WorldWideScience

Sample records for sensitive bioanalytical method

  1. The 10th Annual Bioassays and Bioanalytical Method Development Conference.

    Science.gov (United States)

    Ma, Mark; Tudan, Christopher; Koltchev, Dolly

    2015-01-01

    The 10th Annual Bioassays and Bioanalytical Method Development Conference was hosted in Boston, MA, USA on 20-22 October 2014. This meeting brought together scientists from the biopharmaceutical and life sciences industries, the regulatory agency and academia to share and discuss current trends in cell-based assays and bioanalysis, challenges and ideas for the future of the bioassays and bioanalytical method development. The experiences associated with new and innovative technologies were evaluated as well as their impact on the current bioassays methodologies and bioanalysis workflow, including quality, feasibility, outsourcing strategies and challenges, productivity and compliance. Several presentations were also provided by members of the US FDA, sharing both scientific and regulatory paradigms including a most recent update on the position of the FDA with specific aspects of the draft Bioanalytical Method Validation guidance following its review of the industry's responses. The meeting was jointly coincided with the 15th Annual Immunogenicity for Biotherapeutics meeting, allowing for attendees to also familiarize themselves with new and emerging approaches to overcome the effect of immunogenicity, in addition to investigative strategies.

  2. Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review ☆

    OpenAIRE

    Datar, Prasanna A.

    2015-01-01

    Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharmacology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application). Various methods such as GC, LC–MS/MS, HPLC, HPTLC, micellar electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and qua...

  3. Bioanalytical method transfer considerations of chromatographic-based assays.

    Science.gov (United States)

    Williard, Clark V

    2016-07-01

    Bioanalysis is an important part of the modern drug development process. The business practice of outsourcing and transferring bioanalytical methods from laboratory to laboratory has increasingly become a crucial strategy for successful and efficient delivery of therapies to the market. This chapter discusses important considerations when transferring various types of chromatographic-based assays in today's pharmaceutical research and development environment.

  4. Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review

    Directory of Open Access Journals (Sweden)

    Prasanna A. Datar

    2015-08-01

    Full Text Available Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharmacology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application. Various methods such as GC, LC–MS/MS, HPLC, HPTLC, micellar electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and quantitative analysis of carbamazepine in biological samples throughout all phases of clinical research and quality control. The article incorporates various reported methods developed to help analysts in choosing crucial parameters for new method development of carbamazepine and its derivatives and also enumerates metabolites, and impurities reported so far. Keywords: Carbamazepine, HPLC, LC–MS/MS, HPTLC, RP-UFLC, Micellar electrokinetic chromatography

  5. Impact of Chiral Bioanalytical Methods on the Bioequivalence of Ibuprofen Products Containing Ibuprofen Lysinate and Ibuprofen Base.

    Science.gov (United States)

    García-Arieta, Alfredo; Ferrero-Cafiero, Juan Manuel; Puntes, Montse; Gich, Ignasi; Morales-Alcelay, Susana; Tarré, Maite; Font, Xavier; Antonijoan, Rosa Maria

    2016-05-01

    The purpose was to assess the impact of the use of a chiral bioanalytical method on the conclusions of a bioequivalence study that compared two ibuprofen suspensions with different rates of absorption. A comparison of the conclusion of bioequivalence between a chiral method and an achiral approach was made. Plasma concentrations of R-ibuprofen and S-ibuprofen were determined using a chiral bioanalytical method; bioequivalence was tested for R-ibuprofen and for S-ibuprofen separately and for the sum of both enantiomers as an approach for an achiral bioanalytical method. The 90% confidence interval (90% CI) that would have been obtained with an achiral bioanalytical method (90% CI: Cmax: 117.69-134.46; AUC0 (t) : 104.75-114.45) would have precluded the conclusion of bioequivalence. This conclusion cannot be generalized to the active enantiomer (90% CI: Cmax : 103.36-118.38; AUC0 (t) : 96.52-103.12), for which bioequivalence can be concluded, and/or the distomer (90% CI: Cmax : 132.97-151.33; AUC0 (t) : 115.91-135.77) for which a larger difference was observed. Chiral bioanalytical methods should be required when 1) the enantiomers exhibit different pharmacodynamics and 2) the exposure (AUC or Cmax ) ratio of enantiomers is modified by a difference in the rate of absorption. Furthermore, the bioequivalence conclusion should be based on all enantiomers, since the distomer(s) might not be completely inert, in contrast to what is required in the current regulatory guidelines. In those cases where it is unknown if the ratio between enantiomers is modified by changing the rate of absorption, chiral bioanalytical methods should be employed unless enantiomers exhibit the same pharmacodynamics. Chirality 28:429-433, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Bioanalytical HPTLC Method for Estimation of Zolpidem Tartrate from Human Plasma

    OpenAIRE

    Abhay R. Shirode; Bharti G. Jadhav; Vilasrao J. Kadam

    2016-01-01

    A simple and selective high performance thin layer chromatographic (HPTLC) method was developed and validated for the estimation of zolpidem tartrate from human plasma using eperisone hydrochloride as an internal standard (IS). Analyte and IS were extracted from human plasma by liquid liquid extraction (LLE) technique. The Camag HPTLC system, employed with software winCATS (ver.1.4.1.8) was used for the proposed bioanalytical work. Planar chromatographic development was carried out with the h...

  7. Pharmacokinetic-pharmacodynamic correlation of imipenem in pediatric burn patients using a bioanalytical liquid chromatographic method

    Directory of Open Access Journals (Sweden)

    Silvia Regina Cavani Jorge Santos

    2015-06-01

    Full Text Available A bioanalytical method was developed and applied to quantify the free imipenem concentrations for pharmacokinetics and PK/PD correlation studies of the dose adjustments required to maintain antimicrobial effectiveness in pediatric burn patients. A reverse-phase Supelcosil LC18 column (250 x 4.6 mm 5 micra, binary mobile phase consisting of 0.01 M, pH 7.0 phosphate buffer and acetonitrile (99:1, v/v, flow rate of 0.8 mL/min, was applied. The method showed good absolute recovery (above 90%, good linearity (0.25-100.0 µg/mL, r2=0.999, good sensitivity (LLOQ: 0.25 µg/mL; LLOD: 0.12 µg/mL and acceptable stability. Inter/intraday precision values were 7.3/5.9%, and mean accuracy was 92.9%. A bioanalytical method was applied to quantify free drug concentrations in children with burns. Six pediatric burn patients (median 7.0 years old, 27.5 kg, normal renal function, and 33% total burn surface area were prospectively investigated; inhalation injuries were present in 4/6 (67% of the patients. Plasma monitoring and PK assessments were performed using a serial blood sample collection for each set, totaling 10 sets. The PK/PD target attained (40%T>MIC for each minimum inhibitory concentration (MIC: 0.5, 1.0, 2.0, 4.0 mg/L occurred at a percentage higher than 80% of the sets investigated and 100% after dose adjustment. In conclusion, the purification of plasma samples using an ultrafiltration technique followed by quantification of imipenem plasma measurements using the LC method is quite simple, useful, and requires small volumes for blood sampling. In addition, a small amount of plasma (0.25 mL is needed to guarantee drug effectiveness in pediatric burn patients. There is also a low risk of neurotoxicity, which is important because pharmacokinetics are unpredictable in these critical patients with severe hospital infection. Finally, the PK/PD target was attained for imipenem in the control of sepsis in pediatric patients with burns.

  8. 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)

  9. Bioanalytical LC-MS/MS of protein-based biopharmaceuticals

    NARCIS (Netherlands)

    Broek, I. van den; Niessen, W.M.A.; Dongen, W.D. van

    2013-01-01

    Biotechnology increasingly delivers highly promising protein-based biopharmaceutical candidates to the drug development funnel. For successful biopharmaceutical drug development, reliable bioanalytical methods enabling quantification of drugs in biological fluids (plasma, urine, tissue, etc.) are

  10. Outsourcing bioanalytical services at Janssen Research and Development: the sequel anno 2017.

    Science.gov (United States)

    Dillen, Lieve; Verhaeghe, Tom

    2017-08-01

    The strategy of outsourcing bioanalytical services at Janssen has been evolving over the last years and an update will be given on the recent changes in our processes. In 2016, all internal GLP-related activities were phased out and this decision lead to the re-orientation of the in-house bioanalytical activities. As a consequence, in-depth experience with the validated bioanalytical assays for new drug candidates is currently gained together with the external partner, since development and validation of the assay and execution of GLP preclinical studies are now transferred to the CRO. The evolution to externalize more bioanalytical support has created opportunities to build even stronger partnerships with the CROs and to refocus internal resources. Case studies are presented illustrating challenges encountered during method development and validation at preferred partners when limited internal experience is obtained or with introduction of new technology.

  11. 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

  12. Bioanalytical outsourcing strategy at Janssen Research and Development.

    Science.gov (United States)

    Verhaeghe, Tom

    2014-05-01

    The times when all bioanalytical work was supported in-house are long behind us. In the modern bioanalytical laboratory, workload is divided between in-house support and outsourcing to contract research organizations. This paper outlines the outsourcing strategy of the Janssen-regulated bioanalytical group. Keeping the knowledge of the assay and the compound internally is a cornerstone of this strategy and is a driver for balancing the workload between the internal laboratory and contract laboratories. The number of contract laboratories that are being used is limited and criteria for selecting laboratories are discussed. Special attention is paid to the experience with outsourcing clinical studies to China.

  13. Calculations for Adjusting Endogenous Biomarker Levels During Analytical Recovery Assessments for Ligand-Binding Assay Bioanalytical Method Validation.

    Science.gov (United States)

    Marcelletti, John F; Evans, Cindy L; Saxena, Manju; Lopez, Adriana E

    2015-07-01

    It is often necessary to adjust for detectable endogenous biomarker levels in spiked validation samples (VS) and in selectivity determinations during bioanalytical method validation for ligand-binding assays (LBA) with a matrix like normal human serum (NHS). Described herein are case studies of biomarker analyses using multiplex LBA which highlight the challenges associated with such adjustments when calculating percent analytical recovery (%AR). The LBA test methods were the Meso Scale Discovery V-PLEX® proinflammatory and cytokine panels with NHS as test matrix. The NHS matrix blank exhibited varied endogenous content of the 20 individual cytokines before spiking, ranging from undetectable to readily quantifiable. Addition and subtraction methods for adjusting endogenous cytokine levels in %AR calculations are both used in the bioanalytical field. The two methods were compared in %AR calculations following spiking and analysis of VS for cytokines having detectable endogenous levels in NHS. Calculations for %AR obtained by subtracting quantifiable endogenous biomarker concentrations from the respective total analytical VS values yielded reproducible and credible conclusions. The addition method, in contrast, yielded %AR conclusions that were frequently unreliable and discordant with values obtained with the subtraction adjustment method. It is shown that subtraction of assay signal attributable to matrix is a feasible alternative when endogenous biomarkers levels are below the limit of quantitation, but above the limit of detection. These analyses confirm that the subtraction method is preferable over that using addition to adjust for detectable endogenous biomarker levels when calculating %AR for biomarker LBA.

  14. 3D-printed Bioanalytical Devices

    Science.gov (United States)

    Bishop, Gregory W; Satterwhite-Warden, Jennifer E; Kadimisetty, Karteek; Rusling, James F

    2016-01-01

    While 3D printing technologies first appeared in the 1980s, prohibitive costs, limited materials, and the relatively small number of commercially available printers confined applications mainly to prototyping for manufacturing purposes. As technologies, printer cost, materials, and accessibility continue to improve, 3D printing has found widespread implementation in research and development in many disciplines due to ease-of-use and relatively fast design-to-object workflow. Several 3D printing techniques have been used to prepare devices such as milli- and microfluidic flow cells for analyses of cells and biomolecules as well as interfaces that enable bioanalytical measurements using cellphones. This review focuses on preparation and applications of 3D-printed bioanalytical devices. PMID:27250897

  15. Advanced bioanalytics for precision medicine.

    Science.gov (United States)

    Roda, Aldo; Michelini, Elisa; Caliceti, Cristiana; Guardigli, Massimo; Mirasoli, Mara; Simoni, Patrizia

    2018-01-01

    Precision medicine is a new paradigm that combines diagnostic, imaging, and analytical tools to produce accurate diagnoses and therapeutic interventions tailored to the individual patient. This approach stands in contrast to the traditional "one size fits all" concept, according to which researchers develop disease treatments and preventions for an "average" patient without considering individual differences. The "one size fits all" concept has led to many ineffective or inappropriate treatments, especially for pathologies such as Alzheimer's disease and cancer. Now, precision medicine is receiving massive funding in many countries, thanks to its social and economic potential in terms of improved disease prevention, diagnosis, and therapy. Bioanalytical chemistry is critical to precision medicine. This is because identifying an appropriate tailored therapy requires researchers to collect and analyze information on each patient's specific molecular biomarkers (e.g., proteins, nucleic acids, and metabolites). In other words, precision diagnostics is not possible without precise bioanalytical chemistry. This Trend article highlights some of the most recent advances, including massive analysis of multilayer omics, and new imaging technique applications suitable for implementing precision medicine. Graphical abstract Precision medicine combines bioanalytical chemistry, molecular diagnostics, and imaging tools for performing accurate diagnoses and selecting optimal therapies for each patient.

  16. Sample Preparation and Extraction in Small Sample Volumes Suitable for Pediatric Clinical Studies: Challenges, Advances, and Experiences of a Bioanalytical HPLC-MS/MS Method Validation Using Enalapril and Enalaprilat

    Science.gov (United States)

    Burckhardt, Bjoern B.; Laeer, Stephanie

    2015-01-01

    In USA and Europe, medicines agencies force the development of child-appropriate medications and intend to increase the availability of information on the pediatric use. This asks for bioanalytical methods which are able to deal with small sample volumes as the trial-related blood lost is very restricted in children. Broadly used HPLC-MS/MS, being able to cope with small volumes, is susceptible to matrix effects. The latter restrains the precise drug quantification through, for example, causing signal suppression. Sophisticated sample preparation and purification utilizing solid-phase extraction was applied to reduce and control matrix effects. A scale-up from vacuum manifold to positive pressure manifold was conducted to meet the demands of high-throughput within a clinical setting. Faced challenges, advances, and experiences in solid-phase extraction are exemplarily presented on the basis of the bioanalytical method development and validation of low-volume samples (50 μL serum). Enalapril, enalaprilat, and benazepril served as sample drugs. The applied sample preparation and extraction successfully reduced the absolute and relative matrix effect to comply with international guidelines. Recoveries ranged from 77 to 104% for enalapril and from 93 to 118% for enalaprilat. The bioanalytical method comprising sample extraction by solid-phase extraction was fully validated according to FDA and EMA bioanalytical guidelines and was used in a Phase I study in 24 volunteers. PMID:25873972

  17. Sample Preparation and Extraction in Small Sample Volumes Suitable for Pediatric Clinical Studies: Challenges, Advances, and Experiences of a Bioanalytical HPLC-MS/MS Method Validation Using Enalapril and Enalaprilat

    Directory of Open Access Journals (Sweden)

    Bjoern B. Burckhardt

    2015-01-01

    Full Text Available In USA and Europe, medicines agencies force the development of child-appropriate medications and intend to increase the availability of information on the pediatric use. This asks for bioanalytical methods which are able to deal with small sample volumes as the trial-related blood lost is very restricted in children. Broadly used HPLC-MS/MS, being able to cope with small volumes, is susceptible to matrix effects. The latter restrains the precise drug quantification through, for example, causing signal suppression. Sophisticated sample preparation and purification utilizing solid-phase extraction was applied to reduce and control matrix effects. A scale-up from vacuum manifold to positive pressure manifold was conducted to meet the demands of high-throughput within a clinical setting. Faced challenges, advances, and experiences in solid-phase extraction are exemplarily presented on the basis of the bioanalytical method development and validation of low-volume samples (50 μL serum. Enalapril, enalaprilat, and benazepril served as sample drugs. The applied sample preparation and extraction successfully reduced the absolute and relative matrix effect to comply with international guidelines. Recoveries ranged from 77 to 104% for enalapril and from 93 to 118% for enalaprilat. The bioanalytical method comprising sample extraction by solid-phase extraction was fully validated according to FDA and EMA bioanalytical guidelines and was used in a Phase I study in 24 volunteers.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Cellphone-based devices for bioanalytical sciences

    Science.gov (United States)

    Vashist, Sandeep Kumar; Mudanyali, Onur; Schneider, E.Marion; Zengerle, Roland; Ozcan, Aydogan

    2014-01-01

    During the last decade, there has been a rapidly growing trend toward the use of cellphone-based devices (CBDs) in bioanalytical sciences. For example, they have been used for digital microscopy, cytometry, read-out of immunoassays and lateral flow tests, electrochemical and surface plasmon resonance based bio-sensing, colorimetric detection and healthcare monitoring, among others. Cellphone can be considered as one of the most prospective devices for the development of next-generation point-of-care (POC) diagnostics platforms, enabling mobile healthcare delivery and personalized medicine. With more than 6.5 billion cellphone subscribers worldwide and approximately 1.6 billion new devices being sold each year, cellphone technology is also creating new business and research opportunities. Many cellphone-based devices, such as those targeted for diabetic management, weight management, monitoring of blood pressure and pulse rate, have already become commercially-available in recent years. In addition to such monitoring platforms, several other CBDs are also being introduced, targeting e.g., microscopic imaging and sensing applications for medical diagnostics using novel computational algorithms and components already embedded on cellphones. This manuscript aims to review these recent developments in CBDs for bioanalytical sciences along with some of the challenges involved and the future opportunities. PMID:24287630

  6. BIOANALYTICAL STANDARDIZING FOR SEROLOGICAL DIAGNOSTIC MEDICAL DEVICES

    Directory of Open Access Journals (Sweden)

    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.

  7. 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...

  8. 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.

  9. Synergic development of pharmacokinetics and bioanalytical methods as support of pharmaceutical research.

    Science.gov (United States)

    Marzo, M; Ciccarelli, R; Di Iorio, P; Giuliani, P; Caciagli, F; Marzo, A

    2016-06-01

    The development of pharmacokinetics led this science to achieve a relevant role in the investigation of new chemical entities for therapeutic application, and has allowed a series of new useful realizations of out of patent drugs like prolonged release and delayed release formulations, therapeutic delivery system (TDS) for drugs to be active in systemic circulation avoiding the first pass effect, orodispersible and effervescent formulations, intramuscular and subcutaneous depot formulations acting over a long period, oral inhalatory systems, and drug association at fixed dose. The above applications had pharmacokinetics as protagonist and have required the support from bioanalytical methods to assay drug concentrations, even in pg·mL(-1) of plasma, that really have paralleled the synergic development of pharmacokinetics.The complexity of the above realizations required specific guidelines from the regulatory authorities, mainly the US FDA and EU EMA, which have normalized and, in most cases, simplified the above applications admitting some waivers of in vivo bioequivalence.However, this review highlights some critical points, not yet focused on by operating guidelines, which need to be clarified by regulatory authorities. One of the most relevant issues is about the planning and conducting bioavailability and bioequivalence trials with endogenous substances, that possess own homeostatic equilibria with fluctuations, in some cases with specific rhythms, like melatonin and female sex hormones. The baseline subtraction required by guidelines to define the net contribute to the exogenous absorbed drug in most cases is a non-solvable problem. © The Author(s) 2015.

  10. 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.

  11. Developing a strategy for a regulated electronic bioanalytical laboratory.

    Science.gov (United States)

    McDowall, R D

    2014-01-01

    This perspective article considers the strategy, design and implementation of an electronic bioanalytical laboratory working to GLP and/or GCP regulations. There are a range of available automated systems and laboratory informatics that could be implemented and integrated to make an electronic laboratory. However, which are the appropriate ones to select and what is realistic and cost-effective for an individual laboratory? The answer is to develop an overall automation strategy that is updated periodically after each system or application has been implemented to assess if the strategy is still valid or needs to be changed. As many laboratory informatics applications have functional overlap or convergence, for example, Laboratory Information Management System, Electronic Laboratory Notebook, and Instrument and Chromatography Data Systems, the decision of which application performs a specific task needs to be carefully considered in the overall strategy. Ensuring data integrity and regulatory compliance, especially in light of a number of recent falsification cases, is a mandatory consideration for the overall strategy for an electronic bioanalytical laboratory submitting data to regulatory authorities.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. A high efficiency, high quality and low cost internal regulated bioanalytical laboratory to support drug development needs.

    Science.gov (United States)

    Song, Yan; Dhodda, Raj; Zhang, Jun; Sydor, Jens

    2014-05-01

    In the recent past, we have seen an increase in the outsourcing of bioanalysis in pharmaceutical companies in support of their drug development pipeline. This trend is largely driven by the effort to reduce internal cost, especially in support of late-stage pipeline assets where established bioanalytical assays are used to analyze a large volume of samples. This article will highlight our perspective of how bioanalytical laboratories within pharmaceutical companies can be developed into the best partner in the advancement of drug development pipelines with high-quality support at competitive cost.

  18. 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

  19. 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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. Strategies for the design of bright upconversion nanoparticles for bioanalytical applications

    Science.gov (United States)

    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.

  4. 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.

  5. Bio-analytical method development and validation of Rasagiline by high performance liquid chromatography tandem mass spectrometry detection and its application to pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Ravi Kumar Konda

    2012-10-01

    Full Text Available The most suitable bio-analytical method based on liquid–liquid extraction has been developed and validated for quantification of Rasagiline in human plasma. Rasagiline-13C3 mesylate was used as an internal standard for Rasagiline. Zorbax Eclipse Plus C18 (2.1 mm×50 mm, 3.5 μm column provided chromatographic separation of analyte followed by detection with mass spectrometry. The method involved simple isocratic chromatographic condition and mass spectrometric detection in the positive ionization mode using an API-4000 system. The total run time was 3.0 min. The proposed method has been validated with the linear range of 5–12000 pg/mL for Rasagiline. The intra-run and inter-run precision values were within 1.3%–2.9% and 1.6%–2.2% respectively for Rasagiline. The overall recovery for Rasagiline and Rasagiline-13C3 mesylate analog was 96.9% and 96.7% respectively. This validated method was successfully applied to the bioequivalence and pharmacokinetic study of human volunteers under fasting condition. Keywords: High performance liquid chromatography, Mass spectrometry, Rasagiline, Liquid–liquid extraction

  6. 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...

  7. 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.

  8. 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

  9. 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)....

  10. 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.

  11. 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

  12. 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.

  13. Biological methods used to assess surface water quality

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

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

    Science.gov (United States)

    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

  16. 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.

  17. 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.

  18. 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.

  19. 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

    Directory of Open Access Journals (Sweden)

    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

  20. 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.

  1. 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.

  2. 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.

  3. 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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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...

