination indicate that fast, multivariate evaluation of whole sets of multiple probes is feasible, beyond the visual inspection of individual spectra that has been practiced so far. This suggests multiplexing applications with SERS hybrid nanoprobes and SERS tags in very high density sensing and biological imaging applications, where fast read-out is required. The pH-sensitivity of SERS-Tags that consisted of different reporter molecules attached to aggregated Au and Ag nanoparticles in the range between pH{approx}3-10 was studied. It could be demonstrated that the reporter molecules provided pH-dependent SERS signatures and could therefore be suitable for the sensitive pH-detection, e.g., inside cellular compartments. The construction of targeted SERS probes was based on the integration of a goat-anti-mouse antibody as targeting element Antibodies were coupled to Au and Ag nanoprobes surrounded by a Bovine Serum Albumin (BSA) coating which served as a carrier for the covalent linkage of a Raman reporter molecule and the targeting units at the same time In experiments with BSA and a conjugated reporter the spectra of the BSA-coupled re- porters provided an indication

Cadmium-free aqueous synthesis of ZnSe and ZnSe@ZnS core-shell quantum dots and their differential bioanalyte sensing potential

Science.gov (United States)

Mir, Irshad Ahmad; Rawat, Kamla; Bohidar, H. B.

2016-10-01

Herein we report a facile and cadmium-free approach to prepare water-soluble fluorescent ZnSe@ZnS core-shell quantum dots (QDs), using thioglycolic acid (TGA) ligand as a stabilizer and thiourea as a sulfur source. The optical properties and morphology of the obtained core-shell QDs were characterized by UV-vis and fluorescence spectroscopy, transmission electron microscopy (TEM), energy-dispersive x-ray analysis (EDX), x-ray diffraction (XRD), electrophoresis and dynamic light scattering (DLS) techniques. TEM analysis, and electrophoresis data showed that ZnSe core had an average size of 3.60 ± 0.12 nm and zeta potential of -38 mV; and for ZnSe@ZnS QDs, the mean size was 4.80 ± 0.20 nm and zeta potential was -45 mV. Compared to the core ZnSe QDs, the quantum yield of these core-shell structures was higher (13% versus 32%). These were interacted with five common bioanalytes such as, ascorbic acid, citric acid, oxalic acid, glucose and cholesterol which revealed fluorescence quenching due to concentration dependent binding of analytes to the core only, and core-shell QDs. The binding pattern followed the sequence: cholesterol ascorbic acid acid acid for ZnSe, and cholesterol acid ascorbic acid acid for core-shell QDs. Thus, enhanced binding was noticed for the analyte citric acid which may facilitate development of a fluorescence-based sensor based on the ZnSe core-only quantum dot platform. Further, the hydrophilic core-shell structure may find use in cell imaging applications.

Bioanalytical methods for the determination of cocaine and metabolites in human biological samples.

Science.gov (United States)

Barroso, M; Gallardo, E; Queiroz, J A

2009-08-01

Determination of cocaine and its metabolites in biological specimens is of great importance, not only in clinical and forensic toxicology, but also in workplace drug testing. These compounds are normally screened for using sensitive immunological methods. However, screening methods are unspecific and, therefore, the posterior confirmation of presumably positive samples by a specific technique is mandatory. Although GC-MS-based techniques are still the most commonly used for confirmation purposes of cocaine and its metabolites in biological specimens, the advent of LC-MS and LC-MS/MS has enabled the detection of even lower amounts of these drugs, which assumes particular importance when sample volume available is small, as frequently occurs with oral fluid. This paper will review recently-published papers that describe procedures for detection of cocaine and metabolites, not only in the most commonly used specimens, such as blood and urine, but also in other 'alternative' matrices (e.g., oral fluid and hair) with a special focus on sample preparation and chromatographic analysis.

Sensitive Bioanalytical Methods for Mustard Gas Exposure Diagnosis

Science.gov (United States)

2006-11-01

bis (2-chloreoethyl0-1- nitrosourea ), thio-TEPA (N, N’N’-triethylenethiophosphoramide), busulfan (1, 4-butanediol dimethanesulfonate), MNNG (1...N- nitrosourea ), mounting solution, sucrose, and colloidal gold solution were purchased from Sigma (St. Louis, MO). 2.2 Cell culture Frozen

Development and validation of an ultra-high performance liquid chromatography-tandem mass spectrometry method to measure creatinine in human urine.

Science.gov (United States)

Fraselle, S; De Cremer, K; Coucke, W; Glorieux, G; Vanmassenhove, J; Schepers, E; Neirynck, N; Van Overmeire, I; Van Loco, J; Van Biesen, W; Vanholder, R

2015-04-15

Despite decades of creatinine measurement in biological fluids using a large variety of analytical methods, an accurate determination of this compound remains challenging. Especially with the novel trend to assess biomarkers on large sample sets preserved in biobanks, a simple and fast method that could cope with both a high sample throughput and a low volume of sample is still of interest. In answer to these challenges, a fast and accurate ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to measure creatinine in small volumes of human urine. In this method, urine samples are simply diluted with a basic mobile phase and injected directly under positive electrospray ionization (ESI) conditions, without further purification steps. The combination of an important diluting factor (10(4) times) due to the use of a very sensitive triple quadrupole mass spectrometer (XEVO TQ) and the addition of creatinine-d3 as internal standard completely eliminates matrix effects coming from the urine. The method was validated in-house in 2012 according to the EMA guideline on bioanalytical method validation using Certified Reference samples from the German External Quality Assessment Scheme (G-Equas) proficiency test. All obtained results for accuracy and recovery are within the authorized tolerance ranges defined by G-Equas. The method is linear between 0 and 5 g/L, with LOD and LOQ of 5 × 10(-3) g/L and 10(-2) g/L, respectively. The repeatability (CV(r) = 1.03-2.07%) and intra-laboratory reproducibility (CV(RW) = 1.97-2.40%) satisfy the EMA 2012 guideline. The validated method was firstly applied to perform the German G-Equas proficiency test rounds 51 and 53, in 2013 and 2014, respectively. The obtained results were again all within the accepted tolerance ranges and very close to the reference values defined by the organizers of the proficiency test scheme, demonstrating an excellent accuracy of the developed method. The

Plant-based food and feed protein structure changes induced by gene-transformation, heating and bio-ethanol processing: a synchrotron-based molecular structure and nutrition research program.

Science.gov (United States)

Yu, Peiqiang

2010-11-01

Unlike traditional "wet" analytical methods which during processing for analysis often result in destruction or alteration of the intrinsic protein structures, advanced synchrotron radiation-based Fourier transform infrared microspectroscopy has been developed as a rapid and nondestructive and bioanalytical technique. This cutting-edge synchrotron-based bioanalytical technology, taking advantages of synchrotron light brightness (million times brighter than sun), is capable of exploring the molecular chemistry or structure of a biological tissue without destruction inherent structures at ultra-spatial resolutions. In this article, a novel approach is introduced to show the potential of the advanced synchrotron-based analytical technology, which can be used to study plant-based food or feed protein molecular structure in relation to nutrient utilization and availability. Recent progress was reported on using synchrotron-based bioanalytical technique synchrotron radiation-based Fourier transform infrared microspectroscopy and diffused reflectance infrared Fourier transform spectroscopy to detect the effects of gene-transformation (Application 1), autoclaving (Application 2), and bio-ethanol processing (Application 3) on plant-based food and feed protein structure changes on a molecular basis. The synchrotron-based technology provides a new approach for plant-based protein structure research at ultra-spatial resolutions at cellular and molecular levels.

A simple assay of paracetamol based on dried blood spot suitable ...

African Journals Online (AJOL)

Dried blood spots in Guthrie cards are a reliable means of blood sampling suitable for pharmacoki-netic analysis in children. The aim of this study was to develop a simple and reliable bioanalytical method to measure the concentration of paracetamol in dried blood spots. Paracetamol was ex-tracted from dry blood spots by ...

A Liquid Chromatography-Tandem Mass Spectrometry Method for Evaluation of Two Brands of Enalapril 20 mg Tablets in Healthy Human Volunteers

Directory of Open Access Journals (Sweden)

Wael Abu Dayyih

2017-01-01

Full Text Available Enalapril is an angiotensin-converting enzyme inhibitor used for treatment of hypertension and chronic heart disease. Enalaprilat is its active metabolite responsible for the activity. This study aimed to develop and validate a method for enalapril and enalaprilat analysis and to determine the bioequivalence of two tablet formulae of enalapril. LC-MS/MS bioanalytical method was developed and validated and then applied to evaluate the bioavailability of two enalapril formulae. Antihyperglycemic sitagliptin was used as internal standard (IS. The method was accurate for the within- and between-days analysis, and precise CV% was 85% and the LOD was 0.907 and 0.910 ng/ml for enalapril and enalaprilat, respectively, and LLOQ was 1 ng/ml. The pharmacokinetic parameters Cmax, tmax, AUC0–72, and AUC0–∞ values of enalapril and enalaprilat of the two formulae were calculated and nonsignificant differences were found. A linearity, specific, accurate, and precise method was developed and applied for the analysis of enalapril and enalaprilat in human plasma after oral administration of two formulae of enalapril 20 mg tablets in healthy volunteers. Depending on the statistical analysis it was concluded that the two enalapril formulae were bioequivalent.

Quantitative determination of amitriptyline and its metabolite in rat plasma by liquid chromatography-tandem mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Chae, Jungwoo; Baek, Inhwan; An, Junghwa; Kim, Eun Jung; Kwon, Kwangil [Chungnam National Univ., Daejeon (Korea, Republic of)

2012-07-15

A rapid, specific, and reliable LC-MS/MS-based bioanalytical method was developed and validated in rat plasma for the simultaneous quantitation of amitriptyline and its metabolite nortriptyline. Chromatographic separation of these analytes was achieved on a Gemini C18 column (50 X 4.60 mm, 5 {mu}m) using reversed-phase chromatography. The mobile phase was an isocratic solvent system consisting of 1% formic acid in water and methanol (10:90, v/v), at a flow rate of 0.2 mL/min. The analytical range was set as 0.1-500 ng/mL for amitriptyline and 0.08-500 ng/mL for nortriptyline using a 200 {mu}L plasma sample. The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. The validated method was successfully applied to a pharmacokinetic study in six rats after oral administration of amitriptyline (15 mg/kg). This method allows laboratory scientists to rapidly determine amitriptyline and nortriptyline concentrations in plasma.

Toxicological Studies of Mycotoxins Using Enzymatic and Histochemical Methods

Energy Technology Data Exchange (ETDEWEB)

Badea, Mihaela, E-mail: badeamihaela@yahoo.com; Taus, Nicoleta [Transilvania University of Brasov, Faculty of Medicine (Romania); Potrovita, Monica [Sanitary-Veterinary and Food Safety Direction of Brasov (Romania); Moarcas, Monica [Transilvania University of Brasov, Faculty of Medicine (Romania)

2009-08-15

Studies concerning mycotoxins involve activities of relevant potential for furthering knowledge in the fields of toxicology and environmental analysis. Using bioanalytical methods (biosensors, histochemistry), the conducted research aims at contributing to raising the awareness of local, national, and international media in relation to the safety of obtaining and processing vegetal and animal foods, by analyzing the possible effects of aflatoxins and ochratoxins, promoting animal health, food hygiene, in view of ensuring animal and human health. The study using laboratory animals (mice) while being part of one of the current national research directions, also holds international priority, by its contribution to a better understanding of several fundamental mechanisms of life at molecular level and to the characterization of certain biological processes that appear in mycotoxicosis.

A new liquid chromatography-mass spectrometry-based method to quantitate exogenous recombinant transferrin in cerebrospinal fluid: a potential approach for pharmacokinetic studies of transferrin-based therapeutics in the central nervous systems.

Science.gov (United States)

Wang, Shunhai; Bobst, Cedric E; Kaltashov, Igor A

2015-01-01

Transferrin (Tf) is an 80 kDa iron-binding protein that is viewed as a promising drug carrier to target the central nervous system as a result of its ability to penetrate the blood-brain barrier. Among the many challenges during the development of Tf-based therapeutics, the sensitive and accurate quantitation of the administered Tf in cerebrospinal fluid (CSF) remains particularly difficult because of the presence of abundant endogenous Tf. Herein, we describe the development of a new liquid chromatography-mass spectrometry-based method for the sensitive and accurate quantitation of exogenous recombinant human Tf in rat CSF. By taking advantage of a His-tag present in recombinant Tf and applying Ni affinity purification, the exogenous human serum Tf can be greatly enriched from rat CSF, despite the presence of the abundant endogenous protein. Additionally, we applied a newly developed (18)O-labeling technique that can generate internal standards at the protein level, which greatly improved the accuracy and robustness of quantitation. The developed method was investigated for linearity, accuracy, precision, and lower limit of quantitation, all of which met the commonly accepted criteria for bioanalytical method validation.

Selecting the correct weighting factors for linear and quadratic calibration curves with least-squares regression algorithm in bioanalytical LC-MS/MS assays and impacts of using incorrect weighting factors on curve stability, data quality, and assay performance.

Science.gov (United States)

Gu, Huidong; Liu, Guowen; Wang, Jian; Aubry, Anne-Françoise; Arnold, Mark E

2014-09-16

A simple procedure for selecting the correct weighting factors for linear and quadratic calibration curves with least-squares regression algorithm in bioanalytical LC-MS/MS assays is reported. The correct weighting factor is determined by the relationship between the standard deviation of instrument responses (σ) and the concentrations (x). The weighting factor of 1, 1/x, or 1/x(2) should be selected if, over the entire concentration range, σ is a constant, σ(2) is proportional to x, or σ is proportional to x, respectively. For the first time, we demonstrated with detailed scientific reasoning, solid historical data, and convincing justification that 1/x(2) should always be used as the weighting factor for all bioanalytical LC-MS/MS assays. The impacts of using incorrect weighting factors on curve stability, data quality, and assay performance were thoroughly investigated. It was found that the most stable curve could be obtained when the correct weighting factor was used, whereas other curves using incorrect weighting factors were unstable. It was also found that there was a very insignificant impact on the concentrations reported with calibration curves using incorrect weighting factors as the concentrations were always reported with the passing curves which actually overlapped with or were very close to the curves using the correct weighting factor. However, the use of incorrect weighting factors did impact the assay performance significantly. Finally, the difference between the weighting factors of 1/x(2) and 1/y(2) was discussed. All of the findings can be generalized and applied into other quantitative analysis techniques using calibration curves with weighted least-squares regression algorithm.

Optimization and validation of high-performance liquid chromatography method for analyzing 25-desacetyl rifampicin in human urine

Science.gov (United States)

Lily; Laila, L.; Prasetyo, B. E.

2018-03-01

A selective, reproducibility, effective, sensitive, simple and fast High-Performance Liquid Chromatography (HPLC) was developed, optimized and validated to analyze 25-Desacetyl Rifampicin (25-DR) in human urine which is from tuberculosis patient. The separation was performed by HPLC Agilent Technologies with column Agilent Eclipse XDB- Ci8 and amobile phase of 65:35 v/v methanol: 0.01 M sodium phosphate buffer pH 5.2, at 254 nm and flow rate of 0.8ml/min. The mean retention time was 3.016minutes. The method was linear from 2–10μg/ml 25-DR with a correlation coefficient of 0.9978. Standard deviation, relative standard deviation and coefficient variation of 2, 6, 10μg/ml 25-DR were 0-0.0829, 03.1752, 0-0.0317%, respectively. The recovery of 5, 7, 9μg/ml25-DR was 80.8661, 91.3480 and 111.1457%, respectively. Limits of detection (LoD) and quantification (LoQ) were 0.51 and 1.7μg/ml, respectively. The method has fulfilled the validity guidelines of the International Conference on Harmonization (ICH) bioanalytical method which includes parameters of specificity, linearity, precision, accuracy, LoD, and LoQ. The developed method is suitable for pharmacokinetic analysis of various concentrations of 25-DR in human urine.

Bioanalytics of mycotoxins and development of dedicated analyte-selective molecularly imprinted materials for solid-phase extraction

International Nuclear Information System (INIS)

Jodlbauer, H.J.

2001-09-01

Mycotoxins are secondary metabolites produced by several fungal species, growing on agricultural products during cultivation, harvest, transport or storage. Ochratoxin A (OTA) is a mycotoxin of great natural abundance and can be found in various plant products. Due to its frequent occurrence and toxic properties many countries have set up tolerance levels for OTA. Thus, the need for sensitive analytical and in particular selective sample preparation methods for analyte enrichment and removal of interfering matrix compounds is obvious. Molecular imprinting generates polymeric matrices that can selectively recognize and bind target molecules. It was previously demonstrated that molecularly imprinted polymers (MIPs) can be employed in sample preparation. MIPs capable of recognizing OTA have been prepared using an analyte mimic approach. Crucial to the success was the introduction of a novel class of quinuclidine-derived functional monomers which utilize ionic binding increments and hydrophobic interactions for selective recognition of the target analyte and its mimics. Since optimization of SPE procedures demonstrated the convenient use of several solvent systems, the developed MIPs represents an enrichment for the field of mycotoxin analysis. Zeranol has been widely adopted as a growth stimulant for cattle and other animals due to its anabolic and estrogenic properties. Application of zeranol has been banned in the European Union since 1985. Researchers, however, found that the illegal administration of this anabolic agent may not be the only source of zeranol residues in biologically relevant matrices. Previously, it was demonstrated that zeranol was also formed in vivo from the mycotoxins zearalenone (ZON) and α-zearalenol that are carried over from mycotoxin contaminated feed into the animal body. A fast, robust and sensitive LC-MS method for the determination for these compounds in urine and tissue samples has been developed. Crucial for the achievement of low

Multianalytical Method Validation for Qualitative and Quantitative Analysis of Solvents of Abuse in Oral Fluid by HS-GC/MS

Directory of Open Access Journals (Sweden)

Bruna Claudia Coppe

2016-01-01

Full Text Available The use of oral fluid as a biological matrix to monitor the use of drugs of abuse is a global trend because it presents several advantages and good correlation to the blood level. Thus, the present work aimed to develop and validate an analytical method for quantification and detection of solvents used as inhalants of abuse in oral fluid (OF, using Quantisal™ as collector device by headspace and gas chromatography coupled with a mass detector (HS-GC/MS. Chromatographic separation was performed with a ZB-BAC1 column and the total time of analysis was 11.8 min. The method showed good linearity (correlation coefficient higher than 0.99 for all solvents. The limits of detection ranged from 0.05 to 5 mg/L, while the lower limits of quantification ranged from 2.5 to 12.5 mg/L. Accuracy, precision, matrix effect, and residual effect presented satisfactory results, meeting the criteria accepted for the validation of bioanalytical methods. The method showed good selectivity considering that, for solvents coeluting at the same retention time, resolution was performed by the mass detector. The method developed proved to be adequate when applied in OF samples from users of drugs and may be used to monitor the abuse of inhalants in routine forensic analyses.

A biodetection method using magnetic particles and micro traps

KAUST Repository

Li, Fuquan

2012-03-09

The general working principle of magnetoresistive sensors for biological applications is to specifically attach bioanalytesto magnetic particles and then detect the particles that are immobilized on the sensor surface. The immobilization of the particles on the sensor surface commonly uses biomolecular interactions, e.g., antigen-antibody. Thus, the sensor surface needs to be functionalized via biological treatments in order to capture certain bioanalytes. In the presented work, a new method is proposed, which does not rely on functionalization of the sensor surface. Current carrying microstructures in combination with mechanical micro traps are used to immobilize magnetic particles. Analyte detection is based on the difference in size between bare magnetic particles and particles with analyte attached, which causes a different number of particles to be captured in the micro traps.

Hydrophilic Interaction Liquid Chromatography/Mass Spectrometry: An Attractive and Prospective Method for the Quantitative Bioanalysis in Drug Metabolism.

Science.gov (United States)

Li, Zheng; Han, Jie; Sun, Shi-an; Chen, Kai; Tang, Dao-quan

2016-01-01

During the development, dosage optimization and safety evaluation of a drug, rapid and precise monitoring of administered drug and/or its metabolites in biological samples including blood, plasma, serum, tissues and saliva are vital. As drug biotransformation produces more hydrophilic metabolites for the enhancement of drug elimination, which is often a challenge for traditional reversed-phase liquid chromatography (RPLC) separation. Because hydrophilic interaction liquid chromatography (HILIC) is capable of retaining polar compounds and readily compatible with mass spectrometry (MS), HILIC has been used as a complementary separation technique to RPLC for analysis of polar metabolites, especially polar drugs and their metabolites. This review covers core aspects of HILIC-MS/MS method and overall profile of its application in analysis of drug and/or its metabolites. The emphasis of this paper has been placed on the applications of HILIC-MS/MS method in quantitative bioanalysis of drugs alone or along with their metabolites in drug metabolism studies in recent years. As a fundamental and critical step of bioanalytical method, conventional sample preparation techniques of biological matrices for the HILIC-MS/MS analysis of drugs and/or their metabolites are also briefly featured.

Comments on “innovative method for carbon dioxide determination in human postmortem cardiac gas samples using headspace-gas chromatography–mass spectrometry and stable labeled isotope as internal standard” by Varlet et al

Energy Technology Data Exchange (ETDEWEB)

Saffaj, T., E-mail: taoufiq.saffaj@usmba.ac.ma [Centre Universitaire Régional d’Interface, Université Sidi Mohamed Ben Abdellah, BP 2626, route d’Imouzzer, Fes Morocco (Morocco); Laboratoire de Chimie Organique Appliquée, Faculté des Sciences et Techniques, BP 2202, route d’Imouzzer, Fes Morocco (Morocco); Ihssane, B. [Laboratoire de Chimie Organique Appliquée, Faculté des Sciences et Techniques, BP 2202, route d’Imouzzer, Fes Morocco (Morocco)

2014-01-31

Graphical abstract: -- Highlights: •We comment on the validation results of the method for CO{sub 2} analysis in cardiac samples. •We demonstrate that the total error of the method exceeds the acceptance limits. •We show that the method is not valid according to the new SFSTP guideline. -- Abstract: Varlet et al. recently proposed a headspace-gas chromatography–mass spectrometry (HS-GC–MS) method applicable for the routine determination of CO{sub 2} in gaseous biologic matrices. This developed bioanalytical method was fully validated according to the SFSTP 1997 guidelines using the accuracy profile as a graphical decision-making tool.In this letter, we discuss the validity of HS-GC–MS method based on the newest SFSTP guideline. In particular, we demonstrate by the estimation of the β-expectation tolerance interval that the error total exceeds the acceptance limits (30%) for the second concentration level (0.5 μmol mL{sup −1} vial HS). Furthermore, we show through the risk profile that the probability to have future results inside the ±30% acceptance limits is smaller than 95%.

Beyond Antibodies as Binding Partners: The Role of Antibody Mimetics in Bioanalysis.

Science.gov (United States)

Yu, Xiaowen; Yang, Yu-Ping; Dikici, Emre; Deo, Sapna K; Daunert, Sylvia

2017-06-12

The emergence of novel binding proteins or antibody mimetics capable of binding to ligand analytes in a manner analogous to that of the antigen-antibody interaction has spurred increased interest in the biotechnology and bioanalytical communities. The goal is to produce antibody mimetics designed to outperform antibodies with regard to binding affinities, cellular and tumor penetration, large-scale production, and temperature and pH stability. The generation of antibody mimetics with tailored characteristics involves the identification of a naturally occurring protein scaffold as a template that binds to a desired ligand. This scaffold is then engineered to create a superior binder by first creating a library that is then subjected to a series of selection steps. Antibody mimetics have been successfully used in the development of binding assays for the detection of analytes in biological samples, as well as in separation methods, cancer therapy, targeted drug delivery, and in vivo imaging. This review describes recent advances in the field of antibody mimetics and their applications in bioanalytical chemistry, specifically in diagnostics and other analytical methods.

Method Development in Forensic Toxicology.

Science.gov (United States)

Peters, Frank T; Wissenbach, Dirk K; Busardo, Francesco Paolo; Marchei, Emilia; Pichini, Simona

2017-01-01

In the field of forensic toxicology, the quality of analytical methods is of great importance to ensure the reliability of results and to avoid unjustified legal consequences. A key to high quality analytical methods is a thorough method development. The presented article will provide an overview on the process of developing methods for forensic applications. This includes the definition of the method's purpose (e.g. qualitative vs quantitative) and the analytes to be included, choosing an appropriate sample matrix, setting up separation and detection systems as well as establishing a versatile sample preparation. Method development is concluded by an optimization process after which the new method is subject to method validation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Large-volume injection of sample diluents not miscible with the mobile phase as an alternative approach in sample preparation for bioanalysis: an application for fenspiride bioequivalence.

Science.gov (United States)

Medvedovici, Andrei; Udrescu, Stefan; Albu, Florin; Tache, Florentin; David, Victor

2011-09-01

Liquid-liquid extraction of target compounds from biological matrices followed by the injection of a large volume from the organic layer into the chromatographic column operated under reversed-phase (RP) conditions would successfully combine the selectivity and the straightforward character of the procedure in order to enhance sensitivity, compared with the usual approach of involving solvent evaporation and residue re-dissolution. Large-volume injection of samples in diluents that are not miscible with the mobile phase was recently introduced in chromatographic practice. The risk of random errors produced during the manipulation of samples is also substantially reduced. A bioanalytical method designed for the bioequivalence of fenspiride containing pharmaceutical formulations was based on a sample preparation procedure involving extraction of the target analyte and the internal standard (trimetazidine) from alkalinized plasma samples in 1-octanol. A volume of 75 µl from the octanol layer was directly injected on a Zorbax SB C18 Rapid Resolution, 50 mm length × 4.6 mm internal diameter × 1.8 µm particle size column, with the RP separation being carried out under gradient elution conditions. Detection was made through positive ESI and MS/MS. Aspects related to method development and validation are discussed. The bioanalytical method was successfully applied to assess bioequivalence of a modified release pharmaceutical formulation containing 80 mg fenspiride hydrochloride during two different studies carried out as single-dose administration under fasting and fed conditions (four arms), and multiple doses administration, respectively. The quality attributes assigned to the bioanalytical method, as resulting from its application to the bioequivalence studies, are highlighted and fully demonstrate that sample preparation based on large-volume injection of immiscible diluents has an increased potential for application in bioanalysis.

IoT System Development Methods

NARCIS (Netherlands)

Giray, G.; Tekinerdogan, B.; Tüzün, E.

2018-01-01

It is generally believed that the application of methods plays an important role in developing quality systems. A development method is mainly necessary for structuring the process in producing largescale and complex systems that involve high costs. Similar to the development of other systems, it is

METHODS TO DEVELOP A TOROIDAL SURFACE

Directory of Open Access Journals (Sweden)

DANAILA Ligia

2017-05-01

Full Text Available The paper work presents two practical methods to draw the development of a surface unable to be developed applying classical methods of Descriptive Geometry, the toroidal surface, frequently met in technical practice. The described methods are approximate ones; the development is obtained with the help of points. The accuracy of the methods is given by the number of points used when drawing. As for any other approximate method, when practically manufactured the development may need to be adjusted on site.

GEM simulation methods development

International Nuclear Information System (INIS)

Tikhonov, V.; Veenhof, R.

2002-01-01

A review of methods used in the simulation of processes in gas electron multipliers (GEMs) and in the accurate calculation of detector characteristics is presented. Such detector characteristics as effective gas gain, transparency, charge collection and losses have been calculated and optimized for a number of GEM geometries and compared with experiment. A method and a new special program for calculations of detector macro-characteristics such as signal response in a real detector readout structure, and spatial and time resolution of detectors have been developed and used for detector optimization. A detailed development of signal induction on readout electrodes and electronics characteristics are included in the new program. A method for the simulation of charging-up effects in GEM detectors is described. All methods show good agreement with experiment

Methodology for developing new test methods

Directory of Open Access Journals (Sweden)

A. I. Korobko

2017-06-01

Full Text Available The paper describes the methodology for developing new test methods and forming solutions for the development of new test methods. The basis of the methodology for developing new test methods is the individual elements of the system and process approaches. They contribute to the development of an effective research strategy for the object, the study of interrelations, the synthesis of an adequate model of the test method. The effectiveness of the developed test method is determined by the correct choice of the set of concepts, their interrelations and mutual influence. This allows you to solve the tasks assigned to achieve the goal. The methodology is based on the use of fuzzy cognitive maps. The question of the choice of the method on the basis of which the model for the formation of solutions is based is considered. The methodology provides for recording a model for a new test method in the form of a finite set of objects. These objects are significant for the test method characteristics. Then a causal relationship is established between the objects. Further, the values of fitness indicators and the observability of the method and metrological tolerance for the indicator are established. The work is aimed at the overall goal of ensuring the quality of tests by improving the methodology for developing the test method.

Simple protein precipitation extraction technique followed by validated chromatographic method for linezolid analysis in real human plasma samples to study its pharmacokinetics.

Science.gov (United States)

Mohammed, Samah A; Eissa, Maya S; Ahmed, Hytham M

2017-02-01

Fast and sensitive HPLC method was developed, optimized and validated for quantification of linezolid (LNZ) in human plasma using guaifenesin as an internal standard (IS). Analyte and IS were extracted from plasma by simple protein precipitation extraction technique using methanol as the precipitating solvent. The pretreated samples were injected in a mobile phase formed of acetonitrile:water:methanol (20:70:10v/v/v) in an isocratic mode at a flow rate of 1.5mL/min with UV detection at 251nm. Separation was done using Aglient ODS C 18 . The method showed linearity in the range of 0.75-50μg/mL with correlation coefficients equals to 0.9991. Precision and accuracy were in conformity with the criteria normally accepted in bio-analytical method validation. The RSDs for intra- and inter-day assays were <3.56 and 4.63%, respectively. The intra- and inter-day accuracies were 94.67-98.28% and 91.25-96.18%, respectively. The mean absolute recoveries ranged from 92.56±1.78 to 95.24±2.84. According to stability results, LNZ was stable in human plasma during the storage and analysis. LNZ a pharmacokinetic behavior was studied by applying the proposed analytical method. Copyright © 2016 Elsevier B.V. All rights reserved.

A versatile, stability-indicating and high-throughput ultra-fast liquid chromatography method for the determination of isoflavone aglycones in soybeans, topical formulations, and permeation assays.

Science.gov (United States)

Nemitz, Marina C; Yatsu, Francini K J; Bidone, Juliana; Koester, Letícia S; Bassani, Valquiria L; Garcia, Cássia V; Mendez, Andreas S L; von Poser, Gilsane L; Teixeira, Helder F

2015-03-01

There is a growing interest in the pharmaceutical field concerning isoflavones topical delivery systems, especially with regard to their skin care properties and antiherpetic activity. In this context, the present work describes an ultra-fast liquid chromatography method (UFLC) for determining daidzein, glycitein, and genistein in different matrices during the development of topical systems containing isoflavone aglycones (IA) obtained from soybeans. The method showed to be specific, precise, accurate, and linear (0.1 to 5 µg mL(-1)) for IA determination in soybean acid extract, IA-rich fraction obtained after the purification process, IA loaded-nanoemulsions, and topical hydrogel, as well as for permeation/retention assays in porcine skin and porcine esophageal mucosa. The matrix effect was determined for all complex matrices, demonstrating low effect during the analysis. The stability indicating UFLC method was verified by submitting IA to acidic, alkaline, oxidative, and thermal stress conditions, and no interference of degradation products was detected during analysis. Mass spectrometry was performed to show the main compounds produced after acid hydrolysis of soybeans, as well as suggest the main degradation products formed after stress conditions. Besides the IA, hydroxymethylfurfural and ethoxymethylfurfural were produced and identified after acid hydrolysis of the soybean extract and well separated by the UFLC method. The method's robustness was confirmed using the Plackett-Burman experimental design. Therefore, the new method affords fast IA analysis during routine processes, extract purification, products development, and bioanalytical assays. Copyright © 2014 Elsevier B.V. All rights reserved.

A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor

Directory of Open Access Journals (Sweden)

Xun Bao

2018-02-01

Full Text Available A rapid, sensitive, and robust reversed-phase liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of total and unbound ceritinib, a second-generation ALK inhibitor, in patient plasma and brain tumor tissue samples. Sample preparation involved simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C18 column using a 4-min gradient elution consisting of mobile phase A (0.1% formic acid in water and mobile phase B (0.1% formic acid in acetonitrile, at a flow rate of 0.4 mL/min. Ceritinib and the internal standard ([13C6]ceritinib were monitored using multiple reaction monitoring mode under positive electrospray ionization. The lower limit of quantitation (LLOQ was 1 nM of ceritinib in plasma. The calibration curve was linear over ceritinib concentration range of 1–2000 nM in plasma. The intra- and inter-day precision and accuracy were within the generally accepted criteria for bioanalytical method (<15%. The method was successfully applied to assess ceritinib brain tumor penetration, as assessed by the unbound drug brain concentration to unbound drug plasma concentration ratio, in patients with brain tumors.

Tropical Journal of Pharmaceutical Research - Vol 13, No 3 (2014)

African Journals Online (AJOL)

... In situ Forming Implants: Effect of Sterilization, Storage Condition and Degradation ... A Simple HPLC Bioanalytical Method for the Determination of Doxorubicin ... Reported Case of Paracetamol and Non-Steroidal Anti- Inflammatory Drug ...

Negotiating a Systems Development Method

Science.gov (United States)

Karlsson, Fredrik; Hedström, Karin

Systems development methods (or methods) are often applied in tailored version to fit the actual situation. Method tailoring is in most the existing literature viewed as either (a) a highly rational process with the method engineer as the driver where the project members are passive information providers or (b) an unstructured process where the systems developer makes individual choices, a selection process without any driver. The purpose of this chapter is to illustrate that important design decisions during method tailoring are made by project members through negotiation. The study has been carried out using the perspective of actor-network theory. Our narratives depict method tailoring as more complex than (a) and (b) show the driver role rotates between the project members, and design decisions are based on influences from several project members. However, these design decisions are not consensus decisions.

4th Global CRO Council for Bioanalysis: coadministered drugs stability, EMA/US FDA guidelines, 483s and carryover.

Science.gov (United States)

Lowes, Steve; Jersey, Jim; Shoup, Ronald; Garofolo, Fabio; Needham, Shane; Couerbe, Philippe; Lansing, Tim; Bhatti, Masood; Sheldon, Curtis; Hayes, Roger; Islam, Rafiq; Lin, Zhongping; Garofolo, Wei; Moussallie, Marc; Teixeira, Leonardo de Souza; Rocha, Thais; Jardieu, Paula; Truog, James; Lin, Jenny; Lundberg, Richard; Breau, Alan; Dilger, Carmen; Bouhajib, Mohammed; Levesque, Ann; Gagnon-Carignan, Sofi; Jenkins, Rand; Nicholson, Robert; Lin, Ming Hung; Karnik, Shane; DeMaio, William; Smith, Kirk; Cojocaru, Laura; Allen, Mike; Fatmi, Saadya; Sayyarpour, Farhad; Malone, Michele; Fang, Xinping

2012-04-01

The Global CRO Council for Bioanalysis (GCC) was formed in September 2010. Since then, the representatives of the member companies come together periodically to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. The 4th GCC Closed Forum brought together experts from bioanalytical CROs to share and discuss recent issues in regulated bioanalysis, such as the impact of coadministered drugs on stability, some differences between European Medicines Agency and US FDA bioanalytical guidance documents and lessons learned following recent Untitled Letters. Recent 483s and agency findings, as well as issues on method carryover, were also part of the topics discussed.

Method Engineering: Engineering of Information Systems Development Methods and Tools

NARCIS (Netherlands)

Brinkkemper, J.N.; Brinkkemper, Sjaak

1996-01-01

This paper proposes the term method engineering for the research field of the construction of information systems development methods and tools. Some research issues in method engineering are identified. One major research topic in method engineering is discussed in depth: situational methods, i.e.

Moral counselling: a method in development.

Science.gov (United States)

de Groot, Jack; Leget, Carlo

2011-01-01

This article describes a method of moral counselling developed in the Radboud University Medical Centre Nijmegen (The Netherlands). The authors apply insights of Paul Ricoeur to the non-directive counselling method of Carl Rogers in their work of coaching patients with moral problems in health care. The developed method was shared with other health care professionals in a training course. Experiences in the course and further practice led to further improvement of the method.

Quantitative evaluation of the matrix effect in bioanalytical methods based on LC-MS: A comparison of two approaches.

Science.gov (United States)

Rudzki, Piotr J; Gniazdowska, Elżbieta; Buś-Kwaśnik, Katarzyna

2018-06-05

Liquid chromatography coupled to mass spectrometry (LC-MS) is a powerful tool for studying pharmacokinetics and toxicokinetics. Reliable bioanalysis requires the characterization of the matrix effect, i.e. influence of the endogenous or exogenous compounds on the analyte signal intensity. We have compared two methods for the quantitation of matrix effect. The CVs(%) of internal standard normalized matrix factors recommended by the European Medicines Agency were evaluated against internal standard normalized relative matrix effects derived from Matuszewski et al. (2003). Both methods use post-extraction spiked samples, but matrix factors require also neat solutions. We have tested both approaches using analytes of diverse chemical structures. The study did not reveal relevant differences in the results obtained with both calculation methods. After normalization with the internal standard, the CV(%) of the matrix factor was on average 0.5% higher than the corresponding relative matrix effect. The method adopted by the European Medicines Agency seems to be slightly more conservative in the analyzed datasets. Nine analytes of different structures enabled a general overview of the problem, still, further studies are encouraged to confirm our observations. Copyright © 2018 Elsevier B.V. All rights reserved.

Reactor physics methods development at Westinghouse

International Nuclear Information System (INIS)

Mueller, E.; Mayhue, L.; Zhang, B.

2007-01-01

The current state of reactor physics methods development at Westinghouse is discussed. The focus is on the methods that have been or are under development within the NEXUS project which was launched a few years ago. The aim of this project is to merge and modernize the methods employed in the PWR and BWR steady-state reactor physics codes of Westinghouse. (author)

A method for the direct injection and analysis of small volume human blood spots and plasma extracts containing high concentrations of organic solvents using revered-phase 2D UPLC/MS.

Science.gov (United States)

Rainville, Paul D; Simeone, Jennifer L; Root, Dan S; Mallet, Claude R; Wilson, Ian D; Plumb, Robert S

2015-03-21

The emergence of micro sampling techniques holds great potential to improve pharmacokinetic data quality, reduce animal usage, and save costs in safety assessment studies. The analysis of these samples presents new challenges for bioanalytical scientists, both in terms of sample processing and analytical sensitivity. The use of two dimensional LC/MS with, at-column-dilution for the direct analysis of highly organic extracts prepared from biological fluids such as dried blood spots and plasma is demonstrated. This technique negated the need to dry down and reconstitute, or dilute samples with water/aqueous buffer solutions, prior to injection onto a reversed-phase LC system. A mixture of model drugs, including bromhexine, triprolidine, enrofloxacin, and procaine were used to test the feasibility of the method. Finally an LC/MS assay for the probe pharmaceutical rosuvastatin was developed from dried blood spots and protein-precipitated plasma. The assays showed acceptable recovery, accuracy and precision according to US FDA guidelines. The resulting analytical method showed an increase in assay sensitivity of up to forty fold as compared to conventional methods by maximizing the amount loaded onto the system and the MS response for the probe pharmaceutical rosuvastatin from small volume samples.