  7. Sensitive magnetic biodetection using magnetic multi-core nanoparticles and RCA coils

    Energy Technology Data Exchange (ETDEWEB)

    Ahrentorp, Fredrik; Blomgren, Jakob; Jonasson, Christian; Sarwe, Anna [Acreo Swedish ICT AB, Arvid Hedvalls Backe 4, Göteborg (Sweden); Sepehri, Sobhan; Eriksson, Emil; Kalaboukhov, Alexei; Jesorka, Aldo; Winkler, Dag [Department of Microtechnology and Nanoscience – MC2, Chalmers University of Technology, Göteborg (Sweden); Schneiderman, Justin F. [Institute of Neuroscience and Physiology, University of Gothenburg and MedTech West, Göteborg (Sweden); Nilsson, Mats [Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm (Sweden); Albert, Jan [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm (Sweden); Department of Clinical Microbiology, Karolinska University Hospital, Stockholm (Sweden); Zardán Gómez de la Torre, Teresa; Strømme, Maria [Uppsala University, Uppsala (Sweden); Johansson, Christer, E-mail: christer.johansson@acreo.se [Acreo Swedish ICT AB, Arvid Hedvalls Backe 4, Göteborg (Sweden)

    2017-04-01

    We use functionalized iron oxide magnetic multi-core particles of 100 nm in size (hydrodynamic particle diameter) and AC susceptometry (ACS) methods to measure the binding reactions between the magnetic nanoparticles (MNPs) and bio-analyte products produced from DNA segments using the rolling circle amplification (RCA) method. We use sensitive induction detection techniques in order to measure the ACS response. The DNA is amplified via RCA to generate RCA coils with a specific size that is dependent on the amplification time. After about 75 min of amplification we obtain an average RCA coil diameter of about 1 µm. We determine a theoretical limit of detection (LOD) in the range of 11 attomole (corresponding to an analyte concentration of 55 fM for a sample volume of 200 µL) from the ACS dynamic response after the MNPs have bound to the RCA coils and the measured ACS readout noise. We also discuss further possible improvements of the LOD. - Highlights: • Biosensing using Brownian relaxation of functionalized magnetic nanoparticles. • Rolling circle amplification and magnetic nanoparticles enables biosensing. • Theoretical limit of detection estimated from the signal noise gives about 55 fM.

  8. 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...

  9. 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.

  10. 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 ...

  11. 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.

  12. Multiple predictor smoothing methods for sensitivity analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Helton, Jon Craig; Storlie, Curtis B.

    2006-08-01

    The use of multiple predictor smoothing methods in sampling-based sensitivity analyses of complex models is investigated. Specifically, sensitivity analysis procedures based on smoothing methods employing the stepwise application of the following nonparametric regression techniques are described: (1) locally weighted regression (LOESS), (2) additive models, (3) projection pursuit regression, and (4) recursive partitioning regression. The indicated procedures are illustrated with both simple test problems and results from a performance assessment for a radioactive waste disposal facility (i.e., the Waste Isolation Pilot Plant). As shown by the example illustrations, the use of smoothing procedures based on nonparametric regression techniques can yield more informative sensitivity analysis results than can be obtained with more traditional sensitivity analysis procedures based on linear regression, rank regression or quadratic regression when nonlinear relationships between model inputs and model predictions are present.

  13. Multiple predictor smoothing methods for sensitivity analysis

    International Nuclear Information System (INIS)

    Helton, Jon Craig; Storlie, Curtis B.

    2006-01-01

    The use of multiple predictor smoothing methods in sampling-based sensitivity analyses of complex models is investigated. Specifically, sensitivity analysis procedures based on smoothing methods employing the stepwise application of the following nonparametric regression techniques are described: (1) locally weighted regression (LOESS), (2) additive models, (3) projection pursuit regression, and (4) recursive partitioning regression. The indicated procedures are illustrated with both simple test problems and results from a performance assessment for a radioactive waste disposal facility (i.e., the Waste Isolation Pilot Plant). As shown by the example illustrations, the use of smoothing procedures based on nonparametric regression techniques can yield more informative sensitivity analysis results than can be obtained with more traditional sensitivity analysis procedures based on linear regression, rank regression or quadratic regression when nonlinear relationships between model inputs and model predictions are present

  14. 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, ...

  15. 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.; hide

    2016-01-01

    We will present details and initial lab test results from an integrated bioanalytical microsystem designed to conduct the first biology experiments beyond low Earth orbit (LEO) since Apollo 17 (1972). The 14-kg, 12x24x37-cm BioSentinel spacecraft (Figure 1) assays radiation-responsive yeast in its science payload by measuring DNA double-strand breaks (DSBs) repaired via homologous recombination, a mechanism common to all eukaryotes including humans. S. cerevisiae (brewer's yeast) in 288 microwells are provided with nutrient and optically assayed for growth and metabolism via 3-color absorptimetry monthly during the 18-month mission. BioSentinel is one of several secondary payloads to be deployed by NASA's Exploration Mission 1 (EM-1) launch vehicle into approximately 0.95 AU heliocentric orbit in July 2018; it will communicate with Earth from up to 100 million km.

  16. 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.

  17. 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

  18. 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.

  19. An ESDIRK Method with Sensitivity Analysis Capabilities

    DEFF Research Database (Denmark)

    Kristensen, Morten Rode; Jørgensen, John Bagterp; Thomsen, Per Grove

    2004-01-01

    of the sensitivity equations. A key feature is the reuse of information already computed for the state integration, hereby minimizing the extra effort required for sensitivity integration. Through case studies the new algorithm is compared to an extrapolation method and to the more established BDF based approaches...

  20. A New Computationally Frugal Method For Sensitivity Analysis Of Environmental Models

    Science.gov (United States)

    Rakovec, O.; Hill, M. C.; Clark, M. P.; Weerts, A.; Teuling, R.; Borgonovo, E.; Uijlenhoet, R.

    2013-12-01

    Effective and efficient parameter sensitivity analysis methods are crucial to understand the behaviour of complex environmental models and use of models in risk assessment. This paper proposes a new computationally frugal method for analyzing parameter sensitivity: the Distributed Evaluation of Local Sensitivity Analysis (DELSA). The DELSA method can be considered a hybrid of local and global methods, and focuses explicitly on multiscale evaluation of parameter sensitivity across the parameter space. Results of the DELSA method are compared with the popular global, variance-based Sobol' method and the delta method. We assess the parameter sensitivity of both (1) a simple non-linear reservoir model with only two parameters, and (2) five different "bucket-style" hydrologic models applied to a medium-sized catchment (200 km2) in the Belgian Ardennes. Results show that in both the synthetic and real-world examples, the global Sobol' method and the DELSA method provide similar sensitivities, with the DELSA method providing more detailed insight at much lower computational cost. The ability to understand how sensitivity measures vary through parameter space with modest computational requirements provides exciting new opportunities.

  1. A general first-order global sensitivity analysis method

    International Nuclear Information System (INIS)

    Xu Chonggang; Gertner, George Zdzislaw

    2008-01-01

    Fourier amplitude sensitivity test (FAST) is one of the most popular global sensitivity analysis techniques. The main mechanism of FAST is to assign each parameter with a characteristic frequency through a search function. Then, for a specific parameter, the variance contribution can be singled out of the model output by the characteristic frequency. Although FAST has been widely applied, there are two limitations: (1) the aliasing effect among parameters by using integer characteristic frequencies and (2) the suitability for only models with independent parameters. In this paper, we synthesize the improvement to overcome the aliasing effect limitation [Tarantola S, Gatelli D, Mara TA. Random balance designs for the estimation of first order global sensitivity indices. Reliab Eng Syst Safety 2006; 91(6):717-27] and the improvement to overcome the independence limitation [Xu C, Gertner G. Extending a global sensitivity analysis technique to models with correlated parameters. Comput Stat Data Anal 2007, accepted for publication]. In this way, FAST can be a general first-order global sensitivity analysis method for linear/nonlinear models with as many correlated/uncorrelated parameters as the user specifies. We apply the general FAST to four test cases with correlated parameters. The results show that the sensitivity indices derived by the general FAST are in good agreement with the sensitivity indices derived by the correlation ratio method, which is a non-parametric method for models with correlated parameters

  2. Application of Stochastic Sensitivity Analysis to Integrated Force Method

    Directory of Open Access Journals (Sweden)

    X. F. Wei

    2012-01-01

    Full Text Available As a new formulation in structural analysis, Integrated Force Method has been successfully applied to many structures for civil, mechanical, and aerospace engineering due to the accurate estimate of forces in computation. Right now, it is being further extended to the probabilistic domain. For the assessment of uncertainty effect in system optimization and identification, the probabilistic sensitivity analysis of IFM was further investigated in this study. A set of stochastic sensitivity analysis formulation of Integrated Force Method was developed using the perturbation method. Numerical examples are presented to illustrate its application. Its efficiency and accuracy were also substantiated with direct Monte Carlo simulations and the reliability-based sensitivity method. The numerical algorithm was shown to be readily adaptable to the existing program since the models of stochastic finite element and stochastic design sensitivity are almost identical.

  3. Method-independent, Computationally Frugal Convergence Testing for Sensitivity Analysis Techniques

    Science.gov (United States)

    Mai, J.; Tolson, B.

    2017-12-01

    The increasing complexity and runtime of environmental models lead to the current situation that the calibration of all model parameters or the estimation of all of their uncertainty is often computationally infeasible. Hence, techniques to determine the sensitivity of model parameters are used to identify most important parameters. All subsequent model calibrations or uncertainty estimation procedures focus then only on these subsets of parameters and are hence less computational demanding. While the examination of the convergence of calibration and uncertainty methods is state-of-the-art, the convergence of the sensitivity methods is usually not checked. If any, bootstrapping of the sensitivity results is used to determine the reliability of the estimated indexes. Bootstrapping, however, might as well become computationally expensive in case of large model outputs and a high number of bootstraps. We, therefore, present a Model Variable Augmentation (MVA) approach to check the convergence of sensitivity indexes without performing any additional model run. This technique is method- and model-independent. It can be applied either during the sensitivity analysis (SA) or afterwards. The latter case enables the checking of already processed sensitivity indexes. To demonstrate the method's independency of the convergence testing method, we applied it to two widely used, global SA methods: the screening method known as Morris method or Elementary Effects (Morris 1991) and the variance-based Sobol' method (Solbol' 1993). The new convergence testing method is first scrutinized using 12 analytical benchmark functions (Cuntz & Mai et al. 2015) where the true indexes of aforementioned three methods are known. This proof of principle shows that the method reliably determines the uncertainty of the SA results when different budgets are used for the SA. The results show that the new frugal method is able to test the convergence and therefore the reliability of SA results in an

  4. 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.

  5. 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.

    Directory of Open Access Journals (Sweden)

    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

  6. Temperature sensitive surfaces and methods of making same

    Science.gov (United States)

    Liang, Liang [Richland, WA; Rieke, Peter C [Pasco, WA; Alford, Kentin L [Pasco, WA

    2002-09-10

    Poly-n-isopropylacrylamide surface coatings demonstrate the useful property of being able to switch charateristics depending upon temperature. More specifically, these coatings switch from being hydrophilic at low temperature to hydrophobic at high temperature. Research has been conducted for many years to better characterize and control the properties of temperature sensitive coatings. The present invention provides novel temperature sensitive coatings on articles and novel methods of making temperature sensitive coatings that are disposed on the surfaces of various articles. These novel coatings contain the reaction products of n-isopropylacrylamide and are characterized by their properties such as advancing contact angles. Numerous other characteristics such as coating thickness, surface roughness, and hydrophilic-to-hydrophobic transition temperatures are also described. The present invention includes articles having temperature-sensitve coatings with improved properties as well as improved methods for forming temperature sensitive coatings.

  7. Comparing sensitivity analysis methods to advance lumped watershed model identification and evaluation

    Directory of Open Access Journals (Sweden)

    Y. Tang

    2007-01-01

    Full Text Available This study seeks to identify sensitivity tools that will advance our understanding of lumped hydrologic models for the purposes of model improvement, calibration efficiency and improved measurement schemes. Four sensitivity analysis methods were tested: (1 local analysis using parameter estimation software (PEST, (2 regional sensitivity analysis (RSA, (3 analysis of variance (ANOVA, and (4 Sobol's method. The methods' relative efficiencies and effectiveness have been analyzed and compared. These four sensitivity methods were applied to the lumped Sacramento soil moisture accounting model (SAC-SMA coupled with SNOW-17. Results from this study characterize model sensitivities for two medium sized watersheds within the Juniata River Basin in Pennsylvania, USA. Comparative results for the 4 sensitivity methods are presented for a 3-year time series with 1 h, 6 h, and 24 h time intervals. The results of this study show that model parameter sensitivities are heavily impacted by the choice of analysis method as well as the model time interval. Differences between the two adjacent watersheds also suggest strong influences of local physical characteristics on the sensitivity methods' results. This study also contributes a comprehensive assessment of the repeatability, robustness, efficiency, and ease-of-implementation of the four sensitivity methods. Overall ANOVA and Sobol's method were shown to be superior to RSA and PEST. Relative to one another, ANOVA has reduced computational requirements and Sobol's method yielded more robust sensitivity rankings.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. Resonance-induced sensitivity enhancement method for conductivity sensors

    Science.gov (United States)

    Tai, Yu-Chong (Inventor); Shih, Chi-yuan (Inventor); Li, Wei (Inventor); Zheng, Siyang (Inventor)

    2009-01-01

    Methods and systems for improving the sensitivity of a variety of conductivity sensing devices, in particular capacitively-coupled contactless conductivity detectors. A parallel inductor is added to the conductivity sensor. The sensor with the parallel inductor is operated at a resonant frequency of the equivalent circuit model. At the resonant frequency, parasitic capacitances that are either in series or in parallel with the conductance (and possibly a series resistance) is substantially removed from the equivalent circuit, leaving a purely resistive impedance. An appreciably higher sensor sensitivity results. Experimental verification shows that sensitivity improvements of the order of 10,000-fold are possible. Examples of detecting particulates with high precision by application of the apparatus and methods of operation are described.

  11. NK sensitivity of neuroblastoma cells determined by a highly sensitive coupled luminescent method

    International Nuclear Information System (INIS)

    Ogbomo, Henry; Hahn, Anke; Geiler, Janina; Michaelis, Martin; Doerr, Hans Wilhelm; Cinatl, Jindrich

    2006-01-01

    The measurement of natural killer (NK) cells toxicity against tumor or virus-infected cells especially in cases with small blood samples requires highly sensitive methods. Here, a coupled luminescent method (CLM) based on glyceraldehyde-3-phosphate dehydrogenase release from injured target cells was used to evaluate the cytotoxicity of interleukin-2 activated NK cells against neuroblastoma cell lines. In contrast to most other methods, CLM does not require the pretreatment of target cells with labeling substances which could be toxic or radioactive. The effective killing of tumor cells was achieved by low effector/target ratios ranging from 0.5:1 to 4:1. CLM provides highly sensitive, safe, and fast procedure for measurement of NK cell activity with small blood samples such as those obtained from pediatric patients

  12. Sensitivity analysis methods and a biosphere test case implemented in EIKOS

    Energy Technology Data Exchange (ETDEWEB)

    Ekstroem, P.A.; Broed, R. [Facilia AB, Stockholm, (Sweden)

    2006-05-15

    Computer-based models can be used to approximate real life processes. These models are usually based on mathematical equations, which are dependent on several variables. The predictive capability of models is therefore limited by the uncertainty in the value of these. Sensitivity analysis is used to apportion the relative importance each uncertain input parameter has on the output variation. Sensitivity analysis is therefore an essential tool in simulation modelling and for performing risk assessments. Simple sensitivity analysis techniques based on fitting the output to a linear equation are often used, for example correlation or linear regression coefficients. These methods work well for linear models, but for non-linear models their sensitivity estimations are not accurate. Usually models of complex natural systems are non-linear. Within the scope of this work, various sensitivity analysis methods, which can cope with linear, non-linear, as well as non-monotone problems, have been implemented, in a software package, EIKOS, written in Matlab language. The following sensitivity analysis methods are supported by EIKOS: Pearson product moment correlation coefficient (CC), Spearman Rank Correlation Coefficient (RCC), Partial (Rank) Correlation Coefficients (PCC), Standardized (Rank) Regression Coefficients (SRC), Sobol' method, Jansen's alternative, Extended Fourier Amplitude Sensitivity Test (EFAST) as well as the classical FAST method and the Smirnov and the Cramer-von Mises tests. A graphical user interface has also been developed, from which the user easily can load or call the model and perform a sensitivity analysis as well as uncertainty analysis. The implemented sensitivity analysis methods has been benchmarked with well-known test functions and compared with other sensitivity analysis software, with successful results. An illustration of the applicability of EIKOS is added to the report. The test case used is a landscape model consisting of several

  13. Sensitivity analysis methods and a biosphere test case implemented in EIKOS

    International Nuclear Information System (INIS)

    Ekstroem, P.A.; Broed, R.

    2006-05-01

    Computer-based models can be used to approximate real life processes. These models are usually based on mathematical equations, which are dependent on several variables. The predictive capability of models is therefore limited by the uncertainty in the value of these. Sensitivity analysis is used to apportion the relative importance each uncertain input parameter has on the output variation. Sensitivity analysis is therefore an essential tool in simulation modelling and for performing risk assessments. Simple sensitivity analysis techniques based on fitting the output to a linear equation are often used, for example correlation or linear regression coefficients. These methods work well for linear models, but for non-linear models their sensitivity estimations are not accurate. Usually models of complex natural systems are non-linear. Within the scope of this work, various sensitivity analysis methods, which can cope with linear, non-linear, as well as non-monotone problems, have been implemented, in a software package, EIKOS, written in Matlab language. The following sensitivity analysis methods are supported by EIKOS: Pearson product moment correlation coefficient (CC), Spearman Rank Correlation Coefficient (RCC), Partial (Rank) Correlation Coefficients (PCC), Standardized (Rank) Regression Coefficients (SRC), Sobol' method, Jansen's alternative, Extended Fourier Amplitude Sensitivity Test (EFAST) as well as the classical FAST method and the Smirnov and the Cramer-von Mises tests. A graphical user interface has also been developed, from which the user easily can load or call the model and perform a sensitivity analysis as well as uncertainty analysis. The implemented sensitivity analysis methods has been benchmarked with well-known test functions and compared with other sensitivity analysis software, with successful results. An illustration of the applicability of EIKOS is added to the report. The test case used is a landscape model consisting of several linked

  14. Sensitivity analysis of infectious disease models: methods, advances and their application

    Science.gov (United States)

    Wu, Jianyong; Dhingra, Radhika; Gambhir, Manoj; Remais, Justin V.

    2013-01-01

    Sensitivity analysis (SA) can aid in identifying influential model parameters and optimizing model structure, yet infectious disease modelling has yet to adopt advanced SA techniques that are capable of providing considerable insights over traditional methods. We investigate five global SA methods—scatter plots, the Morris and Sobol’ methods, Latin hypercube sampling-partial rank correlation coefficient and the sensitivity heat map method—and detail their relative merits and pitfalls when applied to a microparasite (cholera) and macroparasite (schistosomaisis) transmission model. The methods investigated yielded similar results with respect to identifying influential parameters, but offered specific insights that vary by method. The classical methods differed in their ability to provide information on the quantitative relationship between parameters and model output, particularly over time. The heat map approach provides information about the group sensitivity of all model state variables, and the parameter sensitivity spectrum obtained using this method reveals the sensitivity of all state variables to each parameter over the course of the simulation period, especially valuable for expressing the dynamic sensitivity of a microparasite epidemic model to its parameters. A summary comparison is presented to aid infectious disease modellers in selecting appropriate methods, with the goal of improving model performance and design. PMID:23864497

  15. Method of characteristics - Based sensitivity calculations for international PWR benchmark

    International Nuclear Information System (INIS)

    Suslov, I. R.; Tormyshev, I. V.; Komlev, O. G.

    2013-01-01

    Method to calculate sensitivity of fractional-linear neutron flux functionals to transport equation coefficients is proposed. Implementation of the method on the basis of MOC code MCCG3D is developed. Sensitivity calculations for fission intensity for international PWR benchmark are performed. (authors)

  16. 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).

  17. Improved sensitivity testing of explosives using transformed Up-Down methods

    International Nuclear Information System (INIS)

    Brown, Geoffrey W

    2014-01-01

    Sensitivity tests provide data that help establish guidelines for the safe handling of explosives. Any sensitivity test is based on assumptions to simplify the method or reduce the number of individual sample evaluations. Two common assumptions that are not typically checked after testing are 1) explosive response follows a normal distribution as a function of the applied stimulus levels and 2) the chosen test level spacing is close to the standard deviation of the explosive response function (for Bruceton Up-Down testing for example). These assumptions and other limitations of traditional explosive sensitivity testing can be addressed using Transformed Up-Down (TUD) test methods. TUD methods have been developed extensively for psychometric testing over the past 50 years and generally use multiple tests at a given level to determine how to adjust the applied stimulus. In the context of explosive sensitivity we can use TUD methods that concentrate testing around useful probability levels. Here, these methods are explained and compared to Bruceton Up-Down testing using computer simulation. The results show that the TUD methods are more useful for many cases but that they do require more tests as a consequence. For non-normal distributions, however, the TUD methods may be the only accurate assessment method.

  18. Exploring Intercultural Sensitivity in Early Adolescence: A Mixed Methods Study

    Science.gov (United States)

    Mellizo, Jennifer M.

    2017-01-01

    The purpose of this mixed methods study was to explore levels of intercultural sensitivity in a sample of fourth to eighth grade students in the United States (n = 162). "Intercultural sensitivity" was conceptualised through Bennett's Developmental Model of Sensitivity, and assessed through the Adapted Intercultural Sensitivity Index.…

  19. Are LOD and LOQ Reliable Parameters for Sensitivity Evaluation of Spectroscopic Methods?

    Science.gov (United States)

    Ershadi, Saba; Shayanfar, Ali

    2018-03-22

    The limit of detection (LOD) and the limit of quantification (LOQ) are common parameters to assess the sensitivity of analytical methods. In this study, the LOD and LOQ of previously reported terbium sensitized analysis methods were calculated by different methods, and the results were compared with sensitivity parameters [lower limit of quantification (LLOQ)] of U.S. Food and Drug Administration guidelines. The details of the calibration curve and standard deviation of blank samples of three different terbium-sensitized luminescence methods for the quantification of mycophenolic acid, enrofloxacin, and silibinin were used for the calculation of LOD and LOQ. A comparison of LOD and LOQ values calculated by various methods and LLOQ shows a considerable difference. The significant difference of the calculated LOD and LOQ with various methods and LLOQ should be considered in the sensitivity evaluation of spectroscopic methods.

  20. 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

  1. Sensitivity Analysis of Structures by Virtual Distortion Method

    DEFF Research Database (Denmark)

    Gierlinski, J.T.; Holnicki-Szulc, J.; Sørensen, John Dalsgaard

    1991-01-01

    are used in structural optimization, see Haftka [4]. The recently developed Virtual Distortion Method (VDM) is a numerical technique which offers an efficient approach to calculation of the sensitivity derivatives. This method has been orginally applied to structural remodelling and collapse analysis, see...

  2. Evaluation of a high-throughput peptide reactivity format assay for assessment of the skin sensitization potential of chemicals

    Directory of Open Access Journals (Sweden)

    Chin Lin eWong

    2016-03-01

    Full Text Available The direct peptide reactivity assay (DPRA is a validated method for in vitro assessment of the skin sensitization potential of chemicals. In the present work, we describe a peptide reactivity assay using 96-well plate format and systematically identified the optimal assay conditions for accurate and reproducible classification of chemicals with known sensitizing capacity. The aim of the research is to ensure that the analytical component of the peptide reactivity assay is robust, accurate and reproducible in accordance with criteria that are used for the validation of bioanalytical methods. Analytical performance was evaluated using quality control samples (QCs; heptapeptides at low, medium and high concentrations and incubation of control chemicals (chemicals with known sensitization capacity, weak, moderate, strong, extreme and non-sensitizers with each of three synthetic heptapeptides, viz Cor1-C420 (Ac-NKKCDLF, cysteine- (Ac-RFAACAA and lysine- (Ac-RFAAKAA containing heptapeptides. The optimal incubation temperature for all three heptapeptides was 25°C. Apparent heptapeptide depletion was affected by vial material composition. Incubation of test chemicals with Cor1-C420, showed that peptide depletion was unchanged in polypropylene vials over 3-days storage in an autosampler but this was not the case for borosilicate glass vials. For cysteine-containing heptapeptide, the concentration was not stable by day 3 post-incubation in borosilicate glass vials. Although the lysine-containing heptapeptide concentration was unchanged in both polypropylene and borosilicate glass vials, the apparent extent of lysine-containing heptapeptide depletion by ethyl acrylate, differed between polypropylene (24.7% and glass (47.3% vials. Additionally, the peptide-chemical complexes for Cor1-C420-cinnamaldehyde and cysteine-containing heptapeptide-2,4-dinitrochlorobenzene were partially reversible during 3-days of autosampler storage. These observations further

  3. Fluorimetry as a Simple and Sensitive Method for Determination of Catalase

    Directory of Open Access Journals (Sweden)

    Mehdi Hedayati

    2014-02-01

    Full Text Available Background: Catalase enzyme plays an important role in the anti-oxidation defense of body so it is important to measure its activity. Nowadays catalase activity measurement is performed by expensive imported kits in various scientific fields. The purpose of this study was to design a sensitive fluorimetry method for measuring catalase activity with improved sensitivity, accuracy and speed. Materials and Methods: In this study, the reaction of hydrogen peroxide with peroxidase (as a reaction accelerator was used in fluorimetry for catalase activity measuring in serum samples in order to increase the sensitivity of the assay. The sensitivity and intra- and inter-assay accuracy, verification test, recovery and parallelism tests, comparison method and correlation and coherence investigation methods were also performed. In order to increase the accuracy and speed of reading, the assay was performed in microplates and reading was done in fluorimetry plates. Results: The percentage of intra- and inter-assay variation coefficients were measured 3.8- 6.6 % and 4.1-7.3%, respectively. Comparison of the results of mentioned method for 50 serum samples with common colorimetric method showed a good correlation (0.917. In assessing the accuracy, the recovery percent was obtained 91% to 107%. The test sensitivity was measured 0.02 IU/ml. Conclusion: The fluorimetry method by microplate reading has a sufficient precision, accuracy and efficiency for catalase activity measuring as well as speed of measurement. Thus it can be an alternative method to conventional imported colorimetric methods.

  4. 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

  5. Multiple predictor smoothing methods for sensitivity analysis: Example results

    International Nuclear Information System (INIS)

    Storlie, Curtis B.; Helton, Jon C.

    2008-01-01

    The use of multiple predictor smoothing methods in sampling-based sensitivity analyses of complex models is investigated. Specifically, sensitivity analysis procedures based on smoothing methods employing the stepwise application of the following nonparametric regression techniques are described in the first part of this presentation: (i) locally weighted regression (LOESS), (ii) additive models, (iii) projection pursuit regression, and (iv) recursive partitioning regression. In this, the second and concluding part of the presentation, the indicated procedures are illustrated with both simple test problems and results from a performance assessment for a radioactive waste disposal facility (i.e., the Waste Isolation Pilot Plant). As shown by the example illustrations, the use of smoothing procedures based on nonparametric regression techniques can yield more informative sensitivity analysis results than can be obtained with more traditional sensitivity analysis procedures based on linear regression, rank regression or quadratic regression when nonlinear relationships between model inputs and model predictions are present

  6. 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.

  7. 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.

  8. SCALE-6 Sensitivity/Uncertainty Methods and Covariance Data

    International Nuclear Information System (INIS)

    Williams, Mark L.; Rearden, Bradley T.

    2008-01-01

    Computational methods and data used for sensitivity and uncertainty analysis within the SCALE nuclear analysis code system are presented. The methodology used to calculate sensitivity coefficients and similarity coefficients and to perform nuclear data adjustment is discussed. A description is provided of the SCALE-6 covariance library based on ENDF/B-VII and other nuclear data evaluations, supplemented by 'low-fidelity' approximate covariances. SCALE (Standardized Computer Analyses for Licensing Evaluation) is a modular code system developed by Oak Ridge National Laboratory (ORNL) to perform calculations for criticality safety, reactor physics, and radiation shielding applications. SCALE calculations typically use sequences that execute a predefined series of executable modules to compute particle fluxes and responses like the critical multiplication factor. SCALE also includes modules for sensitivity and uncertainty (S/U) analysis of calculated responses. The S/U codes in SCALE are collectively referred to as TSUNAMI (Tools for Sensitivity and UNcertainty Analysis Methodology Implementation). SCALE-6-scheduled for release in 2008-contains significant new capabilities, including important enhancements in S/U methods and data. The main functions of TSUNAMI are to (a) compute nuclear data sensitivity coefficients and response uncertainties, (b) establish similarity between benchmark experiments and design applications, and (c) reduce uncertainty in calculated responses by consolidating integral benchmark experiments. TSUNAMI includes easy-to-use graphical user interfaces for defining problem input and viewing three-dimensional (3D) geometries, as well as an integrated plotting package.

  9. Studies on analytical method and nondestructive measuring method on the sensitization of austenitic stainless steels

    International Nuclear Information System (INIS)

    Onimura, Kichiro; Arioka, Koji; Horai, Manabu; Noguchi, Shigeru.

    1982-03-01

    Austenitic stainless steels are widely used as structural materials for the machine and equipment of various kinds of plants, such as thermal power, nuclear power, and chemical plants. The machines and equipment using this kind of material, however, have the possibility of suffering corrosion damage while in service, and these damages are considered to be largely due to the sensitization of the material in sometimes. So, it is necessary to develop an analytical method for grasping the sensitization of the material more in detail and a quantitative nondestructive measuring method which is applicable to various kinds of structures in order to prevent the corrosion damage. From the above viewpoint, studies have been made on the analytical method based on the theory of diffusion of chromium in austenitic stainless steels and on Electro-Potentiokinetics Reactivation Method (EPR Method) as a nondestructive measuring method, using 304 and 316 austenitic stainless steels having different carbon contents in base metals. This paper introduces the results of EPR test on the sensitization of austenitic stainless steels and the correlation between analytical and experimental results. (author)

  10. Sensitivity analysis of the Two Geometry Method

    International Nuclear Information System (INIS)

    Wichers, V.A.

    1993-09-01

    The Two Geometry Method (TGM) was designed specifically for the verification of the uranium enrichment of low enriched UF 6 gas in the presence of uranium deposits on the pipe walls. Complications can arise if the TGM is applied under extreme conditions, such as deposits larger than several times the gas activity, small pipe diameters less than 40 mm and low pressures less than 150 Pa. This report presents a comprehensive sensitivity analysis of the TGM. The impact of the various sources of uncertainty on the performance of the method is discussed. The application to a practical case is based on worst case conditions with regards to the measurement conditions, and on realistic conditions with respect to the false alarm probability and the non detection probability. Monte Carlo calculations were used to evaluate the sensitivity for sources of uncertainty which are experimentally inaccessible. (orig.)

  11. Comparison of global sensitivity analysis methods – Application to fuel behavior modeling

    Energy Technology Data Exchange (ETDEWEB)

    Ikonen, Timo, E-mail: timo.ikonen@vtt.fi

    2016-02-15

    Highlights: • Several global sensitivity analysis methods are compared. • The methods’ applicability to nuclear fuel performance simulations is assessed. • The implications of large input uncertainties and complex models are discussed. • Alternative strategies to perform sensitivity analyses are proposed. - Abstract: Fuel performance codes have two characteristics that make their sensitivity analysis challenging: large uncertainties in input parameters and complex, non-linear and non-additive structure of the models. The complex structure of the code leads to interactions between inputs that show as cross terms in the sensitivity analysis. Due to the large uncertainties of the inputs these interactions are significant, sometimes even dominating the sensitivity analysis. For the same reason, standard linearization techniques do not usually perform well in the analysis of fuel performance codes. More sophisticated methods are typically needed in the analysis. To this end, we compare the performance of several sensitivity analysis methods in the analysis of a steady state FRAPCON simulation. The comparison of importance rankings obtained with the various methods shows that even the simplest methods can be sufficient for the analysis of fuel maximum temperature. However, the analysis of the gap conductance requires more powerful methods that take into account the interactions of the inputs. In some cases, moment-independent methods are needed. We also investigate the computational cost of the various methods and present recommendations as to which methods to use in the analysis.

  12. Design Optimization Method for Composite Components Based on Moment Reliability-Sensitivity Criteria

    Science.gov (United States)

    Sun, Zhigang; Wang, Changxi; Niu, Xuming; Song, Yingdong

    2017-08-01

    In this paper, a Reliability-Sensitivity Based Design Optimization (RSBDO) methodology for the design of the ceramic matrix composites (CMCs) components has been proposed. A practical and efficient method for reliability analysis and sensitivity analysis of complex components with arbitrary distribution parameters are investigated by using the perturbation method, the respond surface method, the Edgeworth series and the sensitivity analysis approach. The RSBDO methodology is then established by incorporating sensitivity calculation model into RBDO methodology. Finally, the proposed RSBDO methodology is applied to the design of the CMCs components. By comparing with Monte Carlo simulation, the numerical results demonstrate that the proposed methodology provides an accurate, convergent and computationally efficient method for reliability-analysis based finite element modeling engineering practice.

  13. A method of the sensitivity analysis of build-up and decay of actinides

    International Nuclear Information System (INIS)

    Mitani, Hiroshi; Koyama, Kinji; Kuroi, Hideo

    1977-07-01

    To make sensitivity analysis of build-up and decay of actinides, mathematical methods related to this problem have been investigated in detail. Application of time-dependent perturbation technique and Bateman method to sensitivity analysis is mainly studied. For the purpose, a basic equation and its adjoint equation for build-up and decay of actinides are systematically solved by introducing Laplace and modified Laplace transforms and their convolution theorems. Then, the mathematical method of sensitivity analyses is formulated by the above technique; its physical significance is also discussed. Finally, application of eigenvalue-method is investigated. Sensitivity coefficients can be directly calculated by this method. (auth.)

  14. Sensitivity of radiation methods of diagnosis of electric potentials in dielectric materials

    International Nuclear Information System (INIS)

    Sapozhkov, Yu.I.; Smekalin, L.F.; Yagushkin, N.I.

    1985-01-01

    On the base of the albedo method the characteristics of radiation methods of diagnosis of electric potentials inside dielectrics, such as sensitivity and resolution are considered. Investigations are carried out for electron energies of tens keV. It is shown that with energy growth the sensitivity to electric field in the dielectrics volume drops. The target atomic number growth reduces the sensitivity approximately 1/lnz. The albedo method resolution in the investigated energy range is constant. The results obtained testify to the usability radiation methods of the diagnosis for control of electric fields of dielectric structural materials in the course of their operation

  15. Multiple predictor smoothing methods for sensitivity analysis: Description of techniques

    International Nuclear Information System (INIS)

    Storlie, Curtis B.; Helton, Jon C.

    2008-01-01

    The use of multiple predictor smoothing methods in sampling-based sensitivity analyses of complex models is investigated. Specifically, sensitivity analysis procedures based on smoothing methods employing the stepwise application of the following nonparametric regression techniques are described: (i) locally weighted regression (LOESS), (ii) additive models, (iii) projection pursuit regression, and (iv) recursive partitioning regression. Then, in the second and concluding part of this presentation, the indicated procedures are illustrated with both simple test problems and results from a performance assessment for a radioactive waste disposal facility (i.e., the Waste Isolation Pilot Plant). As shown by the example illustrations, the use of smoothing procedures based on nonparametric regression techniques can yield more informative sensitivity analysis results than can be obtained with more traditional sensitivity analysis procedures based on linear regression, rank regression or quadratic regression when nonlinear relationships between model inputs and model predictions are present

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Deterministic methods for sensitivity and uncertainty analysis in large-scale computer models

    International Nuclear Information System (INIS)

    Worley, B.A.; Oblow, E.M.; Pin, F.G.; Maerker, R.E.; Horwedel, J.E.; Wright, R.Q.; Lucius, J.L.

    1987-01-01

    The fields of sensitivity and uncertainty analysis are dominated by statistical techniques when large-scale modeling codes are being analyzed. This paper reports on the development and availability of two systems, GRESS and ADGEN, that make use of computer calculus compilers to automate the implementation of deterministic sensitivity analysis capability into existing computer models. This automation removes the traditional limitation of deterministic sensitivity methods. The paper describes a deterministic uncertainty analysis method (DUA) that uses derivative information as a basis to propagate parameter probability distributions to obtain result probability distributions. The paper demonstrates the deterministic approach to sensitivity and uncertainty analysis as applied to a sample problem that models the flow of water through a borehole. The sample problem is used as a basis to compare the cumulative distribution function of the flow rate as calculated by the standard statistical methods and the DUA method. The DUA method gives a more accurate result based upon only two model executions compared to fifty executions in the statistical case

  18. 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

  19. 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

  20. 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.

  1. High sensitivity phase retrieval method in grating-based x-ray phase contrast imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zhao; Gao, Kun; Chen, Jian; Wang, Dajiang; Wang, Shenghao; Chen, Heng; Bao, Yuan; Shao, Qigang; Wang, Zhili, E-mail: wangnsrl@ustc.edu.cn [National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230029 (China); Zhang, Kai [Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China); Zhu, Peiping; Wu, Ziyu, E-mail: wuzy@ustc.edu.cn [National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230029, China and Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China)

    2015-02-15

    Purpose: Grating-based x-ray phase contrast imaging is considered as one of the most promising techniques for future medical imaging. Many different methods have been developed to retrieve phase signal, among which the phase stepping (PS) method is widely used. However, further practical implementations are hindered, due to its complex scanning mode and high radiation dose. In contrast, the reverse projection (RP) method is a novel fast and low dose extraction approach. In this contribution, the authors present a quantitative analysis of the noise properties of the refraction signals retrieved by the two methods and compare their sensitivities. Methods: Using the error propagation formula, the authors analyze theoretically the signal-to-noise ratios (SNRs) of the refraction images retrieved by the two methods. Then, the sensitivities of the two extraction methods are compared under an identical exposure dose. Numerical experiments are performed to validate the theoretical results and provide some quantitative insight. Results: The SNRs of the two methods are both dependent on the system parameters, but in different ways. Comparison between their sensitivities reveals that for the refraction signal, the RP method possesses a higher sensitivity, especially in the case of high visibility and/or at the edge of the object. Conclusions: Compared with the PS method, the RP method has a superior sensitivity and provides refraction images with a higher SNR. Therefore, one can obtain highly sensitive refraction images in grating-based phase contrast imaging. This is very important for future preclinical and clinical implementations.

  2. High sensitivity phase retrieval method in grating-based x-ray phase contrast imaging

    International Nuclear Information System (INIS)

    Wu, Zhao; Gao, Kun; Chen, Jian; Wang, Dajiang; Wang, Shenghao; Chen, Heng; Bao, Yuan; Shao, Qigang; Wang, Zhili; Zhang, Kai; Zhu, Peiping; Wu, Ziyu

    2015-01-01

    Purpose: Grating-based x-ray phase contrast imaging is considered as one of the most promising techniques for future medical imaging. Many different methods have been developed to retrieve phase signal, among which the phase stepping (PS) method is widely used. However, further practical implementations are hindered, due to its complex scanning mode and high radiation dose. In contrast, the reverse projection (RP) method is a novel fast and low dose extraction approach. In this contribution, the authors present a quantitative analysis of the noise properties of the refraction signals retrieved by the two methods and compare their sensitivities. Methods: Using the error propagation formula, the authors analyze theoretically the signal-to-noise ratios (SNRs) of the refraction images retrieved by the two methods. Then, the sensitivities of the two extraction methods are compared under an identical exposure dose. Numerical experiments are performed to validate the theoretical results and provide some quantitative insight. Results: The SNRs of the two methods are both dependent on the system parameters, but in different ways. Comparison between their sensitivities reveals that for the refraction signal, the RP method possesses a higher sensitivity, especially in the case of high visibility and/or at the edge of the object. Conclusions: Compared with the PS method, the RP method has a superior sensitivity and provides refraction images with a higher SNR. Therefore, one can obtain highly sensitive refraction images in grating-based phase contrast imaging. This is very important for future preclinical and clinical implementations

  3. An adjoint sensitivity-based data assimilation method and its comparison with existing variational methods

    Directory of Open Access Journals (Sweden)

    Yonghan Choi

    2014-01-01

    Full Text Available An adjoint sensitivity-based data assimilation (ASDA method is proposed and applied to a heavy rainfall case over the Korean Peninsula. The heavy rainfall case, which occurred on 26 July 2006, caused torrential rainfall over the central part of the Korean Peninsula. The mesoscale convective system (MCS related to the heavy rainfall was classified as training line/adjoining stratiform (TL/AS-type for the earlier period, and back building (BB-type for the later period. In the ASDA method, an adjoint model is run backwards with forecast-error gradient as input, and the adjoint sensitivity of the forecast error to the initial condition is scaled by an optimal scaling factor. The optimal scaling factor is determined by minimising the observational cost function of the four-dimensional variational (4D-Var method, and the scaled sensitivity is added to the original first guess. Finally, the observations at the analysis time are assimilated using a 3D-Var method with the improved first guess. The simulated rainfall distribution is shifted northeastward compared to the observations when no radar data are assimilated or when radar data are assimilated using the 3D-Var method. The rainfall forecasts are improved when radar data are assimilated using the 4D-Var or ASDA method. Simulated atmospheric fields such as horizontal winds, temperature, and water vapour mixing ratio are also improved via the 4D-Var or ASDA method. Due to the improvement in the analysis, subsequent forecasts appropriately simulate the observed features of the TL/AS- and BB-type MCSs and the corresponding heavy rainfall. The computational cost associated with the ASDA method is significantly lower than that of the 4D-Var method.

  4. 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

  5. On the Exploitation of Sensitivity Derivatives for Improving Sampling Methods

    Science.gov (United States)

    Cao, Yanzhao; Hussaini, M. Yousuff; Zang, Thomas A.

    2003-01-01

    Many application codes, such as finite-element structural analyses and computational fluid dynamics codes, are capable of producing many sensitivity derivatives at a small fraction of the cost of the underlying analysis. This paper describes a simple variance reduction method that exploits such inexpensive sensitivity derivatives to increase the accuracy of sampling methods. Three examples, including a finite-element structural analysis of an aircraft wing, are provided that illustrate an order of magnitude improvement in accuracy for both Monte Carlo and stratified sampling schemes.

  6. 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.

  7. Demodulation method for tilted fiber Bragg grating refractometer with high sensitivity

    Science.gov (United States)

    Pham, Xuantung; Si, Jinhai; Chen, Tao; Wang, Ruize; Yan, Lihe; Cao, Houjun; Hou, Xun

    2018-05-01

    In this paper, we propose a demodulation method for refractive index (RI) sensing with tilted fiber Bragg gratings (TFBGs). It operates by monitoring the TFBG cladding mode resonance "cut-off wavelengths." The idea of a "cut-off wavelength" and its determination method are introduced. The RI sensitivities of TFBGs are significantly enhanced in certain RI ranges by using our demodulation method. The temperature-induced cross sensitivity is eliminated. We also demonstrate a parallel-double-angle TFBG (PDTFBG), in which two individual TFBGs are inscribed in the fiber core in parallel using a femtosecond laser and a phase mask. The RI sensing range of the PDTFBG is significantly broader than that of a conventional single-angle TFBG. In addition, its RI sensitivity can reach 1023.1 nm/refractive index unit in the 1.4401-1.4570 RI range when our proposed demodulation method is used.

  8. 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)

  9. High sensitive quench detection method using an integrated test wire

    International Nuclear Information System (INIS)

    Fevrier, A.; Tavergnier, J.P.; Nithart, H.; Kiblaire, M.; Duchateau, J.L.

    1981-01-01

    A high sensitive quench detection method which works even in the presence of an external perturbing magnetic field is reported. The quench signal is obtained from the difference in voltages at the superconducting winding terminals and at the terminals at a secondary winding strongly coupled to the primary. The secondary winding could consist of a ''zero-current strand'' of the superconducting cable not connected to one of the winding terminals or an integrated normal test wire inside the superconducting cable. Experimental results on quench detection obtained by this method are described. It is shown that the integrated test wire method leads to efficient and sensitive quench detection, especially in the presence of an external perturbing magnetic field

  10. 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.

  11. The adjoint sensitivity method, a contribution to the code uncertainty evaluation

    International Nuclear Information System (INIS)

    Ounsy, A.; Crecy, F. de; Brun, B.

    1993-01-01

    The application of the ASM (Adjoint Sensitivity Method) to thermohydraulic codes, is examined. The advantage of the method is to be very few CPU time consuming in comparison with usual approach requiring one complete code run per sensitivity determination. The mathematical aspects of the problem are first described, and the applicability of the method of the functional-type response of a thermalhydraulic model is demonstrated. On a simple example of non linear hyperbolic equation (Burgers equation) the problem has been analyzed. It is shown that the formalism used in the literature treating this subject is not appropriate. A new mathematical formalism circumventing the problem is proposed. For the discretized form of the problem, two methods are possible: the Continuous ASM and the Discrete ASM. The equivalence of both methods is demonstrated; nevertheless only the DASM constitutes a practical solution for thermalhydraulic codes. The application of the DASM to the thermalhydraulic safety code CATHARE is then presented for two examples. They demonstrate that ASM constitutes an efficient tool for the analysis of code sensitivity. (authors) 7 figs., 5 tabs., 8 refs

  12. The adjoint sensitivity method. A contribution to the code uncertainty evaluation

    International Nuclear Information System (INIS)

    Ounsy, A.; Brun, B.