Development of an on-line solid phase extraction ultra-high-performance liquid chromatography technique coupled to tandem mass spectrometry for quantification of bisphenol S and bisphenol S glucuronide: Applicability to toxicokinetic investigations.

Science.gov (United States)

Grandin, Flore; Picard-Hagen, Nicole; Gayrard, Véronique; Puel, Sylvie; Viguié, Catherine; Toutain, Pierre-Louis; Debrauwer, Laurent; Lacroix, Marlène Z

2017-12-01

Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by structural analogues, such as Bisphenol S (BPS), in consumer products. At present, no toxicokinetic investigations have been conducted to assess the factors determining human internal exposure to BPS for subsequent risk assessment. Toxicokinetic studies require reliable analytical methods to measure the plasma concentrations of BPS and its main conjugated metabolite, BPS-glucuronide (BPS-G). An efficient on-line SPE-UPLC-MS/MS method for the simultaneous quantification of BPS and BPS-G in ovine plasma was therefore developed and validated in accordance with the European Medicines Agency guidelines for bioanalytical method validation. This method has a limit of quantification of 3ngmL -1 for BPS and 10ngmL -1 for BPS-G, an analytical capacity of 200 samples per day, and is particularly well suited to toxicokinetic studies. Use of this method in toxicokinetic studies in sheep showed that BPS, like BPA, is efficiently metabolized into its glucuronide form. However, the clearances and distributions of BPS and BPS-G were lower than those of the corresponding unconjugated and glucuroconjugated forms of BPA. Copyright © 2017 Elsevier B.V. All rights reserved.

Prognostic aspects of imaging method development

International Nuclear Information System (INIS)

Steinhart, L.

1987-01-01

A survey is presented of X-ray diagnostic methods and techniques and possibilities of their further development. Promising methods include direct imaging using digital radiography. In connection with computer technology these methods achieve higher resolution. The storage of obtained images in the computer memory will allow automated processing and evaluation and the use of expert systems. Development is expected to take place especially in computerized tomography using magnetic resonance, and positron computed tomography and other non-radioactive diagnostic methods. (J.B.). 5 figs., 1 tab., 1 ref

Development of partitioning method

International Nuclear Information System (INIS)

Kubota, Kazuo; Dojiri, Shigeru; Kubota, Masumitsu

1988-10-01

The literature survey was carried out on the amount of natural resources, behaviors in reprocessing process and in separation and recovery methods of the platinum group elements and technetium which are contained in spent fuel. The essential results are described below. (1) The platinum group elements, which are contained in spent fuel, are quantitatively limited, compared with total demand for them in Japan. And estimated separation and recovery cost is rather high. In spite of that, development of these techniques is considered to be very important because the supply of these elements is almost from foreign resources in Japan. (2) For recovery of these elements, studies of recovery from undisolved residue and from high level liquid waste (HLLW) also seem to be required. (3) As separation and recovery methods, following techniques are considered to be effective; lead extraction, liquid metal extraction, solvent extraction, ion-exchange, adsorption, precipitation, distillation, electrolysis or their combination. (4) But each of these methods has both advantages and disadvantages. So development of such processes largely depends on future works. (author) 94 refs

A gold standard method for the evaluation of antibody-based materials functionality: Approach to forced degradation studies.

Science.gov (United States)

Coussot, Gaëlle; Le Postollec, Aurélie; Faye, Clément; Dobrijevic, Michel

2018-04-15

The scope of this paper is to present a gold standard method to evaluate functional activity of antibody (Ab)-based materials during the different phases of their development, after their exposure to forced degradations or even during routine quality control. Ab-based materials play a central role in the development of diagnostic devices, for example, for screening or therapeutic target characterization, in formulation development, and in novel micro(nano)technology approaches to develop immunosensors useful for the analysis of trace substances in pharmaceutical and food industries, clinical and environmental fields. A very important aspect in diagnostic device development is the construction of its biofunctional surfaces. These Ab surfaces require biocompatibility, homogeneity, stability, specificity and functionality. Thus, this work describes the validation and applications of a unique ligand binding assay to directly perform the quantitative measurement of functional Ab binding sites immobilized on the solid surfaces. The method called Antibody Anti-HorseRadish Peroxidase (A2HRP) method, uses a covalently coated anti-HRP antibody (anti-HRP Ab) and does not need for a secondary Ab during the detection step. The A2HRP method was validated and gave reliable results over a wide range of absorbance values. Analyzed validation criteria were fulfilled as requested by the food and drug administration (FDA) and European Medicines Agency (EMA) guidance for the validation of bioanalytical methods with 1) an accuracy mean value within +15% of the nominal value; 2) the within-assay precision less than 7.1%, and 3) the inter-day variability under 12.1%. With the A2HRP method, it is then possible to quantify from 0.04 × 10 12 to 2.98 × 10 12 functional Ab binding sites immobilized on the solid surfaces. A2HRP method was validated according to FDA and EMA guidance, allowing the creation of a gold standard method to evaluate Ab surfaces for their resistance under

Method Engineering: Engineering of Information Systems Development Methods and Tools

OpenAIRE

Brinkkemper, J.N.; Brinkkemper, Sjaak

1996-01-01

This paper proposes the term method engineering for the research field of the construction of information systems development methods and tools. Some research issues in method engineering are identified. One major research topic in method engineering is discussed in depth: situational methods, i.e. the configuration of a project approach that is tuned to the project at hand. A language and support tool for the engineering of situational methods are discussed.

ANALYSIS OF DIOXINS IN CONTAMINATED SOILS WITH THE CALUX AND CAFLUX BIOASSAYS, AN IMMUNOASSAY, AND GAS CHROMATOGRAPHY/HIGH-RESOLUTION MASS SPECTROMETRY

Science.gov (United States)

Nording, Malin; Denison, Michael S.; Baston, David; Persson, Ylva; Spinnel, Erik; Haglund, Peter

2010-01-01

The chemically activated luciferase expression assay, the chemically activated fluorescence expression assay, and the enzyme-linked immunosorbent assay (ELISA) are all bioanalytical methods that have been used for the detection and quantification of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs). However, no comparisons of the results obtained by these three methods have been published analyzing identical replicates of purified sample extracts. Therefore, we have evaluated the performance of each of these methods for analyzing PCDD/Fs in aliquots of extracts from aged-contaminated soil samples and compared the results with those obtained by gas chromatography/high-resolution mass spectrometry (GC/HRMS). The quantitative performance was assessed and the effects of sample purification and data interpretation on the quality of the bioassay results were investigated. Results from the bioanalytical techniques were, in principle, not significantly different from each other or from the GC/HRMS data (p = 0.05). Furthermore, properly used, all of the bioanalytical techniques examined were found to be sufficiently sensitive, selective, and accurate to be used in connection with soil remediation activities when aiming at the remediation goal recommended by the U.S. Environmental Protection Agency (i.e., < 1,000 pg toxic equivalency/g). However, a site-specific correction factor should be applied with the use of the ELISA to account for differences between the toxic equivalency factors and the ELISA cross-reactivities of the various PCDD/F congeners, which otherwise might significantly underestimate the PCDD/F content. PMID:17571676

Development of LEDs-based microplate reader for bioanalytical assay measurements

International Nuclear Information System (INIS)

Alaruri, Sami D; Katzlinger, Michael; Schinwald, Bernhard; Kronberger, Georg; Atzler, Joseph

2013-01-01

The optical design for an LEDs-based microplate reader that can perform fluorescence intensity (top and bottom), absorbance, luminescence and time-resolved fluorescence measurements is described. The microplate reader is the first microplate reader in the marketplace that incorporates LEDs as excitation light sources. Absorbance measurements over the 0–3.5 optical density range for caffeine solution are presented. Additionally, fluorescence intensity readings collected at 535 and 625 nm from a green and a red RediPlate TM are reported. Furthermore, fluorescence decay lifetime measurements obtained for Eu (europium) and Sm (samarium) standard solutions using 370 nm excitation are presented. The microplate reader detection limits for the fluorescence intensity top, fluorescence intensity bottom, fluorescence polarization and time-resolved fluorescence modes are 1.5 fmol 100 µL −1 fluorescein (384-well plate), 25 fmol 100 µL −1 fluorescein (384-well plate), 5 mP at 10 nM fluorescein (black 384-well plate) and 30 amol 100 µL −1 europium solution (white 384-well plate), respectively. (paper)

Development of LEDs-based microplate reader for bioanalytical assay measurements

Science.gov (United States)

Alaruri, Sami D.; Katzlinger, Michael; Schinwald, Bernhard; Kronberger, Georg; Atzler, Joseph

2013-10-01

The optical design for an LEDs-based microplate reader that can perform fluorescence intensity (top and bottom), absorbance, luminescence and time-resolved fluorescence measurements is described. The microplate reader is the first microplate reader in the marketplace that incorporates LEDs as excitation light sources. Absorbance measurements over the 0-3.5 optical density range for caffeine solution are presented. Additionally, fluorescence intensity readings collected at 535 and 625 nm from a green and a red RediPlateTM are reported. Furthermore, fluorescence decay lifetime measurements obtained for Eu (europium) and Sm (samarium) standard solutions using 370 nm excitation are presented. The microplate reader detection limits for the fluorescence intensity top, fluorescence intensity bottom, fluorescence polarization and time-resolved fluorescence modes are 1.5 fmol 100 µL-1 fluorescein (384-well plate), 25 fmol 100 µL-1 fluorescein (384-well plate), 5 mP at 10 nM fluorescein (black 384-well plate) and 30 amol 100 µL-1 europium solution (white 384-well plate), respectively.

A novel UPLC-MS/MS method for sensitive quantitation of boldine in plasma, a potential anti-inflammatory agent: application to a pharmacokinetic study in rats.

Science.gov (United States)

Zeng, Rong-Jie; Li, Yu; Chen, Jian-Zhong; Chou, Gui-Xin; Gao, Yu; Shao, Jing-Wei; Jia, Lee; Wu, Sheng-Dong; Wu, Shui-Sheng

2015-03-01

Boldine is a potential anti-inflammatory agent found in several different plants. Published bioanalytical methods using HPLC with ultraviolet and fluorescent detection lacked enough sensitivity and required tedious sample preparation procedures. Herein, we describe the development of a novel ultra-high performance LC with MS/MS for determination of boldine in plasma. Boldine in plasma was recovered by liquid-liquid extraction using 1 mL of methyl tert-butyl ether. Chromatographic separation was performed on a C18 column at 45°C, with a gradient elution consisting of acetonitrile and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. The detection was performed on an electrospray triple-quadrupole MS/MS by positive ion multiple reaction monitoring mode. Good linearity (r(2) > 0.9926) was achieved in a concentration range of 2.555-2555 ng/mL with a lower limit of quantification of 2.555 ng/mL for boldine. The intra- and inter-day precisions of the assay were 1.2-6.0 and 1.8-7.4% relative standard deviation with an accuracy of -6.0-8.0% relative error. This newly developed method was successfully applied to a single low-dose pharmacokinetic study in rats and was demonstrated to be simpler and more sensitive than the published methods, allowing boldine quantification in reduced plasma volume. Copyright © 2014 John Wiley & Sons, Ltd.

Automated sample preparation using membrane microtiter extraction for bioanalytical mass spectrometry.

Science.gov (United States)

Janiszewski, J; Schneider, P; Hoffmaster, K; Swyden, M; Wells, D; Fouda, H

1997-01-01

The development and application of membrane solid phase extraction (SPE) in 96-well microtiter plate format is described for the automated analysis of drugs in biological fluids. The small bed volume of the membrane allows elution of the analyte in a very small solvent volume, permitting direct HPLC injection and negating the need for the time consuming solvent evaporation step. A programmable liquid handling station (Quadra 96) was modified to automate all SPE steps. To avoid drying of the SPE bed and to enhance the analytical precision a novel protocol for performing the condition, load and wash steps in rapid succession was utilized. A block of 96 samples can now be extracted in 10 min., about 30 times faster than manual solvent extraction or single cartridge SPE methods. This processing speed complements the high-throughput speed of contemporary high performance liquid chromatography mass spectrometry (HPLC/MS) analysis. The quantitative analysis of a test analyte (Ziprasidone) in plasma demonstrates the utility and throughput of membrane SPE in combination with HPLC/MS. The results obtained with the current automated procedure compare favorably with those obtained using solvent and traditional solid phase extraction methods. The method has been used for the analysis of numerous drug prototypes in biological fluids to support drug discovery efforts.

Clinical diagnostic of pleural effusions using a high-speed viscosity measurement method

Science.gov (United States)

Hurth, Cedric; Klein, Katherine; van Nimwegen, Lena; Korn, Ronald; Vijayaraghavan, Krishnaswami; Zenhausern, Frederic

2011-08-01

We present a novel bio-analytical method to discriminate between transudative and exudative pleural effusions based on a high-speed video analysis of a solid glass sphere impacting a liquid. Since the result depends on the solution viscosity, it can ultimately replace the battery of biochemical assays currently used. We present results obtained on a series of 7 pleural effusions obtained from consenting patients by analyzing both the splash observed after the glass impactor hits the liquid surface, and in a configuration reminiscent of the drop ball viscometer with added sensitivity and throughput provided by the high-speed camera. The results demonstrate distinction between the pleural effusions and good correlation with the fluid chemistry analysis to accurately differentiate exudates and transudates for clinical purpose. The exudative effusions display a viscosity around 1.39 ± 0.08 cP whereas the transudative effusion was measured at 0.89 ± 0.09 cP, in good agreement with previous reports.

Development of Methods of Innovative Projects’ Management in Developer Organizations

Directory of Open Access Journals (Sweden)

Papelniuk Oksana

2017-01-01

Full Text Available In article the author studies the conceptual scheme of life cycle of innovative developer project and offers methods of innovative projects' management according to the stages of its lifecycle. The author describes algorithm of the organization of management system of innovative projects in the developer organization representing set of stages and methods. The offered algorithm allows developer organizations achieve one of the main of their objectives, which is the creation of a special environment of comfortable accommodation with the emphasis on ecological compatibility and energy efficiency.

Milestones in the Development of Iterative Solution Methods

Directory of Open Access Journals (Sweden)

Owe Axelsson

2010-01-01

Full Text Available Iterative solution methods to solve linear systems of equations were originally formulated as basic iteration methods of defect-correction type, commonly referred to as Richardson's iteration method. These methods developed further into various versions of splitting methods, including the successive overrelaxation (SOR method. Later, immensely important developments included convergence acceleration methods, such as the Chebyshev and conjugate gradient iteration methods and preconditioning methods of various forms. A major strive has been to find methods with a total computational complexity of optimal order, that is, proportional to the degrees of freedom involved in the equation. Methods that have turned out to have been particularly important for the further developments of linear equation solvers are surveyed. Some of them are presented in greater detail.

Developments in Surrogating Methods

Directory of Open Access Journals (Sweden)

Hans van Dormolen

2005-11-01

Full Text Available In this paper, I would like to talk about the developments in surrogating methods for preservation. My main focus will be on the technical aspects of preservation surrogates. This means that I will tell you something about my job as Quality Manager Microfilming for the Netherlands’ national preservation program, Metamorfoze, which is coordinated by the National Library. I am responsible for the quality of the preservation microfilms, which are produced for Metamorfoze. Firstly, I will elaborate on developments in preservation methods in relation to the following subjects: · Preservation microfilms · Scanning of preservation microfilms · Preservation scanning · Computer Output Microfilm. In the closing paragraphs of this paper, I would like to tell you something about the methylene blue test. This is an important test for long-term storage of preservation microfilms. Also, I will give you a brief report on the Cellulose Acetate Microfilm Conference that was held in the British Library in London, May 2005.

Determination of esculentoside A in dog plasma by LC-MS/MS method: application to pre-clinical pharmacokinetics.

Science.gov (United States)

Guan, Xiaoduo; Chang, Huichao; Sun, Fanlu; Chen, Xiaohui; Zhang, Wen; Fan, Guorong

2013-01-01

A simple and rapid high performance liquid chromatography electrospray ionization ion-trap tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitative determination of esculentoside A (EsA) in dog plasma using ginsenoside Rg1 as the internal standard (IS). After liquid-liquid extraction (LLE) with n-butanol, the analyte and IS were separated on a Diamonsil C(18) (2.1 mm × 50 mm, 3 μm) column with the mobile phase of methanol-water containing 0.1% acetic acid (70:30, v/v) at a flow rate of 0.2 ml/min. An ion trap mass spectrometer equipped with an electrospray ionization source performed in selected reaction monitoring (SRM) mode was used as the detector. The precursor-product ion transitions were m/z 849.3 [M+Na](+)→m/z 805.3 for EsA and m/z 823.3 [M+Na](+)→m/z 643.3 for IS. The total chromatographic run time was 5 min. The method was sensitive enough with a lower limit of quantitation (LLOQ) of 5 ng/ml and had a good linearity (r(2)>0.997) over the linear range of 5-500 ng/ml. The mean extraction recovery of EsA from spiked plasma samples was over 75%. The intra- and inter-precisions were no more than 8.8% and accuracies were within the range of -4.6 to 8.7%. All the validated data were within the accepted criteria as stated in the FDA bioanalytical method validation guideline. The developed method was suitable for the quantification of EsA and successfully applied to the pharmacokinetic study of EsA after an oral administration to beagle dogs. Copyright © 2012 Elsevier B.V. All rights reserved.

A Survey of Formal Methods in Software Development

DEFF Research Database (Denmark)

Bjørner, Dines

2012-01-01

The use of formal methods and formal techniques in industry is steadily growing. In this survey we shall characterise what we mean by software development and by a formal method; briefly overview a history of formal specification languages - some of which are: VDM (Vienna Development Method, 1974...... need for multi-language formalisation (Petri Nets, MSC, StateChart, Temporal Logics); the sociology of university and industry acceptance of formal methods; the inevitability of the use of formal software development methods; while referring to seminal monographs and textbooks on formal methods....

Taxonomic Dimensions for Studying Situational Method Development

NARCIS (Netherlands)

Aydin, Mehmet N.; Harmsen, Frank; van Hillegersberg, Jos; Ralyté, Jolita; Brinkkemper, Sjaak; Henderson-Sellers, Brian

2007-01-01

This paper is concerned with fragmented literature on situational method development, which is one of fundamental topics related to information systems development (ISD) methods. As the topic has attracted many scholars from various and possibly complementary schools of thought, different

The SIESTA method; developments and applicability

International Nuclear Information System (INIS)

Artacho, Emilio; Anglada, E; Dieguez, O; Gale, J D; Garcia, A; Junquera, J; Martin, R M; Ordejon, P; Pruneda, J M; Sanchez-Portal, D; Soler, J M

2008-01-01

Recent developments in and around the SIESTA method of first-principles simulation of condensed matter are described and reviewed, with emphasis on (i) the applicability of the method for large and varied systems (ii) efficient basis sets for the standards of accuracy of density-functional methods (iii) new implementations, and (iv) extensions beyond ground-state calculations

Bioanalysis in microfluidic devices.

Science.gov (United States)

Khandurina, Julia; Guttman, András

2002-01-18

Microfabricated bioanalytical devices (also referred to as laboratory-on-a-chip or micro-TAS) offer highly efficient platforms for simultaneous analysis of a large number of biologically important molecules, possessing great potential for genome, proteome and metabolome studies. Development and implementation of microfluidic-based bioanalytical tools involves both established and evolving technologies, including microlithography, micromachining, micro-electromechanical systems technology and nanotechnology. This article provides an overview of the latest developments in the key device subject areas and the basic interdisciplinary technologies. Important aspects of DNA and protein analysis, interfacing issues and system integration are all thoroughly discussed, along with applications for this novel "synergized" technology in high-throughput separations of biologically important molecules. This review also gives a better understanding of how to utilize these technologies as well as to provide appropriate technical solutions to problems perceived as being more fundamental.

The J-Matrix Method Developments and Applications

CERN Document Server

Alhaidari, Abdulaziz D; Heller, Eric J; Abdelmonem, Mohamed S

2008-01-01

This volume aims to provide the fundamental knowledge to appreciate the advantages of the J-matrix method and to encourage its use and further development. The J-matrix method is an algebraic method of quantum scattering with substantial success in atomic and nuclear physics. The accuracy and convergence property of the method compares favourably with other successful scattering calculation methods. Despite its thirty-year long history new applications are being found for the J-matrix method. This book gives a brief account of the recent developments and some selected applications of the method in atomic and nuclear physics. New findings are reported in which experimental results are compared to theoretical calculations. Modifications, improvements and extensions of the method are discussed using the language of the J-matrix. The volume starts with a Foreword by the two co-founders of the method, E.J. Heller and H.A. Yamani and it contains contributions from 24 prominent international researchers.

Biological Methods and Manual Development

Science.gov (United States)

EPA scientists conduct research to develop and evaluate analytical methods for the identification, enumeration, evaluation of aquatic organisms exposed to environmental stressors and to correlate exposures with effects on chemical and biological indicators

Bioassay battery interlaboratory investigation of emerging contaminants in spiked water extracts - Towards the implementation of bioanalytical monitoring tools in water quality assessment and monitoring.

Science.gov (United States)

Di Paolo, Carolina; Ottermanns, Richard; Keiter, Steffen; Ait-Aissa, Selim; Bluhm, Kerstin; Brack, Werner; Breitholtz, Magnus; Buchinger, Sebastian; Carere, Mario; Chalon, Carole; Cousin, Xavier; Dulio, Valeria; Escher, Beate I; Hamers, Timo; Hilscherová, Klára; Jarque, Sergio; Jonas, Adam; Maillot-Marechal, Emmanuelle; Marneffe, Yves; Nguyen, Mai Thao; Pandard, Pascal; Schifferli, Andrea; Schulze, Tobias; Seidensticker, Sven; Seiler, Thomas-Benjamin; Tang, Janet; van der Oost, Ron; Vermeirssen, Etienne; Zounková, Radka; Zwart, Nick; Hollert, Henner

2016-11-01

Bioassays are particularly useful tools to link the chemical and ecological assessments in water quality monitoring. Different methods cover a broad range of toxicity mechanisms in diverse organisms, and account for risks posed by non-target compounds and mixtures. Many tests are already applied in chemical and waste assessments, and stakeholders from the science-police interface have recommended their integration in regulatory water quality monitoring. Still, there is a need to address bioassay suitability to evaluate water samples containing emerging pollutants, which are a current priority in water quality monitoring. The presented interlaboratory study (ILS) verified whether a battery of miniaturized bioassays, conducted in 11 different laboratories following their own protocols, would produce comparable results when applied to evaluate blinded samples consisting of a pristine water extract spiked with four emerging pollutants as single chemicals or mixtures, i.e. triclosan, acridine, 17α-ethinylestradiol (EE2) and 3-nitrobenzanthrone (3-NBA). Assays evaluated effects on aquatic organisms from three different trophic levels (algae, daphnids, zebrafish embryos) and mechanism-specific effects using in vitro estrogenicity (ER-Luc, YES) and mutagenicity (Ames fluctuation) assays. The test battery presented complementary sensitivity and specificity to evaluate the different blinded water extract spikes. Aquatic organisms differed in terms of sensitivity to triclosan (algae > daphnids > fish) and acridine (fish > daphnids > algae) spikes, confirming the complementary role of the three taxa for water quality assessment. Estrogenicity and mutagenicity assays identified with high precision the respective mechanism-specific effects of spikes even when non-specific toxicity occurred in mixture. For estrogenicity, although differences were observed between assays and models, EE2 spike relative induction EC 50 values were comparable to the literature, and E2/EE2

Magnetic techniques for the detection and determination of xenobiotics and cells in water

Czech Academy of Sciences Publication Activity Database

Šafařík, Ivo; Horská, Kateřina; Popisková, K.; Šafaříková, Miroslava

2012-01-01

Roč. 404, č. 4 (2012), s. 1257-1273 ISSN 1618-2642 R&D Projects: GA ČR(CZ) GAP503/11/2263 Institutional support: RVO:67179843 Keywords : bioanalytical methods * enzymes * immunoassays/ELISA * organic compounds * water * preconcentration Subject RIV: CE - Biochemistry Impact factor: 3.659, year: 2012

DDOT MXD+ method development report.

Science.gov (United States)

2015-09-01

Mixed-use development has become increasingly common across the country, including Washington, D.C. : However, a straightforward and empirically validated method for evaluating the traffic impacts of such : projects is still needed. The data presente...

Liquid chromatography-tandem mass spectrometric assay for the quantitative determination of the tyrosine kinase inhibitor quizartinib in mouse plasma using salting-out liquid-liquid extraction

NARCIS (Netherlands)

Retmana, Irene A; Wang, Jing; Schinkel, Alfred H; Schellens, Jan H M; Beijnen, Jos H; Sparidans, Rolf W

2017-01-01

A bioanalytical assay for quizartinib -a potent, and selective FLT3 tyrosine kinase inhibitor- in mouse plasma was developed and validated. Salting-out assisted liquid-liquid extraction (SALLE), using acetonitrile and magnesium sulfate, was selected as sample pretreatment with deuterated quizartinib

Liquid chromatography-tandem mass spectrometric assay for the tyrosine kinase inhibitor afatinib in mouse plasma using salting-out liquid-liquid extraction

NARCIS (Netherlands)

Sparidans, Rolf W; van Hoppe, Stephanie; Rood, Johannes J M; Schinkel, Alfred H; Schellens, Jan H M; Beijnen, Jos H

2016-01-01

A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay for afatinib, an irreversible inhibitor of the ErbB (erythroblastic leukemia viral oncogene homolog) tyrosine kinase family, was developed and validated. Plasma samples were pre-treated using salting-out

Highly tailorable thiol-ene based emulsion-templated monoliths

DEFF Research Database (Denmark)

Lafleur, J. P.; Kutter, J. P.

2014-01-01

The attractive surface properties of thiol-ene polymers combined with their ease of processing make them ideal substrates in many bioanalytical applications. We report the synthesis of highly tailorable emulsion-templated porous polymers and beads in microfluidic devices based on off-stoichiometr......The attractive surface properties of thiol-ene polymers combined with their ease of processing make them ideal substrates in many bioanalytical applications. We report the synthesis of highly tailorable emulsion-templated porous polymers and beads in microfluidic devices based on off......-stoichiometry thiolene chemistry. The method allows monolith synthesis and anchoring inside thiol-ene microchannels in a single step. Variations in the monomer stoichiometric ratios and/or amount of porogen used allow for the creation of extremely varied polymer morphologies, from foam-like materials to dense networks...

Development of spectrophotometric fingerprinting method for ...

African Journals Online (AJOL)

Selective and efficient analytical methods are required not only for quality assurance but also for authentication of herbal formulations. A simple, rapid and validated fingerprint method has developed for estimation of piperine in 'Talisadi churna', a well known herbal formulation in India. The estimation was carried out in two ...

A simple and sensitive method for the determination of fibric acids in the liver by liquid chromatography.

Science.gov (United States)

Karahashi, Minako; Fukuhara, Hiroto; Hoshina, Miki; Sakamoto, Takeshi; Yamazaki, Tohru; Mitsumoto, Atsushi; Kawashima, Yoichi; Kudo, Naomi

2014-01-01

Fibrates are used in biochemical and pharmacological studies as bioactive tools. Nevertheless, most studies have lacked information concerning the concentrations of fibric acids working inside tissues because a simple and sensitive method is not available for their quantitation. This study aimed to develop a simple and sensitive bioanalytical method for the quantitation of clofibric, bezafibric and fenofibric acids in samples of very small portions of tissues. Fibric acids were extracted into n-hexane-ethyl acetate from tissue homogenates (10 mg of liver, kidney or muscle) or serum (100 µL) and were derivatized with 4-bromomethyl-6,7-dimethoxycoumarin, followed by HPLC with fluorescence detection. These compounds were separated isocratically on a reversed phase with acetonitrile-water. Standard analytical curves were linear over the concentration range of 0.2-20 nmol/10 mg of liver. Precision and accuracy were within acceptable limits. Recovery from liver homogenates ranged from 93.03 to 112.29%. This method enabled the quantitation of fibric acids in 10 mg of liver from rats treated with clofibric acid, bezafibric acid or fenofibrate. From these analytical data, it became clear that there was no large difference in ratio of acyl-CoA oxidase 1 (Acox1) mRNA level to fibric acid content in the liver among the three fibric acids, suggesting that these three fibric acids have similar potency to increase expression of the Acox1 gene, which is a target of peroxisome proliferator-activated receptor α. Thus, the proposed method is a simple, sensitive and reliable tool for the quantitation of fibric acids working in vivo inside livers.

Development of a high performance liquid chromatography method ...

African Journals Online (AJOL)

Development of a high performance liquid chromatography method for simultaneous ... Purpose: To develop and validate a new low-cost high performance liquid chromatography (HPLC) method for ..... Several papers have reported the use of ...

Transfer of High Performance Liquid Chromatography with Diode ...

African Journals Online (AJOL)

2013-08-22

Aug 22, 2013 ... Rwanda Journal Series F:Medicine and Health Sciences Vol 4 No.1, 2017 ... 1Laboratory of Analysis of Foodstuffs, Drugs, Water and Toxics, University of Rwanda, School of Medicine and Pharmacy, 117 Huye, ..... Cooperation for the financial support. .... for the transfer of quantitative methods: Bioanalytical.

Hydrogen deuterium exchange mass spectrometry in biopharmaceutical discovery and development – A review

International Nuclear Information System (INIS)

Deng, Bin; Lento, Cristina; Wilson, Derek J.

2016-01-01

Protein therapeutics have emerged as a major class of biopharmaceuticals over the past several decades, a trend that has motivated the advancement of bioanalytical technologies for protein therapeutic characterization. Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful and sensitive technique that can probe the higher order structure of proteins and has been used in the assessment and development of monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs) and biosimilar antibodies. It has also been used to quantify protein-ligand, protein-receptor and other protein-protein interactions involved in signaling pathways. In manufacturing and development, HDX-MS can validate storage formulations and manufacturing processes for various biotherapeutics. Currently, HDX-MS is being refined to provide additional coverage, sensitivity and structural specificity and implemented on the millisecond timescale to reveal residual structure and dynamics in disordered domains and intrinsically disordered proteins. - Highlights: • The pharmaceuticals industry is increasingly shifting to protein therapeutics. • Hydrogen deuterium exchange mass spectrometry is uniquely well suited to support biopharmaceutical development. • Applications for hydrogen deuterium exchange span drug discovery, development and manufacturing. • Future developments will allow improved sensitivity, structural resolution and a broader range of dynamics to be monitored.

Hydrogen deuterium exchange mass spectrometry in biopharmaceutical discovery and development – A review

Energy Technology Data Exchange (ETDEWEB)

Deng, Bin, E-mail: dengbin@yorku.ca [Chemistry Department, York University, 4700 Keele Street, Toronto, ON, M3J 1P3 (Canada); The Centre for Research in Mass Spectrometry, York University, Toronto, ON, M3J1P3 (Canada); Lento, Cristina, E-mail: clento@yorku.ca [Chemistry Department, York University, 4700 Keele Street, Toronto, ON, M3J 1P3 (Canada); The Centre for Research in Mass Spectrometry, York University, Toronto, ON, M3J1P3 (Canada); Wilson, Derek J., E-mail: dkwilson@yorku.ca [Chemistry Department, York University, 4700 Keele Street, Toronto, ON, M3J 1P3 (Canada); The Centre for Research in Mass Spectrometry, York University, Toronto, ON, M3J1P3 (Canada)

2016-10-12

Protein therapeutics have emerged as a major class of biopharmaceuticals over the past several decades, a trend that has motivated the advancement of bioanalytical technologies for protein therapeutic characterization. Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful and sensitive technique that can probe the higher order structure of proteins and has been used in the assessment and development of monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs) and biosimilar antibodies. It has also been used to quantify protein-ligand, protein-receptor and other protein-protein interactions involved in signaling pathways. In manufacturing and development, HDX-MS can validate storage formulations and manufacturing processes for various biotherapeutics. Currently, HDX-MS is being refined to provide additional coverage, sensitivity and structural specificity and implemented on the millisecond timescale to reveal residual structure and dynamics in disordered domains and intrinsically disordered proteins. - Highlights: • The pharmaceuticals industry is increasingly shifting to protein therapeutics. • Hydrogen deuterium exchange mass spectrometry is uniquely well suited to support biopharmaceutical development. • Applications for hydrogen deuterium exchange span drug discovery, development and manufacturing. • Future developments will allow improved sensitivity, structural resolution and a broader range of dynamics to be monitored.

Some problems on Monte Carlo method development

International Nuclear Information System (INIS)

Pei Lucheng

1992-01-01

This is a short paper on some problems of Monte Carlo method development. The content consists of deep-penetration problems, unbounded estimate problems, limitation of Mdtropolis' method, dependency problem in Metropolis' method, random error interference problems and random equations, intellectualisation and vectorization problems of general software

A reliable and validated LC-MS/MS method for the simultaneous quantification of 4 cannabinoids in 40 consumer products.

Directory of Open Access Journals (Sweden)

Qingfang Meng

Full Text Available In the past 50 years, Cannabis sativa (C. sativa has gone from a substance essentially prohibited worldwide to one that is gaining acceptance both culturally and legally in many countries for medicinal and recreational use. As additional jurisdictions legalize Cannabis products and the variety and complexity of these products surpass the classical dried plant material, appropriate methods for measuring the biologically active constituents is paramount to ensure safety and regulatory compliance. While there are numerous active compounds in C. sativa the primary cannabinoids of regulatory and safety concern are (--Δ⁹-tetrahydrocannabinol (THC, cannabidiol (CBD, and their respective acidic forms THCA-A and CBDA. Using the US Food and Drug Administration (FDA bioanalytical method validation guidelines we developed a sensitive, selective, and accurate method for the simultaneous analysis CBD, CBDA, THC, and THCA-A in oils and THC & CBD in more complex matrices. This HPLC-MS/MS method was simple and reliable using standard sample dilution and homogenization, an isocratic chromatographic separation, and a triple quadrupole mass spectrometer. The lower limit of quantification (LLOQ for analytes was 0.195 ng/mL over a 0.195-50.0 ng/mL range of quantification with a coefficient of correlation of >0.99. Average intra-day and inter-day accuracies were 94.2-112.7% and 97.2-110.9%, respectively. This method was used to quantify CBD, CBDA, THC, and THCA-A in 40 commercial hemp products representing a variety of matrices including oils, plant materials, and creams/cosmetics. All products tested met the federal regulatory restrictions on THC content in Canada (1,000 (an oil-based product. Overall, the method proved amenable to the analysis of various commercial products including oils, creams, and plant material and may be diagnostically indicative of adulteration with non-hemp C. sativa, specialized hemp cultivars, or unique manufacturing methods.

Development and Validation of Analytical Method for Losartan ...

African Journals Online (AJOL)

Development and Validation of Analytical Method for Losartan-Copper Complex Using UV-Vis Spectrophotometry. ... Tropical Journal of Pharmaceutical Research ... Purpose: To develop a new spectrophotometric method for the analysis of losartan potassium in pharmaceutical formulations by making its complex with ...

Development of the numerical method for liquid metal magnetohydrodynamics (I). Investigation of the method and development of the 2D method

International Nuclear Information System (INIS)

Ohira, H.; Ara, K.

2002-11-01

Advanced electromagnetic components are investigated in Feasibility Studies on Commercialized FR Cycle System to apply to the main cooling systems of Liquid Metal Fast Reactor. Although a lot of experiments and numerical analysis were carried out on both high Reynolds numbers and high magnetic Reynolds numbers, the complex phenomena could not be evaluated in detail. As the first step of the development of the numerical methods for the liquid metal magnetohydrodynamics, we investigated numerical methods that could be applied to the electromagnetic components with both complex structures and high magnetic turbulent field. As a result, we selected GSMAC (Generalized-Simplified MArker and Cell) method for calculating the liquid metal fluid dynamics because it could be easily applied to the complex flow field. We also selected the vector-FEM for calculating the magnetic field of the large components because the method had no interaction procedure. In the high magnetic turbulent field, the dynamic-SGS models would be also a promising model for the good estimation, because it could calculate the field directly without any experimental constant. In order to verify the GSMAC and the vector-FEM, we developed the 2D numerical models and calculated the magnetohydrodynamics in the large electromagnetic pump. It was estimated from these results that the methods were basically reasonable, because the calculated pressure differences had the similar tendencies to the experimental ones. (author)

Usability Evaluation Method for Agile Software Development

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Saad Masood Butt

2015-02-01

Full Text Available Agile methods are the best fit for tremendously growing software industry due to its flexible and dynamic nature. But the software developed using agile methods do meet the usability standards? To answer this question we can see that majority of agile software development projects currently involve interactive user interface designs, which can only be possible by following User Centered Design (UCD in agile methods. The question here is, how to integrate UCD with agile models. Both Agile models and UCD are iterative in nature but agile models focus on coding and development of software; whereas, UCD focuses on user interface of the software. Similarly, both of them have testing features where the agile model involves automated tested code while UCD involves an expert or a user to test the user interface. In this paper, a new agile usability model is proposed and the evaluation is of the proposed model is presented by practically implementing it in three real life projects. . Key results from these projects clearly show: the proposed agile model incorporates usability evaluation methods, improves the relationship between usability experts to work with agile software experts; in addition, allows agile developers to incorporate the result from UCD into subsequent interactions.

Process development for waveguide chemical sensors with integrated polymeric sensitive layers

Science.gov (United States)

Amberkar, Raghu; Gao, Zhan; Park, Jongwon; Henthorn, David B.; Kim, Chang-Soo

2008-02-01

Due to the proper optical property and flexibility in the process development, an epoxy-based, high-aspect ratio photoresist SU-8 is now attracting attention in optical sensing applications. Manipulation of the surface properties of SU-8 waveguides is critical to attach functional films such as chemically-sensitive layers. We describe a new integration process to immobilize fluorescence molecules on SU-8 waveguide surface for application to intensity-based optical chemical sensors. We use two polymers for this application. Spin-on, hydrophobic, photopatternable silicone is a convenient material to contain fluorophore molecules and to pattern a photolithographically defined thin layer on the surface of SU-8. We use fumed silica powders as an additive to uniformly disperse the fluorophores in the silicone precursor. In general, additional processes are not critically required to promote the adhesion between the SU-8 and silicone. The other material is polyethylene glycol diacrylate (PEGDA). Recently we demonstrated a novel photografting method to modify the surface of SU-8 using a surface bound initiator to control its wettability. The activated surface is then coated with a monomer precursor solution. Polymerization follows when the sample is exposed to UV irradiation, resulting in a grafted PEGDA layer incorporating fluorophores within the hydrogel matrix. Since this method is based the UV-based photografting reaction, it is possible to grow off photolithographically defined hydrogel patterns on the waveguide structures. The resulting films will be viable integrated components in optical bioanalytical sensors. This is a promising technique for integrated chemical sensors both for planar type waveguide and vertical type waveguide chemical sensors.

Development and Validation of a Dissolution Test Method for ...

African Journals Online (AJOL)

Purpose: To develop and validate a dissolution test method for dissolution release of artemether and lumefantrine from tablets. Methods: A single dissolution method for evaluating the in vitro release of artemether and lumefantrine from tablets was developed and validated. The method comprised of a dissolution medium of ...