    1993-01-01

    The application of the ASM (Adjoint Sensitivity Method) to thermohydraulic codes, is examined. The advantage of the method is to be very few CPU time consuming in comparison with usual approach requiring one complete code run per sensitivity determination. The mathematical aspects of the problem are first described, and the applicability of the method of the functional-type response of a thermalhydraulic model is demonstrated. On a simple example of non linear hyperbolic equation (Burgers equation) the problem has been analyzed. It is shown that the formalism used in the literature treating this subject is not appropriate. A new mathematical formalism circumventing the problem is proposed. For the discretized form of the problem, two methods are possible: the Continuous ASM and the Discrete ASM. The equivalence of both methods is demonstrated; nevertheless only the DASM constitutes a practical solution for thermalhydraulic codes. The application of the DASM to the thermalhydraulic safety code CATHARE is then presented for two examples. They demonstrate that ASM constitutes an efficient tool for the analysis of code sensitivity. (authors) 7 figs., 5 tabs., 8 refs

  13. The adjoint sensitivity method. A contribution to the code uncertainty evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Ounsy, A; Brun, B

    1994-12-31

    The application of the ASM (Adjoint Sensitivity Method) to thermohydraulic codes, is examined. The advantage of the method is to be very few CPU time consuming in comparison with usual approach requiring one complete code run per sensitivity determination. The mathematical aspects of the problem are first described, and the applicability of the method of the functional-type response of a thermalhydraulic model is demonstrated. On a simple example of non linear hyperbolic equation (Burgers equation) the problem has been analyzed. It is shown that the formalism used in the literature treating this subject is not appropriate. A new mathematical formalism circumventing the problem is proposed. For the discretized form of the problem, two methods are possible: the Continuous ASM and the Discrete ASM. The equivalence of both methods is demonstrated; nevertheless only the DASM constitutes a practical solution for thermalhydraulic codes. The application of the DASM to the thermalhydraulic safety code CATHARE is then presented for two examples. They demonstrate that ASM constitutes an efficient tool for the analysis of code sensitivity. (authors) 7 figs., 5 tabs., 8 refs.

  14. The adjoint sensitivity method, a contribution to the code uncertainty evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Ounsy, A; Crecy, F de; Brun, B

    1994-12-31

    The application of the ASM (Adjoint Sensitivity Method) to thermohydraulic codes, is examined. The advantage of the method is to be very few CPU time consuming in comparison with usual approach requiring one complete code run per sensitivity determination. The mathematical aspects of the problem are first described, and the applicability of the method of the functional-type response of a thermalhydraulic model is demonstrated. On a simple example of non linear hyperbolic equation (Burgers equation) the problem has been analyzed. It is shown that the formalism used in the literature treating this subject is not appropriate. A new mathematical formalism circumventing the problem is proposed. For the discretized form of the problem, two methods are possible: the Continuous ASM and the Discrete ASM. The equivalence of both methods is demonstrated; nevertheless only the DASM constitutes a practical solution for thermalhydraulic codes. The application of the DASM to the thermalhydraulic safety code CATHARE is then presented for two examples. They demonstrate that ASM constitutes an efficient tool for the analysis of code sensitivity. (authors) 7 figs., 5 tabs., 8 refs.

  15. Adjoint sensitivity analysis of plasmonic structures using the FDTD method.

    Science.gov (United States)

    Zhang, Yu; Ahmed, Osman S; Bakr, Mohamed H

    2014-05-15

    We present an adjoint variable method for estimating the sensitivities of arbitrary responses with respect to the parameters of dispersive discontinuities in nanoplasmonic devices. Our theory is formulated in terms of the electric field components at the vicinity of perturbed discontinuities. The adjoint sensitivities are computed using at most one extra finite-difference time-domain (FDTD) simulation regardless of the number of parameters. Our approach is illustrated through the sensitivity analysis of an add-drop coupler consisting of a square ring resonator between two parallel waveguides. The computed adjoint sensitivities of the scattering parameters are compared with those obtained using the accurate but computationally expensive central finite difference approach.

  16. Statistical Sensitive Data Protection and Inference Prevention with Decision Tree Methods

    National Research Council Canada - National Science Library

    Chang, LiWu

    2003-01-01

    .... We consider inference as correct classification and approach it with decision tree methods. As in our previous work, sensitive data are viewed as classes of those test data and non-sensitive data are the rest attribute values...

  17. 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.

  18. Prediction of skin sensitizers using alternative methods to animal experimentation.

    Science.gov (United States)

    Johansson, Henrik; Lindstedt, Malin

    2014-07-01

    Regulatory frameworks within the European Union demand that chemical substances are investigated for their ability to induce sensitization, an adverse health effect caused by the human immune system in response to chemical exposure. A recent ban on the use of animal tests within the cosmetics industry has led to an urgent need for alternative animal-free test methods that can be used for assessment of chemical sensitizers. To date, no such alternative assay has yet completed formal validation. However, a number of assays are in development and the understanding of the biological mechanisms of chemical sensitization has greatly increased during the last decade. In this MiniReview, we aim to summarize and give our view on the recent progress of method development for alternative assessment of chemical sensitizers. We propose that integrated testing strategies should comprise complementary assays, providing measurements of a wide range of mechanistic events, to perform well-educated risk assessments based on weight of evidence. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  19. Application of Wielandt method in continuous-energy nuclear data sensitivity analysis with RMC code

    International Nuclear Information System (INIS)

    Qiu Yishu; Wang Kan; She Ding

    2015-01-01

    The Iterated Fission Probability (IFP) method, an accurate method to estimate adjoint-weighted quantities in the continuous-energy Monte Carlo criticality calculations, has been widely used for calculating kinetic parameters and nuclear data sensitivity coefficients. By using a strategy of waiting, however, this method faces the challenge of high memory usage to store the tallies of original contributions which size is proportional to the number of particle histories in each cycle. Recently, the Wielandt method, applied by Monte Carlo code McCARD to calculate kinetic parameters, estimates adjoint fluxes in a single particle history and thus can save memory usage. In this work, the Wielandt method has been applied in Rector Monte Carlo code RMC for nuclear data sensitivity analysis. The methodology and algorithm of applying Wielandt method in estimation of adjoint-based sensitivity coefficients are discussed. Verification is performed by comparing the sensitivity coefficients calculated by Wielandt method with analytical solutions, those computed by IFP method which is also implemented in RMC code for sensitivity analysis, and those from the multi-group TSUNAMI-3D module in SCALE code package. (author)

  20. 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.

  1. 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.

  2. Sensitive high performance liquid chromatographic method for the ...

    African Journals Online (AJOL)

    A new simple, sensitive, cost-effective and reproducible high performance liquid chromatographic (HPLC) method for the determination of proguanil (PG) and its metabolites, cycloguanil (CG) and 4-chlorophenylbiguanide (4-CPB) in urine and plasma is described. The extraction procedure is a simple three-step process ...

  3. 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.

  4. 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.

  5. Space-partition method for the variance-based sensitivity analysis: Optimal partition scheme and comparative study

    International Nuclear Information System (INIS)

    Zhai, Qingqing; Yang, Jun; Zhao, Yu

    2014-01-01

    Variance-based sensitivity analysis has been widely studied and asserted itself among practitioners. Monte Carlo simulation methods are well developed in the calculation of variance-based sensitivity indices but they do not make full use of each model run. Recently, several works mentioned a scatter-plot partitioning method to estimate the variance-based sensitivity indices from given data, where a single bunch of samples is sufficient to estimate all the sensitivity indices. This paper focuses on the space-partition method in the estimation of variance-based sensitivity indices, and its convergence and other performances are investigated. Since the method heavily depends on the partition scheme, the influence of the partition scheme is discussed and the optimal partition scheme is proposed based on the minimized estimator's variance. A decomposition and integration procedure is proposed to improve the estimation quality for higher order sensitivity indices. The proposed space-partition method is compared with the more traditional method and test cases show that it outperforms the traditional one

  6. The adjoint sensitivity method, a contribution to the code uncertainty evaluation

    International Nuclear Information System (INIS)

    Ounsy, A.; Brun, B.; De Crecy, F.

    1994-01-01

    This paper deals with the application of the adjoint sensitivity method (ASM) to thermal hydraulic codes. The advantage of the method is to use small central processing unit time in comparison with the usual approach requiring one complete code run per sensitivity determination. In the first part the mathematical aspects of the problem are treated, and the applicability of the method of the functional-type response of a thermal hydraulic model is demonstrated. On a simple example of non-linear hyperbolic equation (Burgers equation) the problem has been analysed. It is shown that the formalism used in the literature treating this subject is not appropriate. A new mathematical formalism circumventing the problem is proposed. For the discretized form of the problem, two methods are possible: the continuous ASM and the discrete ASM. The equivalence of both methods is demonstrated; nevertheless only the discrete ASM constitutes a practical solution for thermal hydraulic codes. The application of the discrete ASM to the thermal hydraulic safety code CATHARE is then presented for two examples. They demonstrate that the discrete ASM constitutes an efficient tool for the analysis of code sensitivity. ((orig.))

  7. Application of Monte Carlo filtering method in regional sensitivity analysis of AASHTOWare Pavement ME design

    Directory of Open Access Journals (Sweden)

    Zhong Wu

    2017-04-01

    Full Text Available Since AASHTO released the Mechanistic-Empirical Pavement Design Guide (MEPDG for public review in 2004, many highway research agencies have performed sensitivity analyses using the prototype MEPDG design software. The information provided by the sensitivity analysis is essential for design engineers to better understand the MEPDG design models and to identify important input parameters for pavement design. In literature, different studies have been carried out based on either local or global sensitivity analysis methods, and sensitivity indices have been proposed for ranking the importance of the input parameters. In this paper, a regional sensitivity analysis method, Monte Carlo filtering (MCF, is presented. The MCF method maintains many advantages of the global sensitivity analysis, while focusing on the regional sensitivity of the MEPDG model near the design criteria rather than the entire problem domain. It is shown that the information obtained from the MCF method is more helpful and accurate in guiding design engineers in pavement design practices. To demonstrate the proposed regional sensitivity method, a typical three-layer flexible pavement structure was analyzed at input level 3. A detailed procedure to generate Monte Carlo runs using the AASHTOWare Pavement ME Design software was provided. The results in the example show that the sensitivity ranking of the input parameters in this study reasonably matches with that in a previous study under a global sensitivity analysis. Based on the analysis results, the strengths, practical issues, and applications of the MCF method were further discussed.

  8. Sensitivity analysis of a complex, proposed geologic waste disposal system using the Fourier Amplitude Sensitivity Test method

    International Nuclear Information System (INIS)

    Lu Yichi; Mohanty, Sitakanta

    2001-01-01

    The Fourier Amplitude Sensitivity Test (FAST) method has been used to perform a sensitivity analysis of a computer model developed for conducting total system performance assessment of the proposed high-level nuclear waste repository at Yucca Mountain, Nevada, USA. The computer model has a large number of random input parameters with assigned probability density functions, which may or may not be uniform, for representing data uncertainty. The FAST method, which was previously applied to models with parameters represented by the uniform probability distribution function only, has been modified to be applied to models with nonuniform probability distribution functions. Using an example problem with a small input parameter set, several aspects of the FAST method, such as the effects of integer frequency sets and random phase shifts in the functional transformations, and the number of discrete sampling points (equivalent to the number of model executions) on the ranking of the input parameters have been investigated. Because the number of input parameters of the computer model under investigation is too large to be handled by the FAST method, less important input parameters were first screened out using the Morris method. The FAST method was then used to rank the remaining parameters. The validity of the parameter ranking by the FAST method was verified using the conditional complementary cumulative distribution function (CCDF) of the output. The CCDF results revealed that the introduction of random phase shifts into the functional transformations, proposed by previous investigators to disrupt the repetitiveness of search curves, does not necessarily improve the sensitivity analysis results because it destroys the orthogonality of the trigonometric functions, which is required for Fourier analysis

  9. Further development of LLNA:DAE method as stand-alone skin-sensitization testing method and applied for evaluation of relative skin-sensitizing potency between chemicals.

    Science.gov (United States)

    Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Itagaki, Hiroshi

    2015-04-01

    To date, there has been no well-established local lymph node assay (LLNA) that includes an elicitation phase. Therefore, we developed a modified local lymph node assay with an elicitation phase (LLNA:DAE) to discriminate true skin sensitizers from chemicals that gave borderline positive results and previously reported this assay. To develop the LLNA:DAE method as a useful stand-alone testing method, we investigated the complete procedure for the LLNA:DAE method using hexyl cinnamic aldehyde (HCA), isoeugenol, and 2,4-dinitrochlorobenzene (DNCB) as test compounds. We defined the LLNA:DAE procedure as follows: in the dose-finding test, four concentrations of chemical applied to dorsum of the right ear on days 1, 2, and 3 and dorsum of both ears on day 10. Ear thickness and skin irritation score were measured on days 1, 3, 5, 10, and 12. Local lymph nodes were excised and weighed on day 12. The test dose for the primary LLNA:DAE study was selected as the dose that gave the highest left ear lymph node weight in the dose-finding study, or the lowest dose that produced a left ear lymph node of over 4 mg. This procedure was validated using nine different chemicals. Furthermore, qualitative relationship was observed between the degree of elicitation response in the left ear lymph node and the skin sensitizing potency of 32 chemicals tested in this study and the previous study. These results indicated that LLNA:DAE method was as first LLNA method that was able to evaluate the skin sensitizing potential and potency in elicitation response.

  10. A Sensitive Validated Spectrophotometric Method for the Determination of Flucloxacillin Sodium

    Directory of Open Access Journals (Sweden)

    R. Singh Gujral

    2009-01-01

    Full Text Available A simple and sensitive spectrophotometric method has been proposed for the determination of flucloxacillin sodium. The determination method is based on charge transfer complexation reaction of the drug with iodine in methanol-dichloromethane medium. The absorbance was measured at 362 nm against the reagent blank. Under optimized experimental conditions, Beer's law is obeyed in the concentration ranges 1-9 μg/mL for flucloxacillin. The method was validated for specificity, linearity, precision, accuracy. The degree of linearity of the calibration curves, the percent recoveries, limit of detection and quantitation for the spectrophotometric method were determined. No interferences could be observed from the additives commonly present in the pharmaceutical formulations. The method was successfully applied for in vitro determination of human urine samples with low RSD value. This is simple, specific, accurate and sensitive spectrophotometric method.

  11. A combination between the differential and the perturbation theory methods for calculating sensitivity coefficients

    International Nuclear Information System (INIS)

    Borges, Antonio Andrade

    1998-01-01

    A new method for the calculation of sensitivity coefficients is developed. The new method is a combination of two methodologies used for calculating theses coefficients, which are the differential and the generalized perturbation theory methods. The method utilizes as integral parameter the average flux in an arbitrary region of the system. Thus, the sensitivity coefficient contains only the component corresponding to the neutron flux. To obtain the new sensitivity coefficient, the derivatives of the integral parameter, Φ, with respect to σ are calculated using the perturbation method and the functional derivatives of this generic integral parameter with respect to σ and Φ are calculated using the differential method. (author)

  12. 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...

  13. Method and apparatus for formation logging using position sensitive neutron detectors

    International Nuclear Information System (INIS)

    Gadken, L.L.

    1986-01-01

    This patent describes a method for logging earth formations using position sensitive neutron detectors. The method consists of: 1) Irradiation of earth formations in the vicinity of a well borehole with a source of fast neutrons. 2) At four longitudinally spaced distances from the neutron source in the borehole, the epithermal neutron population is detected. Each of the four separate populations is detected in an epithermally sensitive and substantially thermally insensitive portion of the same position sensitive neutron detector. A representative signal from each is then individually generated. 3) First, second, third, and fourth neutron population representative signals are combined. They derive a simultaneous measurement signal. This signal is functionally related to the porosity and also a signal functionally related to a neutron characteristic length of the earth formations in the vicinity of the borehole

  14. A combination of differential method and perturbation theory for the calculation of sensitivity coefficients

    International Nuclear Information System (INIS)

    Santos, Adimir dos; Borges, A.A.

    2000-01-01

    A new method for the calculation of sensitivity coefficients is developed. The new method is a combination of two methodologies used for calculating these coefficients, which are the differential and the generalized perturbation theory methods. The proposed method utilizes as integral parameter the average flux in an arbitrary region of the system. Thus, the sensitivity coefficient contains only the component corresponding to the neutron flux. To obtain the new sensitivity coefficient, the derivates of the integral parameter, φ(ξ), with respect to σ are calculated using the perturbation method and the functional derivates of this generic integral parameter with respect to σ and φ are calculated using the differential method. The new method merges the advantages of the differential and generalized perturbation theory methods and eliminates their disadvantages. (author)

  15. Sensitivity Analysis of Dynamic Tariff Method for Congestion Management in Distribution Networks

    DEFF Research Database (Denmark)

    Huang, Shaojun; Wu, Qiuwei; Liu, Zhaoxi

    2015-01-01

    The dynamic tariff (DT) method is designed for the distribution system operator (DSO) to alleviate the congestions that might occur in a distribution network with high penetration of distribute energy resources (DERs). Sensitivity analysis of the DT method is crucial because of its decentralized...... control manner. The sensitivity analysis can obtain the changes of the optimal energy planning and thereby the line loading profiles over the infinitely small changes of parameters by differentiating the KKT conditions of the convex quadratic programming, over which the DT method is formed. Three case...

  16. Sensitivity analysis for decision-making using the MORE method-A Pareto approach

    International Nuclear Information System (INIS)

    Ravalico, Jakin K.; Maier, Holger R.; Dandy, Graeme C.

    2009-01-01

    Integrated Assessment Modelling (IAM) incorporates knowledge from different disciplines to provide an overarching assessment of the impact of different management decisions. The complex nature of these models, which often include non-linearities and feedback loops, requires special attention for sensitivity analysis. This is especially true when the models are used to form the basis of management decisions, where it is important to assess how sensitive the decisions being made are to changes in model parameters. This research proposes an extension to the Management Option Rank Equivalence (MORE) method of sensitivity analysis; a new method of sensitivity analysis developed specifically for use in IAM and decision-making. The extension proposes using a multi-objective Pareto optimal search to locate minimum combined parameter changes that result in a change in the preferred management option. It is demonstrated through a case study of the Namoi River, where results show that the extension to MORE is able to provide sensitivity information for individual parameters that takes into account simultaneous variations in all parameters. Furthermore, the increased sensitivities to individual parameters that are discovered when joint parameter variation is taken into account shows the importance of ensuring that any sensitivity analysis accounts for these changes.

  17. An efficient method of reducing glass dispersion tolerance sensitivity

    Science.gov (United States)

    Sparrold, Scott W.; Shepard, R. Hamilton

    2014-12-01

    Constraining the Seidel aberrations of optical surfaces is a common technique for relaxing tolerance sensitivities in the optimization process. We offer an observation that a lens's Abbe number tolerance is directly related to the magnitude by which its longitudinal and transverse color are permitted to vary in production. Based on this observation, we propose a computationally efficient and easy-to-use merit function constraint for relaxing dispersion tolerance sensitivity. Using the relationship between an element's chromatic aberration and dispersion sensitivity, we derive a fundamental limit for lens scale and power that is capable of achieving high production yield for a given performance specification, which provides insight on the point at which lens splitting or melt fitting becomes necessary. The theory is validated by comparing its predictions to a formal tolerance analysis of a Cooke Triplet, and then applied to the design of a 1.5x visible linescan lens to illustrate optimization for reduced dispersion sensitivity. A selection of lenses in high volume production is then used to corroborate the proposed method of dispersion tolerance allocation.

  18. A highly sensitive method for detection of molybdenum-containing proteins

    International Nuclear Information System (INIS)

    Kalakutskii, K.L.; Shvetsov, A.A.; Bursakov, S.A.; Letarov, A.V.; Zabolotnyi, A.I.; L'vov, N.P.

    1992-01-01

    A highly sensitive method for detection of molybdenum-containing proteins in gels after electrophoresis has been developed. The method involves in vitro labeling of the proteins with the radioactive isotope 185 W. The method used to detect molybdenum-accumulating proteins in lupine seeds, xanthine dehydrogenase and another molybdenum-containing protein in wheat, barley, and pea seedlings, and nitrate reductase and xanthine dehydrogenase in bacteroides from lupine nodules. Nitrogenase could not be detected by the method. 16 refs., 5 figs

  19. A simple method to estimate the episode and programme sensitivity of breast cancer screening programmes.

    Science.gov (United States)

    Zorzi, Manuel; Guzzinati, Stefano; Puliti, Donella; Paci, Eugenio

    2010-01-01

    The estimation of breast cancer screening sensitivity is a major aim in the quality assessment of screening programmes. The proportional incidence method for the estimation of the sensitivity of breast cancer screening programmes is rarely used to estimate the underlying incidence rates. We present a method to estimate episode and programme sensitivity of screening programmes, based solely on cancers detected within screening cycles (excluding breast cancer cases at prevalent screening round) and on the number of incident cases in the total target population (steady state). The assumptions, strengths and limitations of the method are discussed. An example of calculation of episode and programme sensitivities is given, on the basis of the data from the IMPACT study, a large observational study of breast cancer screening programmes in Italy. The programme sensitivity from the fifth year of screening onwards ranged between 41% and 48% of the total number of cases in the target population. At steady state episode sensitivity was 0.70, with a trend across age groups, with lowest values in women aged 50-54 years (0.52) and highest in those 65-69 (0.77). The method is a very serviceable tool for estimating sensitivity in service screening programmes, and the results are comparable with those of other methods of estimation.

  20. Sensitivity evaluation of dynamic speckle activity measurements using clustering methods

    International Nuclear Information System (INIS)

    Etchepareborda, Pablo; Federico, Alejandro; Kaufmann, Guillermo H.

    2010-01-01

    We evaluate and compare the use of competitive neural networks, self-organizing maps, the expectation-maximization algorithm, K-means, and fuzzy C-means techniques as partitional clustering methods, when the sensitivity of the activity measurement of dynamic speckle images needs to be improved. The temporal history of the acquired intensity generated by each pixel is analyzed in a wavelet decomposition framework, and it is shown that the mean energy of its corresponding wavelet coefficients provides a suited feature space for clustering purposes. The sensitivity obtained by using the evaluated clustering techniques is also compared with the well-known methods of Konishi-Fujii, weighted generalized differences, and wavelet entropy. The performance of the partitional clustering approach is evaluated using simulated dynamic speckle patterns and also experimental data.

  1. Drop weight impact measurements of HE sensitivity: modified detection methods

    International Nuclear Information System (INIS)

    Preston, D N; Brown, G W; Tappan, B C; Oshwald, D M; Koby, J R; Schoonover, M L

    2014-01-01

    High explosives small-scale sensitivity testing has been a hallmark of safety screening since WWII. Sensitivity testing was once crude and simple; broom sticks were used to scrape explosives on the floor while experimenters would look, listen, and smell for signs of a reaction. Since then, a wide variety of testing apparatus have been developed to explore the effects of different stimuli on explosives. In concert with the development of the machines themselves, the reaction detection methods have also evolved. This paper's focus is on the Los Alamos National Laboratory's (LANL) drop weight impact machine and reaction detection methods. A critical evaluation of results is presented with cautionary examples of false positives that can occur with non-explosive materials.

  2. An easily implemented static condensation method for structural sensitivity analysis

    Science.gov (United States)

    Gangadharan, S. N.; Haftka, R. T.; Nikolaidis, E.

    1990-01-01

    A black-box approach to static condensation for sensitivity analysis is presented with illustrative examples of a cube and a car structure. The sensitivity of the structural response with respect to joint stiffness parameter is calculated using the direct method, forward-difference, and central-difference schemes. The efficiency of the various methods for identifying joint stiffness parameters from measured static deflections of these structures is compared. The results indicate that the use of static condensation can reduce computation times significantly and the black-box approach is only slightly less efficient than the standard implementation of static condensation. The ease of implementation of the black-box approach recommends it for use with general-purpose finite element codes that do not have a built-in facility for static condensation.

  3. Development of a localized probabilistic sensitivity method to determine random variable regional importance

    International Nuclear Information System (INIS)

    Millwater, Harry; Singh, Gulshan; Cortina, Miguel

    2012-01-01

    There are many methods to identify the important variable out of a set of random variables, i.e., “inter-variable” importance; however, to date there are no comparable methods to identify the “region” of importance within a random variable, i.e., “intra-variable” importance. Knowledge of the critical region of an input random variable (tail, near-tail, and central region) can provide valuable information towards characterizing, understanding, and improving a model through additional modeling or testing. As a result, an intra-variable probabilistic sensitivity method was developed and demonstrated for independent random variables that computes the partial derivative of a probabilistic response with respect to a localized perturbation in the CDF values of each random variable. These sensitivities are then normalized in absolute value with respect to the largest sensitivity within a distribution to indicate the region of importance. The methodology is implemented using the Score Function kernel-based method such that existing samples can be used to compute sensitivities for negligible cost. Numerical examples demonstrate the accuracy of the method through comparisons with finite difference and numerical integration quadrature estimates. - Highlights: ► Probabilistic sensitivity methodology. ► Determines the “region” of importance within random variables such as left tail, near tail, center, right tail, etc. ► Uses the Score Function approach to reuse the samples, hence, negligible cost. ► No restrictions on the random variable types or limit states.

  4. Radiation sensitive devices and systems for detection of radioactive materials and related methods

    Science.gov (United States)

    Kotter, Dale K

    2014-12-02

    Radiation sensitive devices include a substrate comprising a radiation sensitive material and a plurality of resonance elements coupled to the substrate. Each resonance element is configured to resonate responsive to non-ionizing incident radiation. Systems for detecting radiation from a special nuclear material include a radiation sensitive device and a sensor located remotely from the radiation sensitive device and configured to measure an output signal from the radiation sensitive device. In such systems, the radiation sensitive device includes a radiation sensitive material and a plurality of resonance elements positioned on the radiation sensitive material. Methods for detecting a presence of a special nuclear material include positioning a radiation sensitive device in a location where special nuclear materials are to be detected and remotely interrogating the radiation sensitive device with a sensor.

  5. Computational Methods for Sensitivity and Uncertainty Analysis in Criticality Safety

    International Nuclear Information System (INIS)

    Broadhead, B.L.; Childs, R.L.; Rearden, B.T.

    1999-01-01

    Interest in the sensitivity methods that were developed and widely used in the 1970s (the FORSS methodology at ORNL among others) has increased recently as a result of potential use in the area of criticality safety data validation procedures to define computational bias, uncertainties and area(s) of applicability. Functional forms of the resulting sensitivity coefficients can be used as formal parameters in the determination of applicability of benchmark experiments to their corresponding industrial application areas. In order for these techniques to be generally useful to the criticality safety practitioner, the procedures governing their use had to be updated and simplified. This paper will describe the resulting sensitivity analysis tools that have been generated for potential use by the criticality safety community

  6. Use of selenium to detect mercury in water and cells: an enhancement of the sensitivity and specificity of a seleno fluorescent probe.

    Science.gov (United States)

    Tang, Bo; Ding, Baiyu; Xu, Kehua; Tong, Lili

    2009-01-01

    Seleno fluorescent probe: An organoselenium fluorescent probe (FSe-1) for mercury was designed based on the irreversible deselenation mechanism. FSe-1 exhibits an ultrahigh selectivity and sensitivity for Hg(2+) detection only for reactive selenium atom sites, due the strong affinity between Se and Hg. Furthermore, the new probe has been successfully used for imaging mercury ions in RAW 264.7 cells (a mouse macrophage cell line; see figure).Inspired by the antitoxic function of selenium towards heavy-metal ions, we designed an organoselenium fluorescent probe (FSe-1) for mercury. The reaction of FSe-1 and Hg(2+) is an irreversible deselenation mechanism based on the selenophilic character of mercury. FSe-1 exhibits an ultrahigh selectivity and sensitivity for Hg(2+) detection only for reactive selenium atom sites due to the strong affinity between Se and Hg. The experimental results proved that FSe-1 was selective for Hg(2+) ions over other relevant metal ions and bioanalytes, and also showed an enhancement in sensitivity of up to 1.0 nM, which is lower than the current Environmental Protection Agency standard for drinking water. Furthermore, the new probe has been successfully applied to the imaging of mercury ions in RAW 264.7 cells (a mouse macrophage cell line) with high sensitivity and selectivity.

  7. 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.

  8. A sensitive new method of ex vivo platelet deposition

    International Nuclear Information System (INIS)

    Badimon, L.; Fuster, V.; Dewanjee, M.K.; Romero, J.C.

    1982-01-01

    In 1978, an in vivo quantitative method of platelet aggregation based on the increment of weight of a rabbit tendon when superfused with flowing blood (3 ml/min) derived from a carotid artery of a cat and reentering the contralateral jugular vein was reported. TO increase the sensitivity of the method, researches labeled platelets with indium-111 and reinjected them after two hours; then, with a gamma counter, researches quantitated the 111 In-labeled platelets deposited on the superfused rabbit tendon. Results of the radioactivity method and of the weight method were compared. Researchers found that the 111 In-labeling of platelets was more precise and reproducible method, rendering possible the use of a small amount of blood without need for reentry into the venous system

  9. Computing eigenvalue sensitivity coefficients to nuclear data based on the CLUTCH method with RMC code

    International Nuclear Information System (INIS)

    Qiu, Yishu; She, Ding; Tang, Xiao; Wang, Kan; Liang, Jingang

    2016-01-01

    Highlights: • A new algorithm is proposed to reduce memory consumption for sensitivity analysis. • The fission matrix method is used to generate adjoint fission source distributions. • Sensitivity analysis is performed on a detailed 3D full-core benchmark with RMC. - Abstract: Recently, there is a need to develop advanced methods of computing eigenvalue sensitivity coefficients to nuclear data in the continuous-energy Monte Carlo codes. One of these methods is the iterated fission probability (IFP) method, which is adopted by most of Monte Carlo codes of having the capabilities of computing sensitivity coefficients, including the Reactor Monte Carlo code RMC. Though it is accurate theoretically, the IFP method faces the challenge of huge memory consumption. Therefore, it may sometimes produce poor sensitivity coefficients since the number of particles in each active cycle is not sufficient enough due to the limitation of computer memory capacity. In this work, two algorithms of the Contribution-Linked eigenvalue sensitivity/Uncertainty estimation via Tracklength importance CHaracterization (CLUTCH) method, namely, the collision-event-based algorithm (C-CLUTCH) which is also implemented in SCALE and the fission-event-based algorithm (F-CLUTCH) which is put forward in this work, are investigated and implemented in RMC to reduce memory requirements for computing eigenvalue sensitivity coefficients. While the C-CLUTCH algorithm requires to store concerning reaction rates of every collision, the F-CLUTCH algorithm only stores concerning reaction rates of every fission point. In addition, the fission matrix method is put forward to generate the adjoint fission source distribution for the CLUTCH method to compute sensitivity coefficients. These newly proposed approaches implemented in RMC code are verified by a SF96 lattice model and the MIT BEAVRS benchmark problem. The numerical results indicate the accuracy of the F-CLUTCH algorithm is the same as the C

  10. 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

  11. Investigation of modern methods of probalistic sensitivity analysis of final repository performance assessment models (MOSEL)

    International Nuclear Information System (INIS)

    Spiessl, Sabine; Becker, Dirk-Alexander

    2017-06-01

    Sensitivity analysis is a mathematical means for analysing the sensitivities of a computational model to variations of its input parameters. Thus, it is a tool for managing parameter uncertainties. It is often performed probabilistically as global sensitivity analysis, running the model a large number of times with different parameter value combinations. Going along with the increase of computer capabilities, global sensitivity analysis has been a field of mathematical research for some decades. In the field of final repository modelling, probabilistic analysis is regarded a key element of a modern safety case. An appropriate uncertainty and sensitivity analysis can help identify parameters that need further dedicated research to reduce the overall uncertainty, generally leads to better system understanding and can thus contribute to building confidence in the models. The purpose of the project described here was to systematically investigate different numerical and graphical techniques of sensitivity analysis with typical repository models, which produce a distinctly right-skewed and tailed output distribution and can exhibit a highly nonlinear, non-monotonic or even non-continuous behaviour. For the investigations presented here, three test models were defined that describe generic, but typical repository systems. A number of numerical and graphical sensitivity analysis methods were selected for investigation and, in part, modified or adapted. Different sampling methods were applied to produce various parameter samples of different sizes and many individual runs with the test models were performed. The results were evaluated with the different methods of sensitivity analysis. On this basis the methods were compared and assessed. This report gives an overview of the background and the applied methods. The results obtained for three typical test models are presented and explained; conclusions in view of practical applications are drawn. At the end, a recommendation

  12. Investigation of modern methods of probalistic sensitivity analysis of final repository performance assessment models (MOSEL)

    Energy Technology Data Exchange (ETDEWEB)

    Spiessl, Sabine; Becker, Dirk-Alexander

    2017-06-15

    Sensitivity analysis is a mathematical means for analysing the sensitivities of a computational model to variations of its input parameters. Thus, it is a tool for managing parameter uncertainties. It is often performed probabilistically as global sensitivity analysis, running the model a large number of times with different parameter value combinations. Going along with the increase of computer capabilities, global sensitivity analysis has been a field of mathematical research for some decades. In the field of final repository modelling, probabilistic analysis is regarded a key element of a modern safety case. An appropriate uncertainty and sensitivity analysis can help identify parameters that need further dedicated research to reduce the overall uncertainty, generally leads to better system understanding and can thus contribute to building confidence in the models. The purpose of the project described here was to systematically investigate different numerical and graphical techniques of sensitivity analysis with typical repository models, which produce a distinctly right-skewed and tailed output distribution and can exhibit a highly nonlinear, non-monotonic or even non-continuous behaviour. For the investigations presented here, three test models were defined that describe generic, but typical repository systems. A number of numerical and graphical sensitivity analysis methods were selected for investigation and, in part, modified or adapted. Different sampling methods were applied to produce various parameter samples of different sizes and many individual runs with the test models were performed. The results were evaluated with the different methods of sensitivity analysis. On this basis the methods were compared and assessed. This report gives an overview of the background and the applied methods. The results obtained for three typical test models are presented and explained; conclusions in view of practical applications are drawn. At the end, a recommendation

  13. Survey of sampling-based methods for uncertainty and sensitivity analysis

    International Nuclear Information System (INIS)

    Helton, J.C.; Johnson, J.D.; Sallaberry, C.J.; Storlie, C.B.

    2006-01-01

    Sampling-based methods for uncertainty and sensitivity analysis are reviewed. The following topics are considered: (i) definition of probability distributions to characterize epistemic uncertainty in analysis inputs (ii) generation of samples from uncertain analysis inputs (iii) propagation of sampled inputs through an analysis (iv) presentation of uncertainty analysis results, and (v) determination of sensitivity analysis results. Special attention is given to the determination of sensitivity analysis results, with brief descriptions and illustrations given for the following procedures/techniques: examination of scatterplots, correlation analysis, regression analysis, partial correlation analysis, rank transformations, statistical tests for patterns based on gridding, entropy tests for patterns based on gridding, nonparametric regression analysis, squared rank differences/rank correlation coefficient test, two-dimensional Kolmogorov-Smirnov test, tests for patterns based on distance measures, top down coefficient of concordance, and variance decomposition

  14. Survey of sampling-based methods for uncertainty and sensitivity analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Jay Dean; Helton, Jon Craig; Sallaberry, Cedric J. PhD. (.; .); Storlie, Curt B. (Colorado State University, Fort Collins, CO)

    2006-06-01

    Sampling-based methods for uncertainty and sensitivity analysis are reviewed. The following topics are considered: (1) Definition of probability distributions to characterize epistemic uncertainty in analysis inputs, (2) Generation of samples from uncertain analysis inputs, (3) Propagation of sampled inputs through an analysis, (4) Presentation of uncertainty analysis results, and (5) Determination of sensitivity analysis results. Special attention is given to the determination of sensitivity analysis results, with brief descriptions and illustrations given for the following procedures/techniques: examination of scatterplots, correlation analysis, regression analysis, partial correlation analysis, rank transformations, statistical tests for patterns based on gridding, entropy tests for patterns based on gridding, nonparametric regression analysis, squared rank differences/rank correlation coefficient test, two dimensional Kolmogorov-Smirnov test, tests for patterns based on distance measures, top down coefficient of concordance, and variance decomposition.

  15. A simple and sensitive method for determination of Norfloxacin in pharmaceutical preparations

    Directory of Open Access Journals (Sweden)

    Zhuo Ye

    2015-06-01

    Full Text Available In this approach, a new voltammetric method for determination of norfloxacin was proposed with high sensitivity and wider detection linear range. The used voltammetric sensor was fabricated simply by coating a layer of graphene oxide (GO and Nafion composited film on glassy carbon electrode. The advantage of proposed method was sensitive electrochemical response for norfloxacin, which was attributed to the excellent electrical conductivity of GO and the accumulating function of Nafion under optimum experimental conditions, the present method revealed a good linear response for determination of norfloxacin in the range of 1×10-8mol/L-7×10-6 mol/L with a detection limit of 5×10-9 mol/L. The proposed method was successfully applied in the determination of norfloxacin in capsules with satisfactory results.

  16. 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

  17. 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.

  18. Aquifer sensitivity to pesticide leaching: Testing a soils and hydrogeologic index method

    Science.gov (United States)

    Mehnert, E.; Keefer, D.A.; Dey, W.S.; Wehrmann, H.A.; Wilson, S.D.; Ray, C.

    2005-01-01

    For years, researchers have sought index and other methods to predict aquifer sensitivity and vulnerability to nonpoint pesticide contamination. In 1995, an index method and map were developed to define aquifer sensitivity to pesticide leaching based on a combination of soil and hydrogeologic factors. The soil factor incorporated three soil properties: hydraulic conductivity, amount of organic matter within individual soil layers, and drainage class. These properties were obtained from a digital soil association map. The hydrogeologic factor was depth to uppermost aquifer material. To test this index method, a shallow ground water monitoring well network was designed, installed, and sampled in Illinois. The monitoring wells had a median depth of 7.6 m and were located adjacent to corn and soybean fields where the only known sources of pesticides were those used in normal agricultural production. From September 1998 through February 2001, 159 monitoring wells were sampled for 14 pesticides but no pesticide metabolites. Samples were collected and analyzed to assess the distribution of pesticide occurrence across three units of aquifer sensitivity. Pesticides were detected in 18% of all samples and nearly uniformly from samples from the three units of aquifer sensitivity. The new index method did not predict pesticide occurrence because occurrence was not dependent on the combined soil and hydrogeologic factors. However, pesticide occurrence was dependent on the tested hydrogeologic factor and was three times higher in areas where the depth to the uppermost aquifer was <6 m than in areas where the depth to the uppermost aquifer was 6 to <15 m. Copyright ?? 2005 National Ground Water Association.

  19. Highly sensitive high resolution Raman spectroscopy using resonant ionization methods

    International Nuclear Information System (INIS)

    Owyoung, A.; Esherick, P.

    1984-05-01

    In recent years, the introduction of stimulated Raman methods has offered orders of magnitude improvement in spectral resolving power for gas phase Raman studies. Nevertheless, the inherent weakness of the Raman process suggests the need for significantly more sensitive techniques in Raman spectroscopy. In this we describe a new approach to this problem. Our new technique, which we call ionization-detected stimulated Raman spectroscopy (IDSRS), combines high-resolution SRS with highly-sensitive resonant laser ionization to achieve an increase in sensitivity of over three orders of magnitude. The excitation/detection process involves three sequential steps: (1) population of a vibrationally excited state via stimulated Raman pumping; (2) selective ionization of the vibrationally excited molecule with a tunable uv source; and (3) collection of the ionized species at biased electrodes where they are detected as current in an external circuit

  20. Estimation of the sensitivity of various environmental sampling methods for detection of Salmonella in duck flocks.

    Science.gov (United States)

    Arnold, Mark E; Mueller-Doblies, Doris; Gosling, Rebecca J; Martelli, Francesca; Davies, Robert H

    2015-01-01

    Reports of Salmonella in ducks in the UK currently rely upon voluntary submissions from the industry, and as there is no harmonized statutory monitoring and control programme, it is difficult to compare data from different years in order to evaluate any trends in Salmonella prevalence in relation to sampling methodology. Therefore, the aim of this project was to assess the sensitivity of a selection of environmental sampling methods, including the sampling of faeces, dust and water troughs or bowls for the detection of Salmonella in duck flocks, and a range of sampling methods were applied to 67 duck flocks. Bayesian methods in the absence of a gold standard were used to provide estimates of the sensitivity of each of the sampling methods relative to the within-flock prevalence. There was a large influence of the within-flock prevalence on the sensitivity of all sample types, with sensitivity reducing as the within-flock prevalence reduced. Boot swabs (individual and pool of four), swabs of faecally contaminated areas and whole house hand-held fabric swabs showed the overall highest sensitivity for low-prevalence flocks and are recommended for use to detect Salmonella in duck flocks. The sample type with the highest proportion positive was a pool of four hair nets used as boot swabs, but this was not the most sensitive sample for low-prevalence flocks. All the environmental sampling types (faeces swabs, litter pinches, drag swabs, water trough samples and dust) had higher sensitivity than individual faeces sampling. None of the methods consistently identified all the positive flocks, and at least 10 samples would be required for even the most sensitive method (pool of four boot swabs) to detect a 5% prevalence. The sampling of dust had a low sensitivity and is not recommended for ducks.

  1. 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.

  2. 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.

  3. 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...

  4. A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Avonto, Cristina; Chittiboyina, Amar G. [National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States); Rua, Diego [The Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD 20740 (United States); Khan, Ikhlas A., E-mail: ikhan@olemiss.edu [National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States); Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States)

    2015-12-01

    Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, ‘HTS-DCYA assay’, is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens™ were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first time. - Highlights: • A novel fluorescence-based method to detect electrophilic sensitizers is proposed. • A model fluorescent thiol was used to directly quantify the reaction products. • A discussion of the reaction workflow

  5. A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

    International Nuclear Information System (INIS)

    Avonto, Cristina; Chittiboyina, Amar G.; Rua, Diego; Khan, Ikhlas A.

    2015-01-01

    Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, ‘HTS-DCYA assay’, is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens™ were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first time. - Highlights: • A novel fluorescence-based method to detect electrophilic sensitizers is proposed. • A model fluorescent thiol was used to directly quantify the reaction products. • A discussion of the reaction workflow

  6. Application of perturbation methods for sensitivity analysis for nuclear power plant steam generators

    International Nuclear Information System (INIS)

    Gurjao, Emir Candeia

    1996-02-01

    The differential and GPT (Generalized Perturbation Theory) formalisms of the Perturbation Theory were applied in this work to a simplified U-tubes steam generator model to perform sensitivity analysis. The adjoint and importance equations, with the corresponding expressions for the sensitivity coefficients, were derived for this steam generator model. The system was numerically was numerically solved in a Fortran program, called GEVADJ, in order to calculate the sensitivity coefficients. A transient loss of forced primary coolant in the nuclear power plant Angra-1 was used as example case. The average and final values of functionals: secondary pressure and enthalpy were studied in relation to changes in the secondary feedwater flow, enthalpy and total volume in secondary circuit. Absolute variations in the above functionals were calculated using the perturbative methods, considering the variations in the feedwater flow and total secondary volume. Comparison with the same variations obtained via direct model showed in general good agreement, demonstrating the potentiality of perturbative methods for sensitivity analysis of nuclear systems. (author)

  7. A sensitive new microculture method for diagnosis of cutaneous leishmaniasis.

    Science.gov (United States)

    Allahverdiyev, Adil M; Uzun, Soner; Bagirova, Malahat; Durdu, Murat; Memisoglu, Hamdi R

    2004-03-01

    A sensitive microcapillary culture method (MCM) was developed for rapid diagnosis of cutaneous leishmaniasis (CL). The MCM is superior to the traditional culture method (TCM) as determined by the smaller inoculum size, the higher sensitivity for detection of promastigotes, and the more rapid time for emergence of promastigotes. With lesion amastigote loads from grade III to 0, the positive rates and the periods for promastigote emergence were 3-4-fold higher and faster with the MCM than with the TCM, e.g., 83-97% positive in 4-7 days versus 20-40% positive in 15-30 days (P = 0.0001). The higher Pco(2) and lower Po(2) and pH presumably encourage a rapid amastigote-to-promastigote differentiation and/or the survival or growth of the latter. This MCM has the advantage of simplicity, and may be suitable for diagnostic use and for parasite retrieval in many other endemic sites where parasites are known to be difficult to grow.

  8. Manufacturing error sensitivity analysis and optimal design method of cable-network antenna structures

    Science.gov (United States)

    Zong, Yali; Hu, Naigang; Duan, Baoyan; Yang, Guigeng; Cao, Hongjun; Xu, Wanye

    2016-03-01

    Inevitable manufacturing errors and inconsistency between assumed and actual boundary conditions can affect the shape precision and cable tensions of a cable-network antenna, and even result in failure of the structure in service. In this paper, an analytical sensitivity analysis method of the shape precision and cable tensions with respect to the parameters carrying uncertainty was studied. Based on the sensitivity analysis, an optimal design procedure was proposed to alleviate the effects of the parameters that carry uncertainty. The validity of the calculated sensitivities is examined by those computed by a finite difference method. Comparison with a traditional design method shows that the presented design procedure can remarkably reduce the influence of the uncertainties on the antenna performance. Moreover, the results suggest that especially slender front net cables, thick tension ties, relatively slender boundary cables and high tension level can improve the ability of cable-network antenna structures to resist the effects of the uncertainties on the antenna performance.

  9. 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.