A Model-Driven Development Method for Management Information Systems

Science.gov (United States)

Mizuno, Tomoki; Matsumoto, Keinosuke; Mori, Naoki

Traditionally, a Management Information System (MIS) has been developed without using formal methods. By the informal methods, the MIS is developed on its lifecycle without having any models. It causes many problems such as lack of the reliability of system design specifications. In order to overcome these problems, a model theory approach was proposed. The approach is based on an idea that a system can be modeled by automata and set theory. However, it is very difficult to generate automata of the system to be developed right from the start. On the other hand, there is a model-driven development method that can flexibly correspond to changes of business logics or implementing technologies. In the model-driven development, a system is modeled using a modeling language such as UML. This paper proposes a new development method for management information systems applying the model-driven development method to a component of the model theory approach. The experiment has shown that a reduced amount of efforts is more than 30% of all the efforts.

Recent developments in automatic solid-phase extraction with renewable surfaces exploiting flow-based approaches

DEFF Research Database (Denmark)

Miró, Manuel; Hartwell, Supaporn Kradtap; Jakmunee, Jaroon

2008-01-01

,on-line SPE assays performed in permanent mode lack sufficient reliability as a consequence of progressively tighter packing of the bead reactor, contamination of the solid surfaces and potential leakage of functional moieties. This article overviews the current state-of-the-art of an appealing tool...... chemical-derivatization reactions, and it pinpoints the most common instrumental detection techniques utilized. We present and discuss in detail relevant environmental and bioanalytical applications reported in the past few years....

Feedback of reactor operating data to nuclear methods development

International Nuclear Information System (INIS)

Crowther, R.L.; Kang, C.M.; Parkos, G.R.; Wolters, R.A.

1978-01-01

The problems in obtaining power reactor data for reliable nuclear methods development and the major sources of power reactor data for this purpose are reviewed. Specific examples of the use of power reactor data in nuclear methods development are discussed. The paper concludes with recommendations on the key elements of an effective program to use power reactor data in nuclear methods development

Development of Dissolution Test Method for Drotaverine ...

African Journals Online (AJOL)

Development of Dissolution Test Method for Drotaverine ... Methods: Sink conditions, drug stability and specificity in different dissolution media were tested to optimize a dissolution test .... test by Prism 4.0 software, and differences between ...

Tracking maize pollen development by the Leaf Collar Method.

Science.gov (United States)

Begcy, Kevin; Dresselhaus, Thomas

2017-12-01

An easy and highly reproducible nondestructive method named the Leaf Collar Method is described to identify and characterize the different stages of pollen development in maize. In plants, many cellular events such as meiosis, asymmetric cell division, cell cycle regulation, cell fate determination, nucleus movement, vacuole formation, chromatin condensation and epigenetic modifications take place during pollen development. In maize, pollen development occurs in tassels that are confined within the internal stalk of the plant. Hence, identification of the different pollen developmental stages as a tool to investigate above biological processes is impossible without dissecting the entire plant. Therefore, an efficient and reproducible method is necessary to isolate homogeneous cell populations at individual stages throughout pollen development without destroying the plant. Here, we describe a method to identify the various stages of pollen development in maize. Using the Leaf Collar Method in the maize inbreed line B73, we have determined the duration of each stage from pollen mother cells before meiosis to mature tricellular pollen. Anther and tassel size as well as percentage of pollen stages were correlated with vegetative stages, which are easily recognized. The identification of stage-specific genes indicates the reproducibility of the method. In summary, we present an easy and highly reproducible nondestructive method to identify and characterize the different stages of pollen development in maize. This method now opens the way for many subsequent physiological, morphological and molecular analyses to study, for instance, transcriptomics, metabolomics, DNA methylation and chromatin patterns during normal and stressful conditions throughout pollen development in one of the economically most important grass species.

Extending product modeling methods for integrated product development

DEFF Research Database (Denmark)

Bonev, Martin; Wörösch, Michael; Hauksdóttir, Dagný

2013-01-01

Despite great efforts within the modeling domain, the majority of methods often address the uncommon design situation of an original product development. However, studies illustrate that development tasks are predominantly related to redesigning, improving, and extending already existing products...... and PVM methods, in a presented Product Requirement Development model some of the individual drawbacks of each method could be overcome. Based on the UML standard, the model enables the representation of complex hierarchical relationships in a generic product model. At the same time it uses matrix....... Updated design requirements have then to be made explicit and mapped against the existing product architecture. In this paper, existing methods are adapted and extended through linking updated requirements to suitable product models. By combining several established modeling techniques, such as the DSM...

METHOD TO DEVELOP THE DOUBLE-CURVED SURFACE OF THE ROOF

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JURCO Ancuta Nadia

2017-05-01

Full Text Available This work present two methods for determining the development of double-curved surface. The aims of this paper is to show a comparative study between methods for determination of the sheet metal requirements for complex roof cover shape. In first part of the paper are presented the basic sketch and information about the roof shape and some consecrated buildings, which have a complex roof shape. The second part of the paper shows two methods for determining the developed of the spherical roof. The graphical method is the first method used for developing of the spherical shape. In this method it used the poly-cylindrical method to develop the double-curved surface. The second method is accomplishing by using the dedicated CAD software method.

USING ANALYTIC HIERARCHY PROCESS (AHP METHOD IN RURAL DEVELOPMENT

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Tülay Cengiz

2003-04-01

Full Text Available Rural development is a body of economical and social policies towards improving living conditions in rural areas through enabling rural population to utilize economical, social, cultural and technological blessing of city life in place, without migrating. As it is understood from this description, rural development is a very broad concept. Therefore, in development efforts problem should be stated clearly, analyzed and many criterias should be evaluated by experts. Analytic Hierarchy Process (AHP method can be utilized at there stages of development efforts. AHP methods is one of multi-criteria decision method. After degrading a problem in smaller pieces, relative importance and level of importance of two compared elements are determined. It allows evaluation of quality and quantity factors. At the same time, it permits utilization of ideas of many experts and use them in decision process. Because mentioned features of AHP method, it could be used in rural development works. In this article, cultural factors, one of the important components of rural development is often ignored in many studies, were evaluated as an example. As a result of these applications and evaluations, it is concluded that AHP method could be helpful in rural development efforts.

Development and validation of UPLC/ESI-Q-TOF-MS for carteolol in aqueous humour: Stability, stress degradation and application in pharmacokinetics of nanoformulation

Directory of Open Access Journals (Sweden)

Ameeduzzafar

2017-05-01

Full Text Available Carteolol (CRT is currently under development as a potential therapeutic agent for the treatment of open angle glaucoma. The purpose of the present work is to develop and validate a stability indicating assay method and its application to estimate CRT in aqueous humour and study the pharmacokinetic parameters. An ultra performance liquid chromatographic tandem mass spectroscopy (UPLC–MS/MS method was developed and validated for the quantitative determination of CRT in rabbit aqueous humour, using propranolol as the internal standard (I.S.. Aqueous humour samples were prepared by a simple liquid–liquid extraction technique (LLE. The analyte and internal standard were separated by an Acquity UPLC BEH C18 (100.0 × 2.1 mm; 1.7 μm column with a mobile phase of acetonitrile – 2 mM (milli mole ammonium acetate (90/10, v/v over 3 min of retention time. Detection was based on the multiple reactions monitoring with the precursor-to-product ion transitions m/z 293.2 → 237.12 for CRT and m/z 260.09 → 183.04 for I.S. The method was validated according to FDA guidelines on the bio-analytical method validation. The method developed was linear (r2 = 0.999 over the concentration range of 1–1000 ng/mL. The selectivity, sensitivity, linearity, accuracy, precision, extraction recovery, and stability were within the acceptable ranges. Forced degradation studies were performed on bulk sample of CRT as per ICH prescribed stress conditions, such as acid, base, oxidative and photolytic to show the forced of the method. Significant degradation was observed during basic stress condition. The pharmacokinetic study of CRT solution and nanoparticles in aqueous humour of rabbit eye was performed and results showed that CRT nanoparticles enhance the ocular bioavailability by 5.61-fold as compared to CRT-solution.

Validated modified Lycopodium spore method development for ...

African Journals Online (AJOL)

Validated modified lycopodium spore method has been developed for simple and rapid quantification of herbal powdered drugs. Lycopodium spore method was performed on ingredients of Shatavaryadi churna, an ayurvedic formulation used as immunomodulator, galactagogue, aphrodisiac and rejuvenator. Estimation of ...

Development of Three Methods for Simultaneous Quantitative ...

African Journals Online (AJOL)

Development of Three Methods for Simultaneous Quantitative Determination of Chlorpheniramine Maleate and Dexamethasone in the Presence of Parabens in ... Tropical Journal of Pharmaceutical Research ... Results: All the proposed methods were successfully applied to the analysis of raw materials and dosage form.

Simple method for the determination of rosiglitazone in human plasma using a commercially available internal standard.

Science.gov (United States)

Mamidi, Rao N V S; Benjamin, Biju; Ramesh, Mullangi; Srinivas, Nuggehally R

2003-09-01

To the best of our knowledge, bioanalytical methods to determine rosiglitazone in human plasma reported in literature use internal standards that are not commercially available. Our purpose was to develop a simple method for the determination of rosiglitazone in plasma employing a commercially available internal standard (IS). After the addition of celecoxib (IS), plasma (0.25 mL) samples were extracted into ethyl acetate. The residue after evaporation of the organic layer was dissolved in 750 microL of mobile phase and 50 microL was injected on to HPLC. The separation was achieved using a Hichrom KR 100, 250 x 4.6 mm C(18) with a mobile phase composition potassium dihydrogen phosphate buffer (0.01 m, pH 6.5):acetonitrile:methanol (40:50:10, v/v/v). The flow-rate of the mobile phase was set at 1 mL/min. The column eluate was monitored by fluorescence detector set at an excitation wavelength of 247 nm and emission wavelength of 367 nm. Linear relationships (r(2) > 0.99) were observed between the peak area ratio rosiglitazone to IS vs rosiglitazone concentrations across the concentration range 5-1000 ng/mL. The intra-run precision (%RSD) and accuracy (%Dev) in the measurement of rosiglitazone were 80% for both rosiglitazone and IS from human plasma. The lower limit of quantitation of the assay was 5 ng/mL. In summary, the methodology for rosiglitazone measurement in plasma was simple, sensitive and employed a commercially available IS. Copyright 2003 John Wiley & Sons, Ltd.

Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of irinotecan and its main metabolites in human plasma and its application in a clinical pharmacokinetic study.

Directory of Open Access Journals (Sweden)

Elena Marangon

Full Text Available Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC. This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients' genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28 has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite to SN-38 glucuronide (SN-38G leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients' plasma, we developed and validated a new, sensitive and specific HPLC-MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 μM, 100 mm x 2.0 mm using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R2 ≥0.9962 over the concentration ranges (10-10000 ng/mL for irinotecan, 1-500 ng/mL for SN-38 and SN-38G and 1-5000 ng/mL for APC and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to a pharmacokinetic study in

Novel polymeric biochips for enhanced detection of infectious diseases

CERN Document Server

Hosseini, Samira

2016-01-01

This book focuses on the creation and development of polymeric platforms (different compositions) from a specific polymer system. This system can be used as an adaptive technique for producing sensitive analytical devices, or for simple integration into existing bioanalytical tools in order to enhance the detection signal.

Method æ, the agile software development method tailored for the pharmaceutical industry.

NARCIS (Netherlands)

Hajou, A.; Batenburg, R.S.; Jansen, S.

2015-01-01

Agile software development methods have a high adoption rate due to their proven business benefits. Its success has not yet been identified in the pharmaceutical industry, due to the industry’s incompatibility with generic agile methods. Comprehensive research has been done to engineer a tailored

CASE METHOD: THE STORY OF THE DEVELOPMENT AND USE OF THE METHOD IN EDUCATION

Directory of Open Access Journals (Sweden)

Светлана Юрьевна Грузкова

2013-08-01

Full Text Available This article deals with the history of origin and issue of case-study method (of a кейс-method in the practice of professional education, which is based on case studies. The distinctive feature of the case-study method is to create a problematic situation on the basis of the facts of real life. As a method, analysis of situations-has become widespread in the world in the 70-80 years, in the same period, he became known in the USSR. This method was used at the beginning, when training managers mainly economic universities to form the students ' ability to make decisions. It is connected with the changes taking place in the economy, because at that time, it has generated substantial reform demand for specialists who know how to act in situations of uncertainty, high risk specialists who can analyze and make decisions. On the one hand, as the authors note, the wide dissemination of this method in education due to its orientation, so that the case method is focused not so much on the development of specific knowledge or skills, as on the development of the common intellectual and communicative capacity of the trainee and the training. In addition, the case method is quite effective in training, he can be connected easily enough with other learning methods. On the other hand, have been certain difficulties in introducing the case-study method in the practice of professional education: general orientation for the development of education and development of the quality requirements for surface treatment, specialist teachers to the methodological basis for the other method.DOI: http://dx.doi.org/10.12731/2218-7405-2013-6-24

Bioanalytical Applications of Real-Time ATP Imaging Via Bioluminescence

Energy Technology Data Exchange (ETDEWEB)

Gruenhagen, Jason Alan [Iowa State Univ., Ames, IA (United States)

2003-01-01

The research discussed within involves the development of novel applications of real-time imaging of adenosine 5'-triphosphate (ATP). ATP was detected via bioluminescence and the firefly luciferase-catalyzed reaction of ATP and luciferin. The use of a microscope and an imaging detector allowed for spatially resolved quantitation of ATP release. Employing this method, applications in both biological and chemical systems were developed. First, the mechanism by which the compound 48/80 induces release of ATP from human umbilical vein endothelial cells (HUVECs) was investigated. Numerous enzyme activators and inhibitors were utilized to probe the second messenger systems involved in release. Compound 48/80 activated a G{sub q}-type protein to initiate ATP release from HUVECs. Ca²⁺ imaging along with ATP imaging revealed that activation of phospholipase C and induction of intracellular Ca²⁺ signaling were necessary for release of ATP. Furthermore, activation of protein kinase C inhibited the activity of phospholipase C and thus decreased the magnitude of ATP release. This novel release mechanism was compared to the existing theories of extracellular release of ATP. Bioluminescence imaging was also employed to examine the role of ATP in the field of neuroscience. The central nervous system (CNS) was dissected from the freshwater snail Lymnaea stagnalis. Electrophysiological experiments demonstrated that the neurons of the Lymnaea were not damaged by any of the components of the imaging solution. ATP was continuously released by the ganglia of the CNS for over eight hours and varied from ganglion to ganglion and within individual ganglia. Addition of the neurotransmitters K⁺ and serotonin increased release of ATP in certain regions of the Lymnaea CNS. Finally, the ATP imaging technique was investigated for the study of drug release systems. MCM-41-type mesoporous nanospheres were loaded with ATP and end-capped with mercaptoethanol

Characterization, thermal stability studies, and analytical method development of Paromomycin for formulation development.

Science.gov (United States)

Khan, Wahid; Kumar, Neeraj

2011-06-01

Paromomycin (PM) is an aminoglycoside antibiotic, first isolated in the 1950s, and approved in 2006 for treatment of visceral leishmaniasis. Although isolated six decades back, sufficient information essential for development of pharmaceutical formulation is not available for PM. The purpose of this paper was to determine thermal stability and development of new analytical method for formulation development of PM. PM was characterized by thermoanalytical (DSC, TGA, and HSM) and by spectroscopic (FTIR) techniques and these techniques were used to establish thermal stability of PM after heating PM at 100, 110, 120, and 130 °C for 24 h. Biological activity of these heated samples was also determined by microbiological assay. Subsequently, a simple, rapid and sensitive RP-HPLC method for quantitative determination of PM was developed using pre-column derivatization with 9-fluorenylmethyl chloroformate. The developed method was applied to estimate PM quantitatively in two parenteral dosage forms. PM was successfully characterized by various stated techniques. These techniques indicated stability of PM for heating up to 120 °C for 24 h, but when heated at 130 °C, PM is liable to degradation. This degradation is also observed in microbiological assay where PM lost ∼30% of its biological activity when heated at 130 °C for 24 h. New analytical method was developed for PM in the concentration range of 25-200 ng/ml with intra-day and inter-day variability of stability of PM was determined successfully. Developed analytical method was found sensitive, accurate, and precise for quantification of PM. Copyright © 2010 John Wiley & Sons, Ltd. Copyright © 2010 John Wiley & Sons, Ltd.

Method Development and Monitoring of Cyanotoxins in Water

Science.gov (United States)

This presentation describes method development of two ambient water LC/MS/MS methods for microcystins, cylindrospermopsin and anatoxin-a. Ruggedness of the methods will be demonstrated by evaluation of quality control samples derived from various water bodies across the country.

Radiocarbon mass spectrometry for drug development

International Nuclear Information System (INIS)

Ulrich, Schulze-Konig Tim

2011-01-01

Full text: Radiocarbon has a huge potential as a tracer for metabolism studies in humans. By using Accelerator Mass Spectrometry (AMS) for its detection, a unique sensitivity is reached reducing required radiation doses to a negligible level. Until recently, a widespread use of AMS in biomedical research was impeded by the high complexity of the instrument, time-consuming sample preparation, and a limited availability of measurement capacity. Over the last few years, tremendous progress has been achieved in the reduction of size and complexity of AMS instruments. It allowed designing a compact AMS system, dubbed BioMICADAS to address the needs of biomedical users. For more than two years, this system is in successful operation at a commercial service provider for the pharmaceutical industry. A further drastic simplification of radiocarbon mass spectrometers seems possible and could establish a regular usage of this technology in drug development. However, to reach this goal a better integration of AMS into the workflow of bioanalytical laboratories will be necessary. For this purpose, CO 2 accepting ion sources may be a key, since they enable an almost automated sample preparation. The status of radiocarbon AMS in biomedical research and its perspective will be discussed

Development of analysis methods for seismically isolated nuclear structures

International Nuclear Information System (INIS)

Yoo, Bong; Lee, Jae-Han; Koo, Gyeng-Hoi

2002-01-01

KAERI's contributions to the project entitled Development of Analysis Methods for Seismically Isolated Nuclear Structures under IAEA CRP of the intercomparison of analysis methods for predicting the behaviour of seismically isolated nuclear structures during 1996-1999 in effort to develop the numerical analysis methods and to compare the analysis results with the benchmark test results of seismic isolation bearings and isolated nuclear structures provided by participating countries are briefly described. Certain progress in the analysis procedures for isolation bearings and isolated nuclear structures has been made throughout the IAEA CRPs and the analysis methods developed can be improved for future nuclear facility applications. (author)

Development and Application of Kinetic Spectrophotometric Method ...

African Journals Online (AJOL)

Purpose: To develop an improved kinetic-spectrophotometric procedure for the determination of metronidazole (MNZ) in pharmaceutical formulations. Methods: The method is based on oxidation reaction of MNZ by hydrogen peroxide in the presence of Fe(II) ions at pH 4.5 (acetate buffer). The reaction was monitored ...

How Qualitative Methods Can be Used to Inform Model Development.

Science.gov (United States)

Husbands, Samantha; Jowett, Susan; Barton, Pelham; Coast, Joanna

2017-06-01

Decision-analytic models play a key role in informing healthcare resource allocation decisions. However, there are ongoing concerns with the credibility of models. Modelling methods guidance can encourage good practice within model development, but its value is dependent on its ability to address the areas that modellers find most challenging. Further, it is important that modelling methods and related guidance are continually updated in light of any new approaches that could potentially enhance model credibility. The objective of this article was to highlight the ways in which qualitative methods have been used and recommended to inform decision-analytic model development and enhance modelling practices. With reference to the literature, the article discusses two key ways in which qualitative methods can be, and have been, applied. The first approach involves using qualitative methods to understand and inform general and future processes of model development, and the second, using qualitative techniques to directly inform the development of individual models. The literature suggests that qualitative methods can improve the validity and credibility of modelling processes by providing a means to understand existing modelling approaches that identifies where problems are occurring and further guidance is needed. It can also be applied within model development to facilitate the input of experts to structural development. We recommend that current and future model development would benefit from the greater integration of qualitative methods, specifically by studying 'real' modelling processes, and by developing recommendations around how qualitative methods can be adopted within everyday modelling practice.

Development of standard testing methods for nuclear-waste forms

International Nuclear Information System (INIS)

Mendel, J.E.; Nelson, R.D.

1981-11-01

Standard test methods for waste package component development and design, safety analyses, and licensing are being developed for the Nuclear Waste Materials Handbook. This paper describes mainly the testing methods for obtaining waste form materials data

New trends in bioanalytical tools for the detection of genetically modified organisms: an update.

Science.gov (United States)

Michelini, Elisa; Simoni, Patrizia; Cevenini, Luca; Mezzanotte, Laura; Roda, Aldo

2008-10-01

Despite the controversies surrounding genetically modified organisms (GMOs), the production of GM crops is increasing, especially in developing countries. Thanks to new technologies involving genetic engineering and unprecedented access to genomic resources, the next decade will certainly see exponential growth in GMO production. Indeed, EU regulations based on the precautionary principle require any food containing more than 0.9% GM content to be labeled as such. The implementation of these regulations necessitates sampling protocols, the availability of certified reference materials and analytical methodologies that allow the accurate determination of the content of GMOs. In order to qualify for the validation process, a method should fulfil some criteria, defined as "acceptance criteria" by the European Network of GMO Laboratories (ENGL). Several methods have recently been developed for GMO detection and quantitation, mostly based on polymerase chain reaction (PCR) technology. PCR (including its different formats, e.g., double competitive PCR and real-time PCR) remains the technique of choice, thanks to its ability to detect even small amounts of transgenes in raw materials and processed foods. Other approaches relying on DNA detection are based on quartz crystal microbalance piezoelectric biosensors, dry reagent dipstick-type sensors and surface plasmon resonance sensors. The application of visible/near-infrared (vis/NIR) spectroscopy or mass spectrometry combined with chemometrics techniques has also been envisaged as a powerful GMO detection tool. Furthermore, in order to cope with the multiplicity of GMOs released onto the market, the new challenge is the development of routine detection systems for the simultaneous detection of numerous GMOs, including unknown GMOs.

Electromembrane extraction as a rapid and selective miniaturized sample preparation technique for biological fluids

DEFF Research Database (Denmark)

Gjelstad, Astrid; Pedersen-Bjergaard, Stig; Seip, Knut Fredrik

2015-01-01

This special report discusses the sample preparation method electromembrane extraction, which was introduced in 2006 as a rapid and selective miniaturized extraction method. The extraction principle is based on isolation of charged analytes extracted from an aqueous sample, across a thin film....... Technical aspects of electromembrane extraction, important extraction parameters as well as a handful of examples of applications from different biological samples and bioanalytical areas are discussed in the paper....

Developing a reliable signal wire attachment method for rail.

Science.gov (United States)

2014-11-01

The goal of this project was to develop a better attachment method for rail signal wires to improve the reliability of signaling : systems. EWI conducted basic research into the failure mode of current attachment methods and developed and tested a ne...

Financing modes and methods for nuclear power development in developing countries

International Nuclear Information System (INIS)

Su Qun

1999-02-01

In financing for nuclear power project in developing countries, governmental support is significant in reducing the risk of the project and improving the financing environment. Issues studied and discussed include financing conditions and methods, export credit and supply. An appropriate solution of the financing problem will play an important role in developing nuclear power

Harbourscape Aalborg - Design Based Methods in Waterfront Development

DEFF Research Database (Denmark)

Kiib, Hans

2012-01-01

How can city planners and developers gain knowledge and develop new sustainable concepts for water front developments? The waterfront is far too often threatened by new privatisation, lack of public access and bad architecture. And in a time where low growth rates and crises in the building...... industry is leaving great parts of the harbour as urban voids planners are in search of new tools for bridging the time gap until new projects can be a reality. This chapter presents the development of waterfront regeneration concepts that resulted from design based workshops, Harbourscape Aalborg in 2005...... and Performative Architecture Workshop in 2008, and evaluates the method and the thinking behind this. The design workshops provide different design-based development methods which can be tested with the purpose of developing new concepts for the relationship between the city and its harbour, and in addition...

Rapid determination of quetiapine in blood by gas chromatography-mass spectrometry. Application to post-mortem cases.

Science.gov (United States)

López-Guarnido, Olga; Tabernero, María Jesús; Hernández, Antonio F; Rodrigo, Lourdes; Bermejo, Ana M

2014-10-01

A simple, fast and sensitive method for the determination of quetiapine in human blood has been developed and validated. The method involved a basic liquid-liquid extraction procedure and subsequent analysis by gas chromatography-mass spectrometry, previous derivatization with bis(trimethylsilyl)-trifluoro-acetamide and chorotrimethylsilane (99 : 1). The methods of validation included linearity with a correlation coefficient > 0.99 over the range 0.02-1 µg ml(-1), intra- and interday precision (always < 12%) and accuracy (mean relative error always < 12%) to meet the bioanalytical acceptance criteria. The limit of detection was 0.005 µg ml(-1). The procedure was further applied to post mortems from the Institute of Legal Medicine, University of Santiago de Compostela. Copyright © 2013 John Wiley & Sons, Ltd.

The Unified Problem-Solving Method Development Language UPML

OpenAIRE

Fensel, Dieter; Motta, Enrico; van Harmelen, Frank; Benjamins, V. Richard; Crubezy, Monica; Decker, Stefan; Gaspari, Mauro; Groenboom, Rix; Grosso, William; Musen, Mark; Plaza, Enric; Schreiber, Guus; Studer, Rudi; Wielinga, Bob

2003-01-01

Problem-solving methods provide reusable architectures and components for implementing the reasoning part of knowledge-based systems. The UNIFIED PROBLEM-SOLVING METHOD DESCRIPTION LANGUAGE (UPML) has been developed to describe and implement such architectures and components to facilitate their semi-automatic reuse and adaptation. In a nutshell, UPML is a framework for developing knowledge-intensive reasoning systems based on libraries ofg eneric problem-solving components. The paper describe...

Statistical Data Analyses of Trace Chemical, Biochemical, and Physical Analytical Signatures

Energy Technology Data Exchange (ETDEWEB)

Udey, Ruth Norma [Michigan State Univ., East Lansing, MI (United States)

2013-01-01

Analytical and bioanalytical chemistry measurement results are most meaningful when interpreted using rigorous statistical treatments of the data. The same data set may provide many dimensions of information depending on the questions asked through the applied statistical methods. Three principal projects illustrated the wealth of information gained through the application of statistical data analyses to diverse problems.

Evaluation index system of steel industry sustainable development based on entropy method and topsis method

Science.gov (United States)

Ronglian, Yuan; Mingye, Ai; Qiaona, Jia; Yuxuan, Liu

2018-03-01

Sustainable development is the only way for the development of human society. As an important part of the national economy, the steel industry is an energy-intensive industry and needs to go further for sustainable development. In this paper, we use entropy method and Topsis method to evaluate the development of China’s steel industry during the “12th Five-Year Plan” from four aspects: resource utilization efficiency, main energy and material consumption, pollution status and resource reuse rate. And we also put forward some suggestions for the development of China’s steel industry.

Automating Object-Oriented Software Development Methods

NARCIS (Netherlands)

Tekinerdogan, B.; Saeki, Motoshi; Sunyé, Gerson; van den Broek, P.M.; Hruby, Pavel; Tekinerdogan, B.; van den Broek, P.M.; Saeki, M.; Hruby, P.; Sunye, G.

2001-01-01

Current software projects have generally to deal with producing and managing large and complex software products. It is generally believed that applying software development methods are useful in coping with this complexity and for supporting quality. As such numerous object-oriented software

Automating Object-Oriented Software Development Methods

NARCIS (Netherlands)

Tekinerdogan, B.; Frohner, A´ kos; Saeki, Motoshi; Sunyé, Gerson; van den Broek, P.M.; Hruby, Pavel

2002-01-01

Current software projects have generally to deal with producing and managing large and complex software products. It is generally believed that applying software development methods are useful in coping with this complexity and for supporting quality. As such numerous object-oriented software

Specific bioanalytical optical and photoelectrochemical assays for detection of methanol in alcoholic beverages.

Science.gov (United States)

Barroso, Javier; Díez-Buitrago, Beatriz; Saa, Laura; Möller, Marco; Briz, Nerea; Pavlov, Valeri

2018-03-15

Methanol is a poison which is frequently discovered in alcoholic beverages. Innovative methods to detect methanol in alcoholic beverages are being constantly developed. We report for the first time a new strategy for the detection of methanol using fluorescence spectroscopy and photoelectrochemical (PEC) analysis. The analytical system is based on the oxidation of cysteine (CSH) with hydrogen peroxide (H 2 O 2 ) enzymatically generated by alcohol oxidase (AOx). H 2 O 2 oxidizes capping agent CSH, modulating the growth of CSH-stabilized cadmium sulphide quantum dots (CdS QDs). Disposable screen-printed carbon electrodes (SPCEs) modified with a conductive osmium polymer (Os-PVP) complex were employed to quantify resulting CdS QDs. This polymer facilitates the "wiring" of in situ enzymatically generated CdS QDs, which photocatalyze oxidation of 1-thioglycerol (TG), generating photocurrent as the readout signal. Likewise, we proved that our systems did not suffer from interference by ethanol. The PEC assays showed better sensitivity than conventional methods, covering a wide range of potential applications for methanol quantification. Copyright © 2017 Elsevier B.V. All rights reserved.

An exploratory survey of methods used to develop measures of performance

Science.gov (United States)

Hamner, Kenneth L.; Lafleur, Charles A.

1993-09-01

Nonmanufacturing organizations are being challenged to provide high-quality products and services to their customers, with an emphasis on continuous process improvement. Measures of performance, referred to as metrics, can be used to foster process improvement. The application of performance measurement to nonmanufacturing processes can be very difficult. This research explored methods used to develop metrics in nonmanufacturing organizations. Several methods were formally defined in the literature, and the researchers used a two-step screening process to determine the OMB Generic Method was most likely to produce high-quality metrics. The OMB Generic Method was then used to develop metrics. A few other metric development methods were found in use at nonmanufacturing organizations. The researchers interviewed participants in metric development efforts to determine their satisfaction and to have them identify the strengths and weaknesses of, and recommended improvements to, the metric development methods used. Analysis of participants' responses allowed the researchers to identify the key components of a sound metrics development method. Those components were incorporated into a proposed metric development method that was based on the OMB Generic Method, and should be more likely to produce high-quality metrics that will result in continuous process improvement.

Simultaneous determination of vancomycin and ceftazidime in cerebrospinal fluid in craniotomy patients by high-performance liquid chromatography.

Science.gov (United States)

Ye, Guangming; Cai, Xuejian; Wang, Biao; Zhou, Zhongxian; Yu, Xiaohua; Wang, Weibin; Zhang, Jiandong; Wang, Yuhai; Dong, Jierong; Jiang, Yunyun

2008-11-04

A simple, accurate and rapid method for simultaneous analysis of vancomycin and ceftazidime in cerebrospinal fluid (CSF), utilizing high-performance liquid chromatography (HPLC), has been developed and thoroughly validated to satisfy strict FDA guidelines for bioanalytical methods. Protein precipitation was used as the sample pretreatment method. In order to increase the accuracy, tinidazole was chosen as the internal standard. Separation was achieved on a Diamonsil C18 column (200 mm x 4.6mm I.D., 5 microm) using a mobile phase composed of acetonitrile and acetate buffer (pH 3.5) (8:92, v/v) at room temperature (25 degrees C), and the detection wavelength was 240 nm. All the validation data, such as accuracy, precision, and inter-day repeatability, were within the required limits. The method was applied to determine vancomycin and ceftazidime concentrations in CSF in five craniotomy patients.

Development of Reverse-Phase HPLC Method for Simultaneous ...

African Journals Online (AJOL)

Erah

Purpose: To develop a simple, sensitive and rapid reverse phase HPLC method for the simultaneous analysis of metoprolol succinate and hydrochlorothiazide in a solid dosage form. Methods: The .... Extraction was carried out three times with.

Application of nanomaterials in the bioanalytical detection of disease-related genes.

Science.gov (United States)

Zhu, Xiaoqian; Li, Jiao; He, Hanping; Huang, Min; Zhang, Xiuhua; Wang, Shengfu

2015-12-15

In the diagnosis of genetic diseases and disorders, nanomaterials-based gene detection systems have significant advantages over conventional diagnostic systems in terms of simplicity, sensitivity, specificity, and portability. In this review, we describe the application of nanomaterials for disease-related genes detection in different methods excluding PCR-related method, such as colorimetry, fluorescence-based methods, electrochemistry, microarray methods, surface-enhanced Raman spectroscopy (SERS), quartz crystal microbalance (QCM) methods, and dynamic light scattering (DLS). The most commonly used nanomaterials are gold, silver, carbon and semiconducting nanoparticles. Various nanomaterials-based gene detection methods are introduced, their respective advantages are discussed, and selected examples are provided to illustrate the properties of these nanomaterials and their emerging applications for the detection of specific nucleic acid sequences. Copyright © 2015. Published by Elsevier B.V.

Development of Early Warning Methods for Electric Power Systems

DEFF Research Database (Denmark)

Jóhannsson, Hjörtur

This thesis concerns the development of methods that can provide, in realtime, an early warning for an emerging blackout in electric power systems. The blackout in E-Denmark and S-Sweden on September 23, 2003 is the main motivation for the method development. The blackout was caused by occurrence...

Study of immunoglobulin G thin layers obtained by the Langmuir-Blodgett method: application to immunosensors.

Science.gov (United States)

Barraud, A; Perrot, H; Billard, V; Martelet, C; Therasse, J

1993-01-01

Nowadays, immunosensors play a leading part in the field of bioanalytical chemistry research. As with any biosensor, they need appropriate transducers and a suitable technique to immobilize the active biocomponents. In this study, two transduction modes were chosen: mass effects (quartz microbalance measurements) and geometric and dielectric effects (capacitance measurements). The Langmuir-Blodgett (LB) method appears to be quite suitable for generating biospecific surfaces. This work has focused on the detection of staphylococcal enterotoxin B, the corresponding antibody being immobilized at the surface of fatty acids by a variant of the LB method. The composition of the film and the nature of antibody-fatty acid interactions were studied by means of the two transducers mentioned above. FTIR (Fourier transform infra-red) spectroscopy and protein diagnostic assay. Influence of several parameters (pH, ionic strength, transfer pressure, antibody concentration in the subphase) was investigated. The immobilization rate reached its maximum when experimental conditions allowed optimal electrostatic interactions. In this case, the quartz crystal microbalance response, in air, reached 55 Hz per monolayer of immobilized immunoglobulin G and the equivalent capacitance variation, measured in liquid media, was around 300 pF cm-2. Activity of the biospecific LB films, when binding enterotoxin, was checked by the classical ELISA (enzyme immuno-linked assay) technique.

Development and application of (bio)analytical methodologies in capillary electrophoresis. Enantioselectivity considerations

OpenAIRE

Asensi Bernardi, Lucía

2014-01-01

El desarrollo de nuevos fármacos es un proceso largo, complejo y costoso que incluye la evaluación en diferentes etapas de propiedades farmacocinéticas y farmacodinámicas de la nueva molécula. En las primeras etapas del desarrollo de un fármaco es habitual el uso de métodos in vitro para el cribado de alto rendimiento de las propiedades de nuevas moléculas, con el objetivo de obtener datos preliminares sobre la potencial actividad farmacológica de una molécula y sobre su farmacocinética. Cuan...

Development of 3-D FBR heterogeneous core calculation method based on characteristics method

International Nuclear Information System (INIS)

Takeda, Toshikazu; Maruyama, Manabu; Hamada, Yuzuru; Nishi, Hiroshi; Ishibashi, Junichi; Kitano, Akihiro

2002-01-01

A new 3-D transport calculation method taking into account the heterogeneity of fuel assemblies has been developed by combining the characteristics method and the nodal transport method. In the axial direction the nodal transport method is applied, and the characteristics method is applied to take into account the radial heterogeneity of fuel assemblies. The numerical calculations have been performed to verify 2-D radial calculations of FBR assemblies and partial core calculations. Results are compared with the reference Monte-Carlo calculations. A good agreement has been achieved. It is shown that the present method has an advantage in calculating reaction rates in a small region

Generating and testing methods for consumer-oriented product development

International Nuclear Information System (INIS)

2001-10-01

In order to obtain a good insight into various design methods that can be used by product developers to enable them to develop and test useful domotics products (domotics: intelligent systems for the home), an inventory has been made of the methods used in the Netherlands. The inventory is directed at two categories of methods: (1) Methods of getting better acquainted with the user and/or the problem, and of generating novel solutions: generative methods; and (2) Methods of assessing solutions (through various phases of the designing process): testing methods. The first category of methods concentrates on the designing process. In other words: how can the designer realise as much as possible of the workability of (domotics) products during the designing process? The second category aims at testing a design (in whatever shape: drawing, prototype, functional computer animation, etc.) through its users. These are methods of assessing a design at various stages of the designing process [nl

Development of advanced MCR task analysis methods

International Nuclear Information System (INIS)

Na, J. C.; Park, J. H.; Lee, S. K.; Kim, J. K.; Kim, E. S.; Cho, S. B.; Kang, J. S.

2008-07-01

This report describes task analysis methodology for advanced HSI designs. Task analyses was performed by using procedure-based hierarchical task analysis and task decomposition methods. The results from the task analysis were recorded in a database. Using the TA results, we developed static prototype of advanced HSI and human factors engineering verification and validation methods for an evaluation of the prototype. In addition to the procedure-based task analysis methods, workload estimation based on the analysis of task performance time and analyses for the design of information structure and interaction structures will be necessary

New high-performance liquid chromatography method for the determination of (R)-warfarin and (S)-warfarin using chiral separation on a glycopeptide-based stationary phase.

Science.gov (United States)

Malakova, Jana; Pavek, Petr; Svecova, Lucie; Jokesova, Iveta; Zivny, Pavel; Palicka, Vladimir

2009-10-01

Warfarin is a well-known anticoagulant agent that occurs in two enantiomers, (R)-(+)-warfarin and (S)-(-)-warfarin. A new liquid chromatography method for the determination of both enantiomers was developed, validated and applied in in vitro studies with the aim of evaluating the accumulation of (R)-warfarin and (S)-warfarin in the hepatoma HepG2 cell line. OptiMEM cell cultivation medium samples and cellular lysates were purified using Waters Oasis MAX extraction cartridges. The chiral separation of warfarin and the internal standard p-chlorowarfarin enantiomers was performed on an Astec Chirobiotic V2 column at a flow rate of 1.2mL/min. The mobile phase was composed of 31% acetonitrile, 5% of methanol and 64% of ammonium acetate buffer (10mmol/L, pH 4.1). The enantiomers were quantified using a fluorescence detector (lambda(excit)=320nm, lambda(emiss)=415nm). The limit of detection was found to be 0.121micromol/L of (S)-warfarin and 0.109micromol/L of (R)-warfarin. The range of applicability and linearity was estimated from 0.25 to 100micromol/L. The precision ranged from 1.3% to 12.2% of the relative standard deviation, and the accuracy reached acceptable values from 95.5% to 108.4%. The new bioanalytical method confirmed the same accumulation of (R)-warfarin and (S)-warfarin in the hepatoma HepG2 cell line.