  10. Approximate method in estimation sensitivity responses to variations in delayed neutron energy spectra

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, J; Shin, H S; Song, T Y; Park, W S [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1998-12-31

    Previous our numerical results in computing point kinetics equations show a possibility in developing approximations to estimate sensitivity responses of nuclear reactor. We recalculate sensitivity responses by maintaining the corrections with first order of sensitivity parameter. We present a method for computing sensitivity responses of nuclear reactor based on an approximation derived from point kinetics equations. Exploiting this approximation, we found that the first order approximation works to estimate variations in the time to reach peak power because of their linear dependence on a sensitivity parameter, and that there are errors in estimating the peak power in the first order approximation for larger sensitivity parameters. To confirm legitimacy of out approximation, these approximate results are compared with exact results obtained from out previous numerical study. 4 refs., 2 figs., 3 tabs. (Author)

  11. Approximate method in estimation sensitivity responses to variations in delayed neutron energy spectra

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, J.; Shin, H. S.; Song, T. Y.; Park, W. S. [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1997-12-31

    Previous our numerical results in computing point kinetics equations show a possibility in developing approximations to estimate sensitivity responses of nuclear reactor. We recalculate sensitivity responses by maintaining the corrections with first order of sensitivity parameter. We present a method for computing sensitivity responses of nuclear reactor based on an approximation derived from point kinetics equations. Exploiting this approximation, we found that the first order approximation works to estimate variations in the time to reach peak power because of their linear dependence on a sensitivity parameter, and that there are errors in estimating the peak power in the first order approximation for larger sensitivity parameters. To confirm legitimacy of out approximation, these approximate results are compared with exact results obtained from out previous numerical study. 4 refs., 2 figs., 3 tabs. (Author)

  12. Capillary Electrophoresis Sensitivity Enhancement Based on Adaptive Moving Average Method.

    Science.gov (United States)

    Drevinskas, Tomas; Telksnys, Laimutis; Maruška, Audrius; Gorbatsova, Jelena; Kaljurand, Mihkel

    2018-06-05

    In the present work, we demonstrate a novel approach to improve the sensitivity of the "out of lab" portable capillary electrophoretic measurements. Nowadays, many signal enhancement methods are (i) underused (nonoptimal), (ii) overused (distorts the data), or (iii) inapplicable in field-portable instrumentation because of a lack of computational power. The described innovative migration velocity-adaptive moving average method uses an optimal averaging window size and can be easily implemented with a microcontroller. The contactless conductivity detection was used as a model for the development of a signal processing method and the demonstration of its impact on the sensitivity. The frequency characteristics of the recorded electropherograms and peaks were clarified. Higher electrophoretic mobility analytes exhibit higher-frequency peaks, whereas lower electrophoretic mobility analytes exhibit lower-frequency peaks. On the basis of the obtained data, a migration velocity-adaptive moving average algorithm was created, adapted, and programmed into capillary electrophoresis data-processing software. Employing the developed algorithm, each data point is processed depending on a certain migration time of the analyte. Because of the implemented migration velocity-adaptive moving average method, the signal-to-noise ratio improved up to 11 times for sampling frequency of 4.6 Hz and up to 22 times for sampling frequency of 25 Hz. This paper could potentially be used as a methodological guideline for the development of new smoothing algorithms that require adaptive conditions in capillary electrophoresis and other separation methods.

  13. Non-animal methods to predict skin sensitization (II): an assessment of defined approaches *.

    Science.gov (United States)

    Kleinstreuer, Nicole C; Hoffmann, Sebastian; Alépée, Nathalie; Allen, David; Ashikaga, Takao; Casey, Warren; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Göbel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Strickland, Judy; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk

    2018-05-01

    Skin sensitization is a toxicity endpoint of widespread concern, for which the mechanistic understanding and concurrent necessity for non-animal testing approaches have evolved to a critical juncture, with many available options for predicting sensitization without using animals. Cosmetics Europe and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods collaborated to analyze the performance of multiple non-animal data integration approaches for the skin sensitization safety assessment of cosmetics ingredients. The Cosmetics Europe Skin Tolerance Task Force (STTF) collected and generated data on 128 substances in multiple in vitro and in chemico skin sensitization assays selected based on a systematic assessment by the STTF. These assays, together with certain in silico predictions, are key components of various non-animal testing strategies that have been submitted to the Organization for Economic Cooperation and Development as case studies for skin sensitization. Curated murine local lymph node assay (LLNA) and human skin sensitization data were used to evaluate the performance of six defined approaches, comprising eight non-animal testing strategies, for both hazard and potency characterization. Defined approaches examined included consensus methods, artificial neural networks, support vector machine models, Bayesian networks, and decision trees, most of which were reproduced using open source software tools. Multiple non-animal testing strategies incorporating in vitro, in chemico, and in silico inputs demonstrated equivalent or superior performance to the LLNA when compared to both animal and human data for skin sensitization.

  14. Sensitive emission spectrometric method for the analysis of airborne particulate matter

    International Nuclear Information System (INIS)

    Sugimae, A.

    1975-01-01

    A rapid and sensitive emission spectrometric method for the routine analysis of airborne particulate matter collected on the glass fiber filter is reported. The method is a powder--dc arc technique involving no chemical pre-enrichment procedures. The elements--Ag, BA: Be, Bi, Cd, Co, Cr, Cu, Fe, Ga, La, Mn, Ni, Pb, Sn, V, Y, Yb, and Zn--were determined. (U.S.)

  15. Complex finite element sensitivity method for creep analysis

    International Nuclear Information System (INIS)

    Gomez-Farias, Armando; Montoya, Arturo; Millwater, Harry

    2015-01-01

    The complex finite element method (ZFEM) has been extended to perform sensitivity analysis for mechanical and structural systems undergoing creep deformation. ZFEM uses a complex finite element formulation to provide shape, material, and loading derivatives of the system response, providing an insight into the essential factors which control the behavior of the system as a function of time. A complex variable-based quadrilateral user element (UEL) subroutine implementing the power law creep constitutive formulation was incorporated within the Abaqus commercial finite element software. The results of the complex finite element computations were verified by comparing them to the reference solution for the steady-state creep problem of a thick-walled cylinder in the power law creep range. A practical application of the ZFEM implementation to creep deformation analysis is the calculation of the skeletal point of a notched bar test from a single ZFEM run. In contrast, the standard finite element procedure requires multiple runs. The value of the skeletal point is that it identifies the location where the stress state is accurate, regardless of the certainty of the creep material properties. - Highlights: • A novel finite element sensitivity method (ZFEM) for creep was introduced. • ZFEM has the capability to calculate accurate partial derivatives. • ZFEM can be used for identification of the skeletal point of creep structures. • ZFEM can be easily implemented in a commercial software, e.g. Abaqus. • ZFEM results were shown to be in excellent agreement with analytical solutions

  16. Measuring sensitivity in pharmacoeconomic studies. Refining point sensitivity and range sensitivity by incorporating probability distributions.

    Science.gov (United States)

    Nuijten, M J

    1999-07-01

    The aim of the present study is to describe a refinement of a previously presented method, based on the concept of point sensitivity, to deal with uncertainty in economic studies. The original method was refined by the incorporation of probability distributions which allow a more accurate assessment of the level of uncertainty in the model. In addition, a bootstrap method was used to create a probability distribution for a fixed input variable based on a limited number of data points. The original method was limited in that the sensitivity measurement was based on a uniform distribution of the variables and that the overall sensitivity measure was based on a subjectively chosen range which excludes the impact of values outside the range on the overall sensitivity. The concepts of the refined method were illustrated using a Markov model of depression. The application of the refined method substantially changed the ranking of the most sensitive variables compared with the original method. The response rate became the most sensitive variable instead of the 'per diem' for hospitalisation. The refinement of the original method yields sensitivity outcomes, which greater reflect the real uncertainty in economic studies.

  17. An adjoint method of sensitivity analysis for residual vibrations of structures subject to impacts

    Science.gov (United States)

    Yan, Kun; Cheng, Gengdong

    2018-03-01

    For structures subject to impact loads, the residual vibration reduction is more and more important as the machines become faster and lighter. An efficient sensitivity analysis of residual vibration with respect to structural or operational parameters is indispensable for using a gradient based optimization algorithm, which reduces the residual vibration in either active or passive way. In this paper, an integrated quadratic performance index is used as the measure of the residual vibration, since it globally measures the residual vibration response and its calculation can be simplified greatly with Lyapunov equation. Several sensitivity analysis approaches for performance index were developed based on the assumption that the initial excitations of residual vibration were given and independent of structural design. Since the resulting excitations by the impact load often depend on structural design, this paper aims to propose a new efficient sensitivity analysis method for residual vibration of structures subject to impacts to consider the dependence. The new method is developed by combining two existing methods and using adjoint variable approach. Three numerical examples are carried out and demonstrate the accuracy of the proposed method. The numerical results show that the dependence of initial excitations on structural design variables may strongly affects the accuracy of sensitivities.

  18. Isolation of uv-sensitive variants of human FL cells by a viral suicide method

    International Nuclear Information System (INIS)

    Shiomi, T.; Sato, K.

    1979-01-01

    A new method (viral suicide method) for the isolation of uv-sensitive mutants is described. Colonies of mutagenized human FL cells were infected with uv-irradiated Herpes simplex viruses and surviving ones which seemed to be deficient in host cell reactivation (HCR) were examined for their uv sensitivity. Nineteen of 238 clones examined were sensitive to uv irradiation at the time of the isolation. After recloning, four of these clones have been studied and two (UVS-1 and UVS-2) of them are stable in their uv sensitivity for 4 months in culture. uv sensitivity of UVS-1, UVS-2, and the parental FL cells are as follows: the extrapolation numbers (n) are 2.2, 2.1, and 1.8 and mean lethal doses (DO) are 2.9, 3.7, and 7.8 J/m 2 for UVS-1, UVS-2, and the parental FL cells, respectively. They are no more sensitive than FL cells to x-irradiation. The ability of HCR in UVS-2 cells is apparently lower than that in FL cells, whereas UVS-1 cells are the same as FL cells in the ability

  19. Easy method enhancing the sensitivity of a helium mass-spectrometer leak detector

    International Nuclear Information System (INIS)

    Firpo, G.; Pozzo, A.

    2004-01-01

    Commercial He mass spectrometer leak detectors usually do not provide sufficient sensitivity to perform accurate measurements of the permeation rate of He through glass. Ultrasensitive dedicated systems have adeguate sensitivity but involve high costs and complex procedures. However, both cryogenics and photomultiplier technology routinely demand this goal. Here, we propose a novel method to increase the sensitivity of commercial devices to easily measure accurate permeation rate. We modified a commercial leak detector by reducing the pumping speed at the inlet of the rotary pump, thus increasing its sensitivity by one order of magnitude. The modified detector was used to measure the leak rate of the permeation of He through the glass walls of a photomultiplier. Further improvements made to decrease the minimum detectable signal were limited by the high ultimate pressure in the spectrometer tube

  20. Isolation of UV-sensitive mutants of mouse L5178Y cells by a cell suspension spotting method

    International Nuclear Information System (INIS)

    Shiomi, T.; Hieda-Shiomi, N.; Sato, K.

    1982-01-01

    We have isolated 56 UV-sensitive mutant clones from a mouse L51 T/t line of L5178Y cells by a cell suspension spotting method. Five mutants have also been isolated from L51 T/t and L5178Y cells by the method reported by Thompson and coworkers. We divided the mutants into two groups, highly sensitive and moderately sensitive mutants, according to their sensitivity to UV irradiation. Fifty-eight mutants were highly sensitive and three were moderately sensitive to UV. The reconstruction experiments indicate that more than 90% of highly sensitive mutants were recovered by the cell suspension spotting method. Frequencies of recovered mutants highly sensitive to UV increased with increasing dose of mutagens. Recovered mutant frequency reached 10(-2) after treatment with 1.5 micrograms/ml of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (survival 0.2%). Eight UV-sensitive mutants were divided into four complementation groups. These mutants were 2-6 times more sensitive to UV than parental L51 T/t cells in terms of D37 (dose required to reduce survival to 37%). Four representative UV-sensitive mutants which are classified into different complementation groups were examined for their sensitivity to killing by UV, 4-nitroquinoline-1-oxide (4NQO), mitomycin C (MMC), X-rays, and MNNG. All four classes of mutants were found to be cross-sensitive to UV, 4NQO, and MMC, but not sensitive to X-rays and MNNG

  1. Sensitivity-based virtual fields for the non-linear virtual fields method

    Science.gov (United States)

    Marek, Aleksander; Davis, Frances M.; Pierron, Fabrice

    2017-09-01

    The virtual fields method is an approach to inversely identify material parameters using full-field deformation data. In this manuscript, a new set of automatically-defined virtual fields for non-linear constitutive models has been proposed. These new sensitivity-based virtual fields reduce the influence of noise on the parameter identification. The sensitivity-based virtual fields were applied to a numerical example involving small strain plasticity; however, the general formulation derived for these virtual fields is applicable to any non-linear constitutive model. To quantify the improvement offered by these new virtual fields, they were compared with stiffness-based and manually defined virtual fields. The proposed sensitivity-based virtual fields were consistently able to identify plastic model parameters and outperform the stiffness-based and manually defined virtual fields when the data was corrupted by noise.

  2. 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

  3. 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.

  4. Aptamer-mediated colorimetric method for rapid and sensitive detection of chloramphenicol in food.

    Science.gov (United States)

    Yan, Chao; Zhang, Jing; Yao, Li; Xue, Feng; Lu, Jianfeng; Li, Baoguang; Chen, Wei

    2018-09-15

    We report an aptamer-mediated colorimetric method for sensitive detection of chloramphenicol (CAP). The aptamer of CAP is immobilized by the hybridization with pre-immobilized capture probe in the microtiter plate. The horseradish peroxidase (HRP) is covalently attached to the aptamer by the biotin-streptavidin system for signal production. CAP will preferably bind with aptamer due to the high binding affinity, which attributes to the release of aptamer and HRP and thus, affects the optical signal intensity. Quantitative determination of CAP is successfully achieved in the wide range from 0.001 to 1000 ng/mL with detection limit of 0.0031 ng/mL, which is more sensitive than traditional immunoassays. This method is further validated by measuring the recovery of CAP spiked in two different food matrices (honey and fish). The aptamer-mediated colorimetric method can be a useful protocol for rapid and sensitive screening of CAP, and may be used as an alternative means for traditional immunoassays. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Sensitivity and Uncertainty Analysis of Coupled Reactor Physics Problems : Method Development for Multi-Physics in Reactors

    NARCIS (Netherlands)

    Perkó, Z.

    2015-01-01

    This thesis presents novel adjoint and spectral methods for the sensitivity and uncertainty (S&U) analysis of multi-physics problems encountered in the field of reactor physics. The first part focuses on the steady state of reactors and extends the adjoint sensitivity analysis methods well

  6. A sensitive method for assay of beryllium with chromazurol S and 2,2'-bipyridyl

    International Nuclear Information System (INIS)

    Buhl, F.; Kwapulinska, G.

    1980-01-01

    A spectrophotometric method of assay for microgram amounts of beryllium by means of chromazurol S in presence of 2,2'-bipyridyl was described. The latter appreciably enhances the sensitivity of the method; epsilonsub(lambda=610nm) is 5.4X10 4 . The complex compound obeys the Lambert-Beer law in the concentration range 0.002 to 0.2 ppm Be. The maximum colour intensity is immediately attained at pH 5. The molar ratio Be: CHAS: bip is 1 : 2 : 1. The suggested method is sensitive and has satisfactory selectivity when EDTA is applied as masking agent. (author)

  7. Dynamic pressure sensitivity determination with Mach number method

    Science.gov (United States)

    Sarraf, Christophe; Damion, Jean-Pierre

    2018-05-01

    Measurements of pressure in fast transient conditions are often performed even if the dynamic characteristic of the transducer are not traceable to international standards. Moreover, the question of a primary standard in dynamic pressure is still open, especially for gaseous applications. The question is to improve dynamic standards in order to respond to expressed industrial needs. In this paper, the method proposed in the EMRP IND09 ‘Dynamic’ project, which can be called the ‘ideal shock tube method’, is compared with the ‘collective standard method’ currently used in the Laboratoire de Métrologie Dynamique (LNE/ENSAM). The input is a step of pressure generated by a shock tube. The transducer is a piezoelectric pressure sensor. With the ‘ideal shock tube method’ the sensitivity of a pressure sensor is first determined dynamically. This method requires a shock tube implemented with piezoelectric shock wave detectors. The measurement of the Mach number in the tube allows an evaluation of the incident pressure amplitude of a step using a theoretical 1D model of the shock tube. Heat transfer, other actual effects and effects of the shock tube imperfections are not taken into account. The amplitude of the pressure step is then used to determine the sensitivity in dynamic conditions. The second method uses a frequency bandwidth comparison to determine pressure at frequencies from quasi-static conditions, traceable to static pressure standards, to higher frequencies (up to 10 kHz). The measurand is also a step of pressure generated by a supposed ideal shock tube or a fast-opening device. The results are provided as a transfer function with an uncertainty budget assigned to a frequency range, also deliverable frequency by frequency. The largest uncertainty in the bandwidth of comparison is used to trace the final pressure step level measured in dynamic conditions, owing that this pressure is not measurable in a steady state on a shock tube. A reference

  8. A nanosilver-based spectrophotometry method for sensitive determination of tartrazine in food samples.

    Science.gov (United States)

    Sahraei, R; Farmany, A; Mortazavi, S S

    2013-06-01

    A new method is reported for sensitive determination of tartrazine in the food samples. The method is based on the catalytic effect of silver nanoparticle (AgNPs) on the oxidation reaction of tartrazine by potassium iodate in the acetate buffer medium. The reaction is followed spectrophotometrically by measuring the change in absorbance (ΔA) at 420 nm using a fixed time method (70 s). The reaction variables were optimised in order to achieve the highest sensitivity. The thirty six criterion detection limit was 0.3 ng/mL, and the relative standard deviation for ten replicate measurements of 30 ng/mL of tartrazine was 0.98% (n=10). The method was successfully applied to the determination of tartrazine in lemon, and papaya-flavoured gelatin, candy, and in fruit syrup. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. The Role of Numerical Methods in the Sensitivity Analysis of a ...

    African Journals Online (AJOL)

    The mathematical modelling of physiochemical interaction in the framework of industrial and environmental physics which relies on an initial value problem is defined by a first order ordinary differential equation. Two numerical methods of studying sensitivity analysis of physiochemical interaction data are developed.

  10. A sensitive fluorescence quenching method for determination of bismuth with tiron

    Energy Technology Data Exchange (ETDEWEB)

    Taher, Mohammad Ali; Rahimi, Mina [Department of Chemistry, Shahid Bahonar University of Kerman, Kerman (Iran, Islamic Republic of); Fazelirad, Hamid, E-mail: hamidfazelirad@gmail.com [Department of Chemistry, Shahid Bahonar University of Kerman, Kerman (Iran, Islamic Republic of); Department of Chemistry, Science and Research Branch, Islamic Azad University, Yazd (Iran, Islamic Republic of); Young Researchers Society, Shahid Bahonar University of Kerman, P.O. Box 76175-133, Kerman (Iran, Islamic Republic of)

    2014-01-15

    We describe a fluorescence quenching method for determination of bismuth with tiron. The method is based on the reaction of tiron by bismuth(III) in acidic media. The influence of variables such as the pH, type of buffer, tiron concentration, reaction time and temperature were investigated. Under optimized conditions, the fluorescence quenching extent is proportional to the concentration of bismuth for Bi–tiron system at the range 0.13–2.09 μg mL{sup −1} and the detection limit is 0.05 μg mL{sup −1}. The proposed sensor presented good repeatability, evaluated in terms of relative standard deviation (R.S.D.=±0.498%) for 11 replicates. This sensitive, rapid and accurate method has been successfully applied to the determination of trace bismuth(III) in water and hair samples and certified reference materials. -- Highlights: • No previous paper report on use of fluorescence quenching for determination of Bi. • Fluorescence quenching of trion is a sensitive method for determination of Bi(III). • Under the optimum conditions the detection limit is very low (0.05 μg mL{sup −1}). • The procedure is simple and safe and has high tolerance limit to interferences.

  11. Calibration method of the pulsed X-ray relative sensitivity for ST401 plastic scintillators

    International Nuclear Information System (INIS)

    Xie Hongwei; Song Guzhou; Wang Kuilu

    2011-01-01

    The relative sensitivity calibration method of the pulsed X-ray in ST401 plastic scintillator is presented. Experimental relative sensitivity calibrations of the plastic scintillators of different thicknesses from 1 mm to 50 mm are accomplished on the 'Chenguang' pulsed X-ray source and a Co radioactive source, The uncertainty of the calibration data is evaluated, which can be treated as the experimental evidence for the relative sensitivity conversion of ST401 plastic scintillator. (authors)

  12. Application of a path sensitizing method on automated generation of test specifications for control software

    International Nuclear Information System (INIS)

    Morimoto, Yuuichi; Fukuda, Mitsuko

    1995-01-01

    An automated generation method for test specifications has been developed for sequential control software in plant control equipment. Sequential control software can be represented as sequential circuits. The control software implemented in a control equipment is designed from these circuit diagrams. In logic tests of VLSI's, path sensitizing methods are widely used to generate test specifications. But the method generates test specifications at a single time only, and can not be directly applied to sequential control software. The basic idea of the proposed method is as follows. Specifications of each logic operator in the diagrams are defined in the software design process. Therefore, test specifications of each operator in the control software can be determined from these specifications, and validity of software can be judged by inspecting all of the operators in the logic circuit diagrams. Candidates for sensitized paths, on which test data for each operator propagates, can be generated by the path sensitizing method. To confirm feasibility of the method, it was experimentally applied to control software in digital control equipment. The program could generate test specifications exactly, and feasibility of the method was confirmed. (orig.) (3 refs., 7 figs.)

  13. Overview of hybrid subspace methods for uncertainty quantification, sensitivity analysis

    International Nuclear Information System (INIS)

    Abdel-Khalik, Hany S.; Bang, Youngsuk; Wang, Congjian

    2013-01-01

    Highlights: ► We overview the state-of-the-art in uncertainty quantification and sensitivity analysis. ► We overview new developments in above areas using hybrid methods. ► We give a tutorial introduction to above areas and the new developments. ► Hybrid methods address the explosion in dimensionality in nonlinear models. ► Representative numerical experiments are given. -- Abstract: The role of modeling and simulation has been heavily promoted in recent years to improve understanding of complex engineering systems. To realize the benefits of modeling and simulation, concerted efforts in the areas of uncertainty quantification and sensitivity analysis are required. The manuscript intends to serve as a pedagogical presentation of the material to young researchers and practitioners with little background on the subjects. We believe this is important as the role of these subjects is expected to be integral to the design, safety, and operation of existing as well as next generation reactors. In addition to covering the basics, an overview of the current state-of-the-art will be given with particular emphasis on the challenges pertaining to nuclear reactor modeling. The second objective will focus on presenting our own development of hybrid subspace methods intended to address the explosion in the computational overhead required when handling real-world complex engineering systems.

  14. Liquid chromatography-tandem mass spectrometric assay for the simultaneous determination of the irreversible BTK inhibitor ibrutinib and its dihydrodiol-metabolite in plasma and its application in mouse pharmacokinetic studies

    NARCIS (Netherlands)

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

    2016-01-01

    A validated simple, fast and sensitive bio-analytical assay for ibrutinib and its dihydrodiol metabolite in human and mouse plasma was set up. Sample preparation was performed by protein precipitation, and addition of the respective deuterated internal standards, followed by LC-MS/MS analysis.

  15. Overview of methods for uncertainty analysis and sensitivity analysis in probabilistic risk assessment

    International Nuclear Information System (INIS)

    Iman, R.L.; Helton, J.C.

    1985-01-01

    Probabilistic Risk Assessment (PRA) is playing an increasingly important role in the nuclear reactor regulatory process. The assessment of uncertainties associated with PRA results is widely recognized as an important part of the analysis process. One of the major criticisms of the Reactor Safety Study was that its representation of uncertainty was inadequate. The desire for the capability to treat uncertainties with the MELCOR risk code being developed at Sandia National Laboratories is indicative of the current interest in this topic. However, as yet, uncertainty analysis and sensitivity analysis in the context of PRA is a relatively immature field. In this paper, available methods for uncertainty analysis and sensitivity analysis in a PRA are reviewed. This review first treats methods for use with individual components of a PRA and then considers how these methods could be combined in the performance of a complete PRA. In the context of this paper, the goal of uncertainty analysis is to measure the imprecision in PRA outcomes of interest, and the goal of sensitivity analysis is to identify the major contributors to this imprecision. There are a number of areas that must be considered in uncertainty analysis and sensitivity analysis for a PRA: (1) information, (2) systems analysis, (3) thermal-hydraulic phenomena/fission product behavior, (4) health and economic consequences, and (5) display of results. Each of these areas and the synthesis of them into a complete PRA are discussed

  16. Non-animal methods to predict skin sensitization (I): the Cosmetics Europe database.

    Science.gov (United States)

    Hoffmann, Sebastian; Kleinstreuer, Nicole; Alépée, Nathalie; Allen, David; Api, Anne Marie; Ashikaga, Takao; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Goebel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Lalko, Jon F; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Parakhia, Rahul; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk

    2018-05-01

    Cosmetics Europe, the European Trade Association for the cosmetics and personal care industry, is conducting a multi-phase program to develop regulatory accepted, animal-free testing strategies enabling the cosmetics industry to conduct safety assessments. Based on a systematic evaluation of test methods for skin sensitization, five non-animal test methods (DPRA (Direct Peptide Reactivity Assay), KeratinoSens TM , h-CLAT (human cell line activation test), U-SENS TM , SENS-IS) were selected for inclusion in a comprehensive database of 128 substances. Existing data were compiled and completed with newly generated data, the latter amounting to one-third of all data. The database was complemented with human and local lymph node assay (LLNA) reference data, physicochemical properties and use categories, and thoroughly curated. Focused on the availability of human data, the substance selection resulted nevertheless resulted in a high diversity of chemistries in terms of physico-chemical property ranges and use categories. Predictivities of skin sensitization potential and potency, where applicable, were calculated for the LLNA as compared to human data and for the individual test methods compared to both human and LLNA reference data. In addition, various aspects of applicability of the test methods were analyzed. Due to its high level of curation, comprehensiveness, and completeness, we propose our database as a point of reference for the evaluation and development of testing strategies, as done for example in the associated work of Kleinstreuer et al. We encourage the community to use it to meet the challenge of conducting skin sensitization safety assessment without generating new animal data.

  17. Hydrocoin level 3 - Testing methods for sensitivity/uncertainty analysis

    International Nuclear Information System (INIS)

    Grundfelt, B.; Lindbom, B.; Larsson, A.; Andersson, K.

    1991-01-01

    The HYDROCOIN study is an international cooperative project for testing groundwater hydrology modelling strategies for performance assessment of nuclear waste disposal. The study was initiated in 1984 by the Swedish Nuclear Power Inspectorate and the technical work was finalised in 1987. The participating organisations are regulatory authorities as well as implementing organisations in 10 countries. The study has been performed at three levels aimed at studying computer code verification, model validation and sensitivity/uncertainty analysis respectively. The results from the first two levels, code verification and model validation, have been published in reports in 1988 and 1990 respectively. This paper focuses on some aspects of the results from Level 3, sensitivity/uncertainty analysis, for which a final report is planned to be published during 1990. For Level 3, seven test cases were defined. Some of these aimed at exploring the uncertainty associated with the modelling results by simply varying parameter values and conceptual assumptions. In other test cases statistical sampling methods were applied. One of the test cases dealt with particle tracking and the uncertainty introduced by this type of post processing. The amount of results available is substantial although unevenly spread over the test cases. It has not been possible to cover all aspects of the results in this paper. Instead, the different methods applied will be illustrated by some typical analyses. 4 figs., 9 refs

  18. A simple in chemico method for testing skin sensitizing potential of chemicals using small endogenous molecules.

    Science.gov (United States)

    Nepal, Mahesh Raj; Shakya, Rajina; Kang, Mi Jeong; Jeong, Tae Cheon

    2018-06-01

    Among many of the validated methods for testing skin sensitization, direct peptide reactivity assay (DPRA) employs no cells or animals. Although no immune cells are involved in this assay, it reliably predicts the skin sensitization potential of a chemical in chemico. Herein, a new method was developed using endogenous small-molecular-weight compounds, cysteamine and glutathione, rather than synthetic peptides, to differentiate skin sensitizers from non-sensitizers with an accuracy as high as DPRA. The percent depletion of cysteamine and glutathione by test chemicals was measured by an HPLC equipped with a PDA detector. To detect small-size molecules, such as cysteamine and glutathione, a derivatization by 4-(4-dimethylaminophenylazo) benzenesulfonyl chloride (DABS-Cl) was employed prior to the HPLC analysis. Following test method optimization, a cut-off criterion of 7.14% depletion was applied to differentiate skin sensitizers from non-sensitizers in combination of the ratio of 1:25 for cysteamine:test chemical with 1:50 for glutathione:test chemical for the best predictivity among various single or combination conditions. Although overlapping HPLC peaks could not be fully resolved for some test chemicals, high levels of sensitivity (100.0%), specificity (81.8%), and accuracy (93.3%) were obtained for 30 chemicals tested, which were comparable or better than those achieved with DPRA. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Sensitivity kernels for viscoelastic loading based on adjoint methods

    Science.gov (United States)

    Al-Attar, David; Tromp, Jeroen

    2014-01-01

    kernel' Kη determines the linearized sensitivity of J to viscosity perturbations defined with respect to a laterally heterogeneous reference earth model, while the `rate-of-loading kernel' K_{dot{σ }} determines the sensitivity to variations in the time derivative of the surface load. By restricting attention to spherically symmetric viscosity perturbations, we also obtain a `radial viscosity kernel' overline{K}_{η } such that the associated contribution to δJ can be written int _{IS}overline{K}_{η }δ ln η dr, where IS denotes the subset of radii lying in solid regions. In order to illustrate this theory, we describe its numerical implementation in the case of a spherically symmetric earth model using a 1-D spectral element method, and calculate sensitivity kernels for a range of realistic observables.

  20. Prospective memory tasks: a more sensitive method for screening cognitive impairment in ALS?

    Directory of Open Access Journals (Sweden)

    Ji Ying

    2012-11-01

    Full Text Available Abstract Background Cognitive change is prevalent in patients with amyotrophic lateral sclerosis (ALS, but still lack a widely accepted and sensitive screening method. In this study, we try to find a sensitive screening battery for detecting subtle cognitive deficits in patients with ALS. Methods Eighty consecutive ALS patients and 57 matched normal controls underwent the Mini-Mental Status Examination (MMSE, the verbal fluency test (VFT, the Stroop Color Word Interference Test (CWT, and the prospective memory (PM tests, including event-based (EBPM and time-based (TBPM. Results The patients did not differ from the controls in the MMSE, the VFT and the CWT. By contrast, statistically significant differences were found in the PM tests (EBPM: P=0.043; TBPM: P Conclusions Prefrontal lobar dysfunction does exist among ALS patients and may spread from the medial to the lateral region. The PM tests seem more sensitive in ALS patients with frontotemporal dysfunction than are the classical cognitive measures.

  1. Reliability and Sensitivity Analysis for Laminated Composite Plate Using Response Surface Method

    International Nuclear Information System (INIS)

    Lee, Seokje; Kim, Ingul; Jang, Moonho; Kim, Jaeki; Moon, Jungwon

    2013-01-01

    Advanced fiber-reinforced laminated composites are widely used in various fields of engineering to reduce weight. The material property of each ply is well known; specifically, it is known that ply is less reliable than metallic materials and very sensitive to the loading direction. Therefore, it is important to consider this uncertainty in the design of laminated composites. In this study, reliability analysis is conducted using Callosum and Meatball interactions for a laminated composite plate for the case in which the tip deflection is the design requirement and the material property is a random variable. Furthermore, the efficiency and accuracy of the approximation method is identified, and a probabilistic sensitivity analysis is conducted. As a result, we can prove the applicability of the advanced design method for the stabilizer of an underwater vehicle

  2. Reliability and Sensitivity Analysis for Laminated Composite Plate Using Response Surface Method

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seokje; Kim, Ingul [Chungnam National Univ., Daejeon (Korea, Republic of); Jang, Moonho; Kim, Jaeki; Moon, Jungwon [LIG Nex1, Yongin (Korea, Republic of)

    2013-04-15

    Advanced fiber-reinforced laminated composites are widely used in various fields of engineering to reduce weight. The material property of each ply is well known; specifically, it is known that ply is less reliable than metallic materials and very sensitive to the loading direction. Therefore, it is important to consider this uncertainty in the design of laminated composites. In this study, reliability analysis is conducted using Callosum and Meatball interactions for a laminated composite plate for the case in which the tip deflection is the design requirement and the material property is a random variable. Furthermore, the efficiency and accuracy of the approximation method is identified, and a probabilistic sensitivity analysis is conducted. As a result, we can prove the applicability of the advanced design method for the stabilizer of an underwater vehicle.

  3. Using the Delphi method to develop nursing-sensitive quality indicators for the NICU.

    Science.gov (United States)

    Chen, Lin; Huang, Li-Hua; Xing, Mei-Yuan; Feng, Zhi-Xian; Shao, Le-Wen; Zhang, Mei-Yun; Shao, Rong-Ya

    2017-02-01

    To develop nursing-sensitive quality indicators consistent with current medical practices in Chinese neonatal intensive care units. The development of nursing-sensitive quality indicators has become a top priority in nursing management. To the best of our knowledge, there has been no objective, scientific and sensitive evaluation of the quality of neonatal intensive care unit nursing in China. A modified Delphi technique was used to seek opinions from experts about what should be used and prioritised as indicators of quality care in neonatal intensive care unit nursing. Based on a literature review, we identified 21 indicators of nursing-sensitive quality in the neonatal intensive care unit. Our group of 11 consultants chose 13 indicators to be discussed using the Delphi method. In October and November 2014, 39 neonatal intensive care unit experts in 18 tertiary hospitals spread across six provinces participated in two rounds of Delphi panels. Of the 13 indicators discussed, 11 were identified as indicators of nursing-sensitive quality in the neonatal intensive care unit: rate of nosocomial infections, rate of accidental endotracheal extubation, rate of errors in medication administration, rate of treatment for pain, rate of peripheral venous extravasation, rate of compliance with handwashing techniques, incidence of pressure ulcers, incidence of noise, the bed-to-care ratio, the proportion of nurses with greater than five years neonatal intensive care unit experience and incidence of retinopathy. The 11 neonatal intensive care unit nursing-sensitive indicators identified by the Delphi method integrated with basic Chinese practices provide a basis for nursing management and the monitoring of nursing quality. This study identified nursing-sensitive quality indicators for neonatal intensive care unit care that are suitable for current clinical practice in China. © 2016 John Wiley & Sons Ltd.

  4. Perturbative methods applied for sensitive coefficients calculations in thermal-hydraulic systems

    International Nuclear Information System (INIS)

    Andrade Lima, F.R. de

    1993-01-01

    The differential formalism and the Generalized Perturbation Theory (GPT) are applied to sensitivity analysis of thermal-hydraulics problems related to pressurized water reactor cores. The equations describing the thermal-hydraulic behavior of these reactors cores, used in COBRA-IV-I code, are conveniently written. The importance function related to the response of interest and the sensitivity coefficient of this response with respect to various selected parameters are obtained by using Differential and Generalized Perturbation Theory. The comparison among the results obtained with the application of these perturbative methods and those obtained directly with the model developed in COBRA-IV-I code shows a very good agreement. (author)

  5. EPR method for the detection of sensitization in stainless steels

    International Nuclear Information System (INIS)

    Clarke, W.L.; Cowan, R.L.

    1980-01-01

    The overall objective of the program was to improve the reliability of reactor system piping by increasing knowledge of failure causing mechanisms and by enhancing the capability for design evaluation and analysis. Toward the attainment of that objective, a technique has been developed to measure the degree of sensitization quantitatively in thermally treated AISI-304, -304L, -316 and 316L stainless steels. The Electrochemical Potentiokinetic Reactivation (EPR) test was developed because of an industrial need for a rapid, nondestructive, quantitative field test which could be used for assessing sensitization in reactor components. The EPR method consists of developing potentiokinetic curves on a polarized sample obtained by controlled potential sweep from the passive to the active region (reactivation) in a specific electrolyte; details of the test technique have been reported

  6. Perturbative methods for sensitivity calculation in safety problems of nuclear reactors: state-of-the-art

    International Nuclear Information System (INIS)

    Lima, Fernando R.A.; Lira, Carlos A.B.O.; Gandini, Augusto

    1995-01-01

    During the last two decades perturbative methods became an efficient tool to perform sensitivity analysis in nuclear reactor safety problems. In this paper, a comparative study taking into account perturbation formalisms (Diferential and Matricial Mthods and generalized Perturbation Theory - GPT) is considered. Then a few number of applications are described to analyze the sensitivity of some functions relavant to thermal hydraulics designs or safety analysis of nuclear reactor cores and steam generators. The behaviours of the nuclear reactor cores and steam generators are simulated, respectively, by the COBRA-IV-I and GEVAP codes. Results of sensitivity calculations have shown a good agreement when compared to those obtained directly by using the mentioned codes. So, a significative computational time safe can be obtained with perturbative methods performing sensitivity analysis in nuclear power plants. (author). 25 refs., 5 tabs

  7. Technical Note: Method of Morris effectively reduces the computational demands of global sensitivity analysis for distributed watershed models

    Directory of Open Access Journals (Sweden)

    J. D. Herman

    2013-07-01

    Full Text Available The increase in spatially distributed hydrologic modeling warrants a corresponding increase in diagnostic methods capable of analyzing complex models with large numbers of parameters. Sobol' sensitivity analysis has proven to be a valuable tool for diagnostic analyses of hydrologic models. However, for many spatially distributed models, the Sobol' method requires a prohibitive number of model evaluations to reliably decompose output variance across the full set of parameters. We investigate the potential of the method of Morris, a screening-based sensitivity approach, to provide results sufficiently similar to those of the Sobol' method at a greatly reduced computational expense. The methods are benchmarked on the Hydrology Laboratory Research Distributed Hydrologic Model (HL-RDHM over a six-month period in the Blue River watershed, Oklahoma, USA. The Sobol' method required over six million model evaluations to ensure reliable sensitivity indices, corresponding to more than 30 000 computing hours and roughly 180 gigabytes of storage space. We find that the method of Morris is able to correctly screen the most and least sensitive parameters with 300 times fewer model evaluations, requiring only 100 computing hours and 1 gigabyte of storage space. The method of Morris proves to be a promising diagnostic approach for global sensitivity analysis of highly parameterized, spatially distributed hydrologic models.

  8. Singularity-sensitive gauge-based radar rainfall adjustment methods for urban hydrological applications

    Directory of Open Access Journals (Sweden)

    L.-P. Wang

    2015-09-01

    Full Text Available Gauge-based radar rainfall adjustment techniques have been widely used to improve the applicability of radar rainfall estimates to large-scale hydrological modelling. However, their use for urban hydrological applications is limited as they were mostly developed based upon Gaussian approximations and therefore tend to smooth off so-called "singularities" (features of a non-Gaussian field that can be observed in the fine-scale rainfall structure. Overlooking the singularities could be critical, given that their distribution is highly consistent with that of local extreme magnitudes. This deficiency may cause large errors in the subsequent urban hydrological modelling. To address this limitation and improve the applicability of adjustment techniques at urban scales, a method is proposed herein which incorporates a local singularity analysis into existing adjustment techniques and allows the preservation of the singularity structures throughout the adjustment process. In this paper the proposed singularity analysis is incorporated into the Bayesian merging technique and the performance of the resulting singularity-sensitive method is compared with that of the original Bayesian (non singularity-sensitive technique and the commonly used mean field bias adjustment. This test is conducted using as case study four storm events observed in the Portobello catchment (53 km2 (Edinburgh, UK during 2011 and for which radar estimates, dense rain gauge and sewer flow records, as well as a recently calibrated urban drainage model were available. The results suggest that, in general, the proposed singularity-sensitive method can effectively preserve the non-normality in local rainfall structure, while retaining the ability of the original adjustment techniques to generate nearly unbiased estimates. Moreover, the ability of the singularity-sensitive technique to preserve the non-normality in rainfall estimates often leads to better reproduction of the urban

  9. Singularity-sensitive gauge-based radar rainfall adjustment methods for urban hydrological applications

    Science.gov (United States)

    Wang, L.-P.; Ochoa-Rodríguez, S.; Onof, C.; Willems, P.

    2015-09-01

    Gauge-based radar rainfall adjustment techniques have been widely used to improve the applicability of radar rainfall estimates to large-scale hydrological modelling. However, their use for urban hydrological applications is limited as they were mostly developed based upon Gaussian approximations and therefore tend to smooth off so-called "singularities" (features of a non-Gaussian field) that can be observed in the fine-scale rainfall structure. Overlooking the singularities could be critical, given that their distribution is highly consistent with that of local extreme magnitudes. This deficiency may cause large errors in the subsequent urban hydrological modelling. To address this limitation and improve the applicability of adjustment techniques at urban scales, a method is proposed herein which incorporates a local singularity analysis into existing adjustment techniques and allows the preservation of the singularity structures throughout the adjustment process. In this paper the proposed singularity analysis is incorporated into the Bayesian merging technique and the performance of the resulting singularity-sensitive method is compared with that of the original Bayesian (non singularity-sensitive) technique and the commonly used mean field bias adjustment. This test is conducted using as case study four storm events observed in the Portobello catchment (53 km2) (Edinburgh, UK) during 2011 and for which radar estimates, dense rain gauge and sewer flow records, as well as a recently calibrated urban drainage model were available. The results suggest that, in general, the proposed singularity-sensitive method can effectively preserve the non-normality in local rainfall structure, while retaining the ability of the original adjustment techniques to generate nearly unbiased estimates. Moreover, the ability of the singularity-sensitive technique to preserve the non-normality in rainfall estimates often leads to better reproduction of the urban drainage system

  10. Increased sensitivity of OSHA method analysis of diacetyl and 2,3-pentanedione in air.

    Science.gov (United States)

    LeBouf, Ryan; Simmons, Michael

    2017-05-01

    Gas chromatography/mass spectrometry (GC/MS) operated in selected ion monitoring mode was used to enhance the sensitivity of OSHA Methods 1013/1016 for measuring diacetyl and 2,3-pentanedione in air samples. The original methods use flame ionization detection which cannot achieve the required sensitivity to quantify samples at or below the NIOSH recommended exposure limits (REL: 5 ppb for diacetyl and 9.3 ppb for 2,3-pentanedione) when sampling for both diacetyl and 2,3-pentanedione. OSHA Method 1012 was developed to measure diacetyl at lower levels but requires an electron capture detector, and a sample preparation time of 36 hours. Using GC/MS allows detection of these two alpha-diketones at lower levels than OSHA Method 1012 for diacetyl and OSHA Method 1016 for 2,3-pentanedione. Acetoin and 2,3-hexanedione may also be measured using this technique. Method quantification limits were 1.1 ppb for diacetyl (22% of the REL), 1.1 ppb for 2,3-pentanedione (12% of the REL), 1.1 ppb for 2,3-hexanedione, and 2.1 ppb for acetoin. Average extraction efficiencies above the limit of quantitation were 100% for diacetyl, 92% for 2,3-pentanedione, 89% for 2,3-hexanedione, and 87% for acetoin. Mass spectrometry with OSHA Methods 1013/1016 could be used by analytical laboratories to provide more sensitive and accurate measures of exposure to diacetyl and 2,3-pentanedione.

  11. 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.

  12. 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.

  13. New computer-aided diagnosis of dementia using positron emission tomography: brain regional sensitivity-mapping method.

    Directory of Open Access Journals (Sweden)

    Akihiro Kakimoto

    Full Text Available PURPOSE: We devised a new computer-aided diagnosis method to segregate dementia using one estimated index (Total Z score derived from the Brodmann area (BA sensitivity map on the stereotaxic brain atlas. The purpose of this study is to investigate its accuracy to differentiate patients with Alzheimer's disease (AD or mild cognitive impairment (MCI from normal adults (NL. METHODS: We studied 101 adults (NL: 40, AD: 37, MCI: 24 who underwent (18FDG positron emission tomography (PET measurement. We divided NL and AD groups into two categories: a training group with (Category A and a test group without (Category B clinical information. In Category A, we estimated sensitivity by comparing the standard uptake value per BA (SUVR between NL and AD groups. Then, we calculated a summated index (Total Z score by utilizing the sensitivity-distribution maps and each BA z-score to segregate AD patterns. To confirm the validity of this method, we examined the accuracy in Category B. Finally, we applied this method to MCI patients. RESULTS: In Category A, we found that the sensitivity and specificity of differentiation between NL and AD were all 100%. In Category B, those were 100% and 95%, respectively. Furthermore, we found this method attained 88% to differentiate AD-converters from non-converters in MCI group. CONCLUSIONS: The present automated computer-aided evaluation method based on a single estimated index provided good accuracy for differential diagnosis of AD and MCI. This good differentiation power suggests its usefulness not only for dementia diagnosis but also in a longitudinal study.

  14. New Computer-Aided Diagnosis of Dementia Using Positron Emission Tomography: Brain Regional Sensitivity-Mapping Method

    Science.gov (United States)

    Kakimoto, Akihiro; Kamekawa, Yuichi; Ito, Shigeru; Yoshikawa, Etsuji; Okada, Hiroyuki; Nishizawa, Sadahiko; Minoshima, Satoshi; Ouchi, Yasuomi

    2011-01-01

    Purpose We devised a new computer-aided diagnosis method to segregate dementia using one estimated index (Total Z score) derived from the Brodmann area (BA) sensitivity map on the stereotaxic brain atlas. The purpose of this study is to investigate its accuracy to differentiate patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) from normal adults (NL). Methods We studied 101 adults (NL: 40, AD: 37, MCI: 24) who underwent 18FDG positron emission tomography (PET) measurement. We divided NL and AD groups into two categories: a training group with (Category A) and a test group without (Category B) clinical information. In Category A, we estimated sensitivity by comparing the standard uptake value per BA (SUVR) between NL and AD groups. Then, we calculated a summated index (Total Z score) by utilizing the sensitivity-distribution maps and each BA z-score to segregate AD patterns. To confirm the validity of this method, we examined the accuracy in Category B. Finally, we applied this method to MCI patients. Results In Category A, we found that the sensitivity and specificity of differentiation between NL and AD were all 100%. In Category B, those were 100% and 95%, respectively. Furthermore, we found this method attained 88% to differentiate AD-converters from non-converters in MCI group. Conclusions The present automated computer-aided evaluation method based on a single estimated index provided good accuracy for differential diagnosis of AD and MCI. This good differentiation power suggests its usefulness not only for dementia diagnosis but also in a longitudinal study. PMID:21966405

  15. Community sensitization and decision-making for trial participation: a mixed-methods study from The Gambia.

    Science.gov (United States)

    Dierickx, Susan; O'Neill, Sarah; Gryseels, Charlotte; Immaculate Anyango, Edna; Bannister-Tyrrell, Melanie; Okebe, Joseph; Mwesigwa, Julia; Jaiteh, Fatou; Gerrets, René; Ravinetto, Raffaella; D'Alessandro, Umberto; Peeters Grietens, Koen

    2017-08-16

    Ensuring individual free and informed decision-making for research participation is challenging. It is thought that preliminarily informing communities through 'community sensitization' procedures may improve individual decision-making. This study set out to assess the relevance of community sensitization for individual decision-making in research participation in rural Gambia. This anthropological mixed-methods study triangulated qualitative methods and quantitative survey methods in the context of an observational study and a clinical trial on malaria carried out by the Medical Research Council Unit Gambia. Although 38.7% of the respondents were present during sensitization sessions, 91.1% of the respondents were inclined to participate in the trial when surveyed after the sensitization and prior to the informed consent process. This difference can be explained by the informal transmission of information within the community after the community sensitization, expectations such as the benefits of participation based on previous research experiences, and the positive reputation of the research institute. Commonly mentioned barriers to participation were blood sampling and the potential disapproval of the household head. Community sensitization is effective in providing first-hand, reliable information to communities as the information is cascaded to those who could not attend the sessions. However, further research is needed to assess how the informal spread of information further shapes people's expectations, how the process engages with existing social relations and hierarchies (e.g. local political power structures; permissions of heads of households) and how this influences or changes individual consent. © 2017 The Authors Developing World Bioethics Published by John Wiley & Sons Ltd.