Development Optimization and Uncertainty Analysis Methods for Oil and Gas Reservoirs

Energy Technology Data Exchange (ETDEWEB)

Ettehadtavakkol, Amin, E-mail: amin.ettehadtavakkol@ttu.edu [Texas Tech University (United States); Jablonowski, Christopher [Shell Exploration and Production Company (United States); Lake, Larry [University of Texas at Austin (United States)

2017-04-15

Uncertainty complicates the development optimization of oil and gas exploration and production projects, but methods have been devised to analyze uncertainty and its impact on optimal decision-making. This paper compares two methods for development optimization and uncertainty analysis: Monte Carlo (MC) simulation and stochastic programming. Two example problems for a gas field development and an oilfield development are solved and discussed to elaborate the advantages and disadvantages of each method. Development optimization involves decisions regarding the configuration of initial capital investment and subsequent operational decisions. Uncertainty analysis involves the quantification of the impact of uncertain parameters on the optimum design concept. The gas field development problem is designed to highlight the differences in the implementation of the two methods and to show that both methods yield the exact same optimum design. The results show that both MC optimization and stochastic programming provide unique benefits, and that the choice of method depends on the goal of the analysis. While the MC method generates more useful information, along with the optimum design configuration, the stochastic programming method is more computationally efficient in determining the optimal solution. Reservoirs comprise multiple compartments and layers with multiphase flow of oil, water, and gas. We present a workflow for development optimization under uncertainty for these reservoirs, and solve an example on the design optimization of a multicompartment, multilayer oilfield development.

Development Optimization and Uncertainty Analysis Methods for Oil and Gas Reservoirs

International Nuclear Information System (INIS)

Ettehadtavakkol, Amin; Jablonowski, Christopher; Lake, Larry

2017-01-01

Uncertainty complicates the development optimization of oil and gas exploration and production projects, but methods have been devised to analyze uncertainty and its impact on optimal decision-making. This paper compares two methods for development optimization and uncertainty analysis: Monte Carlo (MC) simulation and stochastic programming. Two example problems for a gas field development and an oilfield development are solved and discussed to elaborate the advantages and disadvantages of each method. Development optimization involves decisions regarding the configuration of initial capital investment and subsequent operational decisions. Uncertainty analysis involves the quantification of the impact of uncertain parameters on the optimum design concept. The gas field development problem is designed to highlight the differences in the implementation of the two methods and to show that both methods yield the exact same optimum design. The results show that both MC optimization and stochastic programming provide unique benefits, and that the choice of method depends on the goal of the analysis. While the MC method generates more useful information, along with the optimum design configuration, the stochastic programming method is more computationally efficient in determining the optimal solution. Reservoirs comprise multiple compartments and layers with multiphase flow of oil, water, and gas. We present a workflow for development optimization under uncertainty for these reservoirs, and solve an example on the design optimization of a multicompartment, multilayer oilfield development.

Development and Validation of Improved Method for Fingerprint ...

African Journals Online (AJOL)

Purpose: To develop and validate an improved method by capillary zone electrophoresis with photodiode array detection for the fingerprint analysis of Ligusticum chuanxiong Hort. (Rhizoma Chuanxiong). Methods: The optimum high performance capillary electrophoresis (HPCE) conditions were 30 mM borax containing 5 ...

A reliable and validated LC-MS/MS method for the simultaneous quantification of 4 cannabinoids in 40 consumer products.

Science.gov (United States)

Meng, Qingfang; Buchanan, Beth; Zuccolo, Jonathan; Poulin, Mathieu-Marc; Gabriele, Joseph; Baranowski, David Charles

2018-01-01

In the past 50 years, Cannabis sativa (C. sativa) has gone from a substance essentially prohibited worldwide to one that is gaining acceptance both culturally and legally in many countries for medicinal and recreational use. As additional jurisdictions legalize Cannabis products and the variety and complexity of these products surpass the classical dried plant material, appropriate methods for measuring the biologically active constituents is paramount to ensure safety and regulatory compliance. While there are numerous active compounds in C. sativa the primary cannabinoids of regulatory and safety concern are (-)-Δ⁹-tetrahydrocannabinol (THC), cannabidiol (CBD), and their respective acidic forms THCA-A and CBDA. Using the US Food and Drug Administration (FDA) bioanalytical method validation guidelines we developed a sensitive, selective, and accurate method for the simultaneous analysis CBD, CBDA, THC, and THCA-A in oils and THC & CBD in more complex matrices. This HPLC-MS/MS method was simple and reliable using standard sample dilution and homogenization, an isocratic chromatographic separation, and a triple quadrupole mass spectrometer. The lower limit of quantification (LLOQ) for analytes was 0.195 ng/mL over a 0.195-50.0 ng/mL range of quantification with a coefficient of correlation of >0.99. Average intra-day and inter-day accuracies were 94.2-112.7% and 97.2-110.9%, respectively. This method was used to quantify CBD, CBDA, THC, and THCA-A in 40 commercial hemp products representing a variety of matrices including oils, plant materials, and creams/cosmetics. All products tested met the federal regulatory restrictions on THC content in Canada (CBD, the majority of analyzed products contained low CBD levels and a CBD: CBDA ratio of CBD and a CBD: CBDA ratio of >1,000 (an oil-based product). Overall, the method proved amenable to the analysis of various commercial products including oils, creams, and plant material and may be diagnostically indicative of

Agile Service Development: A Rule-Based Method Engineering Approach

NARCIS (Netherlands)

dr. Martijn Zoet; Stijn Hoppenbrouwers; Inge van de Weerd; Johan Versendaal

2011-01-01

Agile software development has evolved into an increasingly mature software development approach and has been applied successfully in many software vendors’ development departments. In this position paper, we address the broader agile service development. Based on method engineering principles we

LightCDD: Application of a Capability-Driven Development Method for Start-ups Development

Directory of Open Access Journals (Sweden)

Hasan Koç

2017-04-01

Full Text Available Novice innovators and entrepreneurs face the risk of designing naive business models. In fact, lack of viability in business models is perceived to be a major threat for the start-up success. Both the literature and the responses we gathered from experts in incubation present evidences of this problem. The LightCDD method helps entrepreneurs in the analysis, design and specification of start-ups that are context aware and adaptive to contextual changes and evolution. In this article we describe the LightCDD method, a context-aware enterprise modeling method that is tailored for business model generation. The LightCDD applies a lightweight Capability‑Driven Development (CDD methodology. It reduces the set of modeling constructs and guidelines to facilitate its adoption by entrepreneurs, yet keeping it expressive enough for their purposes and, at the same time, compatible with the CDD methodology. We provide a booklet with the LightCDD method for start-ups development. The feasibility of the LightCDD method is validated by means of its application to one start-up development case. From a practitioner viewpoint (entrepreneurs and experts in incubation, it is important to provide integrative modeling perspectives to specify business ideas, but it is vital to keep it light. The LightCDD is giving a step forward in this direction. From a researcher point of view, the LightCDD booklet facilitates the application of LightCDD to different start-up development cases. The feasibility validation has produced important feedback for further empirical validation exercises in which is necessary to study the scalability and sensitivity of LightCDD.

Plasmonic crystal based solid substrate for biomedical application of SERS

Science.gov (United States)

Morasso, Carlo F.; Mehn, Dora; Picciolini, Silvia; Vanna, Renzo; Bedoni, Marzia; Gramatica, Furio; Pellacani, Paola; Frangolho, Ana; Marchesini, Gerardo; Valsesia, Andrea

2014-02-01

Surface Enhanced Raman Spectroscopy is a powerful analytical technique that combines the excellent chemical specificity of Raman spectroscopy with the good sensitivity provided by the enhancement of the signal observed when a molecule is located on (or very close to) the surface of suitable nanostructured metallic materials. The availability of cheap, reliable and easy to use SERS substrates would pave the road to the development of bioanalytical tests that can be used in clinical practice. SERS, in fact, is expected to provide not only higher sensitivity and specificity, but also the simultaneous and markedly improved detection of several targets at the same time with higher speed compared to the conventional analytical methods. Here, we present the SERS activity of 2-D plasmonic crystals made by polymeric pillars embedded in a gold matrix obtained through the combination of soft-lithography and plasma deposition techniques on a transparent substrates. The use of a transparent support material allowed us to perform SERS detection from support side opening the possibility to use these substrates in combination with microfluidic devices. In order to demonstrate the potentialities for bioanalytical applications, we used our SERS active gold surface to detect the oxidation product of apomorphine, a well-known drug molecule used in Parkinson's disease which has been demonstrated being difficult to study by traditional HPLC based approaches.

Adaptation of an Agile Information System Development Method

NARCIS (Netherlands)

Aydin, M.N.; Harmsen, A.F.; van Hillegersberg, Jos; Stegwee, R.A.; Siau, K.

2007-01-01

Little specific research has been conducted to date on the adaptation of agile information systems development (ISD) methods. This chapter presents the work practice in dealing with the adaptation of such a method in the ISD department of one of the leading financial institutes in Europe. The

Development of quadruped walking locomotion gait generator using a hybrid method

International Nuclear Information System (INIS)

Jasni, F; Shafie, A A

2013-01-01

The earth, in many areas is hardly reachable by the wheeled or tracked locomotion system. Thus, walking locomotion system is becoming a favourite option for mobile robot these days. This is because of the ability of walking locomotion to move on the rugged and unlevel terrains. However, to develop a walking locomotion gait for a robot is not a simple task. Central Pattern Generator (CPGs) method is a biological inspired method that is introduced as a method to develop the gait for the walking robot recently to tackle the issue faced by the conventional method of pre-designed trajectory based method. However, research shows that even the CPG method do have some limitations. Thus, in this paper, a hybrid method that combines CPG and the pre-designed trajectory based method is introduced to develop a walking gait for quadruped walking robot. The 3-D foot trajectories and the joint angle trajectories developed using the proposed method are compared with the data obtained via the conventional method of pre-designed trajectory to confirm the performance

The change and development of statistical methods used in research articles in child development 1930-2010.

Science.gov (United States)

Køppe, Simo; Dammeyer, Jesper

2014-09-01

The evolution of developmental psychology has been characterized by the use of different quantitative and qualitative methods and procedures. But how does the use of methods and procedures change over time? This study explores the change and development of statistical methods used in articles published in Child Development from 1930 to 2010. The methods used in every article in the first issue of every volume were categorized into four categories. Until 1980 relatively simple statistical methods were used. During the last 30 years there has been an explosive use of more advanced statistical methods employed. The absence of statistical methods or use of simple methods had been eliminated.

Development of a method for RIA of MLH

International Nuclear Information System (INIS)

Zhang Haoyi; Jin Lichun

2002-01-01

Objective: To develop a method of RIA for MLH to measure the serum level of LH in Rhesus Monkey for animal experiment in reproductive medicine. Methods: 125 I-MLH was prepared with chloramine T-Iodogen method. Rabbit anti-MLH was used as first antibody and sheep anti-rabbit IgG was used as separating agent. RIA was performed with liquid phase competitive radioassay. Results: The specific radioactivity of labelled antigen was 67 μg/mCi; antibody affinity constant was Ka = 3.44 x 10 -9 mol/L the shape of the standard curve was good. r = 0.991, intra-assay error CV = 3.49%, inter-assay error CV = 4.65%. The minimal detectable concentration was 0.42 μg/ml. Mean value of 30 normal Rhesus Monkey serum specimens was 1.17 +- 1.30 μg/ml. Conclusion: The developed method was simple reliable and sensitive. It would be of use in study of contraceptive and sex-physiology drugs

Scientific methods for developing ultrastable structures

International Nuclear Information System (INIS)

Gamble, M.; Thompson, T.; Miller, W.

1990-01-01

Scientific methods used by the Los Alamos National Laboratory for developing an ultrastable structure for study of silicon-based elementary particle tracking systems are addressed. In particular, the design, analysis, and monitoring of this system are explored. The development methodology was based on a triad of analytical, computational, and experimental techniques. These were used to achieve a significant degree of mechanical stability (alignment accuracy >1 μrad) and yet allow dynamic manipulation of the system. Estimates of system thermal and vibratory stability and component performance are compared with experimental data collected using laser interferometry and accelerometers. 8 refs., 5 figs., 4 tabs

METHODIC OF DEVELOPMENT OF MOTOR GIFTEDNESS OF PRESCHOOL CHILDREN

Directory of Open Access Journals (Sweden)

Fedorova Svetlana Yurievna

2013-04-01

Full Text Available Education and training of gifted children today appropriate to consider as an important strategic task of modern society. In this context, the purpose of research is the development motor giftedness, which is particularly relevant at the stage of pre-school education, which is caused by age-preschoolers. Preschoolers' motor giftedness is considered by the author as developing integrated quality, including psychomotor skills, inclinations, increased motivation for motor activity. In the process of study the following methods are used: the study and analysis of the scientific and methodological literature on studies, questioning, interview, testing of physical fitness, statistical data processing. The result of research work is methodic of development of motor giftedness on physical education in preschool. The author's methodic consists of four steps: diagnostic, prognostic, practice and activity, social and pedagogical. Each step determines the inclusion of preschool children in sports and developing environment that meets his or her abilities and needs through the creation of certain social and educational conditions. The area of using results of the author's methodic is preschool and the system of improvement professional skill of teachers.

Advances in electrospun carbon fiber-based electrochemical sensing platforms for bioanalytical applications.

Science.gov (United States)

Mao, Xianwen; Tian, Wenda; Hatton, T Alan; Rutledge, Gregory C

2016-02-01

Electrochemical sensing is an efficient and inexpensive method for detection of a range of chemicals of biological, clinical, and environmental interest. Carbon materials-based electrodes are commonly employed for the development of electrochemical sensors because of their low cost, biocompatibility, and facile electron transfer kinetics. Electrospun carbon fibers (ECFs), prepared by electrospinning of a polymeric precursor and subsequent thermal treatment, have emerged as promising carbon systems for biosensing applications since the electrochemical properties of these carbon fibers can be easily modified by processing conditions and post-treatment. This review addresses recent progress in the use of ECFs for sensor fabrication and analyte detection. We focus on the modification strategies of ECFs and identification of the key components that impart the bioelectroanalytical activities, and point out the future challenges that must be addressed in order to advance the fundamental understanding of the ECF electrochemistry and to realize the practical applications of ECF-based sensing devices.

Water Loss Management: Tools and Methods for Developing Countries

OpenAIRE

Mutikanga, H.E.

2012-01-01

Water utilities in developing countries are struggling to provide customers with a reliable level of service due to their peculiar water distribution characteristics including poorly zoned networks with irregular supply operating under restricted budgets. These unique conditions demand unique tools and methods for water loss control. Water loss management: Tools and Methods for Developing Countries provide a decision support toolbox (appropriate tools and methodologies) for assessing, quantif...

Pharmacokinetics of Rhodamine 110 and Its Organ Distribution in Rats.

Science.gov (United States)

Jiang, Shiau-Han; Cheng, Yung-Yi; Huo, Teh-Ia; Tsai, Tung-Hu

2017-09-06

Rhodamine dyes have been banned as food additives due to their potential tumorigenicity. Rhodamine 110 is illegal as a food additive, although its pharmacokinetics have not been characterized, and no accurate bioanalytical methods are available to quantify rhodamine 110. The aim of this study was to develop and validate a fast, stable, and sensitive method to quantify rhodamine 110 using high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) to assess its pharmacokinetics and organ distribution in awake rats. Rhodamine 110 exhibited linear pharmacokinetics and slow elimination after oral administration. Furthermore, its oral bioavailability was approximately 34-35%. The distribution in the liver and kidney suggests that these organs are primarily responsible for rhodamine 110 metabolism and elimination. Our investigation describes the pharmacokinetics and a quantification method for rhodamine 110, improving our understanding of the food safety of rhodamine dyes.

Quantitative methods for developing C2 system requirement

Energy Technology Data Exchange (ETDEWEB)

Tyler, K.K.

1992-06-01

The US Army established the Army Tactical Command and Control System (ATCCS) Experimentation Site (AES) to provide a place where material and combat developers could experiment with command and control systems. The AES conducts fundamental and applied research involving command and control issues using a number of research methods, ranging from large force-level experiments, to controlled laboratory experiments, to studies and analyses. The work summarized in this paper was done by Pacific Northwest Laboratory under task order from the Army Tactical Command and Control System Experimentation Site. The purpose of the task was to develop the functional requirements for army engineer automation and support software, including MCS-ENG. A client, such as an army engineer, has certain needs and requirements of his or her software; these needs must be presented in ways that are readily understandable to the software developer. A requirements analysis then, such as the one described in this paper, is simply the means of communication between those who would use a piece of software and those who would develop it. The analysis from which this paper was derived attempted to bridge the ``communications gap`` between army combat engineers and software engineers. It sought to derive and state the software needs of army engineers in ways that are meaningful to software engineers. In doing this, it followed a natural sequence of investigation: (1) what does an army engineer do, (2) with which tasks can software help, (3) how much will it cost, and (4) where is the highest payoff? This paper demonstrates how each of these questions was addressed during an analysis of the functional requirements of engineer support software. Systems engineering methods are used in a task analysis and a quantitative scoring method was developed to score responses regarding the feasibility of task automation. The paper discusses the methods used to perform utility and cost-benefits estimates.

Development and validation of a spectroscopic method for the ...

African Journals Online (AJOL)

Development and validation of a spectroscopic method for the simultaneous analysis of ... advanced analytical methods such as high pressure liquid ..... equipment. DECLARATIONS ... high-performance liquid chromatography. J Chromatogr.

Development, validation and clinical application of an online-SPE-LC-HRMS/MS for simultaneous quantification of phenobarbital, phenytoin, carbamazepine, and its active metabolite carbamazepine 10,11-epoxide.

Science.gov (United States)

Qu, Lihua; Fan, Yuanjie; Wang, Wenjun; Ma, Kai; Yin, Zheng

2016-09-01

A simple and efficient bioanalytical method for simultaneous determination of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and its active metabolite carbamazepine 10,11-epoxide (CBZE) in human plasma using online solid phase extraction (SPE)-liquid chromatography (LC) coupled with high resolution mass spectrum (HRMS) under targeted MS/MS (t-MS(2)) analysis mode has been developed. The procedure integrated an automated sample clean-up of human plasma by Oasis®HLB SPE cartridge, a separation by ZORBAX SB-C18 analysis column, and a quantification by Q-Exactive Hybrid Quadrupole-Orbitrap. The total running time was 13min. The lower limit of quantification (LLOQ) of PB, PHT, CBZ, and CBZE were 0.008, 0.008, 0.0016 and 0.0016μgmL(-1) respectively and the linearities were in the range of 0.008-2.500, 0.008-2.500, 0.0016-0.500 and 0.0016-0.500μgmL(-1) respectively. The mean recovery was between 91.82% and 108.27% and the matrix effect was between 93.29% and 102.09%. The relative standard deviations of interday and intraday were less than 6.41%. The method has been successfully applied in therapeutic drug monitoring (TDM) of four Chinese epilepsy patients. This fully automated, simple, sensitive and reliable online-SPE-LC-HRMS/MS method serves well for TDM of PB, PHT, CBZ and CBZE at clinics for either single or combination treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

New developments in the Csub(N) method

International Nuclear Information System (INIS)

Grandjean, Paul; Kavenoky, Alain.

1975-01-01

The most recent developments of the Csub(N) method used for solving transport equations are presented: treatment of the Rayleigh scattering kernel in plane geometry and of the cylindrical problems with an isotropic scattering law [fr

Valid methods: the quality assurance of test method development, validation, approval, and transfer for veterinary testing laboratories.

Science.gov (United States)

Wiegers, Ann L

2003-07-01

Third-party accreditation is a valuable tool to demonstrate a laboratory's competence to conduct testing. Accreditation, internationally and in the United States, has been discussed previously. However, accreditation is only I part of establishing data credibility. A validated test method is the first component of a valid measurement system. Validation is defined as confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled. The international and national standard ISO/IEC 17025 recognizes the importance of validated methods and requires that laboratory-developed methods or methods adopted by the laboratory be appropriate for the intended use. Validated methods are therefore required and their use agreed to by the client (i.e., end users of the test results such as veterinarians, animal health programs, and owners). ISO/IEC 17025 also requires that the introduction of methods developed by the laboratory for its own use be a planned activity conducted by qualified personnel with adequate resources. This article discusses considerations and recommendations for the conduct of veterinary diagnostic test method development, validation, evaluation, approval, and transfer to the user laboratory in the ISO/IEC 17025 environment. These recommendations are based on those of nationally and internationally accepted standards and guidelines, as well as those of reputable and experienced technical bodies. They are also based on the author's experience in the evaluation of method development and transfer projects, validation data, and the implementation of quality management systems in the area of method development.

The Change and Development of Statistical Methods Used in Research Articles in Child Development 1930-2010

DEFF Research Database (Denmark)

Køppe, Simo; Dammeyer, Jesper Herup

2014-01-01

The evolution of developmental psychology has been characterized by the use of different quantitative and qualitative methods and procedures. But how does the use of methods and procedures change over time? This study explores the change and Development of statistical methods used in articles...... published in Child Development from 1930 to 2010. The methods used in every article in the first issue of every volume were categorized into four categories. Until 1980 relatively simple statistical methods were used. During the last 30 years there has been an explosive use of more advanced statistical...... methods employed. The absence of statistical methods or use of simplemethods had been eliminated....

Prioritizing pesticide compounds for analytical methods development

Science.gov (United States)

Norman, Julia E.; Kuivila, Kathryn; Nowell, Lisa H.

2012-01-01

The U.S. Geological Survey (USGS) has a periodic need to re-evaluate pesticide compounds in terms of priorities for inclusion in monitoring and studies and, thus, must also assess the current analytical capabilities for pesticide detection. To meet this need, a strategy has been developed to prioritize pesticides and degradates for analytical methods development. Screening procedures were developed to separately prioritize pesticide compounds in water and sediment. The procedures evaluate pesticide compounds in existing USGS analytical methods for water and sediment and compounds for which recent agricultural-use information was available. Measured occurrence (detection frequency and concentrations) in water and sediment, predicted concentrations in water and predicted likelihood of occurrence in sediment, potential toxicity to aquatic life or humans, and priorities of other agencies or organizations, regulatory or otherwise, were considered. Several existing strategies for prioritizing chemicals for various purposes were reviewed, including those that identify and prioritize persistent, bioaccumulative, and toxic compounds, and those that determine candidates for future regulation of drinking-water contaminants. The systematic procedures developed and used in this study rely on concepts common to many previously established strategies. The evaluation of pesticide compounds resulted in the classification of compounds into three groups: Tier 1 for high priority compounds, Tier 2 for moderate priority compounds, and Tier 3 for low priority compounds. For water, a total of 247 pesticide compounds were classified as Tier 1 and, thus, are high priority for inclusion in analytical methods for monitoring and studies. Of these, about three-quarters are included in some USGS analytical method; however, many of these compounds are included on research methods that are expensive and for which there are few data on environmental samples. The remaining quarter of Tier 1

Antimicrobial Testing Methods & Procedures Developed by EPA's Microbiology Laboratory

Science.gov (United States)

We develop antimicrobial testing methods and standard operating procedures to measure the effectiveness of hard surface disinfectants against a variety of microorganisms. Find methods and procedures for antimicrobial testing.

Development of a new disintegration method for orally disintegrating tablets.

Science.gov (United States)

Kakutani, Ryo; Muro, Hiroyuki; Makino, Tadashi

2010-07-01

Recently, the focus has been on the importance of assessing the oral disintegrative properties of orally disintegrating tablets (ODTs). In particular, in the development stages and the quality control field of ODT products, a physical assessment method which easily measures oral disintegrative properties is desired. For this reason, we developed a new disintegration test method (Kyoto-model disintegration method or KYO method), which is useful to predict the oral disintegrative properties of an ODT easily, and examined the availability of the method. In the KYO method, ODT samples were classified in terms of their water permeability, and a moderate water volume was decided. Subsequently, the disintegrative properties were assessed with the newly proposed method. For 25 commercial prescription ODTs used as samples, a good correlation was shown between the results of a human sensory test by five healthy male volunteers and the results using the KYO method. Furthermore, the KYO method could evaluate time-dependent changes in ODT samples. On the other hand, no correlation was observed between the Japanese Pharmacopeia disintegration test and the human sensory test. These results suggested that the KYO method reflected the disintegration nature of the ODTs in the oral cavity, and could easily be applied to development stages and the quality control field of ODT products.

Developing the Students’ English Speaking Ability Through Impromptu Speaking Method.

Science.gov (United States)

Lumettu, A.; Runtuwene, T. L.

2018-01-01

Having multi -purposes, English mastery has becomea necessary for us.Of the four language skills, speaking skill should get the first priority in English teaching and speaking skills development cannot be separated from listening.One communicative way of developing speaking skill is impromptu speaking,a method sudden speaking which depends only on experience and insight by applying spontaneity or improvisation. It is delivered based on the need of the moment of speaking using simple language.This research aims to know (1). Why impromptu speaking is necessary in teaching speaking? (2). How can impromptu speaking develop the students’ speaking skills.The method of this research is qualitative method and the techniques of data collection are: observation,interview and documentation. The results of data analysis using Correlation shows a strong relation between the students’ speaking ability and impromptu speaking method (r = 0.80).The research show that by using impromptu speaking method, the students are trained to interact faster naturally and spontaneously and enrich their vocabulary and general science to support speaking development through interview, speech, presentation, discussion and storytelling.

Development of digital radiographic inspection method in MINT

International Nuclear Information System (INIS)

Mohd Ashhar Khalid; Abdul Razak Hamzah; Abdul Aziz Mohamad; Anuar Mikdad Muad; Nolida Yussup; Maslina Mohd Ibrahim

2002-01-01

Industrial radiography has been employed for the evaluation of defects, such as cracks, porosity and foreign inclusions found in casting and welds. It has become one of the major techniques in industrial non-destructive testing for the past 40 years. Although this technique has been well developed, further improvement can be implemented especially with the advancement of electronics and computer technology. Digital image processing techniques and application of artificial intelligence methods allow the interpretation of the image to be automated, avoiding the presence of human operators making the inspection system faster, more reliable and reproducible. Numerous works has been reported by various groups on the development of an automated, computer based evaluation algorithms. This paper reports the development and progress of digital radiographic inspection method in MINT. (Author)

Suggestions on the Development of Safety Culture Assessment Method

International Nuclear Information System (INIS)

Choi, Young Sung; Choi, Kwang Sik; Kim, Woong Sik

2006-01-01

Several efforts have been made to assess safety culture of organization that operates nuclear power plants in Korea. The MOST and KINS played a major role to develop assessment methods and KHNP applied them to its NPPs. This paper explains the two methods developed by KINS briefly and presents the insights obtained from the two different applications. It concludes with some suggestions for safety culture assessment based on the insights

Development and application of methods to characterize code uncertainty

International Nuclear Information System (INIS)

Wilson, G.E.; Burtt, J.D.; Case, G.S.; Einerson, J.J.; Hanson, R.G.

1985-01-01

The United States Nuclear Regulatory Commission sponsors both international and domestic studies to assess its safety analysis codes. The Commission staff intends to use the results of these studies to quantify the uncertainty of the codes with a statistically based analysis method. Development of the methodology is underway. The Idaho National Engineering Laboratory contributions to the early development effort, and testing of two candidate methods are the subjects of this paper

Final Report for X-ray Diffraction Sample Preparation Method Development

Energy Technology Data Exchange (ETDEWEB)

Ely, T. M. [Hanford Site (HNF), Richland, WA (United States); Meznarich, H. K. [Hanford Site (HNF), Richland, WA (United States); Valero, T. [Hanford Site (HNF), Richland, WA (United States)

2018-01-30

WRPS-1500790, “X-ray Diffraction Saltcake Sample Preparation Method Development Plan/Procedure,” was originally prepared with the intent of improving the specimen preparation methodology used to generate saltcake specimens suitable for XRD-based solid phase characterization. At the time that this test plan document was originally developed, packed powder in cavity supports with collodion binder was the established XRD specimen preparation method. An alternate specimen preparation method less vulnerable, if not completely invulnerable to preferred orientation effects, was desired as a replacement for the method.

DEVELOPMENT OF A RISK SCREENING METHOD FOR CREDITED OPERATOR ACTIONS

International Nuclear Information System (INIS)

HIGGINS, J.C.; O'HARA, J.M.; LEWIS, P.M.; PERSENSKY, J.; BONGARRA, J.

2002-01-01

DEVELOPMENT OF A RISK SCREENING METHOD FOR CREDITED OPERATOR ACTIONS. THE U.S. NUCLEAR REGULATORY COMMISSION (NRC) REVIEWS THE HUMAN FACTORS ASPECTS OF PROPOSED LICENSE AMENDMENTS THAT IMPACT HUMAN ACTIONS THAT ARE CREDITED IN A PLANTS SAFETY ANALYSIS. THE STAFF IS COMMITTED TO A GRADED APPROACH TO THESE REVIEWS THAT FOCUS RESOURCES ON THE MOST RISK IMPORTANT CHANGES. THEREFORE, A RISK INFORMED SCREENING METHOD WAS DEVELOPED BASED ON AN ADAPTATION OF EXISTING GUIDANCE FOR RISK INFORMED REGULATION AND HUMAN FACTORS. THE METHOD USES BOTH QUANTITATIVE AND QUALITATIVE INFORMATION TO DIVIDE THE AMENDMENT REQUESTS INTO DIFFERENT LEVELS OF REVIEW. THE METHOD WAS EVALUATED USING A VARIETY OF TESTS. THIS PAPER WILL SUMMARIZE THE DEVELOPMENT OF THE METHODOLOGY AND THE EVALUATIONS THAT WERE PERFORMED TO VERIFY ITS USEFULNESS

Stochastic development regression using method of moments

DEFF Research Database (Denmark)

Kühnel, Line; Sommer, Stefan Horst

2017-01-01

This paper considers the estimation problem arising when inferring parameters in the stochastic development regression model for manifold valued non-linear data. Stochastic development regression captures the relation between manifold-valued response and Euclidean covariate variables using...... the stochastic development construction. It is thereby able to incorporate several covariate variables and random effects. The model is intrinsically defined using the connection of the manifold, and the use of stochastic development avoids linearizing the geometry. We propose to infer parameters using...... the Method of Moments procedure that matches known constraints on moments of the observations conditional on the latent variables. The performance of the model is investigated in a simulation example using data on finite dimensional landmark manifolds....

Recently developed methods in neutral-particle transport calculations: overview

International Nuclear Information System (INIS)

Alcouffe, R.E.

1982-01-01

It has become increasingly apparent that successful, general methods for the solution of the neutral particle transport equation involve a close connection between the spatial-discretization method used and the source-acceleration method chosen. The first form of the transport equation, angular discretization which is discrete ordinates is considered as well as spatial discretization based upon a mesh arrangement. Characteristic methods are considered briefly in the context of future, desirable developments. The ideal spatial-discretization method is described as having the following attributes: (1) positive-positive boundary data yields a positive angular flux within the mesh including its boundaries; (2) satisfies the particle balance equation over the mesh, that is, the method is conservative; (3) possesses the diffusion limit independent of spatial mesh size, that is, for a linearly isotropic flux assumption, the transport differencing reduces to a suitable diffusion equation differencing; (4) the method is unconditionally acceleratable, i.e., for each mesh size, the method is unconditionally convergent with a source iteration acceleration. It is doubtful that a single method possesses all these attributes for a general problem. Some commonly used methods are outlined and their computational performance and usefulness are compared; recommendations for future development are detailed, which include practical computational considerations

METHODIC OF DEVELOPMENT OF MOTOR GIFTEDNESS OF PRESCHOOL CHILDREN

Directory of Open Access Journals (Sweden)

Светлана Юрьевна Федорова

2013-05-01

Full Text Available Education and training of gifted children today appropriate to consider as an important strategic task of modern society. In this context, the purpose of research is the development motor giftedness, which is particularly relevant at the stage of pre-school education, which is caused by age-preschoolers. Preschoolers' motor giftedness is considered by the author as developing integrated quality, including psychomotor skills, inclinations, increased motivation for motor activity. In the process of study the following methods are used:  the study and analysis of the scientific and methodological literature on studies, questioning, interview, testing of physical fitness, statistical data processing.The result of research work is methodic of development of motor giftedness on physical education in preschool. The author's methodic consists of four steps:  diagnostic, prognostic, practice and activity, social and pedagogical. Each step determines the inclusion of preschool children in sports and developing environment that meets his or her abilities and needs through the creation of certain social and educational conditions.The area of using results of the author's methodic is preschool and the system of improvement professional skill of teachers. DOI: http://dx.doi.org/10.12731/2218-7405-2013-4-31

Development of a Research Methods and Statistics Concept Inventory

Science.gov (United States)

Veilleux, Jennifer C.; Chapman, Kate M.

2017-01-01

Research methods and statistics are core courses in the undergraduate psychology major. To assess learning outcomes, it would be useful to have a measure that assesses research methods and statistical literacy beyond course grades. In two studies, we developed and provided initial validation results for a research methods and statistical knowledge…

Developing Teaching Material Software Assisted for Numerical Methods

Science.gov (United States)

Handayani, A. D.; Herman, T.; Fatimah, S.

2017-09-01

The NCTM vision shows the importance of two things in school mathematics, which is knowing the mathematics of the 21st century and the need to continue to improve mathematics education to answer the challenges of a changing world. One of the competencies associated with the great challenges of the 21st century is the use of help and tools (including IT), such as: knowing the existence of various tools for mathematical activity. One of the significant challenges in mathematical learning is how to teach students about abstract concepts. In this case, technology in the form of mathematics learning software can be used more widely to embed the abstract concept in mathematics. In mathematics learning, the use of mathematical software can make high level math activity become easier accepted by student. Technology can strengthen student learning by delivering numerical, graphic, and symbolic content without spending the time to calculate complex computing problems manually. The purpose of this research is to design and develop teaching materials software assisted for numerical method. The process of developing the teaching material starts from the defining step, the process of designing the learning material developed based on information obtained from the step of early analysis, learners, materials, tasks that support then done the design step or design, then the last step is the development step. The development of teaching materials software assisted for numerical methods is valid in content. While validator assessment for teaching material in numerical methods is good and can be used with little revision.

Development of the modified sum-peak method and its application

International Nuclear Information System (INIS)

Ogata, Y.; Miyahara, H.; Ishihara, M.; Ishigure, N.; Yamamoto, S.; Kojima, S.

2016-01-01

As the sum-peak method requires the total count rate as well as the peak count rates and the sum peak count rate, this meets difficulties when a sample contains other radionuclides than the one to be measured. To solve the problem, a new method using solely the peak and the sum peak count rates was developed. The method was theoretically and experimentally confirmed using "6"0Co, "2"2Na and "1"3"4Cs. We demonstrate that the modified sum-peak method is quite simple and practical and is useful to measure multiple nuclides. - Highlights: • A modified sum-peak method for simple radioactivity measurement was developed. • The method solely requires the peak count rates and the sum peak count rate. • The method is applicable to multiple radionuclides.

Impact of Shed/Soluble targets on the PK/PD of approved therapeutic monoclonal antibodies.

Science.gov (United States)

Samineni, Divya; Girish, Sandhya; Li, Chunze

2016-12-01

Suboptimal treatment for monoclonal antibodies (mAbs) directed against endogenous circulating soluble targets and the shed extracellular domains (ECD) of the membrane-bound targets is an important clinical concern due to the potential impact of mAbs on the in vivo efficacy and safety. Consequently, there are considerable challenges in the determination of an optimal dose and/or dosing regimen. Areas covered: This review outlines the impact of shed antigen targets from membrane-bound proteins and soluble targets on the PK and/or PD of therapeutic mAbs that have been approved in the last decade. We discuss various bioanalytical techniques that have facilitated the interpretation of the PK/PD properties of therapeutic mAbs and also considered the factors that may impact such measurements. Quantitative approaches include target-mediated PK models and bi- or tri-molecular interaction PK/PD models that describe the relationships between the antibody PK and the ensuing effects on PD biomarkers, to facilitate the mAb PK/PD characterization. Expert commentary: The proper interpretation of PK/PD relationships through the integrated PK/PD modeling and bioanalytical strategy facilitates a mechanistic understanding of the disease processes and dosing regimen optimization, thereby offering insights into developing effective therapeutic regimens. This review provides an overview of the impact of soluble targets or shed ECD on mAb PK/PD properties. We provide examples of quantitative approaches that facilitate the characterization of mAb PK/PD characteristics and their corresponding bioanalytical strategies.

Sample Preparation for Determination of Biological Thiols by Liquid Chromatography and Electromigration Techniques

OpenAIRE

Bald, Edward

2004-01-01

Wydrukowano z dostarczonych Wydawnictwu UŁ gotowych materiałów Majority of the bioanalytical or environmental methods do not use just one chromatografie or electrophoretic step, but rather involve several sample pretreatment steps which simplfy the matrix, and often preconcentrate and chemically modify the analytes. This work surveys typical procedures for sample preparation for most commonly analyzed biofluids with particular emphasis placed on chemical derivatization of su...

Developing a TQM quality management method model

NARCIS (Netherlands)

Zhang, Zhihai

1997-01-01

From an extensive review of total quality management literature, the external and internal environment affecting an organization's quality performance and the eleven primary elements of TQM are identified. Based on the primary TQM elements, a TQM quality management method model is developed. This

Recent development of the passive vibration control method

Science.gov (United States)

Ishida, Yukio

2012-05-01

This paper introduces new passive vibration suppression methods developed recently in our laboratory. First, two methods used to suppress steady-state resonances are explained. One is the improvement of the efficiency of a ball balancer. A simple method to eliminate the influence of friction of balls and to improve its efficiency is introduced. The other is an effective method that utilizes the discontinuous spring characteristics. Secondly, a method to eliminate unstable ranges in rotor systems is explained. Unstable ranges in an asymmetrical shaft, and in a hollow rotor partially filled with liquid, are eliminated by the discontinuous spring characteristics. Thirdly, a method to suppress self-excited oscillations is explained. Self-excited oscillations due to internal damping and rubbing are discussed. Finally, the methods of using a pendulum or roller type absorbers to suppress torsional vibrations are explained.

Quantitative methods for developing C2 system requirement

Energy Technology Data Exchange (ETDEWEB)

Tyler, K.K.

1992-06-01

The US Army established the Army Tactical Command and Control System (ATCCS) Experimentation Site (AES) to provide a place where material and combat developers could experiment with command and control systems. The AES conducts fundamental and applied research involving command and control issues using a number of research methods, ranging from large force-level experiments, to controlled laboratory experiments, to studies and analyses. The work summarized in this paper was done by Pacific Northwest Laboratory under task order from the Army Tactical Command and Control System Experimentation Site. The purpose of the task was to develop the functional requirements for army engineer automation and support software, including MCS-ENG. A client, such as an army engineer, has certain needs and requirements of his or her software; these needs must be presented in ways that are readily understandable to the software developer. A requirements analysis then, such as the one described in this paper, is simply the means of communication between those who would use a piece of software and those who would develop it. The analysis from which this paper was derived attempted to bridge the communications gap'' between army combat engineers and software engineers. It sought to derive and state the software needs of army engineers in ways that are meaningful to software engineers. In doing this, it followed a natural sequence of investigation: (1) what does an army engineer do, (2) with which tasks can software help, (3) how much will it cost, and (4) where is the highest payoff This paper demonstrates how each of these questions was addressed during an analysis of the functional requirements of engineer support software. Systems engineering methods are used in a task analysis and a quantitative scoring method was developed to score responses regarding the feasibility of task automation. The paper discusses the methods used to perform utility and cost-benefits estimates.

Magnetic nanoparticles for bio-analytical applications

Science.gov (United States)

Yedlapalli, Sri Lakshmi

Magnetic nanoparticles are widely being used in various fields of medicine, biology and separations. This dissertation focuses on the synthesis and use of magnetic nanoparticles for targeted drug delivery and analytical separations. The goals of this research include synthesis of biocompatible surface modified monodisperse superparamagnetic iron oxide nanoparticles (SPIONs) by novel techniques for targeted drug delivery and use of SPIONs as analytical sensing tools. Surface modification of SPIONs was performed with two different co-polymers: tri block co-polymer Pluronics and octylamine modified polyacrylic acid. Samples of SPIONs were subsequently modified with 4 different commercially available, FDA approved tri-block copolymers (Pluronics), covering a wide range of molecular weights (5.75-14.6 kDa). A novel, technically simpler and faster phase transfer approach was developed to surface modify the SPIONs with Pluronics for drug delivery and other biomedical applications. The hydrodynamic diameter and aggregation properties of the Pluronic modified SPIONs were studied by dynamic light scattering (DLS). The coverage of SPIONs with Pluronics was supported with IR Spectroscopy and characterized by Thermo gravimetric Analysis (TGA). The drug entrapment capacity of SPIONs was studied by UV-VIS spectroscopy using a hydrophobic carbocyanine dye, which serves as a model for hydrophobic drugs. These studies resulted in a comparison of physical properties and their implications for drug loading capacities of the four types of Pluronic coated SPIONs for drug delivery assessment. These drug delivery systems could be used for passive drug targeting. However, Pluronics lack the functional group necessary for bioconjugation and hence cannot achieve active targeting. SPIONs were functionalized with octylamine modified polyacrylic acid-based copolymer, providing water solubility and facile biomolecular conjugation. Epirubicin was loaded onto SPIONs and the drug entrapment was

Development of methods for body composition studies

International Nuclear Information System (INIS)

Mattsson, Soeren; Thomas, Brian J

2006-01-01

This review is focused on experimental methods for determination of the composition of the human body, its organs and tissues. It summarizes the development and current status of fat determinations from body density, total body water determinations through the dilution technique, whole and partial body potassium measurements for body cell mass estimates, in vivo neutron activation analysis for body protein measurements, dual-energy absorptiometry (DEXA), computed tomography (CT) and magnetic resonance imaging (MRI, fMRI) and spectroscopy (MRS) for body composition studies on tissue and organ levels, as well as single- and multiple-frequency bioimpedance (BIA) and anthropometry as simple easily available methods. Methods for trace element analysis in vivo are also described. Using this wide range of measurement methods, together with gradually improved body composition models, it is now possible to quantify a number of body components and follow their changes in health and disease. (review)

Development of methods for body composition studies

Energy Technology Data Exchange (ETDEWEB)

Mattsson, Soeren [Department of Radiation Physics, Lund University, Malmoe University Hospital, SE-205 02 Malmoe (Sweden); Thomas, Brian J [School of Physical and Chemical Sciences, Queensland University of Technology, Brisbane, QLD 4001 (Australia)

2006-07-07

This review is focused on experimental methods for determination of the composition of the human body, its organs and tissues. It summarizes the development and current status of fat determinations from body density, total body water determinations through the dilution technique, whole and partial body potassium measurements for body cell mass estimates, in vivo neutron activation analysis for body protein measurements, dual-energy absorptiometry (DEXA), computed tomography (CT) and magnetic resonance imaging (MRI, fMRI) and spectroscopy (MRS) for body composition studies on tissue and organ levels, as well as single- and multiple-frequency bioimpedance (BIA) and anthropometry as simple easily available methods. Methods for trace element analysis in vivo are also described. Using this wide range of measurement methods, together with gradually improved body composition models, it is now possible to quantify a number of body components and follow their changes in health and disease. (review)

Development of a transient criticality evaluation method

International Nuclear Information System (INIS)

Pain, C.C.; Eaton, M.D.; Miles, B.; Ziver, A.K.; Gomes, J.L.M.A.; Umpleby, A.P.; Piggott, M.D.; Goddard, A.J.H.; Oliveira, C.R.E. de

2005-01-01

In developing a transient criticality evaluation method we model, in full spatial/temporal detail, the neutron fluxes and consequent power and the evolving material properties - their flows, energies, phase changes etc. These methods are embodied in the generic method FETCH code which is based as far as possible on basic principles and is capable of use in exploring safety-related situations somewhat beyond the range of experiment. FETCH is a general geometry code capable of addressing a range of criticality issues in fissile materials. The code embodies both transient radiation transport and transient fluid dynamics. Work on powders, granular materials, porous media and solutions is reviewed. The capability for modelling transient criticality for chemical plant, waste matrices and advanced reactors is also outlined. (author)

Quality functions for requirements engineering in system development methods.

Science.gov (United States)

Johansson, M; Timpka, T

1996-01-01

Based on a grounded theory framework, this paper analyses the quality characteristics for methods to be used for requirements engineering in the development of medical decision support systems (MDSS). The results from a Quality Function Deployment (QFD) used to rank functions connected to user value and a focus group study were presented to a validation focus group. The focus group studies take advantage of a group process to collect data for further analyses. The results describe factors considered by the participants as important in the development of methods for requirements engineering in health care. Based on the findings, the content which, according to the user a MDSS method should support is established.

USFDA-GUIDELINE BASED VALIDATION OF TESTING METHOD FOR RIFAMPICIN IN INDONESIAN SERUM SPECIMEN

Directory of Open Access Journals (Sweden)

Tri Joko Raharjo

2010-06-01

Full Text Available Regarding a new regulation from Indonesia FDA (Badan POM-RI, all new non patent drugs should show bioequivalence with the originator drug prior to registration. Bioequivalence testing (BE-testing has to be performed to the people that represented of population to which the drug to be administrated. BE testing need a valid bio-analytical method for certain drug target and group of population. This research report specific validation of bio-analysis of Rifampicin in Indonesian serum specimen in order to be used for BE testing. The extraction was performed using acetonitrile while the chromatographic separation was accomplished on a RP 18 column (250 × 4.6 mm i.d., 5 µm, with a mobile phase composed of KH2PO4 10 mM-Acetonitrile (40:60, v/v and UV detection was set at 333 nm. The method shown specificity compared to blank serum specimen with retention time of rifampicin at 2.1 min. Lower limit of quantification (LLOQ was 0.06 µg/mL with dynamic range up to 20 µg/mL (R>0.990. Precision of the method was very good with coefficient of variance (CV 0.58; 7.40 and 5.56% for concentration at 0.06, 5, 15 µg/mL, respectively. Accuracies of the method were 3.22; 1.94; 1.90% for concentration 0.06, 5 and 15 µg/mL respectively. The average recoveries were 97.82, 95.50 and 97.31% for concentration of rifampicin 1, 5 and 5 µg/mL, respectively. The method was also shown reliable result on stability test on freezing-thawing, short-term and long-term stability as well as post preparation stability. Validation result shown that the method was ready to be used for Rifampicin BE testing with Indonesian subject.   Keywords: Rifampicin, Validation, USFDA-Guideline

Peak detection method evaluation for ion mobility spectrometry by using machine learning approaches.

Science.gov (United States)

Hauschild, Anne-Christin; Kopczynski, Dominik; D'Addario, Marianna; Baumbach, Jörg Ingo; Rahmann, Sven; Baumbach, Jan

2013-04-16

Ion mobility spectrometry with pre-separation by multi-capillary columns (MCC/IMS) has become an established inexpensive, non-invasive bioanalytics technology for detecting volatile organic compounds (VOCs) with various metabolomics applications in medical research. To pave the way for this technology towards daily usage in medical practice, different steps still have to be taken. With respect to modern biomarker research, one of the most important tasks is the automatic classification of patient-specific data sets into different groups, healthy or not, for instance. Although sophisticated machine learning methods exist, an inevitable preprocessing step is reliable and robust peak detection without manual intervention. In this work we evaluate four state-of-the-art approaches for automated IMS-based peak detection: local maxima search, watershed transformation with IPHEx, region-merging with VisualNow, and peak model estimation (PME).We manually generated Metabolites 2013, 3 278 a gold standard with the aid of a domain expert (manual) and compare the performance of the four peak calling methods with respect to two distinct criteria. We first utilize established machine learning methods and systematically study their classification performance based on the four peak detectors' results. Second, we investigate the classification variance and robustness regarding perturbation and overfitting. Our main finding is that the power of the classification accuracy is almost equally good for all methods, the manually created gold standard as well as the four automatic peak finding methods. In addition, we note that all tools, manual and automatic, are similarly robust against perturbations. However, the classification performance is more robust against overfitting when using the PME as peak calling preprocessor. In summary, we conclude that all methods, though small differences exist, are largely reliable and enable a wide spectrum of real-world biomedical applications.

Methods for Developing Emissions Scenarios for Integrated Assessment Models

Energy Technology Data Exchange (ETDEWEB)

Prinn, Ronald [MIT; Webster, Mort [MIT

2007-08-20

The overall objective of this research was to contribute data and methods to support the future development of new emissions scenarios for integrated assessment of climate change. Specifically, this research had two main objectives: 1. Use historical data on economic growth and energy efficiency changes, and develop probability density functions (PDFs) for the appropriate parameters for two or three commonly used integrated assessment models. 2. Using the parameter distributions developed through the first task and previous work, we will develop methods of designing multi-gas emission scenarios that usefully span the joint uncertainty space in a small number of scenarios. Results on the autonomous energy efficiency improvement (AEEI) parameter are summarized, an uncertainty analysis of elasticities of substitution is described, and the probabilistic emissions scenario approach is presented.

Development of an HPLC fluorescence method for determination of boldine in plasma, bile and urine of rats and identification of its major metabolites by LC-MS/MS.

Science.gov (United States)

Hroch, Miloš; Mičuda, Stanislav; Cermanová, Jolana; Chládek, Jaroslav; Tomšík, Pavel

2013-10-01

Boldine belongs to the group of aporphine alkaloids isolated from Boldo tree. In contrast with numerous reports on the pharmacological effects of boldine, the data about its pharmacokinetics and biotransformation are scarce. No validated bioanalytical method of sufficient sensitivity has so far been described in the literature which could be used for quantification of boldine in various body fluids collected in pharmacokinetic studies. This work presents, for the first time, the assay for boldine in the plasma, bile and urine of rats. It includes liquid-liquid extraction/back-extraction of boldine, its chromatographic separation and sensitive fluorescence detection. Separation was carried out on a pentafluorophenyl core-shell column (Kinetex PFP, 150×3mm, 2.6μm) in gradient elution mode with solvent system consisting of an acetonitrile-ammonium formate buffer (5mM, pH=3.8). Fluorimetric detection (λEX=320nm, λEM=370nm) was used for quantitative work. Validation according to the EMEA guideline proved the assay LLOQ (0.1μmolL(-1)), linearity over a broad range of 0.1-50μmolL(-1), precision (intra- and inter-day CVs less than 4.5% and 6.1%, respectively) and accuracy (relative errors between -5.8% and 4.8%). In a pilot pharmacokinetic experiment, the concentration-time profiles were described for boldine (single i.v. bolus 50mgkg(-1)) in plasma and bile and cumulative excretion in urine was investigated. The major metabolites identified by means of LC-MS(n) were boldine-O-glucuronide, boldine-O-sulphate and disulphate, boldine-O-glucuronide-O-sulphate and N-demethyl-boldine-O-sulphate. Copyright © 2013 Elsevier B.V. All rights reserved.

Object Oriented Modeling : A method for combining model and software development

NARCIS (Netherlands)

Van Lelyveld, W.

2010-01-01

When requirements for a new model cannot be met by available modeling software, new software can be developed for a specific model. Methods for the development of both model and software exist, but a method for combined development has not been found. A compatible way of thinking is required to

The Development of the TPR-DB as Grounded Theory Method

DEFF Research Database (Denmark)

Carl, Michael; Schaeffer, Moritz

2018-01-01

and refine the emerging concepts and categories and to validate the developing theories, the TPR-DB has been extended with further translation studies in different languages and translation modes. In this respect, it shares many features with Grounded Theory Method. This method was discovered in 1967...... and used in qualitative research in social science ad many other research areas. We analyze the TPR-DB development as a Grounded Theory Method....... on quantitative assessment of well-defined research questions on cognitive processes in human translation production, the integration of the data into the TPR-DB allowed for broader qualitative and exploratory research which has led to new codes, categories and research themes. In a constant effort to develop...

Development of nondestructive evaluation methods for ceramic coatings

International Nuclear Information System (INIS)

Ellingson, W. A.; Deemer, C.; Sun, J. G.; Erdman, S.; Muliere, D.; Wheeler, B.

2002-01-01

Various nondestructive evaluation (NDE) technologies are being developed to study the use of ceramic coatings on components in the hot-gas path of advanced low-emission gas-fired turbines. The types of ceramic coatings include thermal barrier coatings (TBCs) and environmental barrier coatings (EBCs). TBCs are under development for vanes, blades, and combustor liners to allow hotter gas-path temperatures, and EBCs are under development to reduce environmental damage to high-temperature components made of ceramic matrix composites. The NDE methods will be used to (a) provide data to assess the reliability of new coating application processes, (b) identify defective components that could cause unscheduled outages, (c) track growth rates of defects during component use in engines, and (d) allow rational judgment for replace/repair/re-use decisions regarding components. Advances in TBC application, both electron beam-physical vapor deposition (EB-PVD) and air plasma spraying (APS), are allowing higher temperatures in the hot-gas path. However, as TBCs become ''prime reliant,'' their condition at scheduled or unscheduled outages must be known. NDE methods are under development to assess the condition of the TBC for pre-spall conditions. EB-PVD test samples with up to 70 thermal cycles have been studied by a newly developed method involving polarized laser back-scatter NDE. Results suggest a correlation between the NDE laser data and the TBC/bond-coat topography. This finding is important because several theories directed toward understanding the pre-spall condition suggest that the topography in the thermally grown oxide layer changes significantly as a function of the number of thermal cycles. Tests have also been conducted with this NDE method on APS TBCs. Results suggest that the pre-spall condition is detected for these coatings. One-sided, high-speed thermal imaging also has shown promise for NDE of APS coatings. Testing of SiC/SiC composites for combustor liners

Methodical approaches to development of classification state methods of regulation business activity in fishery

OpenAIRE

She Son Gun

2014-01-01

Approaches to development of classification of the state methods of regulation of economy are considered. On the basis of the provided review the complex method of state regulation of business activity is reasonable. The offered principles allow improving public administration and can be used in industry concepts and state programs on support of small business in fishery.

Housing decision making methods for initiation development phase process

Science.gov (United States)

Zainal, Rozlin; Kasim, Narimah; Sarpin, Norliana; Wee, Seow Ta; Shamsudin, Zarina

2017-10-01

Late delivery and sick housing project problems were attributed to poor decision making. These problems are the string of housing developer that prefers to create their own approach based on their experiences and expertise with the simplest approach by just applying the obtainable standards and rules in decision making. This paper seeks to identify the decision making methods for housing development at the initiation phase in Malaysia. The research involved Delphi method by using questionnaire survey which involved 50 numbers of developers as samples for the primary stage of collect data. However, only 34 developers contributed to the second stage of the information gathering process. At the last stage, only 12 developers were left for the final data collection process. Finding affirms that Malaysian developers prefer to make their investment decisions based on simple interpolation of historical data and using simple statistical or mathematical techniques in producing the required reports. It was suggested that they seemed to skip several important decision-making functions at the primary development stage. These shortcomings were mainly due to time and financial constraints and the lack of statistical or mathematical expertise among the professional and management groups in the developer organisations.

Development of pre-critical excore detector linear subchannel calibration method

International Nuclear Information System (INIS)

Choi, Yoo Sun; Goo, Bon Seung; Cha, Kyun Ho; Lee, Chang Seop; Kim, Yong Hee; Ahn, Chul Soo; Kim, Man Soo

2001-01-01

The improved pre-critical excore detector linear subchannel calibration method has been developed to improve the applicability of pre-critical calibration method. The existing calibration method does not always guarantee the accuracy of pre-critical calibration because the calibration results of the previous cycle are not reflected into the current cycle calibration. The developed method has a desirable feature that calibration error would not be propagated in the following cycles since the calibration data determined in previous cycle is incorporated in the current cycle calibration. The pre-critical excore detector linear calibration is tested for YGN unit 3 and UCN unit 3 to evaluate its characteristics and accuracy

Development of Methods and Equipment for Sheet Stamping

Science.gov (United States)

Botashev, A. Yu; Bisilov, N. U.; Malsugenov, R. S.

2018-03-01

New methods of sheet stamping were developed: the gas forming with double-sided heating of a blank part and the gas molding with backpressure. In case of the first method the blank part is heated to the set temperature by means of a double-sided impact of combustion products of gas mixtures, after which, under the influence of gas pressure a stamping process is performed. In case of gas molding with backpressure, the blank part is heated to the set temperature by one-sided impact of the combustion products, while backpressure is created on the opposite side of the blank part by compressed air. In both methods the deformation takes place in the temperature range of warm or hot treatment due to the heating of a blank part. This allows one to form parts of complicated shape within one technological operation, which significantly reduces the cost of production. To implement these methods, original devices were designed and produced, which are new types of forging and stamping equipment. Using these devices, an experimental research on the stamping process was carried out and high-quality parts were obtained, which makes it possible to recommend the developed methods of stamping in the industrial production. Their application in small-scale production will allow one to reduce the cost price of stamped parts 2 or 3 times.

Shielding methods development in the United States

International Nuclear Information System (INIS)

Mynatt, F.R.

1977-01-01

A generalized shielding methodology has been developed in the U.S.A. that is adaptable to the shielding analyses of all reactor types. Thus far used primarily for liquid-metal fast breeder reactors, the methodology includes several component activities: (1) developing methods for calculating radiation transport through reactor-shield systems; (2) processing cross-section libraries; (3) performing design calculations for specific systems; (4) performing and analyzing pertinent integral experiments; (5) performing sensitivity studies on both the design calculations and the experimental analyses; and, finally, (6) calculating shield design parameters and their uncertainties. The criteria for the methodology are a 5 to 10 percent accuracy for responses at locations near the core and a factor of 2 accuracy for responses at distant locations. The methodology has been successfully adapted to most in-vessel and ex-vessel problems encountered in the shield analyses of the Fast Flux Test Facility and the Fast Flux Test Facility and the Clinch River Breeder Reactor; however, improved techniques are needed for calculating regions in which radiation streaming is dominant. Areas of the methodology in which significant progress has recently been made are those involving the development of cross-section libraries, sensitivity analysis methods, and transport codes

A fit-for-purpose LC-MS/MS method for the simultaneous quantitation of ATP and 2,3-DPG in human K2EDTA whole blood.

Science.gov (United States)

Kim, Hyeryun; Kosinski, Penelope; Kung, Charles; Dang, Lenny; Chen, Yue; Yang, Hua; Chen, Yuan-Shek; Kramer, Jordyn; Liu, Guowen

2017-09-01

Many hemolytic anemias results in major metabolic abnormalities: two common metabolite abnormalities include increased levels of 2,3-diphosphoglycerate (2,3-DPG) and decreased levels of adenosine triphosphate (ATP). To better monitor the concentration changes of these metabolites, the development of a reliable LC-MS/MS method to quantitatively profile the concentrations of 2, 3-DPG and ATP in whole blood is essential to understand the effects of investigational therapeutics. Accurate quantification of both compounds imposes great challenges to bioanalytical scientists due to their polar, ionic and endogenous nature. Here we present an LC-MS/MS method for the reliable quantification of 2,3-DPG and ATP from K 2 EDTA human whole blood (WB) simultaneously. Whole blood samples were spiked with stable isotope labeled internal standards, processed by protein precipitation extraction, and analyzed using zwitterionic ion chromatography-hydrophilic interaction chromatography (ZIC-HILIC) coupled with tandem mass spectrometry. The linear analytical range of the assay was 50-3000μg/mL. The fit-for-purpose method demonstrated excellent accuracy and precision. The overall accuracy was within ±10.5% (%RE) for both analytes and the intra- and inter-assay precision (%CV) were less than 6.7% and 6.2% for both analytes, respectively. ATP and 2,3-DPG were found to be stable in human K 2 EDTA blood for at least 8h at 4°C, 96days when stored at -70°C and after three freeze/thaw cycles. The assay has been successfully applied to K 2 EDTA human whole blood samples to support clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of strength evaluation method for high-pressure ceramic components

Energy Technology Data Exchange (ETDEWEB)

Takegami, Hiroaki, E-mail: takegami.hiroaki@jaea.go.jp; Terada, Atsuhiko; Inagaki, Yoshiyuki

2014-05-01

Japan Atomic Energy Agency is conducting R and D on nuclear hydrogen production by the Iodine-Sulfur (IS) process. Since highly corrosive materials such as sulfuric and hydriodic acids are used in the IS process, it is very important to develop components made of corrosion resistant materials. Therefore, we have been developing a sulfuric acid decomposer made of a ceramic material, that is, silicon carbide (SiC), which shows excellent corrosion resistance to sulfuric acid. One of the key technological challenges for the practical use of a ceramic sulfuric acid decomposer made of SiC is to be licensed in accordance with the High Pressure Gas Safety Act for high-pressure operations of the IS process. Since the strength of a ceramic material depends on its geometric form, etc., the strength evaluation method required for a pressure design is not established. Therefore, we propose a novel strength evaluation method for SiC structures based on the effective volume theory in order to extend the range of application of the effective volume. We also developed a design method for ceramic apparatus with the strength evaluation method in order to obtain a license in accordance with the High Pressure Gas Safety Act. In this paper, the minimum strength of SiC components was calculated by Monte Carlo simulation, and the minimum strength evaluation method of SiC components was developed by using the results of simulation. The method was confirmed by fracture test of tube model and reference data.

A Framework for Teaching Software Development Methods

Science.gov (United States)

Dubinsky, Yael; Hazzan, Orit

2005-01-01

This article presents a study that aims at constructing a teaching framework for software development methods in higher education. The research field is a capstone project-based course, offered by the Technion's Department of Computer Science, in which Extreme Programming is introduced. The research paradigm is an Action Research that involves…

Main flexible pavement and mix design methods in Europe and challenges for the development of an European method

Directory of Open Access Journals (Sweden)

Paulo Pereira

2017-08-01

Full Text Available Pavement and mix design represent one of the key components within the life cycle of a road infrastructure, with links to political, economic, technical, societal and environmental issues. Recent researches related to the characteristics of materials and associated behavior models both for materials and pavement, made it appropriate to consider updating current pavement design methods, and especially in the USA this has already been in process while in Europe uses of the methods developed in the early 1970s. Thus, this paper firstly presents a brief historical overview of pavement design methods, highlighting early limitations of old empirical methods. Afterwards, French, UK and Shell methods currently in use in Europe will be presented, underlining their main components in terms of methodology, traffic, climatic conditions and subgrade. The asphalt mix design and modeling in Europe are presented with their inclusion in the pavement design methods. Finally, the main challenges for the development of a European pavement design method are presented as well as the recent research developments that can be used for that method.

A direction of developing a mining method and mining complexes

Energy Technology Data Exchange (ETDEWEB)

Gabov, V.V.; Efimov, I.A. [St. Petersburg State Mining Institute, St. Petersburg (Russian Federation). Vorkuta Branch

1996-12-31

The analyses of a mining method as a main factor determining the development stages of mining units is presented. The paper suggests a perspective mining method which differs from the known ones by following peculiarities: the direction selectivity of cuts with regard to coal seams structure; the cutting speed, thickness and succession of dusts. This method may be done by modulate complexes (a shield carrying a cutting head for coal mining), their mining devices being supplied with hydraulic drive. An experimental model of the module complex has been developed. 2 refs.

Dual quantification of dapivirine and maraviroc in cervicovaginal secretions from ophthalmic tear strips and polyester-based swabs via liquid chromatographic-tandem mass spectrometric (LC-MS/MS) analysis.

Science.gov (United States)

Parsons, Teresa L; Emory, Joshua F; Seserko, Lauren A; Aung, Wutyi S; Marzinke, Mark A

2014-09-01

Topical microbicidal agents are being actively pursued as a modality to prevent HIV viral transmission during sexual intercourse. Quantification of antiretroviral agents in specimen sources where antiviral activity is elicited is critical, and drug measurements in cervicovaginal fluid can provide key information on local drug concentrations. Two antiretroviral drugs, dapivirine and maraviroc, have gained interest as vaginal microbicidal agents, and rugged methods are required for their quantification in cervicovaginal secretions. Cervicovaginal fluid spiked with dapivirine and maraviroc were applied to ophthalmic tear strips or polyester-based swabs to mimic collection procedures used in clinical studies. Following sample extraction and the addition of isotopically labeled internal standards, samples were subjected to liquid chromatographic-tandem mass spectrometric (LC-MS/MS) analysis using a Waters BEH C8, 50mm×2.1mm, 1.7μm particle size column, on an API 4000 mass analyzer operated in selective reaction monitoring mode. The method was validated according to FDA Bioanalytical Method Validation guidelines. Due to the disparate saturation capacity of the tested collection devices, the analytical measuring ranges for dapivirine and maravirocin cervicovaginal fluid on the ophthalmic tear strip were 0.05-25ng/tear strip, and 0.025-25ng/tear strip, respectively. As for the polyester-based swab, the analytical measuring ranges were 0.25-125ng/swab for dapivirine and 0.125-125ng/swab for maraviroc. Dilutional studies were performed for both analytes to extended ranges of 25,000ng/tear strip and 11,250ng/swab. Standard curves were generated via weighted (1/x(2)) linear or quadratic regression of calibrators. Precision, accuracy, stability and matrix effects studies were all performed and deemed acceptable according to the recommendations of the FDA Bioanalytical Method Validation guidelines. A rugged LC-MS/MS method for the dual quantification of dapivirine and

Accurate quantification of endogenous androgenic steroids in cattle's meat by gas chromatography mass spectrometry using a surrogate analyte approach

International Nuclear Information System (INIS)

Ahmadkhaniha, Reza; Shafiee, Abbas; Rastkari, Noushin; Kobarfard, Farzad

2009-01-01

Determination of endogenous steroids in complex matrices such as cattle's meat is a challenging task. Since endogenous steroids always exist in animal tissues, no analyte-free matrices for constructing the standard calibration line will be available, which is crucial for accurate quantification specially at trace level. Although some methods have been proposed to solve the problem, none has offered a complete solution. To this aim, a new quantification strategy was developed in this study, which is named 'surrogate analyte approach' and is based on using isotope-labeled standards instead of natural form of endogenous steroids for preparing the calibration line. In comparison with the other methods, which are currently in use for the quantitation of endogenous steroids, this approach provides improved simplicity and speed for analysis on a routine basis. The accuracy of this method is better than other methods at low concentration and comparable to the standard addition at medium and high concentrations. The method was also found to be valid according to the ICH criteria for bioanalytical methods. The developed method could be a promising approach in the field of compounds residue analysis

Accurate quantification of endogenous androgenic steroids in cattle's meat by gas chromatography mass spectrometry using a surrogate analyte approach

Energy Technology Data Exchange (ETDEWEB)

Ahmadkhaniha, Reza; Shafiee, Abbas [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14174 (Iran, Islamic Republic of); Rastkari, Noushin [Center for Environmental Research, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Kobarfard, Farzad [Department of Medicinal Chemistry, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tavaneer Ave., Valieasr St., Tehran (Iran, Islamic Republic of)], E-mail: farzadkf@yahoo.com

2009-01-05

Determination of endogenous steroids in complex matrices such as cattle's meat is a challenging task. Since endogenous steroids always exist in animal tissues, no analyte-free matrices for constructing the standard calibration line will be available, which is crucial for accurate quantification specially at trace level. Although some methods have been proposed to solve the problem, none has offered a complete solution. To this aim, a new quantification strategy was developed in this study, which is named 'surrogate analyte approach' and is based on using isotope-labeled standards instead of natural form of endogenous steroids for preparing the calibration line. In comparison with the other methods, which are currently in use for the quantitation of endogenous steroids, this approach provides improved simplicity and speed for analysis on a routine basis. The accuracy of this method is better than other methods at low concentration and comparable to the standard addition at medium and high concentrations. The method was also found to be valid according to the ICH criteria for bioanalytical methods. The developed method could be a promising approach in the field of compounds residue analysis.

Development of Immunocapture-LC/MS Assay for Simultaneous ADA Isotyping and Semiquantitation

Science.gov (United States)

2016-01-01

Therapeutic proteins and peptides have potential to elicit immune responses resulting in anti-drug antibodies that can pose problems for both patient safety and product efficacy. During drug development immunogenicity is usually examined by risk-based approach along with specific strategies for developing “fit-for-purpose” bioanalytical approaches. Enzyme-linked immunosorbent assays and electrochemiluminescence immunoassays are the most widely used platform for ADA detection due to their high sensitivity and throughput. During the past decade, LC/MS has emerged as a promising technology for quantitation of biotherapeutics and protein biomarkers in biological matrices, mainly owing to its high specificity, selectivity, multiplexing, and wide dynamic range. In fully taking these advantages, we describe here an immunocapture-LC/MS methodology for simultaneous isotyping and semiquantitation of ADA in human plasma. Briefly, ADA and/or drug-ADA complex is captured by biotinylated drug or anti-drug Ab, immobilized on streptavidin magnetic beads, and separated from human plasma by a magnet. ADA is then released from the beads and subjected to trypsin digestion followed by LC/MS detection of specific universal peptides for each ADA isotype. The LC/MS data are analyzed using cut-point and calibration curve. The proof-of-concept of this methodology is demonstrated by detecting preexisting ADA in human plasma. PMID:27034966

Development of Immunocapture-LC/MS Assay for Simultaneous ADA Isotyping and Semiquantitation.

Science.gov (United States)

Chen, Lin-Zhi; Roos, David; Philip, Elsy

2016-01-01

Therapeutic proteins and peptides have potential to elicit immune responses resulting in anti-drug antibodies that can pose problems for both patient safety and product efficacy. During drug development immunogenicity is usually examined by risk-based approach along with specific strategies for developing "fit-for-purpose" bioanalytical approaches. Enzyme-linked immunosorbent assays and electrochemiluminescence immunoassays are the most widely used platform for ADA detection due to their high sensitivity and throughput. During the past decade, LC/MS has emerged as a promising technology for quantitation of biotherapeutics and protein biomarkers in biological matrices, mainly owing to its high specificity, selectivity, multiplexing, and wide dynamic range. In fully taking these advantages, we describe here an immunocapture-LC/MS methodology for simultaneous isotyping and semiquantitation of ADA in human plasma. Briefly, ADA and/or drug-ADA complex is captured by biotinylated drug or anti-drug Ab, immobilized on streptavidin magnetic beads, and separated from human plasma by a magnet. ADA is then released from the beads and subjected to trypsin digestion followed by LC/MS detection of specific universal peptides for each ADA isotype. The LC/MS data are analyzed using cut-point and calibration curve. The proof-of-concept of this methodology is demonstrated by detecting preexisting ADA in human plasma.

Method for selecting FBR development strategies in the presence of uncertainty

International Nuclear Information System (INIS)

Fraley, D.W.; Burnham, J.B.

1981-12-01

This report describes the methods used to probabilistically analyze data related to the uranium supply the FBR's competitive dates, development strategies' time and costs, and economic benefits. It also describes the econometric methods used to calculate the economic risks of mistiming the development. Seven strategies for developing the FBR are analyzed. The various measures of a strategy's performance - timing, costs, benefits, and risks - are combined into several criteria which are used to evaluate the seven strategies. Methods are described for selecting a strategy based on a number of alternative criteria

APPLICATION OF QUALITY ECONOMY METHODS IN MANAGING INNOVATION CAPACITY DEVELOPMENT

Directory of Open Access Journals (Sweden)

V. V. Okrepilov

2017-01-01

Full Text Available Purpose: to reveal the possibilities of applying the methods of the quality economy to improve the management efficiency of the development of the region's innovative potential.Results: in the article topical questions of development of innovative potential of the region are considered - one of the important factors providing improvement of quality of life of the population and sustainable development of the territory. The content of the concept of "innovation potential of the region" is disclosed and its components are described. The purposes of development of innovative potential are considered. A comparative analysis of the methods of managing the development of potential in the market and planned economy is carried out. Particular attention is paid to the application of quality management methods to improve management effectiveness. In conclusion, the advantages and disadvantages of the economy of the macro-region "North-West" from the point of view of transition to an innovative development path, as well as scenarios for the development of the economy, are discussed.Conclusions and relevance: the use of quality economy tools to manage the development of innovative capacity will help to avoid mistakes and choose the right directions for development. In the era of globalization, improving quality is a prerequisite for successful competition in world markets. Therefore, the issues of innovation capacity assessment should be taken into account in the development of regional plans and programs, as well as socio-economic policy.

A bootstrapping method for development of Treebank

Science.gov (United States)

Zarei, F.; Basirat, A.; Faili, H.; Mirain, M.

2017-01-01

Using statistical approaches beside the traditional methods of natural language processing could significantly improve both the quality and performance of several natural language processing (NLP) tasks. The effective usage of these approaches is subject to the availability of the informative, accurate and detailed corpora on which the learners are trained. This article introduces a bootstrapping method for developing annotated corpora based on a complex and rich linguistically motivated elementary structure called supertag. To this end, a hybrid method for supertagging is proposed that combines both of the generative and discriminative methods of supertagging. The method was applied on a subset of Wall Street Journal (WSJ) in order to annotate its sentences with a set of linguistically motivated elementary structures of the English XTAG grammar that is using a lexicalised tree-adjoining grammar formalism. The empirical results confirm that the bootstrapping method provides a satisfactory way for annotating the English sentences with the mentioned structures. The experiments show that the method could automatically annotate about 20% of WSJ with the accuracy of F-measure about 80% of which is particularly 12% higher than the F-measure of the XTAG Treebank automatically generated from the approach proposed by Basirat and Faili [(2013). Bridge the gap between statistical and hand-crafted grammars. Computer Speech and Language, 27, 1085-1104].

Development of thermal stress screening method. Application of green function method

International Nuclear Information System (INIS)

Furuhashi, Ichiro; Shibamoto, Hiroshi; Kasahara, Naoto

2004-01-01

This work was achieved for the development of the screening method of thermal transient stresses in FBR components. We proposed an approximation method for evaluations of thermal stress under variable heat transfer coefficients (non-linear problems) using the Green functions of thermal stresses with constant heat transfer coefficients (linear problems). Detailed thermal stress analyses provided Green functions for a skirt structure and a tube-sheet of Intermediate Heat Exchanger. The upper bound Green functions were obtained by the analyses using those upper bound heat transfer coefficients. The medium and the lower bound Green functions were got by the analyses of those under medium and the lower bound heat transfer coefficients. Conventional evaluations utilized the upper bound Green functions. On the other hand, we proposed a new evaluation method by using the upper bound, medium and the lower bound Green functions. The comparison of above results gave the results as follows. The conventional evaluations were conservative and appropriate for the cases under one fluid thermal transient structure such as the skirt. The conventional evaluations were generally conservative for the complicated structures under two or more fluids thermal transients such as the tube-sheet. But the danger locations could exists for the complicated structures under two or more fluids transients, namely the conventional evaluations were non-conservative. The proposed evaluations gave good estimations for these complicated structures. Though above results, we have made the basic documents of the screening method of thermal transient stresses using the conventional method and the new method. (author)

Structural reliability methods: Code development status

Science.gov (United States)

Millwater, Harry R.; Thacker, Ben H.; Wu, Y.-T.; Cruse, T. A.

1991-05-01

The Probabilistic Structures Analysis Method (PSAM) program integrates state of the art probabilistic algorithms with structural analysis methods in order to quantify the behavior of Space Shuttle Main Engine structures subject to uncertain loadings, boundary conditions, material parameters, and geometric conditions. An advanced, efficient probabilistic structural analysis software program, NESSUS (Numerical Evaluation of Stochastic Structures Under Stress) was developed as a deliverable. NESSUS contains a number of integrated software components to perform probabilistic analysis of complex structures. A nonlinear finite element module NESSUS/FEM is used to model the structure and obtain structural sensitivities. Some of the capabilities of NESSUS/FEM are shown. A Fast Probability Integration module NESSUS/FPI estimates the probability given the structural sensitivities. A driver module, PFEM, couples the FEM and FPI. NESSUS, version 5.0, addresses component reliability, resistance, and risk.

Development of a benchtop baking method for chemically leavened crackers. II. Validation of the method

Science.gov (United States)

A benchtop baking method has been developed to predict the contribution of gluten functionality to overall flour performance for chemically leavened crackers. Using a diagnostic formula and procedure, dough rheology was analyzed to evaluate the extent of gluten development during mixing and machinin...

Developing an Engineering Design Process Assessment using Mixed Methods.

Science.gov (United States)

Wind, Stefanie A; Alemdar, Meltem; Lingle, Jeremy A; Gale, Jessica D; Moore, Roxanne A

Recent reforms in science education worldwide include an emphasis on engineering design as a key component of student proficiency in the Science, Technology, Engineering, and Mathematics disciplines. However, relatively little attention has been directed to the development of psychometrically sound assessments for engineering. This study demonstrates the use of mixed methods to guide the development and revision of K-12 Engineering Design Process (EDP) assessment items. Using results from a middle-school EDP assessment, this study illustrates the combination of quantitative and qualitative techniques to inform item development and revisions. Overall conclusions suggest that the combination of quantitative and qualitative evidence provides an in-depth picture of item quality that can be used to inform the revision and development of EDP assessment items. Researchers and practitioners can use the methods illustrated here to gather validity evidence to support the interpretation and use of new and existing assessments.

Analytical investigations closer to the patient.

OpenAIRE

Watson, D

1980-01-01

Do-it-yourself bioanalytical equipment that requires no analytical skill to operate is currently available for use in intensive care units, operating suites, side wards, health centres, clinics, general practitioners' surgeries, etc. Agreement is needed between the laboratory consultant and doctors and others using laboratory-type equipment and reagents in near-bedside analyses for diagnosis, clinical management, or health screening of their patients. Choice and safety of method procedure, op...

Development of reliability centered maintenance methods and tools

International Nuclear Information System (INIS)

Jacquot, J.P.; Dubreuil-Chambardel, A.; Lannoy, A.; Monnier, B.

1992-12-01

This paper recalls the development of the RCM (Reliability Centered Maintenance) approach in the nuclear industry and describes the trial study implemented by EDF in the context of the OMF (RCM) Project. The approach developed is currently being applied to about thirty systems (Industrial Project). On a parallel, R and D efforts are being maintained to improve the selectivity of the analysis methods. These methods use Probabilistic Safety Study models, thereby guaranteeing better selectivity in the identification of safety critical elements and enhancing consistency between Maintenance and Safety studies. They also offer more detailed analysis of operation feedback, invoking for example Bayes' methods combining expert judgement and feedback data. Finally, they propose a functional and material representation of the plant. This dual representation describes both the functions assured by maintenance provisions and the material elements required for their implementation. In the final chapter, the targets of the future OMF workstation are summarized and the latter's insertion in the EDF information system is briefly described. (authors). 5 figs., 2 tabs., 7 refs

Tyrosine-Nitrated Proteins: Proteomic and Bioanalytical Aspects.

Science.gov (United States)

Batthyány, Carlos; Bartesaghi, Silvina; Mastrogiovanni, Mauricio; Lima, Analía; Demicheli, Verónica; Radi, Rafael

2017-03-01

"Nitroproteomic" is under active development, as 3-nitrotyrosine in proteins constitutes a footprint left by the reactions of nitric oxide-derived oxidants that are usually associated to oxidative stress conditions. Moreover, protein tyrosine nitration can cause structural and functional changes, which may be of pathophysiological relevance for human disease conditions. Biological protein tyrosine nitration is a free radical process involving the intermediacy of tyrosyl radicals; in spite of being a nonenzymatic process, nitration is selectively directed toward a limited subset of tyrosine residues. Precise identification and quantitation of 3-nitrotyrosine in proteins has represented a "tour de force" for researchers. Recent Advances: A small number of proteins are preferential targets of nitration (usually less than 100 proteins per proteome), contrasting with the large number of proteins modified by other post-translational modifications such as phosphorylation, acetylation, and, notably, S-nitrosation. Proteomic approaches have revealed key features of tyrosine nitration both in vivo and in vitro, including selectivity, site specificity, and effects in protein structure and function. Identification of 3-nitrotyrosine-containing proteins and mapping nitrated residues is challenging, due to low abundance of this oxidative modification in biological samples and its unfriendly behavior in mass spectrometry (MS)-based technologies, that is, MALDI, electrospray ionization, and collision-induced dissociation. The use of (i) classical two-dimensional electrophoresis with immunochemical detection of nitrated proteins followed by protein ID by regular MS/MS in combination with (ii) immuno-enrichment of tyrosine-nitrated peptides and (iii) identification of nitrated peptides by a MIDAS™ experiment is arising as a potent methodology to unambiguously map and quantitate tyrosine-nitrated proteins in vivo. Antioxid. Redox Signal. 26, 313-328.

Research Circles - a method for developing guidance practices

DEFF Research Database (Denmark)

2012-01-01

This video reports on our work with using research circles to improve our understanding of how to provide guidance and counseling to help young people in danger of dropping out of school. The video is based on the paper: Research Circles -- a method for developing guidance practices, and was pres......This video reports on our work with using research circles to improve our understanding of how to provide guidance and counseling to help young people in danger of dropping out of school. The video is based on the paper: Research Circles -- a method for developing guidance practices......, and was presented at the Conference for Social Justice, Prosperity and Sustainable Employment 2012 by assistant professor Helle Merete Nordentoft from DPU (http://edu.au.dk/). The film communicating the research paper was created by Mie Nørgaard...

Development and application of a biorelevant dissolution method using USP apparatus 4 in early phase formulation development.

Science.gov (United States)

Fang, Jiang B; Robertson, Vivian K; Rawat, Archana; Flick, Tawnya; Tang, Zhe J; Cauchon, Nina S; McElvain, James S

2010-10-04

Dissolution testing is frequently used to determine the rate and extent at which a drug is released from a dosage form, and it plays many important roles throughout drug product development. However, the traditional dissolution approach often emphasizes its application in quality control testing and usually strives to obtain 100% drug release. As a result, dissolution methods are not necessarily biorelevant and meaningful application of traditional dissolution methods in the early phases of drug product development can be very limited. This article will describe the development of a biorelevant in vitro dissolution method using USP apparatus 4, biorelevant media, and real-time online UV analysis. Several case studies in the areas of formulation selection, lot-to-lot variability, and food effect will be presented to demonstrate the application of this method in early phase formulation development. This biorelevant dissolution method using USP apparatus 4 provides a valuable tool to predict certain aspects of the in vivo drug release. It can be used to facilitate the formulation development/selection for pharmacokinetic (PK) and clinical studies. It may also potentially be used to minimize the number of PK studies, and to aid in the design of more efficient PK and clinical studies.

Preliminary Tests For Development Of A Non-Pertechnetate Analysis Method

Energy Technology Data Exchange (ETDEWEB)

Diprete, D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); McCabe, D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2016-09-28

The objective of this task was to develop a non-pertechnetate analysis method that 222-S lab could easily implement. The initial scope involved working with 222-S laboratory personnel to adapt the existing Tc analytical method to fractionate the non-pertechnetate and pertechnetate. SRNL then developed and tested a method using commercial sorbents containing Aliquat^® 336 to extract the pertechnetate (thereby separating it from non-pertechnetate), followed by oxidation, extraction, and stripping steps, and finally analysis by beta counting and Mass Spectroscopy. Several additional items were partially investigated, including impacts of a ¹³⁷Cs removal step. The method was initially tested on SRS tank waste samples to determine its viability. Although SRS tank waste does not contain non-pertechnetate, testing with it was useful to investigate the compatibility, separation efficiency, interference removal efficacy, and method sensitivity.

Development of modelling method selection tool for health services management: from problem structuring methods to modelling and simulation methods.

Science.gov (United States)

Jun, Gyuchan T; Morris, Zoe; Eldabi, Tillal; Harper, Paul; Naseer, Aisha; Patel, Brijesh; Clarkson, John P

2011-05-19

There is an increasing recognition that modelling and simulation can assist in the process of designing health care policies, strategies and operations. However, the current use is limited and answers to questions such as what methods to use and when remain somewhat underdeveloped. The aim of this study is to provide a mechanism for decision makers in health services planning and management to compare a broad range of modelling and simulation methods so that they can better select and use them or better commission relevant modelling and simulation work. This paper proposes a modelling and simulation method comparison and selection tool developed from a comprehensive literature review, the research team's extensive expertise and inputs from potential users. Twenty-eight different methods were identified, characterised by their relevance to different application areas, project life cycle stages, types of output and levels of insight, and four input resources required (time, money, knowledge and data). The characterisation is presented in matrix forms to allow quick comparison and selection. This paper also highlights significant knowledge gaps in the existing literature when assessing the applicability of particular approaches to health services management, where modelling and simulation skills are scarce let alone money and time. A modelling and simulation method comparison and selection tool is developed to assist with the selection of methods appropriate to supporting specific decision making processes. In particular it addresses the issue of which method is most appropriate to which specific health services management problem, what the user might expect to be obtained from the method, and what is required to use the method. In summary, we believe the tool adds value to the scarce existing literature on methods comparison and selection.

Epistemological Development and Judgments and Reasoning about Teaching Methods

Science.gov (United States)

Spence, Sarah; Helwig, Charles C.

2013-01-01

Children's, adolescents', and adults' (N = 96 7-8, 10-11, and 13-14-year-olds and university students) epistemological development and its relation to judgments and reasoning about teaching methods was examined. The domain (scientific or moral), nature of the topic (controversial or noncontroversial), and teaching method (direct instruction by…

The development of water quality methods within ecological ...

African Journals Online (AJOL)

The development of water quality methods within ecological Reserve ... Water Act (NWA, No 36 of 1998), the ecological Reserve is defined as the quality and quantity ... provide ecologically important flow-related habitat, or geomorphological ...

Development of Analytical Method for Detection of Some ...

African Journals Online (AJOL)

All rights reserved. ... 3Centre for Water Research and Analysis (ALIR), Faculty of Science and Technology, Universiti Kebangsaan (UKM), ... Purpose: To develop and validate a simple method using solid – phase extraction along with liquid.

An interlaboratory transfer of a multi-analyte assay between continents.

Science.gov (United States)

Georgiou, Alexandra; Dong, Kelly; Hughes, Stephen; Barfield, Matthew

2015-01-01

Alex has worked at GlaxoSmithKline for the past 15 years and currently works within the bioanalytical and toxicokinetic group in the United Kingdom. Alex's role in previous years has been the in-house support of preclinical and clinical bioanalysis, from method development through to sample analysis activities as well as acting as PI for GLP bioanalysis and toxicokinetics. For the past two years, Alex has applied this analytical and regulatory experience to focus on the outsourcing of preclinical bioanalysis, toxicokinetics and clinical bioanalysis, working closely with multiple bioanalytical and in-life CRO partners worldwide. Alex works to support DMPK and Safety Assessment outsourcing activities for GSK across multiple therapeutic areas, from the first GLP study through to late stage clinical PK studies. Transfer and cross-validation of an existing analytical assay between a laboratory providing current analytical support, and a laboratory needed for new or additional support, can present the bioanalyst with numerous challenges. These challenges can be technical or logistical in nature and may prove to be significant when transferring an assay between laboratories in different continents. Part of GlaxoSmithKline's strategy to improve confidence in providing quality data, is to cross-validate between laboratories. If the cross-validation fails predefined acceptance criteria, then a subsequent investigation would follow. This may also prove to be challenging. The importance of thorough planning and good communication throughout assay transfer, cross-validation and any subsequent investigations is illustrated in this case study.

Chromatographic separation of piracetam and its metabolite in a mixture of microsomal preparations, followed by an MS/MS analysis.

Science.gov (United States)

Sahu, Kapendra; Siddiqui, Anees A; Shaharyar, Mohammad; Ahmad, Niyaz; Anwar, Mohammad; Ahmad, Farhan J

2013-07-01

A rapid bioanalytical method was evaluated for the simultaneous determination of piracetam and its metabolite (M1) in human microsomal preparations by fast ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). In addition, a validated method of M1 in rat plasma was developed and successfully applied on pharmacokinetic studies. The present study was carried out to determine the metabolic pathways of piracetam for phase I metabolism and used cytochrome P450 isoforms responsible for the piracetam metabolism in human liver microsomes (HLMs). While additional potential metabolites of piracetam were suggested by computer-modeling. The resulting 2-(2-oxopyrrolidin-1-yl) acetic acid was the sole metabolite detected after the microsomal treatment. The amide hydrolysis mainly underwent to form a metabolite i.e., 2-(2-oxopyrrolidin-1-yl) acetic acid (M1). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Research on pre-staining gel electrophoresis

International Nuclear Information System (INIS)

Zhong Ruibo; Liu Yushuang; Zhang Ping; Liu Jingran; Zhao Guofen; Zhang Feng

2014-01-01

Background: Gel electrophoresis is a powerful biochemical separation technique. Most biological molecules are completely transparent in the visible region of light, so it is necessary to use staining to show the results after gel electrophoresis, and the general steps of conventional staining methods are time-consuming. Purpose: We try to develop a novel approach to simplify the gel electrophoresis: Pre-Staining Gel Electrophoresis (PSGE), which can make the gel electrophoresis results monitored in real time. Methods: Pre-stain the protein samples with Coomassie Brilliant Blue (CBB) for 30 min before loading the sample into the gel well. Results and Conclusion: PSGE can be successfully used to analyze the binding efficiency of Bovine Serum Albumin (BSA) and amphiphilic polymer via chemical coupling and physical absorption, and the double PSGE also shows a great potential in bio-analytical chemistry. (authors)

Investigation of the effect of plasma albumin levels on regorafenib-induced hepatotoxicity using a validated liquid chromatography-tandem mass spectrometry method.

Science.gov (United States)

Pang, Yi Yun; Tan, Yeong Lan; Ho, Han Kiat

2017-09-01

Regorafenib is an oral multikinase inhibitor indicated for metastatic colorectal cancer and gastrointestinal stromal tumour. Due to its extensive plasma protein binding and low calculated hepatic extraction ratio, the hepatotoxicity observed with usage of the drug may be related to its plasma exposure. To investigate the highly dynamic free:bound drug concentration for regorafenib in the plasma, a bioanalytical liquid chromatography-tandem mass spectrometric assay was developed and validated in human plasma. The concentration range of the assay was 2-1000ng/mL. Sample preparation was via protein precipitation using acetonitrile with sorafenib as the internal standard. The supernatant was injected into an ultra-performance liquid chromatographic system coupled to a triple quadrupole mass spectrometer. The analytes were separated on an AQUITY UPLC BEH C 18 column (120Å, 1.7μm, 2.1mm×50mm) and eluted with a gradient elution system. The ions were detected in multiple reaction monitoring mode. The linearity, lower limit of quantification, intra-day and inter-day precision and accuracy conformed to FDA guidelines. The validated method was successfully applied to determine the effect of albumin levels in plasma on the extent of protein binding of regorafenib. The results indicated that physiologically-relevant levels of albumin were found to have no significant effect on the extent of protein binding of regorafenib, hence imposing minimal effect on drug disposition. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a general method for photovoltaic system analysis

Energy Technology Data Exchange (ETDEWEB)

Nolay, P

1987-01-01

The photovoltaic conversion for energetic applications is now widely used, but its development still needs the resolution of many problems for the sizing and for the real working of the installations. The precise analysis of the components and whole system behaviour has led to the development of accurate models for the simulation of such systems. From this modelling phase, a simulation code has been built. The validation of this software has been achieved from experimental test measurements. Since the quality of the software depends on the precision of the input data, an original method of determination of component characteristics, by means of model identification, has been developed. These tools permit the prediction of system behaviour and the dynamic simulation of systems under real conditions. Used for the study of photovoltaic system sizing, this software has allowed the definition of new concepts which will serve as a basis for the development of a sizing method.

Electrochemical sensor for multiplex screening of genetically modified DNA: identification of biotech crops by logic-based biomolecular analysis.

Science.gov (United States)

Liao, Wei-Ching; Chuang, Min-Chieh; Ho, Ja-An Annie

2013-12-15

Genetically modified (GM) technique, one of the modern biomolecular engineering technologies, has been deemed as profitable strategy to fight against global starvation. Yet rapid and reliable analytical method is deficient to evaluate the quality and potential risk of such resulting GM products. We herein present a biomolecular analytical system constructed with distinct biochemical activities to expedite the computational detection of genetically modified organisms (GMOs). The computational mechanism provides an alternative to the complex procedures commonly involved in the screening of GMOs. Given that the bioanalytical system is capable of processing promoter, coding and species genes, affirmative interpretations succeed to identify specified GM event in terms of both electrochemical and optical fashions. The biomolecular computational assay exhibits detection capability of genetically modified DNA below sub-nanomolar level and is found interference-free by abundant coexistence of non-GM DNA. This bioanalytical system, furthermore, sophisticates in array fashion operating multiplex screening against variable GM events. Such a biomolecular computational assay and biosensor holds great promise for rapid, cost-effective, and high-fidelity screening of GMO. Copyright © 2013 Elsevier B.V. All rights reserved.

Development and validation of a spectroscopic method for the ...

African Journals Online (AJOL)

Tropical Journal of Pharmaceutical Research ... Purpose: To develop a new analytical method for the quantitative analysis of miconazole ... a simple, reliable and robust method for the characterization of a mixture of the drugs in a dosage form. ... By Country · List All Titles · Free To Read Titles This Journal is Open Access.

[Adverse events management. Methods and results of a development project].

Science.gov (United States)

Rabøl, Louise Isager; Jensen, Elisabeth Brøgger; Hellebek, Annemarie H; Pedersen, Beth Lilja

2006-11-27

This article describes the methods and results of a project in the Copenhagen Hospital Corporation (H:S) on preventing adverse events. The aim of the project was to raise awareness about patients' safety, test a reporting system for adverse events, develop and test methods of analysis of events and propagate ideas about how to prevent adverse events. H:S developed an action plan and a reporting system for adverse events, founded an organization and developed an educational program on theories and methods of learning from adverse events for both leaders and employees. During the three-year period from 1 January 2002 to 31 December 2004, the H:S staff reported 6011 adverse events. In the same period, the organization completed 92 root cause analyses. More than half of these dealt with events that had been optional to report, the other half events that had been mandatory to report. The number of reports and the front-line staff's attitude towards reporting shows that the H:S succeeded in founding a safety culture. Future work should be centred on developing and testing methods that will prevent adverse events from happening. The objective is to suggest and complete preventive initiatives which will help increase patient safety.

developed algorithm for the application of british method of concret

African Journals Online (AJOL)

t-iyke

Most of the methods of concrete mix design developed over the years were geared towards manual approach. ... Key words: Concrete mix design; British method; Manual Approach; Algorithm. ..... Statistics for Science and Engineering.

Some recent developments of the immersed interface method for flow simulation

Science.gov (United States)

Xu, Sheng

2017-11-01

The immersed interface method is a general methodology for solving PDEs subject to interfaces. In this talk, I will give an overview of some recent developments of the method toward the enhancement of its robustness for flow simulation. In particular, I will present with numerical results how to capture boundary conditions on immersed rigid objects, how to adopt interface triangulation in the method, and how to parallelize the method for flow with moving objects. With these developments, the immersed interface method can achieve accurate and efficient simulation of a flow involving multiple moving complex objects. Thanks to NSF for the support of this work under Grant NSF DMS 1320317.

Bioanalysis Young Investigator: Sadagopan Krishnan.

Science.gov (United States)

Krishnan, Sadagopan

2011-05-01

Supervisor's supporting comments. I am pleased to recommend Sadagopan Krishnan for the Bioanalysis Young Investigator award. Sadagopan is a bright, creative and highly-motivated young bioanalytical chemist. His theses in our laboratory involved the development of electrochemiluminescent arrays for chemical toxicity screening utilizing cytochrome P450 metalloenzymes. He was senior author of a paper in Analytical Chemistry on this that was featured on the cover. He also investigated fundamental properties of human metabolic cytochrome P450s - research was carried out at his own initiative, and explains for the first time the role of iron spin state on enzyme electron transfer rates. He then developed thin films that mimic the natural cytochrome P450 redox cycle for the first time. He worked with several other group members to develop a superparamagnetic labeling scheme for immunosensing of proteins by surface plasmon resonance at unprecedented low levels, down to 10 fg/ml. Sadagopan has also demonstrated strong leadership skills. After his PhD, Sadagopan joined the group of Fraser Armstrong at Oxford University, UK, as a postdoctoral fellow. He is currently expanding his research horizons into the area of biofuel cells. His eventual goal is to join the faculty of a major university and build a world-class research group in bioanalytical chemistry.

The science of laboratory and project management in regulated bioanalysis.

Science.gov (United States)

Unger, Steve; Lloyd, Thomas; Tan, Melvin; Hou, Jingguo; Wells, Edward

2014-05-01

Pharmaceutical drug development is a complex and lengthy process, requiring excellent project and laboratory management skills. Bioanalysis anchors drug safety and efficacy with systemic and site of action exposures. Development of scientific talent and a willingness to innovate or adopt new technology is essential. Taking unnecessary risks, however, should be avoided. Scientists must strategically assess all risks and find means to minimize or negate them. Laboratory Managers must keep abreast of ever-changing technology. Investments in instrumentation and laboratory design are critical catalysts to efficiency and safety. Matrix management requires regular communication between Project Managers and Laboratory Managers. When properly executed, it aligns the best resources at the right times for a successful outcome. Attention to detail is a critical aspect that separates excellent laboratories. Each assay is unique and requires attention in its development, validation and execution. Methods, training and facilities are the foundation of a bioanalytical laboratory.

Development of nondestructive evaluation methods for structural ceramics

International Nuclear Information System (INIS)

Ellingson, W.A.; Roberts, R.A.; Vannier, M.W.; Ackerman, J.L.; Sawicka, B.D.; Gronemeyer, S.; Kriz, R.J.

1987-01-01

Advanced nondestructive evaluation methods are being developed to characterize ceramic materials and allow improvement of process technology. If one can spatially determine porosity, map organic binder/plasticizer distributions, measure average through-volume and in-plane density, as well as detect inclusions, process and machining operations may be modified to enhance the reliability of ceramics. Two modes of X-ray tomographic imaging -- advanced film (analog) tomography and computed tomography -- are being developed to provide flaw detection and density profile mapping capability. Nuclear magnetic resonance imaging is being developed to determine porosity and map the distribution of organic binder/plasticizer. Ultrasonic backscatter and through-transmission are being developed to measure average through-thickness densities and detect surface inclusions

Agile methods in biomedical software development: a multi-site experience report

Directory of Open Access Journals (Sweden)

Kuhlmman Karl F

2006-05-01

Full Text Available Abstract Background Agile is an iterative approach to software development that relies on strong collaboration and automation to keep pace with dynamic environments. We have successfully used agile development approaches to create and maintain biomedical software, including software for bioinformatics. This paper reports on a qualitative study of our experiences using these methods. Results We have found that agile methods are well suited to the exploratory and iterative nature of scientific inquiry. They provide a robust framework for reproducing scientific results and for developing clinical support systems. The agile development approach also provides a model for collaboration between software engineers and researchers. We present our experience using agile methodologies in projects at six different biomedical software development organizations. The organizations include academic, commercial and government development teams, and included both bioinformatics and clinical support applications. We found that agile practices were a match for the needs of our biomedical projects and contributed to the success of our organizations. Conclusion We found that the agile development approach was a good fit for our organizations, and that these practices should be applicable and valuable to other biomedical software development efforts. Although we found differences in how agile methods were used, we were also able to identify a set of core practices that were common to all of the groups, and that could be a focus for others seeking to adopt these methods.

Analytical Methods Development in Support of the Caustic Side Solvent Extraction System

International Nuclear Information System (INIS)

Maskarinec, M.P.

2001-01-01

The goal of the project reported herein was to develop and apply methods for the analysis of the major components of the solvent system used in the Caustic-Side Solvent Extraction Process (CSSX). These include the calix(4)arene, the modifier, 1-(2,2,3,3- tetrafluoropropoxy)-3-(4-sec-butylphenoxy)-2-propanol and tri-n-octylamine. In addition, it was an objective to develop methods that would allow visualization of other components under process conditions. These analyses would include quantitative laboratory methods for each of the components, quantitative analysis of expected breakdown products (4-see-butylphenol and di-n-octylamine), and qualitative investigations of possible additional breakdown products under a variety of process extremes. These methods would also provide a framework for process analysis should a pilot facility be developed. Two methods were implemented for sample preparation of aqueous phases. The first involves solid-phase extraction and produces quantitative recovery of the solvent components and degradation products from the various aqueous streams. This method can be automated and is suitable for use in radiation shielded facilities. The second is a variation of an established EPA liquid-liquid extraction procedure. This method is also quantitative and results in a final extract amenable to virtually any instrumental analysis. Two HPLC methods were developed for quantitative analysis. The first is a reverse-phase system with variable wavelength W detection. This method is excellent from a quantitative point of view. The second method is a size-exclusion method coupled with dual UV and evaporative light scattering detectors. This method is much faster than the reverse-phase method and allows for qualitative analysis of other components of the waste. For tri-n-octylamine and other degradation products, a GC method was developed and subsequently extended to GUMS. All methods have precision better than 5%. The combination of these methods

System Identification Methods for Aircraft Flight Control Development and Validation

Science.gov (United States)

1995-10-01

System-identification methods compose a mathematical model, or series of models, : from measurements of inputs and outputs of dynamic systems. This paper : discusses the use of frequency-domain system-identification methods for the : development and ...

Development of in vitro assay method with radioisotope

International Nuclear Information System (INIS)

Choi, Chang Woon; Lim, S. M.; An, S. H.; Woo, K. S.; Chung, W. S.; Lim, S. J.; Hong, S. W.; Oh, O. D.

1999-04-01

Radioimmunoassay (RIA) and related competitive protein-binding methods began a little over 20 years ago as a cumbersome research methodology in a few specialized laboratories. Endocrinology has been greatly enriched by the new knowledge that has come as a direct result of RIA methods. Establishment of the taxol RIA system will be expected to develop RIA for drug monitoring. Scintillation proximity assay was useful since any separation step is not required, it has the advantage of dealing with multiple samples. The increased sensitivity of the new assay in determining HCV RT([ 125 I]dUTP) suggests that it would be worth investigating whether the system can be applied to analysis. [ 125 I] lodotyramine with 98.5% radiochemical purity. Optimal background counts was certificated using varied radioactivity of radionuclides. Appropriate standard curve was obtained from SPA method successively, and the concentration of hCG from unknown serum was determined by standard curve. The result concentration of hCG from unknown serum was determined by synthesized successively and purified by HPLC system. Hybridoma reducing monoclonal anti thyroglobulin antibodies titer is measured by ELISA. These studies play an important role in development of in vitro assay with radionuclides

Development of in vitro assay method with radioisotope

Energy Technology Data Exchange (ETDEWEB)

Choi, Chang Woon; Lim, S. M.; An, S. H.; Woo, K. S.; Chung, W. S.; Lim, S. J.; Hong, S. W. [Korea Atomic Energy Research Institute. Korea Cancer Center Hospital, Seoul (Korea, Republic of); Oh, O. D. [Yonsei University, Seoul (Korea, Republic of)

1999-04-01

Radioimmunoassay (RIA) and related competitive protein-binding methods began a little over 20 years ago as a cumbersome research methodology in a few specialized laboratories. Endocrinology has been greatly enriched by the new knowledge that has come as a direct result of RIA methods. Establishment of the taxol RIA system will be expected to develop RIA for drug monitoring. Scintillation proximity assay was useful since any separation step is not required, it has the advantage of dealing with multiple samples. The increased sensitivity of the new assay in determining HCV RT([{sup 125}I]dUTP) suggests that it would be worth investigating whether the system can be applied to analysis. [{sup 125}I] lodotyramine with 98.5% radiochemical purity. Optimal background counts was certificated using varied radioactivity of radionuclides. Appropriate standard curve was obtained from SPA method successively, and the concentration of hCG from unknown serum was determined by standard curve. The result concentration of hCG from unknown serum was determined by synthesized successively and purified by HPLC system. Hybridoma reducing monoclonal anti thyroglobulin antibodies titer is measured by ELISA. These studies play an important role in development of in vitro assay with radionuclides.

Waste Tank Organic Safety Program: Analytical methods development. Progress report, FY 1994

International Nuclear Information System (INIS)

Campbell, J.A.; Clauss, S.A.; Grant, K.E.

1994-09-01

The objectives of this task are to develop and document extraction and analysis methods for organics in waste tanks, and to extend these methods to the analysis of actual core samples to support the Waste Tank organic Safety Program. This report documents progress at Pacific Northwest Laboratory (a) during FY 1994 on methods development, the analysis of waste from Tank 241-C-103 (Tank C-103) and T-111, and the transfer of documented, developed analytical methods to personnel in the Analytical Chemistry Laboratory (ACL) and 222-S laboratory. This report is intended as an annual report, not a completed work

A method for determining the actual rate of orientation switching of DNA self-assembled monolayers using optical and electrochemical frequency response analysis.

Science.gov (United States)

Casanova-Moreno, J; Bizzotto, D

2015-02-17

Electrostatic control of the orientation of fluorophore-labeled DNA strands immobilized on an electrode surface has been shown to be an effective bioanalytical tool. Modulation techniques and later time-resolved measurements were used to evaluate the kinetics of the switching between lying and standing DNA conformations. These measurements, however, are the result of a convolution between the DNA "switching" response time and the other frequency limited responses in the measurement. In this work, a method for analyzing the response of a potential driven DNA sensor is presented by calculating the potential effectively dropped across the electrode interface (using electrochemical impedance spectroscopy) as opposed to the potential applied to the electrochemical cell. This effectively deconvolutes the effect of the charging time on the observed frequency response. The corrected response shows that DNA is able to switch conformation faster than previously reported using modulation techniques. This approach will ensure accurate measurements independent of the electrochemical system, removing the uncertainty in the analysis of the switching response, enabling comparison between samples and measurement systems.

Miniaturized tools and devices for bioanalytical applications: an overview

DEFF Research Database (Denmark)

Chudy, M.; Grabowska, I.; Ciosek, P.

2009-01-01

This article presents an overview of various miniaturized devices and technologies developed by our group. Innovative, fast and cheap procedures for the fabrication of laboratory microsystems based on commercially available materials are reported and compared with well-established microfabricatio...... optic detectors, potentiometric sensors platforms, microreactors and capillary electrophoresis (CE) microchips as well as integrated microsystems e. g. double detection microanalytical systems, devices for studying enzymatic reactions and a microsystem for cell culture and lysis....

Development of power change maneuvering method for BWR

International Nuclear Information System (INIS)

Fukuzaki, Takaharu; Yamada, Naoyuki; Kiguchi, Takashi; Sakurai, Mikio.

1985-01-01

A power change maneuvering method for BWR has been proposed to generate an optimal power control maneuver, which realizes the power change operation closest to a power change demand pattern under operating constraints. The method searches for the maneuver as an optimization problem, where the variables are thermal power levels sampled from the demand pattern, the performance index is defined to express the power mismatch between demand and feasible patterns, and the constraints are limit lines on the thermal power-core flow rate map and limits on keeping fuel integrity. The usable feasible direction method is utilized as the optimization algorithm, with newly developed techniques for initial value generation and step length determination, which apply one-dimensional search and inverse-interpolation methods, respectively, to realize the effective search of the optimal solution. Simulation results show that a typical computing time is about 5 min by a general purpose computer and the method has been verified to be practical even for on-line use. (author)

Flammable gas safety program. Analytical methods development: FY 1994 progress report

International Nuclear Information System (INIS)

Campbell, J.A.; Clauss, S.; Grant, K.; Hoopes, V.; Lerner, B.; Lucke, R.; Mong, G.; Rau, J.; Wahl, K.; Steele, R.

1994-09-01

This report describes the status of developing analytical methods to account for the organic components in Hanford waste tanks, with particular focus on tanks assigned to the Flammable Gas Watch List. The methods that have been developed are illustrated by their application to samples obtained from Tank 241-SY-101 (Tank 101-SY)

In silico machine learning methods in drug development.

Science.gov (United States)

Dobchev, Dimitar A; Pillai, Girinath G; Karelson, Mati

2014-01-01

Machine learning (ML) computational methods for predicting compounds with pharmacological activity, specific pharmacodynamic and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties are being increasingly applied in drug discovery and evaluation. Recently, machine learning techniques such as artificial neural networks, support vector machines and genetic programming have been explored for predicting inhibitors, antagonists, blockers, agonists, activators and substrates of proteins related to specific therapeutic targets. These methods are particularly useful for screening compound libraries of diverse chemical structures, "noisy" and high-dimensional data to complement QSAR methods, and in cases of unavailable receptor 3D structure to complement structure-based methods. A variety of studies have demonstrated the potential of machine-learning methods for predicting compounds as potential drug candidates. The present review is intended to give an overview of the strategies and current progress in using machine learning methods for drug design and the potential of the respective model development tools. We also regard a number of applications of the machine learning algorithms based on common classes of diseases.

Development of two dimensional electrophoresis method using single chain DNA

International Nuclear Information System (INIS)

Ikeda, Junichi; Hidaka, So

1998-01-01

By combining a separation method due to molecular weight and a method to distinguish difference of mono-bases, it was aimed to develop a two dimensional single chain DNA labeled with Radioisotope (RI). From electrophoretic pattern difference of parent and variant strands, it was investigated to isolate the root module implantation control gene. At first, a Single Strand Conformation Polymorphism (SSCP) method using concentration gradient gel was investigated. As a result, it was formed that intervals between double chain and single chain DNAs expanded, but intervals of both single chain DNAs did not expand. On next, combination of non-modified acrylic amide electrophoresis method and Denaturing Gradient-Gel Electrophoresis (DGGE) method was examined. As a result, hybrid DNA developed by two dimensional electrophoresis arranged on two lines. But, among them a band of DNA modified by high concentration of urea could not be found. Therefore, in this fiscal year's experiments, no preferable result could be obtained. By the used method, it was thought to be impossible to detect the differences. (G.K.)

Development of environmental risk assessment framework using index method

International Nuclear Information System (INIS)

Ali, M.W.; Wu, Y.

2000-01-01

This paper presents a newly developed framework for assessing the risk from events which are considered to be major accidents to the environment according to the classifications by the United Kingdom Department of Environment (DoE). The application of an environmental risk assessment framework using the newly developed index method is demonstrated by means of a case study. The framework makes use of Environmental Hazard Index (EHI) method by the United Kingdom AEA Technology for releases to river, but improves it by taking account to toxic dose rather than concentration; taking account of long-term effects including persistence and bio accumulation, not just short term effects; extending the method to all aspects of environment, not just rivers; and allowing account to be taken of design changes to mitigate the risk. The development of the framework has also led to a revision of the tolerability criteria to be used with the framework proposed earlier by weakness and recommend further work to improve this newly proposed environmental risk assessment framework. From the study, it is recommended that the environmental risk assessment framework be applied to a wide range of other case studies in order to further improve it. The framework should be modified to maintain consistency when the DoE revises its definitions of major accidents to the environment. Ease-of-use of the framework (and any other environmental framework) would be aided by the compilation of databases for environmental toxicity, river data and available consequence models. Further work could also be done to suggest methods of mitigating the risk and including them as numerical factors within method. (author)

Development of headspace solid-phase microextraction method for ...

African Journals Online (AJOL)

A headspace solid-phase microextraction (HS-SPME) method was developed as a preliminary investigation using univariate approach for the analysis of 14 multiclass pesticide residues in fruits and vegetable samples. The gas chromatography mass spectrometry parameters (desorption temperature and time, column flow ...

A novel HPLC-MS/MS method for the simultaneous determination of astemizole and its major metabolite in dog or monkey plasma and application to pharmacokinetics.

Science.gov (United States)

Back, Hyun-moon; Lee, Jong-Hwa; Chae, Jung-woo; Song, Byungjeong; Seo, Joung-Wook; Yun, Hwi-yeol; Kwon, Kwang-il

2015-10-10

Astemizole (AST), a second-generation antihistamine, is metabolized to desmethyl astemizole (DEA), and although it has been removed from the market for inducing QT interval prolongation, it has reemerged as a potential anticancer and antimalarial agent. This report describes a novel high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneously determining the concentrations of AST and DEA in beagle dog and cynomolgus monkey plasma with simple preparation method and short retention time. Prior to HPLC analyses, the plasma samples were extracted with simple liquid-liquid extraction method. The isocratic mobile phase was 0.025% trifluoroacetic acid (TFA dissolved in acetonitrile) and 20 mM ammonium acetate (94:6) at a flow rate of 0.25 mL/min and diphenhydramine used as internal standard. In MS/MS analyses, precursor ions of the analytes were optimized as protonated molecular ions: [M+H](+). The lower limit of quantification of astemizole was 2.5 ng/mL in both species and desmethyl astemizole were 7.5 ng/mL and 10 ng/mL in dog and monkey plasma, respectively. The accuracy, precision, and stability of the method were in accordance with FDA guidelines for the validation of bioanalytical methods. Finally this validated method was successfully applied to a pharmacokinetic study in dogs and monkeys after oral administration of 10 mg/kg AST. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of motion image prediction method using principal component analysis

International Nuclear Information System (INIS)

Chhatkuli, Ritu Bhusal; Demachi, Kazuyuki; Kawai, Masaki; Sakakibara, Hiroshi; Kamiaka, Kazuma

2012-01-01

Respiratory motion can induce the limit in the accuracy of area irradiated during lung cancer radiation therapy. Many methods have been introduced to minimize the impact of healthy tissue irradiation due to the lung tumor motion. The purpose of this research is to develop an algorithm for the improvement of image guided radiation therapy by the prediction of motion images. We predict the motion images by using principal component analysis (PCA) and multi-channel singular spectral analysis (MSSA) method. The images/movies were successfully predicted and verified using the developed algorithm. With the proposed prediction method it is possible to forecast the tumor images over the next breathing period. The implementation of this method in real time is believed to be significant for higher level of tumor tracking including the detection of sudden abdominal changes during radiation therapy. (author)

[Development and current situation of reconstruction methods following total sacrectomy].

Science.gov (United States)

Huang, Siyi; Ji, Tao; Guo, Wei

2018-05-01

To review the development of the reconstruction methods following total sacrectomy, and to provide reference for finding a better reconstruction method following total sacrectomy. The case reports and biomechanical and finite element studies of reconstruction following total sacrectomy at home and abroad were searched. Development and current situation were summarized. After developing for nearly 30 years, great progress has been made in the reconstruction concept and fixation techniques. The fixation methods can be summarized as the following three strategies: spinopelvic fixation (SPF), posterior pelvic ring fixation (PPRF), and anterior spinal column fixation (ASCF). SPF has undergone technical progress from intrapelvic rod and hook constructs to pedicle and iliac screw-rod systems. PPRF and ASCF could improve the stability of the reconstruction system. Reconstruction following total sacrectomy remains a challenge. Reconstruction combining SPF, PPRF, and ASCF is the developmental direction to achieve mechanical stability. How to gain biological fixation to improve the long-term stability is an urgent problem to be solved.

Development of a smart city planning support tool using the cooperative method

Directory of Open Access Journals (Sweden)

Takeshi Kobayashi

2015-12-01

Full Text Available A reduction of environmental burdens is currently required. In particular, proposing a new approach for the construction of a smart city using renewable energy is important. The technological development of a smart city is founded building equipment and infrastructure. However, planning methods and their techniques using the collaboration approach with residents are only just developing. This study aimed to develop a support tool for the construction of a smart city using renewable energy while facilitating consensus-building efforts among residents using the method for a cooperative housing development. We organized the supporting methods for the construction of residential area using the cooperative method. Then, we developed supporting tools that interface the computer with these methods. We examined the support techniques for the construction of a residential area using renewable energy technology by analyzing Japanese cases of a smart city. Moreover, we developed a support tool for the construction of a smart city on a trial basis. We integrated the smart city construction tools and the cooperative housing construction support tool. This tool has a 3D modeling system that helps residents to easily understand the space image as a result of the examination. We also developed a professional supporting tool that residents can consider for cost-effectiveness in renewable energy and its environmental load reduction rate for the planning of a smart city.

Development of medical application methods using radiation. Radionuclide therapy

International Nuclear Information System (INIS)

Choi, Chang Woon; Lim, S. M.; Kim, E.H.; Woo, K. S.; Chung, W. S.; Lim, S. J.; Choi, T. H.; Hong, S. W.; Chung, H. Y.; No, W. C.; Oh, B. H.; Hong, H. J.

1999-04-01

In this project, we studied following subjects: 1. development of monoclonal antibodies and radiopharmaceuticals 2. clinical applications of radionuclide therapy 3. radioimmunoguided surgery 4. prevention of restenosis with intracoronary radiation. The results can be applied for the following objectives: 1) radionuclide therapy will be applied in clinical practice to treat the cancer patients or other diseases in multi-center trial. 2) The newly developed monoclonal antibodies and biomolecules can be used in biology, chemistry or other basic life science research. 3) The new methods for the analysis of therapeutic effects, such as dosimetry, and quantitative analysis methods of radioactivity, can be applied in basic research, such as radiation oncology and radiation biology

Development of medical application methods using radiation. Radionuclide therapy

Energy Technology Data Exchange (ETDEWEB)

Choi, Chang Woon; Lim, S. M.; Kim, E.H.; Woo, K. S.; Chung, W. S.; Lim, S. J.; Choi, T. H.; Hong, S. W.; Chung, H. Y.; No, W. C. [Korea Atomic Energy Research Institute. Korea Cancer Center Hospital, Seoul, (Korea, Republic of); Oh, B. H. [Seoul National University. Hospital, Seoul (Korea, Republic of); Hong, H. J. [Antibody Engineering Research Unit, Taejon (Korea, Republic of)

1999-04-01

In this project, we studied following subjects: 1. development of monoclonal antibodies and radiopharmaceuticals 2. clinical applications of radionuclide therapy 3. radioimmunoguided surgery 4. prevention of restenosis with intracoronary radiation. The results can be applied for the following objectives: (1) radionuclide therapy will be applied in clinical practice to treat the cancer patients or other diseases in multi-center trial. (2) The newly developed monoclonal antibodies and biomolecules can be used in biology, chemistry or other basic life science research. (3) The new methods for the analysis of therapeutic effects, such as dosimetry, and quantitative analysis methods of radioactivity, can be applied in basic research, such as radiation oncology and radiation biology.

Developing rapid methods for analyzing upland riparian functions and values.

Science.gov (United States)

Hruby, Thomas

2009-06-01

Regulators protecting riparian areas need to understand the integrity, health, beneficial uses, functions, and values of this resource. Up to now most methods providing information about riparian areas are based on analyzing condition or integrity. These methods, however, provide little information about functions and values. Different methods are needed that specifically address this aspect of riparian areas. In addition to information on functions and values, regulators have very specific needs that include: an analysis at the site scale, low cost, usability, and inclusion of policy interpretations. To meet these needs a rapid method has been developed that uses a multi-criteria decision matrix to categorize riparian areas in Washington State, USA. Indicators are used to identify the potential of the site to provide a function, the potential of the landscape to support the function, and the value the function provides to society. To meet legal needs fixed boundaries for assessment units are established based on geomorphology, the distance from "Ordinary High Water Mark" and different categories of land uses. Assessment units are first classified based on ecoregions, geomorphic characteristics, and land uses. This simplifies the data that need to be collected at a site, but it requires developing and calibrating a separate model for each "class." The approach to developing methods is adaptable to other locations as its basic structure is not dependent on local conditions.

Simultaneous quantification of PGI2 and TXA2 metabolites in plasma and urine in NO-deficient mice by a novel UHPLC/MS/MS method.

Science.gov (United States)

Kij, Agnieszka; Mateuszuk, Lukasz; Sitek, Barbara; Przyborowski, Kamil; Zakrzewska, Agnieszka; Wandzel, Krystyna; Walczak, Maria; Chlopicki, Stefan

2016-09-10

The balance between vascular prostacyclin (PGI2) generated mainly via cyclooxygenase-2 (COX-2) and its physiological antagonist platelet-derived thromboxane A2 (TXA2) formed by cyclooxygenase-1 (COX-1) determines cardiovascular homeostasis. In the present work, a novel bioanalytical method for simultaneous quantification of stable plasma and urinary metabolites of PGI2 (6-keto-PGF1α, 2,3-dinor-6-keto-PGF1α) and TXA2 (TXB2, 2,3-dinor-TXB2) using ultra high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC/MS/MS) was developed. The method was validated using artificial plasma and urine and linearity range, intra- and inter-day precision and accuracy, recovery of analytes, relative and absolute matrix effect and stability of analytes were determined. The use of artificial biofluids improved the method sensitivity as it eliminated the contribution of endogenous metabolites present in mice plasma and urine to validation procedure. The newly developed and validated method allowed to quantify 6-keto-PGF1α and TXB2 in mice plasma as well as 2,3-dinor-6-keto-PGF1α and 2,3-dinor-TXB2 in urine samples with high sensitivity and accuracy. The calibration range was established from 0.1 to 100ng/mL for all analytes using artificial biofluids and the recoveries were greater than 89.9%. All validated parameters met the criteria of acceptance specified in FDA and EMA guidance. This method was successfully employed for profiling of the changes in PGI2 and TXA2 generation in NO-deficient mice. This work demonstrated that NO-deficiency induced by L-NAME, evidenced by a fall in nitrite in plasma and urine, was associated with platelet activation, robust increase in TXB2 and mild increase in 6-keto-PGF1α concentration in plasma. Changes in 2,3-dinor-6-keto-PGF1α and 2,3-dinor-TXB2 concentration in urine were less evident suggesting that the measurements in plasma better reflect modest changes in PGI2/TXA2 homeostasis than measurements in urine

Methods for Rapid Screening in Woody Plant Herbicide Development

Directory of Open Access Journals (Sweden)

William Stanley

2014-07-01

Full Text Available Methods for woody plant herbicide screening were assayed with the goal of reducing resources and time required to conduct preliminary screenings for new products. Rapid screening methods tested included greenhouse seedling screening, germinal screening, and seed screening. Triclopyr and eight experimental herbicides from Dow AgroSciences (DAS 313, 402, 534, 548, 602, 729, 779, and 896 were tested on black locust, loblolly pine, red maple, sweetgum, and water oak. Screening results detected differences in herbicide and species in all experiments in much less time (days to weeks than traditional field screenings and consumed significantly less resources (<500 mg acid equivalent per herbicide per screening. Using regression analysis, various rapid screening methods were linked into a system capable of rapidly and inexpensively assessing herbicide efficacy and spectrum of activity. Implementation of such a system could streamline early-stage herbicide development leading to field trials, potentially freeing resources for use in development of beneficial new herbicide products.

Emergency medicine clerkship curriculum in a high-income developing country: methods for development and application.

Science.gov (United States)

Cevik, Arif Alper; Cakal, Elif Dilek; Abu-Zidan, Fikri M

2018-06-07

The published recommendations for international emergency medicine curricula cover the content, but exclude teaching and learning methods, assessment, and evaluation. We aim to provide an overview on available emergency medicine clerkship curricula and report the development and application experience of our own curriculum. Our curriculum is an outcome-based education, enriched by e-learning and various up-to-date pedagogic principles. Teaching and learning methods, assessment, and evaluation are described. The theory behind our practice in the light of recent literature is discussed aiming to help other colleagues from developing countries to have a clear map for developing and tailoring their own curricula depending on their needs. The details of our emergency medicine clerkship will serve as an example for developing and developed countries having immature undergraduate emergency medicine clerkship curricula. However, these recommendations will differ in various settings depending on available resources. The main concept of curriculum development is to create a curriculum having learning outcomes and content relevant to the local context, and then align the teaching and learning activities, assessments, and evaluations to be in harmony. This may assure favorable educational outcome even in resource limited settings.

Development of fluorescent methods for DNA methyltransferase assay

Science.gov (United States)

Li, Yueying; Zou, Xiaoran; Ma, Fei; Tang, Bo; Zhang, Chun-yang

2017-03-01

DNA methylation modified by DNA methyltransferase (MTase) plays an important role in regulating gene transcription, cell growth and proliferation. The aberrant DNA MTase activity may lead to a variety of human diseases including cancers. Therefore, accurate and sensitive detection of DNA MTase activity is crucial to biomedical research, clinical diagnostics and therapy. However, conventional DNA MTase assays often suffer from labor-intensive operations and time-consuming procedures. Alternatively, fluorescent methods have significant advantages of simplicity and high sensitivity, and have been widely applied for DNA MTase assay. In this review, we summarize the recent advances in the development of fluorescent methods for DNA MTase assay. These emerging methods include amplification-free and the amplification-assisted assays. Moreover, we discuss the challenges and future directions of this area.

A review on syntheses, properties, characterization and bioanalytical applications of fluorescent carbon dots

International Nuclear Information System (INIS)

Zuo, Pengli; Lu, Xiuhua; Sun, Zhigang; Guo, Yuhan; He, Hua

2016-01-01

Carbon dots (C-dots) are a kind of fluorescent nanoparticles that are strongly fluorescent, non-blinking, and can be easily synthesized at low cost. Their emission color can be tuned by varying the excitation wavelength. Their properties make them strong competitors to semiconductor quantum dots. Synthetic approaches for C-dots can be classified into two categories, viz. top-down and bottom-up methods. Surface passivated and functionalized C-dots can be utilized to sense pH values, metal ions and organic molecules. Owing to their low cytotoxicity, biocompatibility and impressive photostability, long-term observations become possible. C-dots also show promise as labels and for bioimaging. This review (with 142 refs.) is divided into several sections. The first covers commonly used methods for preparation of C-dots including laser ablation, arc discharge, electrochemical methods, pyrolytic processes, template based methods, microwave assisted methods, chemical oxidation methods, reverse micelle based methods, etc. The first section also covers methods for surface functionalization and passivation. We continue by discussing the spectroscopic properties and other physical and chemical properties of C-dots (fluorescence, up-conversion fluorescence, methods for enhancing photoluminescence, effects of pH value, cytotoxicity, etc.). Another section covers the characterization including TEM and XRD. Applications in biology are summarized and subdivided into in vitro imaging, in vivo imaging, chemical probe, quantitation of biomacromolecules, but also in drug delivery, photoacoustic imaging and anticancer therapy. We finally discuss current challenges and perspectives in this promising field. (author)

Development of three-dimensional transport code by the double finite element method

International Nuclear Information System (INIS)

Fujimura, Toichiro

1985-01-01

Development of a three-dimensional neutron transport code by the double finite element method is described. Both of the Galerkin and variational methods are adopted to solve the problem, and then the characteristics of them are compared. Computational results of the collocation method, developed as a technique for the vaviational one, are illustrated in comparison with those of an Ssub(n) code. (author)

Main issues of pile foundation at waterfront development and its prevention method

Science.gov (United States)

Manap, N.; Tan, K. Y.; Syahrom, N.

2017-12-01

Pile foundation is widely used in construction and building marine structures. This is because pile foundation is an important structure and should have long-term durability. However, in waterfront development, a lot of issues from the seawater should be considered distinctively because it consists of many problems that can affect the building structure especially the foundation of the building. Thus, a research should be conducted to identify issues of pile foundation at waterfront development and determine its prevention methods. The research was carried out through interviews with the developers and contractors from the projects of Lexis Hibiscus at Port Dickson, Negeri Sembilan and Redevelopment for Deep-Water Facilities at Quay 6 in Pasir Gudang, Johor, Malaysia. The objectives of this research are to identify issues of pile foundation and to determine the prevention methods of pile foundation issues at waterfront development. All respondents agreed that the main issues of pile foundations at waterfront development are the wave and tide condition. The prevention methods of the issue faced at waterfront development that are most frequently used for the pile foundation are coating system and concrete cover. This research is beneficial to all developers and contractors to ensure pile foundations at waterfront development can be protected by using the prevention methods.

Development of a Hybrid RANS/LES Method for Turbulent Mixing Layers

Science.gov (United States)

Georgiadis, Nicholas J.; Alexander, J. Iwan D.; Reshotko, Eli

2001-01-01

Significant research has been underway for several years in NASA Glenn Research Center's nozzle branch to develop advanced computational methods for simulating turbulent flows in exhaust nozzles. The primary efforts of this research have concentrated on improving our ability to calculate the turbulent mixing layers that dominate flows both in the exhaust systems of modern-day aircraft and in those of hypersonic vehicles under development. As part of these efforts, a hybrid numerical method was recently developed to simulate such turbulent mixing layers. The method developed here is intended for configurations in which a dominant structural feature provides an unsteady mechanism to drive the turbulent development in the mixing layer. Interest in Large Eddy Simulation (LES) methods have increased in recent years, but applying an LES method to calculate the wide range of turbulent scales from small eddies in the wall-bounded regions to large eddies in the mixing region is not yet possible with current computers. As a result, the hybrid method developed here uses a Reynolds-averaged Navier-Stokes (RANS) procedure to calculate wall-bounded regions entering a mixing section and uses a LES procedure to calculate the mixing-dominated regions. A numerical technique was developed to enable the use of the hybrid RANS-LES method on stretched, non-Cartesian grids. With this technique, closure for the RANS equations is obtained by using the Cebeci-Smith algebraic turbulence model in conjunction with the wall-function approach of Ota and Goldberg. The LES equations are closed using the Smagorinsky subgrid scale model. Although the function of the Cebeci-Smith model to replace all of the turbulent stresses is quite different from that of the Smagorinsky subgrid model, which only replaces the small subgrid turbulent stresses, both are eddy viscosity models and both are derived at least in part from mixing-length theory. The similar formulation of these two models enables the RANS

Development and Validation of a Liquid Chromatographic Method ...

African Journals Online (AJOL)

A liquid chromatographic method for the simultaneous determination of six human immunodeficiency virus (HIV) protease inhibitors, indinavir, saquinavir, ritonavir, amprenavir, nelfinavir and lopinavir, was developed and validated. Optimal separation was achieved on a PLRP-S 100 Å, 250 x 4.6 mm I.D. column maintained ...

A Method for Developing Enterprise Architecture Frameworks: An Interpretive Phenomenology Study

Directory of Open Access Journals (Sweden)

Ali Moeini

2015-03-01

Full Text Available Nowadays, many of organizations, who are involved in enterprise architecting, make their own architecture framework or customize existing frameworks. These endeavors are based on the knowledge and the experience of each organization, and there is no defined method for developing the enterprise architecture framework. Therefore, a method for developing architecture framework is presented in this qualitative research. For this reason, 15 versions of 5 most used architecture frameworks are analyzed based on the interpretive phenomenology. Based on this analysis, a method for developing architecture frameworks is introduced which contains 8 disciplines and 6 phases. Analyzing the qualitative data of the research and also the validation of the research are carried out using the guidelines of Van Manen in the interpretive phenomenology.

The Experiment Method for Manufacturing Grid Development on Single Computer

Institute of Scientific and Technical Information of China (English)

XIAO Youan; ZHOU Zude

2006-01-01

In this paper, an experiment method for the Manufacturing Grid application system development in the single personal computer environment is proposed. The characteristic of the proposed method is constructing a full prototype Manufacturing Grid application system which is hosted on a single personal computer with the virtual machine technology. Firstly, it builds all the Manufacturing Grid physical resource nodes on an abstraction layer of a single personal computer with the virtual machine technology. Secondly, all the virtual Manufacturing Grid resource nodes will be connected with virtual network and the application software will be deployed on each Manufacturing Grid nodes. Then, we can obtain a prototype Manufacturing Grid application system which is working in the single personal computer, and can carry on the experiment on this foundation. Compared with the known experiment methods for the Manufacturing Grid application system development, the proposed method has the advantages of the known methods, such as cost inexpensively, operation simple, and can get the confidence experiment result easily. The Manufacturing Grid application system constructed with the proposed method has the high scalability, stability and reliability. It is can be migrated to the real application environment rapidly.

Development of probabilistic fast reactor fuel design method

International Nuclear Information System (INIS)

Ozawa, Takayuki

1997-01-01

Under the current method of evaluating fuel robustness in FBR fuel rod design, a variety of uncertain quantities including fuel production tolerance and power density are estimated conservatively. In the future, in order to proceed with improvements in the FBR core's performance and optimize the fuel's specifications, a rationalization of fuel design tolerance is required. Among the measures aimed at realizing this rationalization, the introduction of a probabilistic fast reactor fuel design method is currently under consideration. I have developed a probabilistic fast reactor fuel design code named BORNFREE, in order to make use of this method in FBR fuel design. At the same time, I have carried out a trial calculation of the cladding stress using this code and made a study and an evaluation of the possibility of employing tolerance rationalization in fuel rod design. In this paper, I provide an outline description of BORNFREE and report the results of the above study and evaluation. After performing cladding stress trial calculations using the probabilistic method, I was able to confirm that this method promises more rational design evaluation results than the conventional deterministic method. (author)

Capillary Electrophoresis Hyphenated with Mass Spectrometry for Determination of Inflammatory Bowel Disease Drugs in Clinical Urine Samples

Directory of Open Access Journals (Sweden)

Katarína Maráková

2017-11-01

Full Text Available Azathioprine is the main thiopurine drug used in the treatment of immune-based inflammations of gastrointestinal tract. For the purpose of therapy control and optimization, effective and reliable analytical methods for a rapid drug monitoring in biological fluids are essential. Here, we developed a separation method based on the capillary electrophoresis (CE hyphenated with tandem mass spectrometry (MS/MS for the simultaneous determination of azathioprine and its selected metabolites (6-thioguanine, 6-mercaptopurine, and 6-methylmercaptopurine as well as other co-medicated drugs (mesalazine, prednisone, and allopurinol. The optimized CE-MS/MS conditions provided a very efficient and stable system for the separation and sensitive detection of these drugs in human urine matrices. The developed method was successfully applied for the assay of the targeted drugs and their selected metabolites in urine samples collected from patients suffering from inflammatory bowel disease (IBD and receiving azathioprine therapy. The developed CE-MS/MS method, due to its reliability, short analysis time, production of complex clinical profiles, and favorable performance parameters, evaluated according to FDA guidelines for bioanalytical method validation, is proposed for routine clinical laboratories to optimize thiopurine therapy, estimate enzymatic activity, and control patient compliance with medication and co-medication.

Actors’ Competencies or Methods? A Case Study of Successful Information Systems Development

DEFF Research Database (Denmark)

Omland, Hans Olav; Nielsen, Peter Axel

2009-01-01

and methods are exercised. Emphasising the intertwining of competencies and methods, we discuss the character of the intertwining process, how different actors relate to different methods, and how methods may be part of the problem rather than part of the solution to challenges in information systems...... between actors’ competencies and their deployment of methods, arguing that this relationship is described over-simplistically and needs a better explanation. Through a case study of a successful information systems development project we identify some central situations where a variety of competencies...... development. The paper suggests elements for a new model for explaining actors’ competencies and their use of methods....

Wide-field surface plasmon microscopy of nano- and microparticles: features, benchmarking, limitations, and bioanalytical applications

Science.gov (United States)

Nizamov, Shavkat; Scherbahn, Vitali; Mirsky, Vladimir M.

2017-05-01

Detection of nano- and micro-particles is an important task for chemical analytics, food industry, biotechnology, environmental monitoring and many other fields of science and industry. For this purpose, a method based on the detection and analysis of minute signals in surface plasmon resonance images due to adsorption of single nanopartciles was developed. This new technology allows one a real-time detection of interaction of single nano- and micro-particles with sensor surface. Adsorption of each nanoparticle leads to characteristic diffraction image whose intensity depends on the size and chemical composition of the particle. The adsorption rate characterizes volume concentration of nano- and micro-particles. Large monitored surface area of sensor enables a high dynamic range of counting and to a correspondingly high dynamic range in concentration scale. Depending on the type of particles and experimental conditions, the detection limit for aqueous samples can be below 1000 particles per microliter. For application of method in complex media, nanoparticle images are discriminated from image perturbations due to matrix components. First, the characteristic SPRM images of nanoparticles (templates) are collected in aqueous suspensions or spiked real samples. Then, the detection of nanoparticles in complex media using template matching is performed. The detection of various NPs in consumer products like cosmetics, mineral water, juices, and wines was shown at sub-ppb level. The method can be applied for ultrasensitive detection and analysis of nano- and micro-particles of biological (bacteria, viruses, endosomes), biotechnological (liposomes, protein nanoparticles for drug delivery) or technical origin.

Lessons from comparative effectiveness research methods development projects funded under the Recovery Act.

Science.gov (United States)

Zurovac, Jelena; Esposito, Dominick

2014-11-01

The American Recovery and Reinvestment Act of 2009 (ARRA) directed nearly US$29.2 million to comparative effectiveness research (CER) methods development. To help inform future CER methods investments, we describe the ARRA CER methods projects, identify barriers to this research and discuss the alignment of topics with published methods development priorities. We used several existing resources and held discussions with ARRA CER methods investigators. Although funded projects explored many identified priority topics, investigators noted that much work remains. For example, given the considerable investments in CER data infrastructure, the methods development field can benefit from additional efforts to educate researchers about the availability of new data sources and about how best to apply methods to match their research questions and data.

Software Development Methods and Tools: a New Zealand study

OpenAIRE

Chris Phillips; Elizabeth Kemp; Duncan Hedderley

2005-01-01

This study is a more detailed follow-up to a preliminary investigation of the practices of software engineers in New Zealand. The focus of this study is on the methods and tools used by software developers in their current organisation. The project involved detailed questionnaires being piloted and sent out to several hundred software developers. A central part of the research involved the identification of factors affecting the use and take-up of existing software development tools in the wo...

Capillary zone electrophoresis method for a highly glycosylated and sialylated recombinant protein: development, characterization and application for process development.

Science.gov (United States)

Zhang, Le; Lawson, Ken; Yeung, Bernice; Wypych, Jette

2015-01-06

A purity method based on capillary zone electrophoresis (CZE) has been developed for the separation of isoforms of a highly glycosylated protein. The separation was found to be driven by the number of sialic acids attached to each isoform. The method has been characterized using orthogonal assays and shown to have excellent specificity, precision and accuracy. We have demonstrated the CZE method is a useful in-process assay to support cell culture and purification development of this glycoprotein. Compared to isoelectric focusing (IEF), the CZE method provides more quantitative results and higher sample throughput with excellent accuracy, qualities that are required for process development. In addition, the CZE method has been applied in the stability testing of purified glycoprotein samples.

Development of digital image correlation method to analyse crack ...

Indian Academy of Sciences (India)

samples were performed to verify the performance of the digital image correlation method. ... development cannot be measured accurately. ..... Mendelson A 1983 Plasticity: Theory and application (USA: Krieger Publishing company Malabar,.

Method development for the determination of volatile organic compounds in mixed waste

International Nuclear Information System (INIS)

Sandoval, W.F.; Rogers, Y.C.; Schappert, M.F.; Boland, K.S.; Spall, W.D.; Wilkerson, C.W. Jr.

1993-01-01

While analytical methods exist for the determination of Resource Conservation and Recovery Act (RCRA) listed organic and inorganic compounds in hazardous materials, equivalent methods suitable for the characterization of radioactively contaminated samples are not at the same level of maturity. The Mixed Waste Methods Development Lab. has been established at Los Alamos National Lab. to address the need for such procedures. This presentation will focus on the efforts that have been directed toward the determination of volatile organic compounds (VOCs) in mixed waste matrices. The capabilities of the Mixed Waste Methods Development Lab. will be outlined. Modifications to the containment boxes and analytical instrumentation required for the analyses will be described, as will experimental procedures and system performance benchmarks. Preliminary results from surrogate and real mixed waste matrices will be presented, and future directions for our method development effort will be discussed

Method development for trace and ultratrace analysis

International Nuclear Information System (INIS)

Anon.

1992-01-01

Method development, that is, selection of a mode of chromatography and the right column and mobile-phase combination for trace and ultratrace analysis, requires several main considerations. The method should be useful for resolving various trace and ultratrace components present in the sample. If the nature of these components is known, the choice of method may be straightforward, that is, a selection can be made from the following modes of HPLC: (1) adsorption chromatography; (2) normal-phase chromatography; (3) reversed-phase chromatography; (4) ion-pair chromatography; (5) ion-exchange chromatography; (6) ion chromatography. Unfortunately, the nature of all of the components is frequently unknown. However, several intelligent judgments can be made on the nature of impurities. This chapter deals with some basic approaches to mobile-phase selection and optimization. More detailed information may be found in basic texts. Techniques for separation of high-molecular-weight compounds (macromolecules) and chiral compounds may be found elsewhere. Mainly compounds with molecular weight lower than 2,000 are discussed here. 123 refs

Review of various dynamic modeling methods and development of an intuitive modeling method for dynamic systems

International Nuclear Information System (INIS)

Shin, Seung Ki; Seong, Poong Hyun

2008-01-01

Conventional static reliability analysis methods are inadequate for modeling dynamic interactions between components of a system. Various techniques such as dynamic fault tree, dynamic Bayesian networks, and dynamic reliability block diagrams have been proposed for modeling dynamic systems based on improvement of the conventional modeling methods. In this paper, we review these methods briefly and introduce dynamic nodes to the existing Reliability Graph with General Gates (RGGG) as an intuitive modeling method to model dynamic systems. For a quantitative analysis, we use a discrete-time method to convert an RGGG to an equivalent Bayesian network and develop a software tool for generation of probability tables

Recent Development in Rigorous Computational Methods in Dynamical Systems

OpenAIRE

Arai, Zin; Kokubu, Hiroshi; Pilarczyk, Paweł

2009-01-01

We highlight selected results of recent development in the area of rigorous computations which use interval arithmetic to analyse dynamical systems. We describe general ideas and selected details of different ways of approach and we provide specific sample applications to illustrate the effectiveness of these methods. The emphasis is put on a topological approach, which combined with rigorous calculations provides a broad range of new methods that yield mathematically rel...

Development of method quantitative content of dihydroquercetin. Report 1

Directory of Open Access Journals (Sweden)

Олександр Юрійович Владимиров

2016-01-01

Full Text Available Today is markedly increasing scientific interest in the study of flavonoids in plant objects due to their high biological activity. In this regard, the urgent task of analytical chemistry is in developing available analytical techniques of determination for flavonoids in plant objects.Aim. The aim was to develop specific techniques of quantitative determination for dihydroquercetin and determination of its validation characteristics.Methods. The technique for photocolorimetric quantification of DQW, which was based on the specific reaction of cyanidine chloride formation when added zinc powder to dihydroquercetin solution in an acidic medium has been elaborated.Results. Photocolorimetric technique of determining flavonoids recalculating on DQW has been developed, its basic validation characteristics have been determined. The obtained metrological characteristics of photocolorimetric technique for determining DQW did not exceed admissibility criteria in accordance with the requirements of the State Pharmacopoeia of Ukraine.Conclusions. By the results of statistical analysis of experimental data, it has been stated that the developed technique can be used for quantification of DQW. Metrological data obtained indicate that the method reproduced in conditions of two different laboratories with confidence probability 95 % unit value deviation was 101,85±2,54 %

Innovative method of RES integration into the regional energy development scenarios

International Nuclear Information System (INIS)

Klevas, Valentinas; Biekša, Kestutis; Murauskaitė, Lina

2014-01-01

Scarcity or abundance of energy resources usually depends on physical and geographical conditions in the region. However, the energy flow in the region also depends on the efficient use of energy resources, the consumption rate of energy and the possibility to use local renewable and non-renewable energy resources. Production, distribution and the use of energy resources in the region are the challenges for central and local government, business and social service, customers and other stakeholders. Development of regional energy economy should be optimized according to the available energy flow in the region using a network system analysis method, which provides solutions for developing sustainable energy economy models. The network system analysis method enables to optimize the use of local and renewable resources at the regional level and reveals available local energy resources. An efficient use of available regional resources and the use of renewable energy sources (RES) should be the main goals for the development of regional energy system. RES can compete with traditional fossil fuel with the condition that all hidden aspects are revealed. The network system analysis method enables to indicate energy flows in the region as well as indicate pros and cons of using renewable energy technologies. - Highlights: • RES integration into the regional energy development scenarios is done. • Innovative process network system (PNS) analysis method is used. • PNS method is used to optimize the use of local and renewable resources. • Analysis of energy flow in region using PNS method is done

Development of rupture process analysis method for great earthquakes using Direct Solution Method

Science.gov (United States)

Yoshimoto, M.; Yamanaka, Y.; Takeuchi, N.

2010-12-01

Conventional rupture process analysis methods using teleseismic body waves were based on ray theory. Therefore, these methods have the following problems in applying to great earthquakes such as 2004 Sumatra earthquake: (1) difficulty in computing all later phases such as the PP reflection phase, (2) impossibility of computing called “W phase”, the long period phase arriving before S wave, (3) implausibility of hypothesis that the distance is far enough from the observation points to the hypocenter compared to the fault length. To solve above mentioned problems, we have developed a new method which uses the synthetic seismograms computed by the Direct Solution Method (DSM, e.g. Kawai et al. 2006) as Green’s functions. We used the DSM software (http://www.eri.u-tokyo.ac.jp/takeuchi/software/) for computing the Green’s functions up to 1 Hz for the IASP91 (Kennett and Engdahl, 1991) model, and determined the final slip distributions using the waveform inversion method (Kikuchi et al. 2003). First we confirmed whether the Green’s functions computed by DSM were accurate in higher frequencies up to 1 Hz. Next we performed the rupture process analysis of this new method for Mw8.0 (GCMT) large Solomon Islands earthquake on April 1, 2007. We found that this earthquake consisted of two asperities and the rupture propagated across the subducting Sinbo ridge. The obtained slip distribution better correlates to the aftershock distributions than existing method. Furthermore, this new method keep same accuracy of existing method (which has the advantage of calculating) with respect to direct P-wave and reflection phases near the source, and also accurately calculate the later phases such a PP-wave.

Field Sample Preparation Method Development for Isotope Ratio Mass Spectrometry

International Nuclear Information System (INIS)

Leibman, C.; Weisbrod, K.; Yoshida, T.

2015-01-01

Non-proliferation and International Security (NA-241) established a working group of researchers from Los Alamos National Laboratory (LANL), Pacific Northwest National Laboratory (PNNL) and Savannah River National Laboratory (SRNL) to evaluate the utilization of in-field mass spectrometry for safeguards applications. The survey of commercial off-the-shelf (COTS) mass spectrometers (MS) revealed no instrumentation existed capable of meeting all the potential safeguards requirements for performance, portability, and ease of use. Additionally, fieldable instruments are unlikely to meet the International Target Values (ITVs) for accuracy and precision for isotope ratio measurements achieved with laboratory methods. The major gaps identified for in-field actinide isotope ratio analysis were in the areas of: 1. sample preparation and/or sample introduction, 2. size reduction of mass analyzers and ionization sources, 3. system automation, and 4. decreased system cost. Development work in 2 through 4, numerated above continues, in the private and public sector. LANL is focusing on developing sample preparation/sample introduction methods for use with the different sample types anticipated for safeguard applications. Addressing sample handling and sample preparation methods for MS analysis will enable use of new MS instrumentation as it becomes commercially available. As one example, we have developed a rapid, sample preparation method for dissolution of uranium and plutonium oxides using ammonium bifluoride (ABF). ABF is a significantly safer and faster alternative to digestion with boiling combinations of highly concentrated mineral acids. Actinides digested with ABF yield fluorides, which can then be analyzed directly or chemically converted and separated using established column chromatography techniques as needed prior to isotope analysis. The reagent volumes and the sample processing steps associated with ABF sample digestion lend themselves to automation and field

Method Development and Validation for the Determination of Caffeine: An Alkaloid from Coffea arabica by High-performance Liquid Chromatography Method.

Science.gov (United States)

Naveen, P; Lingaraju, H B; Deepak, M; Medhini, B; Prasad, K Shyam

2018-01-01

The present study was investigated to develop and validate a reversed phase high performance liquid chromatography method for the determination of caffeine from bean material of Coffee arabica. The separation was achieved on a reversed-phase C18 column using a mobile phase composed of water: methanol (50:50) at a flow rate of 1.0 mlmin-1. The detection was carried out on a UV detector at 272 nm. The developed method was validated according to the requirements for International Conference on Harmonisation (ICH) guidelines, which includes specificity, linearity, precision, accuracy, limit of detection and limit of quantitation. The developed method validates good linearity with excellent correlation coefficient (R2 > 0.999). In repeatability and intermediate precision, the percentage relative standard deviation (% RSD) of peak area was less than 1% shows high precision of the method. The recovery rate for caffeine was within 98.78% - 101.28% indicates high accuracy of the method. The low limit of detection and limit of quantitation of caffeine enable the detection and quantitation of caffeine from C. arabica at low concentrations. The developed HPLC method is a simple, rapid, precisely, accurately and widely accepted and it is recommended for efficient assays in routine work. A simple, accurate, and sensitive high-performance liquid chromatography (HPLC) method for caffeine from Coffea arabica has been developed and validated. The developed HPLC method was validated for linearity, specificity, precision, recovery, limits of detection, and limits of quantification by the International Conference on Harmonization guidelines. The results revealed that the proposed method is highly reliable. This method could be successfully applied for routine quality work analysis. Abbreviation Used: C. arabica : Coffee arabica, ICH: International Conference on Harmonisation, % RSD: Percentage Relative Standard Deviation, R2: Correlation Coefficient, ppm: Parts per million, LOD: Limits

Viscous wing theory development. Volume 1: Analysis, method and results

Science.gov (United States)

Chow, R. R.; Melnik, R. E.; Marconi, F.; Steinhoff, J.

1986-01-01

Viscous transonic flows at large Reynolds numbers over 3-D wings were analyzed using a zonal viscid-inviscid interaction approach. A new numerical AFZ scheme was developed in conjunction with the finite volume formulation for the solution of the inviscid full-potential equation. A special far-field asymptotic boundary condition was developed and a second-order artificial viscosity included for an improved inviscid solution methodology. The integral method was used for the laminar/turbulent boundary layer and 3-D viscous wake calculation. The interaction calculation included the coupling conditions of the source flux due to the wing surface boundary layer, the flux jump due to the viscous wake, and the wake curvature effect. A method was also devised incorporating the 2-D trailing edge strong interaction solution for the normal pressure correction near the trailing edge region. A fully automated computer program was developed to perform the proposed method with one scalar version to be used on an IBM-3081 and two vectorized versions on Cray-1 and Cyber-205 computers.

Detection of cadmium sulphide nanoparticles by using screen-printed electrodes and a handheld device

International Nuclear Information System (INIS)

Merkoci, Arben; Marcolino-Junior, Luiz Humberto; MarIn, Sergio; Fatibello-Filho, Orlando; Alegret, Salvador

2007-01-01

A simple method based on screen-printed electrodes and a handheld potentiostatic device is reported for the detection of water soluble CdS quantum dots modified with glutathione. The detection method is based on the stripping of electrochemically reduced cadmium at pH 7.0 by using square wave voltammetry. Various parameters that affect the sensitivity of the method are optimized. QD suspension volumes of 20 μl and a number of around 2 x 10 11 CdS quantum dots have been able to be detected. The proposed method should be of special interest for bioanalytical assays, where CdS quantum dots can be used as electrochemical tracers

Development of a practical costing method for hospitals.

Science.gov (United States)

Cao, Pengyu; Toyabe, Shin-Ichi; Akazawa, Kouhei

2006-03-01

To realize an effective cost control, a practical and accurate cost accounting system is indispensable in hospitals. In traditional cost accounting systems, the volume-based costing (VBC) is the most popular cost accounting method. In this method, the indirect costs are allocated to each cost object (services or units of a hospital) using a single indicator named a cost driver (e.g., Labor hours, revenues or the number of patients). However, this method often results in rough and inaccurate results. The activity based costing (ABC) method introduced in the mid 1990s can prove more accurate results. With the ABC method, all events or transactions that cause costs are recognized as "activities", and a specific cost driver is prepared for each activity. Finally, the costs of activities are allocated to cost objects by the corresponding cost driver. However, it is much more complex and costly than other traditional cost accounting methods because the data collection for cost drivers is not always easy. In this study, we developed a simplified ABC (S-ABC) costing method to reduce the workload of ABC costing by reducing the number of cost drivers used in the ABC method. Using the S-ABC method, we estimated the cost of the laboratory tests, and as a result, similarly accurate results were obtained with the ABC method (largest difference was 2.64%). Simultaneously, this new method reduces the seven cost drivers used in the ABC method to four. Moreover, we performed an evaluation using other sample data from physiological laboratory department to certify the effectiveness of this new method. In conclusion, the S-ABC method provides two advantages in comparison to the VBC and ABC methods: (1) it can obtain accurate results, and (2) it is simpler to perform. Once we reduce the number of cost drivers by applying the proposed S-ABC method to the data for the ABC method, we can easily perform the cost accounting using few cost drivers after the second round of costing.

On the Adaptation of an Agile Information Systems Development Method

NARCIS (Netherlands)

Aydin, M.N.; Harmsen, F.; van Slooten, C.; Stegwee, R.A.

2005-01-01

Little specific research has been conducted to date on the adaptation of agile information systems development (ISD) methods. This article presents the work practice in dealing with the adaptation of such a method in the ISD department of one of the leading financial institutes in Europe. Two forms

Use Case Evaluation (UCE): A Method for Early Usability Evaluation in Software Development

DEFF Research Database (Denmark)

Stage, Jan; Høegh, Rune Thaarup; Hornbæk, K.

2007-01-01

t is often argued that usability problems should be identified as early as possible during software development, but many usability evaluation methods do not fit well in early development activities. We propose a method for usability evaluation of use cases, a widely used representation of design...... ideas produced early in software development processes. The method proceeds by systematic inspection of use cases with reference to a set of guidelines for usable design. To validate the method, four evaluators inspected a set of use cases for a health care application....

ICECAP: an integrated, general-purpose, automation-assisted IC50/EC50 assay platform.

Science.gov (United States)

Li, Ming; Chou, Judy; King, Kristopher W; Jing, Jing; Wei, Dong; Yang, Liyu

2015-02-01

IC50 and EC50 values are commonly used to evaluate drug potency. Mass spectrometry (MS)-centric bioanalytical and biomarker labs are now conducting IC50/EC50 assays, which, if done manually, are tedious and error-prone. Existing bioanalytical sample preparation automation systems cannot meet IC50/EC50 assay throughput demand. A general-purpose, automation-assisted IC50/EC50 assay platform was developed to automate the calculations of spiking solutions and the matrix solutions preparation scheme, the actual spiking and matrix solutions preparations, as well as the flexible sample extraction procedures after incubation. In addition, the platform also automates the data extraction, nonlinear regression curve fitting, computation of IC50/EC50 values, graphing, and reporting. The automation-assisted IC50/EC50 assay platform can process the whole class of assays of varying assay conditions. In each run, the system can handle up to 32 compounds and up to 10 concentration levels per compound, and it greatly improves IC50/EC50 assay experimental productivity and data processing efficiency. © 2014 Society for Laboratory Automation and Screening.

Development of concept and neutronic calculation method for large LMFBR core

International Nuclear Information System (INIS)

Shirakata, K.; Ishikawa, M.; Ikegami, T.; Sanda, T.; Kaneto, K.; Kawashima, M.; Kaise, Y.; Shirakawa, M.; Hibi, K.

1991-01-01

Presented in this paper is the state of the art of reactor physics R and Ds for the development of concept and neutronic calculation method for large Liquid Metal Fast Breeder Reactor (LMFBR) core. Physics characteristics of concepts for mixed oxide (MOX) fueled large FBR core were investigated by a series of benchmark critical experiments. Next, an adequacy and accuracy of the current neutronic calculation method was assessed by the experiments analyses, and then neutronic prediction accuracies by the method were evaluated for physics characteristics of the large core. Concerns on core development were discussed in terms of neutronics. (author)

In-situ investigation of protein and DNA structure using UVRRS

Science.gov (United States)

Greek, L. Shane; Schulze, H. Georg; Blades, Michael W.; Haynes, Charles A.; Turner, Robin F. B.

1997-05-01

Ultraviolet resonance Raman spectroscopy (UVRRS) has the potential to become a sensitive, specific, versatile bioanalytical and biophysical technique for routine investigations of proteins, DNA, and their monomeric components, as well as a variety smaller, physiologically important aromatic molecules. The transition of UVRRS from a complex, specialized spectroscopic method to a common laboratory assay depends upon several developments, including a robust sample introduction method permitting routine, in situ analysis in standard laboratory environments. To this end, we recently reported the first fiber-optic probes suitable for deep-UV pulsed laser UVRRS. In this paper, we extend this work by demonstrating the applicability of such probes to studies of biochemical relevance, including investigations of the resonance enhancement of phosphotyrosine, thermal denaturation of RNase T1, and specific and non-specific protein binding. The advantages and disadvantages of the probes are discussed with reference to sample conditions and probe design considerations.

Micro electrochemical sensors and PCR systems: cellular and molecular tools for wine yeast analysis

OpenAIRE

Ress, Cristina

2010-01-01

Nowadays, exciting bioanalytical microsystems are currently receiving increasing attention in biology since they can comply with the considerable demand for reliable, sensitive and low-cost analysis tools. Small reagents volumes, low power consumption, portability, fast analysis, high throughput and systems integration are the key aspects that make these systems more and more appealing within both the academic and industrial communities. In the last years, many microdevices were developed for...

Developing methods of strip cropping cucumbers with rye/vetch

OpenAIRE

Ogutu, Maurice Okendo

2000-01-01

The purpose of this research carried out in 1998 and 1999 was to develop methods for strip cropping of cucumbers with rye/vetch and black plastic mulch. Effects of planting methods, weed control measures, and cover crop management techniques on pest and beneficial insects, petiole sap nitrate-nitrogen, soil moisture, yields and economic viability were assessed. Four treatments, namely cucumber direct seeded in black plastic mulch on tilled bare ground (conventional); cucumber d...

Multidisciplinary Methods in Educational Technology Research and Development

Science.gov (United States)

Randolph, Justus J.

2008-01-01

Over the past thirty years, there has been much dialogue, and debate, about the conduct of educational technology research and development. In this brief volume, the author helps clarify that dialogue by theoretically and empirically charting the research methods used in the field and provides much practical information on how to conduct…

Development op finite volume methods for fluid dynamics

International Nuclear Information System (INIS)

Delcourte, S.

2007-09-01

We aim to develop a finite volume method which applies to a greater class of meshes than other finite volume methods, restricted by orthogonality constraints. We build discrete differential operators over the three staggered tessellations needed for the construction of the method. These operators verify some analogous properties to those of the continuous operators. At first, the method is applied to the Div-Curl problem, which can be viewed as a building block of the Stokes problem. Then, the Stokes problem is dealt with with various boundary conditions. It is well known that when the computational domain is polygonal and non-convex, the order of convergence of numerical methods is deteriorated. Consequently, we have studied how an appropriate local refinement is able to restore the optimal order of convergence for the Laplacian problem. At last, we have discretized the non-linear Navier-Stokes problem, using the rotational formulation of the convection term, associated to the Bernoulli pressure. With an iterative algorithm, we are led to solve a saddle-point problem at each iteration. We give a particular interest to this linear problem by testing some pre-conditioners issued from finite elements, which we adapt to our method. Each problem is illustrated by numerical results on arbitrary meshes, such as strongly non-conforming meshes. (author)

MR imaging methods for assessing fetal brain development.

Science.gov (United States)

Rutherford, Mary; Jiang, Shuzhou; Allsop, Joanna; Perkins, Lucinda; Srinivasan, Latha; Hayat, Tayyib; Kumar, Sailesh; Hajnal, Jo

2008-05-01

Fetal magnetic resonance imaging provides an ideal tool for investigating growth and development of the brain in vivo. Current imaging methods have been hampered by fetal motion but recent advances in image acquisition can produce high signal to noise, high resolution 3-dimensional datasets suitable for objective quantification by state of the art post acquisition computer programs. Continuing development of imaging techniques will allow a unique insight into the developing brain, more specifically process of cell migration, axonal pathway formation, and cortical maturation. Accurate quantification of these developmental processes in the normal fetus will allow us to identify subtle deviations from normal during the second and third trimester of pregnancy either in the compromised fetus or in infants born prematurely.

Dynamical Systems Method and Applications Theoretical Developments and Numerical Examples

CERN Document Server

Ramm, Alexander G

2012-01-01

Demonstrates the application of DSM to solve a broad range of operator equations The dynamical systems method (DSM) is a powerful computational method for solving operator equations. With this book as their guide, readers will master the application of DSM to solve a variety of linear and nonlinear problems as well as ill-posed and well-posed problems. The authors offer a clear, step-by-step, systematic development of DSM that enables readers to grasp the method's underlying logic and its numerous applications. Dynamical Systems Method and Applications begins with a general introduction and

Interactive and Hands-on Methods for Professional Development of Undergraduate Researchers

Science.gov (United States)

Pressley, S. N.; LeBeau, J. E.

2016-12-01

Professional development workshops for undergraduate research programs can range from communicating science (i.e. oral, technical writing, poster presentations), applying for fellowships and scholarships, applying to graduate school, and learning about careers, among others. Novel methods of presenting the information on the above topics can result in positive outcomes beyond the obvious of transferring knowledge. Examples of innovative methods to present professional development information include 1) An interactive session on how to write an abstract where students are given an opportunity to draft an abstract from a short technical article, followed by discussion amongst a group of peers, and comparison with the "published" abstract. 2) Using the Process Oriented Guided Inquiry Learning (POGIL) method to evaluate and critique a research poster. 3) Inviting "experts" such as a Fulbright scholar graduate student to present on applying for fellowships and scholarships. These innovative methods of delivery provide more hands-on activities that engage the students, and in some cases (abstract writing) provide practice for the student. The methods also require that students develop team work skills, communicate amongst their peers, and develop networks with their cohort. All of these are essential non-technical skills needed for success in any career. Feedback from students on these sessions are positive and most importantly, the students walk out of the session with a smile on their face saying how much fun it was. Evaluating the impact of these sessions is more challenging and under investigation currently.

Validation and Clinical Evaluation of a Novel Method To Measure Miltefosine in Leishmaniasis Patients Using Dried Blood Spot Sample Collection

Science.gov (United States)

Rosing, H.; Hillebrand, M. J. X.; Blesson, S.; Mengesha, B.; Diro, E.; Hailu, A.; Schellens, J. H. M.; Beijnen, J. H.

2016-01-01

To facilitate future pharmacokinetic studies of combination treatments against leishmaniasis in remote regions in which the disease is endemic, a simple cheap sampling method is required for miltefosine quantification. The aims of this study were to validate a liquid chromatography-tandem mass spectrometry method to quantify miltefosine in dried blood spot (DBS) samples and to validate its use with Ethiopian patients with visceral leishmaniasis (VL). Since hematocrit (Ht) levels are typically severely decreased in VL patients, returning to normal during treatment, the method was evaluated over a range of clinically relevant Ht values. Miltefosine was extracted from DBS samples using a simple method of pretreatment with methanol, resulting in >97% recovery. The method was validated over a calibration range of 10 to 2,000 ng/ml, and accuracy and precision were within ±11.2% and ≤7.0% (≤19.1% at the lower limit of quantification), respectively. The method was accurate and precise for blood spot volumes between 10 and 30 μl and for Ht levels of 20 to 35%, although a linear effect of Ht levels on miltefosine quantification was observed in the bioanalytical validation. DBS samples were stable for at least 162 days at 37°C. Clinical validation of the method using paired DBS and plasma samples from 16 VL patients showed a median observed DBS/plasma miltefosine concentration ratio of 0.99, with good correlation (Pearson's r = 0.946). Correcting for patient-specific Ht levels did not further improve the concordance between the sampling methods. This successfully validated method to quantify miltefosine in DBS samples was demonstrated to be a valid and practical alternative to venous blood sampling that can be applied in future miltefosine pharmacokinetic studies with leishmaniasis patients, without Ht correction. PMID:26787691

Using mixed methods to develop and evaluate complex interventions in palliative care research.

Science.gov (United States)

Farquhar, Morag C; Ewing, Gail; Booth, Sara

2011-12-01

there is increasing interest in combining qualitative and quantitative research methods to provide comprehensiveness and greater knowledge yield. Mixed methods are valuable in the development and evaluation of complex interventions. They are therefore particularly valuable in palliative care research where the majority of interventions are complex, and the identification of outcomes particularly challenging. this paper aims to introduce the role of mixed methods in the development and evaluation of complex interventions in palliative care, and how they may be used in palliative care research. the paper defines mixed methods and outlines why and how mixed methods are used to develop and evaluate complex interventions, with a pragmatic focus on design and data collection issues and data analysis. Useful texts are signposted and illustrative examples provided of mixed method studies in palliative care, including a detailed worked example of the development and evaluation of a complex intervention in palliative care for breathlessness. Key challenges to conducting mixed methods in palliative care research are identified in relation to data collection, data integration in analysis, costs and dissemination and how these might be addressed. the development and evaluation of complex interventions in palliative care benefit from the application of mixed methods. Mixed methods enable better understanding of whether and how an intervention works (or does not work) and inform the design of subsequent studies. However, they can be challenging: mixed method studies in palliative care will benefit from working with agreed protocols, multidisciplinary teams and engaging staff with appropriate skill sets.

Bioanalytical Applications of Fluorenscence Quenching.

Science.gov (United States)

1986-02-10

fluorescence is observed. Thus, ’ the enzymes (in this case phosphorylase C) which can hydrolyze the lecithin , can be determined by measuring the released...encapsulated in lecithin liposomes. In this manner the fluorescence is self-quenched. When the liposomes are disrupted, the dye is released and

Using containerless methods to develop amorphous pharmaceuticals.

Science.gov (United States)

Weber, J K R; Benmore, C J; Suthar, K J; Tamalonis, A J; Alderman, O L G; Sendelbach, S; Kondev, V; Yarger, J; Rey, C A; Byrn, S R

2017-01-01

Many pipeline drugs have low solubility in their crystalline state and require compounding in special dosage forms to increase bioavailability for oral administration. The use of amorphous formulations increases solubility and uptake of active pharmaceutical ingredients. These forms are rapidly gaining commercial importance for both pre-clinical and clinical use. Synthesis of amorphous drugs was performed using an acoustic levitation containerless processing method and spray drying. The structure of the products was investigated using in-situ high energy X-ray diffraction. Selected solvents for processing drugs were investigated using acoustic levitation. The stability of amorphous samples was measured using X-ray diffraction. Samples processed using both spray drying and containerless synthesis were compared. We review methods for making amorphous pharmaceuticals and present data on materials made by containerless processing and spray drying. It was shown that containerless processing using acoustic levitation can be used to make phase-pure forms of drugs that are known to be difficult to amorphize. The stability and structure of the materials was investigated in the context of developing and making clinically useful formulations. Amorphous compounds are emerging as an important component of drug development and for the oral delivery of drugs with low solubility. Containerless techniques can be used to efficiently synthesize small quantities of pure amorphous forms that are potentially useful in pre-clinical trials and for use in the optimization of clinical products. Developing new pharmaceutical products is an essential enterprise to improve patient outcomes. The development and application of amorphous pharmaceuticals to increase absorption is rapidly gaining importance and it provides opportunities for breakthrough research on new drugs. There is an urgent need to solve problems associated with making formulations that are both stable and that provide high

Development of measure methods of radon in indoor air

International Nuclear Information System (INIS)

Yaginuma, L.T.; Pela, C.A.; Navas, E.A.; Ghilardi, A.J.P.

1992-01-01

The development of some conventional measuring methods, aiming obtain an estimation of radon concentration in air, mainly in indoor air is described, including the charcoal absorption collector, Lucas cell and thermoluminescent dosemeters. (C.G.C)

Effect of Concentrated Language Encounter Method in Developing ...

African Journals Online (AJOL)

The paper examined the effect of concentrated language encounter method in developing sight word recognition skill in primary school pupils in cross river state. The purpose of the study was to find out the effect of Primary One pupils' reading level, English sight word recognition skill. It also examine the extent to which the ...

Human-system safety methods for development of advanced air traffic management systems

International Nuclear Information System (INIS)

Nelson, William R.

1999-01-01

The Idaho National Engineering and Environmental Laboratory (INEEL) is supporting the National Aeronautics and Space Administration in the development of advanced air traffic management (ATM) systems as part of the Advanced Air Transportation Technologies program. As part of this program INEEL conducted a survey of human-system safety methods that have been applied to complex technical systems, to identify lessons learned from these applications and provide recommendations for the development of advanced ATM systems. The domains that were surveyed included offshore oil and gas, commercial nuclear power, commercial aviation, and military. The survey showed that widely different approaches are used in these industries, and that the methods used range from very high-level, qualitative approaches to very detailed quantitative methods such as human reliability analysis (HRA) and probabilistic safety assessment (PSA). In addition, the industries varied widely in how effectively they incorporate human-system safety assessment in the design, development, and testing of complex technical systems. In spite of the lack of uniformity in the approaches and methods used, it was found that methods are available that can be combined and adapted to support the development of advanced air traffic management systems (author) (ml)

The development of interdepartmental audit methods

International Nuclear Information System (INIS)

Thwaites, D.I.; Allahverdi, M.

1995-01-01

The UK Radiotherapy Physics Audit Network is now well-established, with seven network groups and co-ordinated by the IPSM. It is based on visits, using ion chambers as the measurement method, and auditing at least machine calibration, single field parameters and simple multi-field planned irradiations. In addition procedural audit of dosimetry and quality control procedures, and records is incorporated. The general approach has been to use interdepartmental audit involving mutual co-operation with peer professionals from other centres. The different groups have evolved at different paces and in rather different directions. However the IPSM coordinating role ensures a basic common minimum to the system. The Scottish+ group has developed a semi-anatomical phantom to use in audit stages following on from the basic single field and geometric phantom dosimetry audit levels. This has been evaluated experimentally in one department before wider use. The Scottish+ audit system is briefly described. Results from levels 1 and 2 are summarised and the design and testing of the semi-anatomical phantom are discussed. The current and future development of the audit system is presented

A fully validated bioanalytical method using an UHPLC-MS/MS system for quantification of DNA and RNA oxidative stress biomarkers.

Science.gov (United States)

Cervinkova, Barbora; Krcmova, Lenka Kujovska; Sestakova, Veronika; Solichova, Dagmar; Solich, Petr

2017-05-01

A new, rapid and effective ultra-high-performance liquid chromatography method with mass spectrometry detection is described for the separation and quantification of 8-hydroxy-2-deoxyguanosine, 8-hydroxyguanosine and creatinine in human urine. The present study uses an isotope-labelled internal standard ([ 15 N] 5 -8-hydroxy-2-deoxyguanosine), a BIO core-shell stationary phase and an isocratic elution of methanol and water. Sample preparation of human urine was performed by solid-phase extraction (SPE) on Oasis HLB cartridges with methanol/water 50:50 (v/v) elution. Extraction recoveries ranged from 98.1% to 109.2%. Biological extracts showed high short-term stability. Several aspects of this procedure make it suitable for both clinical and research purposes: a short elution time of less than 3.2 min, an intra-day precision of 2.5-8.9%, an inter-day precision of 3.4-8.7% and low limits of quantification (27.7 nM for 8-hydroxyguanosine, 6.0 nM for 8-hydroxy-2-deoxyguanosine). Finally, simultaneous analysis of DNA and RNA oxidative stress biomarkers is a useful tool for monitoring disease progression in neurodegenerative disorders and cancer. Graphical abstract UHPLC-MS/MS analysis of DNA and RNA oxidative stress biomarkers.

Development of new HRA methods based upon operational experience

International Nuclear Information System (INIS)

Cooper, S.E.; Luckas, W.J.; Barriere, M.T.; Wreathall, J.

2004-01-01

Under the auspices of the US Nuclear Regulatory Commission (NRC), previously unaddressed human reliability issues are being investigated in order to support the development of human reliability analysis (HRA) methods for both low power and shutdown (LP and S) and full-power conditions. Actual operational experience, such as that reported in Licensee Event Reports (LERs), have been used to gain insights and provide a basis for the requirements of new HRA methods. In particular, operational experience has shown that new HRA methods for LP and S must address human-induced initiators, errors of commission, mistakes (vs. slips), dependencies, and the effects of multiple performance shaping factors (PSFs). (author)

Prospective comparison of three guideline development methods for treatment of actinic keratosis

NARCIS (Netherlands)

Borgonjen, Rinke J.; van Everdingen, Jannes J.; Bik, Cathelijne M.; Tuut, Mariska K.; Spuls, Phyllis I.; van de Kerkhof, Peter C.

2011-01-01

To compare three methods of guideline development, to see whether using alternative evidence-based methods resulted in variation of recommendations for treating actinic keratosis. Method 1 followed a standard multiple session evidence-based approach with a working group. In method 2 recommendations

A method for studying decision-making by guideline development groups

Directory of Open Access Journals (Sweden)

Michie Susan

2009-08-01

Full Text Available Abstract Background Multidisciplinary guideline development groups (GDGs have considerable influence on UK healthcare policy and practice, but previous research suggests that research evidence is a variable influence on GDG recommendations. The Evidence into Recommendations (EiR study has been set up to document social-psychological influences on GDG decision-making. In this paper we aim to evaluate the relevance of existing qualitative methodologies to the EiR study, and to develop a method best-suited to capturing influences on GDG decision-making. Methods A research team comprised of three postdoctoral research fellows and a multidisciplinary steering group assessed the utility of extant qualitative methodologies for coding verbatim GDG meeting transcripts and semi-structured interviews with GDG members. A unique configuration of techniques was developed to permit data reduction and analysis. Results Our method incorporates techniques from thematic analysis, grounded theory analysis, content analysis, and framework analysis. Thematic analysis of individual interviews conducted with group members at the start and end of the GDG process defines discrete problem areas to guide data extraction from GDG meeting transcripts. Data excerpts are coded both inductively and deductively, using concepts taken from theories of decision-making, social influence and group processes. These codes inform a framework analysis to describe and explain incidents within GDG meetings. We illustrate the application of the method by discussing some preliminary findings of a study of a National Institute for Health and Clinical Excellence (NICE acute physical health GDG. Conclusion This method is currently being applied to study the meetings of three of NICE GDGs. These cover topics in acute physical health, mental health and public health, and comprise a total of 45 full-day meetings. The method offers potential for application to other health care and decision

Methods of the Development Strategy of Service Companies: Logistical Approach

Science.gov (United States)

Toymentseva, Irina A.; Karpova, Natalya P.; Toymentseva, Angelina A.; Chichkina, Vera D.; Efanov, Andrey V.

2016-01-01

The urgency of the analyzed issue is due to lack of attention of heads of service companies to the theory and methodology of strategic management, methods and models of management decision-making in times of economic instability. The purpose of the article is to develop theoretical positions and methodical recommendations on the formation of the…

Recent developments in analytical detection methods for radiation processed foods

International Nuclear Information System (INIS)

Wu Jilan

1993-01-01

A short summary of the programmes of 'ADMIT' (FAO/IAEA) and the developments in analytical detection methods for radiation processed foods has been given. It is suggested that for promoting the commercialization of radiation processed foods and controlling its quality, one must pay more attention to the study of analytical detection methods of irradiated food

Accelerated molecular dynamics methods: introduction and recent developments

Energy Technology Data Exchange (ETDEWEB)

Uberuaga, Blas Pedro [Los Alamos National Laboratory; Voter, Arthur F [Los Alamos National Laboratory; Perez, Danny [Los Alamos National Laboratory; Shim, Y [UNIV OF TOLEDO; Amar, J G [UNIV OF TOLEDO

2009-01-01

A long-standing limitation in the use of molecular dynamics (MD) simulation is that it can only be applied directly to processes that take place on very short timescales: nanoseconds if empirical potentials are employed, or picoseconds if we rely on electronic structure methods. Many processes of interest in chemistry, biochemistry, and materials science require study over microseconds and beyond, due either to the natural timescale for the evolution or to the duration of the experiment of interest. Ignoring the case of liquids xxx, the dynamics on these time scales is typically characterized by infrequent-event transitions, from state to state, usually involving an energy barrier. There is a long and venerable tradition in chemistry of using transition state theory (TST) [10, 19, 23] to directly compute rate constants for these kinds of activated processes. If needed dynamical corrections to the TST rate, and even quantum corrections, can be computed to achieve an accuracy suitable for the problem at hand. These rate constants then allow them to understand the system behavior on longer time scales than we can directly reach with MD. For complex systems with many reaction paths, the TST rates can be fed into a stochastic simulation procedure such as kinetic Monte Carlo xxx, and a direct simulation of the advance of the system through its possible states can be obtained in a probabilistically exact way. A problem that has become more evident in recent years, however, is that for many systems of interest there is a complexity that makes it difficult, if not impossible, to determine all the relevant reaction paths to which TST should be applied. This is a serious issue, as omitted transition pathways can have uncontrollable consequences on the simulated long-time kinetics. Over the last decade or so, we have been developing a new class of methods for treating the long-time dynamics in these complex, infrequent-event systems. Rather than trying to guess in advance what

Accelerated molecular dynamics methods: introduction and recent developments

International Nuclear Information System (INIS)

Uberuaga, Blas Pedro; Voter, Arthur F.; Perez, Danny; Shim, Y.; Amar, J.G.

2009-01-01

A long-standing limitation in the use of molecular dynamics (MD) simulation is that it can only be applied directly to processes that take place on very short timescales: nanoseconds if empirical potentials are employed, or picoseconds if we rely on electronic structure methods. Many processes of interest in chemistry, biochemistry, and materials science require study over microseconds and beyond, due either to the natural timescale for the evolution or to the duration of the experiment of interest. Ignoring the case of liquids xxx, the dynamics on these time scales is typically characterized by infrequent-event transitions, from state to state, usually involving an energy barrier. There is a long and venerable tradition in chemistry of using transition state theory (TST) (10, 19, 23) to directly compute rate constants for these kinds of activated processes. If needed dynamical corrections to the TST rate, and even quantum corrections, can be computed to achieve an accuracy suitable for the problem at hand. These rate constants then allow them to understand the system behavior on longer time scales than we can directly reach with MD. For complex systems with many reaction paths, the TST rates can be fed into a stochastic simulation procedure such as kinetic Monte Carlo xxx, and a direct simulation of the advance of the system through its possible states can be obtained in a probabilistically exact way. A problem that has become more evident in recent years, however, is that for many systems of interest there is a complexity that makes it difficult, if not impossible, to determine all the relevant reaction paths to which TST should be applied. This is a serious issue, as omitted transition pathways can have uncontrollable consequences on the simulated long-time kinetics. Over the last decade or so, we have been developing a new class of methods for treating the long-time dynamics in these complex, infrequent-event systems. Rather than trying to guess in advance what

Developments of an Interactive Sail Design Method

OpenAIRE

S. M. Malpede; M. Vezza

2000-01-01

This paper presents a new tool for performing the integrated design and analysis of a sail. The features of the system are the geometrical definition of a sail shape, using the Bezier surface method, the creation of a finite element model for the non-linear structural analysis and a fluid-dynamic model for the aerodynamic analysis. The system has been developed using MATLAB(r). Recent sail design efforts have been focused on solving the aeroelastic behavior of the sail. The pressure dis...

Maintenance methods: Development, Trends and Recommendations[M]; Underhaallsmetoder: Utveckling, Trender och Rekommendationer

Energy Technology Data Exchange (ETDEWEB)

Ekstroem, Johan; Sonden, Mikael; Haegg, Maria; Johansson, Bernt Aake; Johansson, Mikael; Aagren, Karoline; Gunnarsson, Haakan; Sandin, Paer

2006-12-15

Vaermeforsk has an ambition to map the maintenance management area to improve its decision support to plant owners and increase the level of knowledge in the energy sector. Thus, Inspecta Technology, Fortum and Systecon have been given the task to perform a project with the expressed objectives to: describe the general knowledge level in other sectors of the industry and how the use of improvement methods contributes to the plant reliability; illustrate and recommend improvement methods applicable in the energy industry; and to identify further need for development and make priorities. The project is performed in three steps. The first consists of an inventory of existing methods and strategies. The starting point has been the typical problems you face in the maintenance field. It turns out that there are numerous examples of successful approaches used in other sectors of industry. The next step is an enquiry to describe current status in the energy sector. 21 plants were included in this study and it points out a need both for specific analysis methods and more general strategies for maintenance management. The result from both inventory and enquiry forms the base for development of the guide. The guide is structured from the identified problem areas but also from a notional maintenance process. To improve the basis for Vaermeforsk's priorities, a number of possible development areas are proposed, such as the development of standard performance indicators, pilot projects to emphasize the use of analytical methods and in some cases further development of methods for use within the energy sector.

Maintenance methods: Development, Trends and Recommendations[M]; Underhaallsmetoder: Utveckling, Trender och Rekommendationer

Energy Technology Data Exchange (ETDEWEB)

Ekstroem, Johan; Sonden, Mikael; Haegg, Maria; Johansson, Bernt Aake; Johansson, Mikael; Aagren, Karoline; Gunnarsson, Haakan; Sandin, Paer

2006-12-15

Vaermeforsk has an ambition to map the maintenance management area to improve its decision support to plant owners and increase the level of knowledge in the energy sector. Thus, Inspecta Technology, Fortum and Systecon have been given the task to perform a project with the expressed objectives to: describe the general knowledge level in other sectors of the industry and how the use of improvement methods contributes to the plant reliability; illustrate and recommend improvement methods applicable in the energy industry; and to identify further need for development and make priorities. The project is performed in three steps. The first consists of an inventory of existing methods and strategies. The starting point has been the typical problems you face in the maintenance field. It turns out that there are numerous examples of successful approaches used in other sectors of industry. The next step is an enquiry to describe current status in the energy sector. 21 plants were included in this study and it points out a need both for specific analysis methods and more general strategies for maintenance management. The result from both inventory and enquiry forms the base for development of the guide. The guide is structured from the identified problem areas but also from a notional maintenance process. To improve the basis for Vaermeforsk's priorities, a number of possible development areas are proposed, such as the development of standard performance indicators, pilot projects to emphasize the use of analytical methods and in some cases further development of methods for use within the energy sector.

A random spatial sampling method in a rural developing nation

Science.gov (United States)

Michelle C. Kondo; Kent D.W. Bream; Frances K. Barg; Charles C. Branas

2014-01-01

Nonrandom sampling of populations in developing nations has limitations and can inaccurately estimate health phenomena, especially among hard-to-reach populations such as rural residents. However, random sampling of rural populations in developing nations can be challenged by incomplete enumeration of the base population. We describe a stratified random sampling method...

Development of a New RP-UPLC Method for the Determination of ...

African Journals Online (AJOL)

Erah

Results: The developed method was linear for rabeprazole sodium from 0.03 - 30 µg/ml ... regression obtained was > 0.999. ... cost-effective for routine analysis in the pharmaceutical industry. ... a simple UPLC method for the determination.

Optimization and validation of bioanalytical SPE – HPLC method for the simultaneous determination of carbamazepine and its main metabolite, carbamazepine-10, 11-epoxide, in plasma

Directory of Open Access Journals (Sweden)

Jasmina Tonic – Ribarska

2012-03-01

Full Text Available Carbamazepine is widely used as an antiepileptic drug in the treatment of partial and generalized tonic-clonic seizures. Carbamazepine 10,11-epoxide is the most important metabolite of carbamazepine, because it is a pharmacologically active compound with anticonvulsant properties. According to that, the routine analysis of carbamazepine 10,11-epoxide along with carbamazepine may provide optimal therapeutic monitoring of carbamazepine treatment. The aim of this study was to optimize and validate a simple and reliable solid - phase extraction method followed by RP-HPLC for the simultaneous determination of plasma levels of carbamazepine and carbamazepine-10,11-epoxide, in order to assure the implementation of the method for therapeutic monitoring. The extraction of the analytes from the plasma samples was performed by means of a solid-phase extraction procedure. The separation was carried out on a reversed-phase column using isocratic elution with acetonitrile and water (35:65, v/v as a mobile phase. The temperature was 30°C and UV detection was set at 220 nm. The extraction yield values were more than 98% for all analytes, measured at four concentration levels of the linear concentration range. The method displayed excellent selectivity, sensitivity, linearity, precision and accuracy. Stability studies indicate that stock solutions and plasma samples were stabile under different storage conditions at least during the observed period. The method was successfully applied to determine the carbamazepine and carbamazepine-10,11-epoxide in plasma of epileptic patients treated with carbamazepine as monotherapy and in polytherapy. In conclusion, the proposed method is suitable for application in therapeutic drug monitoring of epileptic patients undergoing treatment with carbamazepine.

A comprehensive environmental impact assessment method for shale gas development

Directory of Open Access Journals (Sweden)

Renjin Sun

2015-03-01

Full Text Available The great success of US commercial shale gas exploitation stimulates the shale gas development in China, subsequently, the corresponding supporting policies were issued in the 12th Five-Year Plan. But from the experience in the US shale gas development, we know that the resulted environmental threats are always an unavoidable issue, but no uniform and standard evaluation system has yet been set up in China. The comprehensive environment refers to the combination of natural ecological environment and external macro-environment. In view of this, we conducted a series of studies on how to set up a comprehensive environmental impact assessment system as well as the related evaluation methodology and models. First, we made an in-depth investigation into shale gas development procedures and any possible environmental impacts, and then compared, screened and modified environmental impact assessment methods for shale gas development. Also, we established an evaluating system and assessment models according to different status of the above two types of environment: the correlation matrix method was employed to assess the impacts on natural ecological environment and the optimization distance method was modified to evaluate the impacts on external macro-environment. Finally, we substitute the two subindexes into the comprehensive environmental impact assessment model and achieved the final numerical result of environmental impact assessment. This model can be used to evaluate if a shale gas project has any impact on environment, compare the impacts before and after a shale gas development project, or the impacts of different projects.

Quantitative Developments of Biomolecular Databases, Measurement Methodology, and Comprehensive Transport Models for Bioanalytical Microfluidics

Science.gov (United States)

2006-10-01

Instead, transport equation is solved for each species independently, using the electrical drift term obtained by solving current conservation, which is...photoinitiated polymerization. The porous structure was photo-defined at a desired location using a reagent injection process (in conjunction with a Mylar ...multiplier tube device). First, it is shown that the use of the device in a CE injection and separation with matched sample and background buffers, i.e. no

DEVELOPMENT OF THE PROBABLY-GEOGRAPHICAL FORECAST METHOD FOR DANGEROUS WEATHER PHENOMENA

Directory of Open Access Journals (Sweden)

Elena S. Popova

2015-12-01

Full Text Available This paper presents a scheme method of probably-geographical forecast for dangerous weather phenomena. Discuss two general realization stages of this method. Emphasize that developing method is response to actual questions of modern weather forecast and it’s appropriate phenomena: forecast is carried out for specific point in space and appropriate moment of time.

Method for developing cost estimates for generic regulatory requirements

International Nuclear Information System (INIS)

1985-01-01

The NRC has established a practice of performing regulatory analyses, reflecting costs as well as benefits, of proposed new or revised generic requirements. A method had been developed to assist the NRC in preparing the types of cost estimates required for this purpose and for assigning priorities in the resolution of generic safety issues. The cost of a generic requirement is defined as the net present value of total lifetime cost incurred by the public, industry, and government in implementing the requirement for all affected plants. The method described here is for commercial light-water-reactor power plants. Estimating the cost for a generic requirement involves several steps: (1) identifying the activities that must be carried out to fully implement the requirement, (2) defining the work packages associated with the major activities, (3) identifying the individual elements of cost for each work package, (4) estimating the magnitude of each cost element, (5) aggregating individual plant costs over the plant lifetime, and (6) aggregating all plant costs and generic costs to produce a total, national, present value of lifetime cost for the requirement. The method developed addresses all six steps. In this paper, we discuss on the first three

Comprehensive Evaluation of the Sustainable Development of Power Grid Enterprises Based on the Model of Fuzzy Group Ideal Point Method and Combination Weighting Method with Improved Group Order Relation Method and Entropy Weight Method

Directory of Open Access Journals (Sweden)

Shuyu Dai

2017-10-01

Full Text Available As an important implementing body of the national energy strategy, grid enterprises bear the important responsibility of optimizing the allocation of energy resources and serving the economic and social development, and their levels of sustainable development have a direct impact on the national economy and social life. In this paper, the model of fuzzy group ideal point method and combination weighting method with improved group order relation method and entropy weight method is proposed to evaluate the sustainable development of power grid enterprises. Firstly, on the basis of consulting a large amount of literature, the important criteria of the comprehensive evaluation of the sustainable development of power grid enterprises are preliminarily selected. The opinions of the industry experts are consulted and fed back for many rounds through the Delphi method and the evaluation criteria system for sustainable development of power grid enterprises is determined, then doing the consistent and non dimensional processing of the evaluation criteria. After that, based on the basic order relation method, the weights of each expert judgment matrix are synthesized to construct the compound matter elements. By using matter element analysis, the subjective weights of the criteria are obtained. And entropy weight method is used to determine the objective weights of the preprocessed criteria. Then, combining the subjective and objective information with the combination weighting method based on the subjective and objective weighted attribute value consistency, a more comprehensive, reasonable and accurate combination weight is calculated. Finally, based on the traditional TOPSIS method, the triangular fuzzy numbers are introduced to better realize the scientific processing of the data information which is difficult to quantify, and the queuing indication value of each object and the ranking result are obtained. A numerical example is taken to prove that the

Developing a Clustering-Based Empirical Bayes Analysis Method for Hotspot Identification

Directory of Open Access Journals (Sweden)

Yajie Zou

2017-01-01

Full Text Available Hotspot identification (HSID is a critical part of network-wide safety evaluations. Typical methods for ranking sites are often rooted in using the Empirical Bayes (EB method to estimate safety from both observed crash records and predicted crash frequency based on similar sites. The performance of the EB method is highly related to the selection of a reference group of sites (i.e., roadway segments or intersections similar to the target site from which safety performance functions (SPF used to predict crash frequency will be developed. As crash data often contain underlying heterogeneity that, in essence, can make them appear to be generated from distinct subpopulations, methods are needed to select similar sites in a principled manner. To overcome this possible heterogeneity problem, EB-based HSID methods that use common clustering methodologies (e.g., mixture models, K-means, and hierarchical clustering to select “similar” sites for building SPFs are developed. Performance of the clustering-based EB methods is then compared using real crash data. Here, HSID results, when computed on Texas undivided rural highway cash data, suggest that all three clustering-based EB analysis methods are preferred over the conventional statistical methods. Thus, properly classifying the road segments for heterogeneous crash data can further improve HSID accuracy.

development of a hydrothermal method to synthesize spherical znse

African Journals Online (AJOL)

Preferred Customer

nanoparticles have a zinc blend structure and in a spherical form with ... optoelectronic devices such as blue-green laser diodes and turnable mid-IR ... Solvothermal methods have also been developed for the synthesis of ZnSe and CdSe. The.

Method development of damage detection in asymmetric buildings

Science.gov (United States)

Wang, Yi; Thambiratnam, David P.; Chan, Tommy H. T.; Nguyen, Andy

2018-01-01

Aesthetics and functionality requirements have caused most buildings to be asymmetric in recent times. Such buildings exhibit complex vibration characteristics under dynamic loads as there is coupling between the lateral and torsional components of vibration, and are referred to as torsionally coupled buildings. These buildings require three dimensional modelling and analysis. In spite of much recent research and some successful applications of vibration based damage detection methods to civil structures in recent years, the applications to asymmetric buildings has been a challenging task for structural engineers. There has been relatively little research on detecting and locating damage specific to torsionally coupled asymmetric buildings. This paper aims to compare the difference in vibration behaviour between symmetric and asymmetric buildings and then use the vibration characteristics for predicting damage in them. The need for developing a special method to detect damage in asymmetric buildings thus becomes evident. Towards this end, this paper modifies the traditional modal strain energy based damage index by decomposing the mode shapes into their lateral and vertical components and to form component specific damage indices. The improved approach is then developed by combining the modified strain energy based damage indices with the modal flexibility method which was modified to suit three dimensional structures to form a new damage indicator. The procedure is illustrated through numerical studies conducted on three dimensional five-story symmetric and asymmetric frame structures with the same layout, after validating the modelling techniques through experimental testing of a laboratory scale asymmetric building model. Vibration parameters obtained from finite element analysis of the intact and damaged building models are then applied into the proposed algorithms for detecting and locating the single and multiple damages in these buildings. The results

Development of precursors recognition methods in vector signals

Science.gov (United States)

Kapralov, V. G.; Elagin, V. V.; Kaveeva, E. G.; Stankevich, L. A.; Dremin, M. M.; Krylov, S. V.; Borovov, A. E.; Harfush, H. A.; Sedov, K. S.

2017-10-01

Precursor recognition methods in vector signals of plasma diagnostics are presented. Their requirements and possible options for their development are considered. In particular, the variants of using symbolic regression for building a plasma disruption prediction system are discussed. The initial data preparation using correlation analysis and symbolic regression is discussed. Special attention is paid to the possibility of using algorithms in real time.

Research on assessment methods for urban public transport development in China.

Science.gov (United States)

Zou, Linghong; Dai, Hongna; Yao, Enjian; Jiang, Tian; Guo, Hongwei

2014-01-01

In recent years, with the rapid increase in urban population, the urban travel demands in Chinese cities have been increasing dramatically. As a result, developing comprehensive urban transport systems becomes an inevitable choice to meet the growing urban travel demands. In urban transport systems, public transport plays the leading role to promote sustainable urban development. This paper aims to establish an assessment index system for the development level of urban public transport consisting of a target layer, a criterion layer, and an index layer. Review on existing literature shows that methods used in evaluating urban public transport structure are dominantly qualitative. To overcome this shortcoming, fuzzy mathematics method is used for describing qualitative issues quantitatively, and AHP (analytic hierarchy process) is used to quantify expert's subjective judgment. The assessment model is established based on the fuzzy AHP. The weight of each index is determined through the AHP and the degree of membership of each index through the fuzzy assessment method to obtain the fuzzy synthetic assessment matrix. Finally, a case study is conducted to verify the rationality and practicability of the assessment system and the proposed assessment method.

Human resource training and development. The outdoor management method.

OpenAIRE

THANOS KRIEMADIS; ANNA KOURTESOPOULOU

2008-01-01

In the age of international competition in today’s economy, companies must train their employees and prepare them for jobs in the future. There are many different types and educational approaches in human resource training, but the present study will focus on the Outdoor Management Development (OMD). For better understanding, the particular training method and the core stages of the training process will be examined and the definitions of OMD as an educational tool for management development ...

Development and validation of analytical methods for dietary supplements

International Nuclear Information System (INIS)

Sullivan, Darryl; Crowley, Richard

2006-01-01

The expanding use of innovative botanical ingredients in dietary supplements and foods has resulted in a flurry of research aimed at the development and validation of analytical methods for accurate measurement of active ingredients. The pressing need for these methods is being met through an expansive collaborative initiative involving industry, government, and analytical organizations. This effort has resulted in the validation of several important assays as well as important advances in the method engineering procedures which have improved the efficiency of the process. The initiative has also allowed researchers to hurdle many of the barricades that have hindered accurate analysis such as the lack of reference standards and comparative data. As the availability for nutraceutical products continues to increase these methods will provide consumers and regulators with the scientific information needed to assure safety and dependable labeling

Design of Embedded Real-time Systems: Developing a Method for Practical Software Engineering

DEFF Research Database (Denmark)

Løvengreen, Hans Henrik; Ravn, Anders P.; Rischel, Hans

1990-01-01

The methodological issues and practical problems in development and industrial use of a theory-based design method for embedded, real-time systems are discussed. The method has been used for several years in a number of smaller industries that develop both electronics and software for a professio......The methodological issues and practical problems in development and industrial use of a theory-based design method for embedded, real-time systems are discussed. The method has been used for several years in a number of smaller industries that develop both electronics and software...... for a professional market. The design is expressed in a notation for communicating sequential processes, while data types and operations are expressed in a notation built on mathematical set theory. The authors present an order in which to use the notations, a technique for deriving states and operations...

Development of K-Nearest Neighbour Regression Method in Forecasting River Stream Flow

Directory of Open Access Journals (Sweden)

Mohammad Azmi

2012-07-01

Full Text Available Different statistical, non-statistical and black-box methods have been used in forecasting processes. Among statistical methods, K-nearest neighbour non-parametric regression method (K-NN due to its natural simplicity and mathematical base is one of the recommended methods for forecasting processes. In this study, K-NN method is explained completely. Besides, development and improvement approaches such as best neighbour estimation, data transformation functions, distance functions and proposed extrapolation method are described. K-NN method in company with its development approaches is used in streamflow forecasting of Zayandeh-Rud Dam upper basin. Comparing between final results of classic K-NN method and modified K-NN (number of neighbour 5, transformation function of Range Scaling, distance function of Mahanalobis and proposed extrapolation method shows that modified K-NN in criteria of goodness of fit, root mean square error, percentage of volume of error and correlation has had performance improvement 45% , 59% and 17% respectively. These results approve necessity of applying mentioned approaches to derive more accurate forecasts.