  16. A new sensitive method for detecting human endogenous (leukocyte) pyrogen.

    Science.gov (United States)

    Bodel, P; Miller, H

    1978-03-01

    Endogenous, or leukocyte pyrogen (EP), the mediator of fever, is currently detected by injection of pyrogen-containing supernatants into rabbits. This assay has been of little value in the study of human fever because it required injection of relatively large amounts of pyrogen. We now report that injection of medium containing human EP produces fever in mice. Supernatant from 1 c 10(5) granulocytes, stimulated by phagocytosis of staphylococci and incubated overnight, or 1 x 10(4) monocytes similarly treated, produce clear pyrogenic responses. This method for detecting EP is about 100-fold more sensitive than the rabbit assay, and it appears to be specific for EP. Preliminary studies of EP released by small samples of needle liver biopsies from febrile and afebrile patients suggests that this sensitive assay may be useful for investigations into the mechanisms of clinical fever.

  17. 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.

  18. Application of perturbation methods and sensitivity analysis to water hammer problems in hydraulic networks

    International Nuclear Information System (INIS)

    Balino, Jorge L.; Larreteguy, Axel E.; Andrade Lima, Fernando R.

    1995-01-01

    The differential method was applied to the sensitivity analysis for water hammer problems in hydraulic networks. Starting from the classical water hammer equations in a single-phase liquid with friction, the state vector comprising the piezometric head and the velocity was defined. Applying the differential method the adjoint operator, the adjoint equations with the general form of their boundary conditions, and the general form of the bilinear concomitant were calculated. The discretized adjoint equations and the corresponding boundary conditions were programmed and solved by using the so called method of characteristics. As an example, a constant-level tank connected through a pipe to a valve discharging to atmosphere was considered. The bilinear concomitant was calculated for this particular case. The corresponding sensitivity coefficients due to the variation of different parameters by using both the differential method and the response surface generated by the computer code WHAT were also calculated. The results obtained with these methods show excellent agreement. (author). 11 refs, 2 figs, 2 tabs

  19. Deterministic sensitivity analysis of two-phase flow systems: forward and adjoint methods. Final report

    International Nuclear Information System (INIS)

    Cacuci, D.G.

    1984-07-01

    This report presents a self-contained mathematical formalism for deterministic sensitivity analysis of two-phase flow systems, a detailed application to sensitivity analysis of the homogeneous equilibrium model of two-phase flow, and a representative application to sensitivity analysis of a model (simulating pump-trip-type accidents in BWRs) where a transition between single phase and two phase occurs. The rigor and generality of this sensitivity analysis formalism stem from the use of Gateaux (G-) differentials. This report highlights the major aspects of deterministic (forward and adjoint) sensitivity analysis, including derivation of the forward sensitivity equations, derivation of sensitivity expressions in terms of adjoint functions, explicit construction of the adjoint system satisfied by these adjoint functions, determination of the characteristics of this adjoint system, and demonstration that these characteristics are the same as those of the original quasilinear two-phase flow equations. This proves that whenever the original two-phase flow problem is solvable, the adjoint system is also solvable and, in principle, the same numerical methods can be used to solve both the original and adjoint equations

  20. Highly sensitive luminescence method of scandium determination in the products of metallurgical reprocessing

    International Nuclear Information System (INIS)

    Matveets, M.A.; Akhmetova, S.D.

    1988-01-01

    Highly sensitive reaction of scandium with 1,10-phenanthroline and eosin is used for the development of luminescence method of its determination in metallurgical products. The effect of interfering elements is eliminated by scandium extraction with monocarboxylic acids. The method permits to determine scandium content from 5 x 10 -5 % (Sr 0.15 - 0.25)

  1. Sensitive spectrophotometric methods for determination of some organophosphorus pesticides in vegetable samples

    Directory of Open Access Journals (Sweden)

    MAGDA A. AKL

    2010-03-01

    Full Text Available Three rapid, simple, reproducible and sensitive spectrophotometric methods (A, B and C are described for the determination of two organophosphorus pesticides, (malathion and dimethoate in formulations and vegetable samples. The methods A and B involve the addition of an excess of Ce4+ into sulphuric acid medium and the determination of the unreacted oxidant by decreasing the red color of chromotrope 2R (C2R at a suitable lmax = 528 nm for method A, or a decrease in the orange pink color of rhodamine 6G (Rh6G at a suitable lmax = = 525 nm. The method C is based on the oxidation of malathion or dimethoate with the slight excess of N-bromosuccinimide (NBS and the determination of unreacted oxidant by reacting it with amaranth dye (AM in hydrochloric acid medium at a suitable lmax = 520 nm. A regression analysis of Beer-Lambert plots showed a good correlation in the concentration range of 0.1-4.2 μg mL−1. The apparent molar absorptivity, Sandell sensitivity, the detection and quantification limits were calculated. For more accurate analysis, Ringbom optimum concentration ranges are 0.25-4.0 μg mL−1. The developed methods were successfully applied to the determination of malathion, and dimethoate in their formulations and environmental vegetable samples.

  2. Comparison of the Sensitivity of Three Methods for the Early Diagnosis of Sporotrichosis in Cats.

    Science.gov (United States)

    Silva, J N; Miranda, L H M; Menezes, R C; Gremião, I D F; Oliveira, R V C; Vieira, S M M; Conceição-Silva, F; Ferreiro, L; Pereira, S A

    2018-04-01

    Sporotrichosis is caused by species of fungi within the Sporothrix schenckii complex that infect man and animals. In Rio de Janeiro, Brazil, an epidemic has been observed since 1998, with most of the cases being related to transmission from infected cats. Although the definitive diagnosis of feline sporotrichosis is made by fungal culture, cytopathological and histopathological examinations are used routinely, because the long culture period may delay treatment onset. However, alternative methods are desirable in cases of low fungal burden. Immunohistochemistry (IHC) has been described as a sensitive method for diagnosing human and canine sporotrichosis, but there are no reports of its application to cats. The aim of this study was to analyse the sensitivity of cytopathological examination (Quick Panoptic method), histopathology (Grocott silver stain) and anti-Sporothrix IHC by blinded comparisons, using fungal culture as the reference standard. Samples were collected from 184 cats with sporotrichosis that exhibited skin ulcers. The sensitivities of Grocott silver stain, cytopathological examination and IHC were 91.3%, 87.0% and 88.6%, respectively. Grocott silver stain showed the best performance. IHC showed high sensitivity, as did cytopathological examination and these may be considered as alternative methodologies. When the three methods were combined, the diagnosis was established in 180 (97.8%) out of 184 cases. Taken together, these findings indicate the need to implement these methods as routine tools for the early diagnosis of sporotrichosis in cats, notably when fungal culture is not available. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. An UPLC-MS/MS method for highly sensitive high-throughput analysis of phytohormones in plant tissues

    Directory of Open Access Journals (Sweden)

    Balcke Gerd Ulrich

    2012-11-01

    Full Text Available Abstract Background Phytohormones are the key metabolites participating in the regulation of multiple functions of plant organism. Among them, jasmonates, as well as abscisic and salicylic acids are responsible for triggering and modulating plant reactions targeted against pathogens and herbivores, as well as resistance to abiotic stress (drought, UV-irradiation and mechanical wounding. These factors induce dramatic changes in phytohormone biosynthesis and transport leading to rapid local and systemic stress responses. Understanding of underlying mechanisms is of principle interest for scientists working in various areas of plant biology. However, highly sensitive, precise and high-throughput methods for quantification of these phytohormones in small samples of plant tissues are still missing. Results Here we present an LC-MS/MS method for fast and highly sensitive determination of jasmonates, abscisic and salicylic acids. A single-step sample preparation procedure based on mixed-mode solid phase extraction was efficiently combined with essential improvements in mobile phase composition yielding higher efficiency of chromatographic separation and MS-sensitivity. This strategy resulted in dramatic increase in overall sensitivity, allowing successful determination of phytohormones in small (less than 50 mg of fresh weight tissue samples. The method was completely validated in terms of analyte recovery, sensitivity, linearity and precision. Additionally, it was cross-validated with a well-established GC-MS-based procedure and its applicability to a variety of plant species and organs was verified. Conclusion The method can be applied for the analyses of target phytohormones in small tissue samples obtained from any plant species and/or plant part relying on any commercially available (even less sensitive tandem mass spectrometry instrumentation.

  4. Short ensembles: An Efficient Method for Discerning Climate-relevant Sensitivities in Atmospheric General Circulation Models

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Hui; Rasch, Philip J.; Zhang, Kai; Qian, Yun; Yan, Huiping; Zhao, Chun

    2014-09-08

    This paper explores the feasibility of an experimentation strategy for investigating sensitivities in fast components of atmospheric general circulation models. The basic idea is to replace the traditional serial-in-time long-term climate integrations by representative ensembles of shorter simulations. The key advantage of the proposed method lies in its efficiency: since fewer days of simulation are needed, the computational cost is less, and because individual realizations are independent and can be integrated simultaneously, the new dimension of parallelism can dramatically reduce the turnaround time in benchmark tests, sensitivities studies, and model tuning exercises. The strategy is not appropriate for exploring sensitivity of all model features, but it is very effective in many situations. Two examples are presented using the Community Atmosphere Model version 5. The first example demonstrates that the method is capable of characterizing the model cloud and precipitation sensitivity to time step length. A nudging technique is also applied to an additional set of simulations to help understand the contribution of physics-dynamics interaction to the detected time step sensitivity. In the second example, multiple empirical parameters related to cloud microphysics and aerosol lifecycle are perturbed simultaneously in order to explore which parameters have the largest impact on the simulated global mean top-of-atmosphere radiation balance. Results show that in both examples, short ensembles are able to correctly reproduce the main signals of model sensitivities revealed by traditional long-term climate simulations for fast processes in the climate system. The efficiency of the ensemble method makes it particularly useful for the development of high-resolution, costly and complex climate models.

  5. Synthesis of SnS nanoparticles by SILAR method for quantum dot-sensitized solar cells.

    Science.gov (United States)

    Tsukigase, Hiroki; Suzuki, Yoshikazu; Berger, Marie-Hélène; Sagawa, Takashi; Yoshikawa, Susumu

    2011-03-01

    SnS-sensitized TiO2 electrodes were applied in quantum dot-sensitized solar cells (QDSSCs) which are environmentally more favorable than conventional Cd or Pb-chalcogenide-sensitized electrodes. SnS nanoparticles were well-distributed over the surface of TiO2 nanoparticles by the successive ionic layer adsorption and reaction (SILAR) method. Deposited SnS nanoparticles had diameter about 3 nm. Under AM1.5 irradiation with 100 mW/cm2 light intensity (at 1 sun), the energy conversion efficiency of obtained cells reached a value of 0.21% (0.25 cm2) at SILAR coating cycles of 5. In addition, the photovoltaic performance was improved by additional ZnS coating on the surface of SnS-sensitized TiO2 electrodes.

  6. Short ensembles: an efficient method for discerning climate-relevant sensitivities in atmospheric general circulation models

    Directory of Open Access Journals (Sweden)

    H. Wan

    2014-09-01

    Full Text Available This paper explores the feasibility of an experimentation strategy for investigating sensitivities in fast components of atmospheric general circulation models. The basic idea is to replace the traditional serial-in-time long-term climate integrations by representative ensembles of shorter simulations. The key advantage of the proposed method lies in its efficiency: since fewer days of simulation are needed, the computational cost is less, and because individual realizations are independent and can be integrated simultaneously, the new dimension of parallelism can dramatically reduce the turnaround time in benchmark tests, sensitivities studies, and model tuning exercises. The strategy is not appropriate for exploring sensitivity of all model features, but it is very effective in many situations. Two examples are presented using the Community Atmosphere Model, version 5. In the first example, the method is used to characterize sensitivities of the simulated clouds to time-step length. Results show that 3-day ensembles of 20 to 50 members are sufficient to reproduce the main signals revealed by traditional 5-year simulations. A nudging technique is applied to an additional set of simulations to help understand the contribution of physics–dynamics interaction to the detected time-step sensitivity. In the second example, multiple empirical parameters related to cloud microphysics and aerosol life cycle are perturbed simultaneously in order to find out which parameters have the largest impact on the simulated global mean top-of-atmosphere radiation balance. It turns out that 12-member ensembles of 10-day simulations are able to reveal the same sensitivities as seen in 4-year simulations performed in a previous study. In both cases, the ensemble method reduces the total computational time by a factor of about 15, and the turnaround time by a factor of several hundred. The efficiency of the method makes it particularly useful for the development of

  7. 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.

  8. Simplified methods of evaluating colonies for levels of Varroa Sensitive Hygiene (VSH)

    Science.gov (United States)

    Varroa sensitive hygiene (VSH) is a trait of honey bees, Apis mellifera, that supports resistance to varroa mites, Varroa destructor. Components of VSH were evaluated to identify simple methods for selection of the trait. Varroa mite population growth was measured in colonies with variable levels of...

  9. A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

    Science.gov (United States)

    Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization integrated approaches combining different chemical, biological and in silico methods are recommended to r...

  10. 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.

  11. 'PSA-SPN' - A Parameter Sensitivity Analysis Method Using Stochastic Petri Nets: Application to a Production Line System

    International Nuclear Information System (INIS)

    Labadi, Karim; Saggadi, Samira; Amodeo, Lionel

    2009-01-01

    The dynamic behavior of a discrete event dynamic system can be significantly affected for some uncertain changes in its decision parameters. So, parameter sensitivity analysis would be a useful way in studying the effects of these changes on the system performance. In the past, the sensitivity analysis approaches are frequently based on simulation models. In recent years, formal methods based on stochastic process including Markov process are proposed in the literature. In this paper, we are interested in the parameter sensitivity analysis of discrete event dynamic systems by using stochastic Petri nets models as a tool for modelling and performance evaluation. A sensitivity analysis approach based on stochastic Petri nets, called PSA-SPN method, will be proposed with an application to a production line system.

  12. Lake and Reservoir Evaporation Estimation: Sensitivity Analysis and Ranking Existing Methods

    Directory of Open Access Journals (Sweden)

    maysam majidi

    2016-02-01

    were acquired from the Doosti Dam weather station. Relative humidity, wind speed, atmospheric pressure and precipitation were acquired from the Pol−Khatoon weather station. Dew point temperature and sunshine data were collected from the Sarakhs weather station. Lake area was estimated from hypsometric curve in relation to lake level data. Temperature measurements were often performed in 16−day periods or biweekly from September 2011 to September 2012. Temperature profile of the lake (required for lake evaporation estimation was measured at different points of the reservoir using a portable multi−meter. The eighteen existing methods were compared and ranked based on Bowen ratio energy balance method (BREB. Results and Discussion: The estimated annual evaporation values by all of the applied methods in this study, ranged from 21 to 113mcm (million cubic meters. BREB annual evaporation obtained value was equal to 69.86mcm and evaporation rate averaged 5.47mm d-1 during the study period. According to the results, there is a relatively large difference between the obtained evaporation values from the adopted methods. The sensitivity analysis of evaporation methods for some input parameters indicated that the Hamon method (Eq. 16 was the most sensitive to the input parameters followed by the Brutsaert−Stricker and BREB, and radiation−temperature methods (Makkink, Jensen−Haise and Stephen−Stewart had the least sensitivity to input data. Besides, the air temperature, solar radiation (sunshine data, water surface temperature and wind speed data had the most effect on lake evaporation estimations, respectively. Finally, all evaporation estimation methods in this study have been ranked based on RMSD values. On a daily basis, the Jensen−Haise and the Makkink (solar radiation, temperature group, Penman (Combination group and Hamon (temperature, day length group methods had a relatively reasonable performance. As the results on a monthly scale, the Jensen−Haise and

  13. Effect of parameters in moving average method for event detection enhancement using phase sensitive OTDR

    Science.gov (United States)

    Kwon, Yong-Seok; Naeem, Khurram; Jeon, Min Yong; Kwon, Il-bum

    2017-04-01

    We analyze the relations of parameters in moving average method to enhance the event detectability of phase sensitive optical time domain reflectometer (OTDR). If the external events have unique frequency of vibration, then the control parameters of moving average method should be optimized in order to detect these events efficiently. A phase sensitive OTDR was implemented by a pulsed light source, which is composed of a laser diode, a semiconductor optical amplifier, an erbium-doped fiber amplifier, a fiber Bragg grating filter, and a light receiving part, which has a photo-detector and high speed data acquisition system. The moving average method is operated with the control parameters: total number of raw traces, M, number of averaged traces, N, and step size of moving, n. The raw traces are obtained by the phase sensitive OTDR with sound signals generated by a speaker. Using these trace data, the relation of the control parameters is analyzed. In the result, if the event signal has one frequency, then the optimal values of N, n are existed to detect the event efficiently.

  14. A Terbium Sensitized Luminescence Method for the Assay of Flubiprofen in Pharmaceutical Formulations

    Directory of Open Access Journals (Sweden)

    Salma M.Z. Al-Kindy

    2014-12-01

    Full Text Available A sensitive time-resolved luminescence method for the determination of flubiprofen (FLP in methanol and in aqueous solution is described. The method is based on the luminescence sensitization of terbium (Tb3+ by the formation of a ternary complex with FLP in the presence of 4,7 diphenyl 1,10 phenanthroline (DPP as co-ligand, and Tween-20 as surfactant. The signal for Tb-FLP-DPP was monitored at λex  = 285 nm and λem  = 552 nm. Optimum conditions for the formation of the complex in an aqueous system were TRIS buffer, pH 8.0, DPP (2.5Å~10−7  M, Tween-20 (0.30% and 4Å~10-5  mol L-1  of Tb3+  which allowed the determination of 20–1000 ng mL-1  of FLP with a limit of detection (LOD of 10 ng mL-1 . The relative standard deviations of the method ranged between 0.6 and 1.4% indicating excellent reproducibility of the method. The proposed method was successfully applied for the assays of FLP in pharmaceutical formulations and spiked tap water samples with average recoveries of 87% – 95%.

  15. 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.

  16. Energetic materials and methods of tailoring electrostatic discharge sensitivity of energetic materials

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, Michael A.; Heaps, Ronald J.; Wallace, Ronald S.; Pantoya, Michelle L.; Collins, Eric S.

    2016-11-01

    An energetic material comprising an elemental fuel, an oxidizer or other element, and a carbon nanofiller or carbon fiber rods, where the carbon nanofiller or carbon fiber rods are substantially homogeneously dispersed in the energetic material. Methods of tailoring the electrostatic discharge sensitivity of an energetic material are also disclosed.

  17. In vivo conditions to identify Prkci phosphorylation targets using the analog-sensitive kinase method in zebrafish.

    Directory of Open Access Journals (Sweden)

    Elena Cibrián Uhalte

    Full Text Available Protein kinase C iota is required for various cell biological processes including epithelial tissue polarity and organ morphogenesis. To gain mechanistic insight into different roles of this kinase, it is essential to identify specific substrate proteins in their cellular context. The analog-sensitive kinase method provides a powerful tool for the identification of kinase substrates under in vivo conditions. However, it has remained a major challenge to establish screens based on this method in multicellular model organisms. Here, we report the methodology for in vivo conditions using the analog-sensitive kinase method in a genetically-tractable vertebrate model organism, the zebrafish. With this approach, kinase substrates can uniquely be labeled in the developing zebrafish embryo using bulky ATPγS analogs which results in the thiophosphorylation of substrates. The labeling of kinase substrates with a thiophosphoester epitope differs from phosphoesters that are generated by all other kinases and allows for an enrichment of thiophosphopeptides by immunoaffinity purification. This study provides the foundation for using the analog-sensitive kinase method in the context of complex vertebrate development, physiology, or disease.

  18. A method for hardening or curing adhesives for flocking thermally sensitive substrata by means of an electron-beam

    International Nuclear Information System (INIS)

    Nablo, S.V.; Fussa, A.D.

    1975-01-01

    The invention relates to a method for hardening or curing adhesives for flocking thermally sensitive substrata by means of an electron-beam. That method consists in accurately adjusting the parameters of irradiation by an electron-beam and the beam velocity so as to obtain, a very rapid hardening of adhesives used for fixing flocking materials, or the like, to thermally sensitive substrate. That can be applied to hardening or curing adhesives for flocking thermally-sensitive substrata which normally restrict the hardening rate [fr

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Efficiencies of Dye-Sensitized Solar Cells using Ferritin-Encapsulated Quantum Dots with Various Staining Methods

    Science.gov (United States)

    Perez, Luis

    Dye-sensitized solar cells (DSSC) have the potential to replace traditional and cost-inefficient crystalline silicon or ruthenium solar cells. This can only be accomplished by optimizing DSSC's energy efficiency. One of the major components in a dye-sensitized solar cell is the porous layer of titanium dioxide. This layer is coated with a molecular dye that absorbs sunlight. The research conducted for this paper focuses on the different methods used to dye the porous TiO2 layer with ferritin-encapsulated quantum dots. Multiple anodes were dyed using a method known as SILAR which involves deposition through alternate immersion in two different solutions. The efficiencies of DSSCs with ferritin-encapsulated lead sulfide dye deposited using SILAR were subsequently compared against the efficiencies produced by cells using the traditional immersion method. It was concluded that both methods resulted in similar efficiencies (? .074%) however, the SILAR method dyed the TiO2 coating significantly faster than the immersion method. On a related note, our experiments concluded that conducting 2 SILAR cycles yields the highest possible efficiency for this particular binding method. National Science Foundation.

  1. 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.

  2. A sensitive immunoblotting method for screening of microalbuminuria in diabetic patient's urine

    International Nuclear Information System (INIS)

    Abdolkhaleg, D.; Behrooz, S.

    2005-01-01

    Urinary albumin excretion is a useful marker in the prognosis of diabetic nephropathy and microvascular diseases. Methods such as enzyme linked immunosorbent assay (ELISA), radio immunoassay(RIA), radial immunodiffusion, albu screen, micro bumin and micral test are usually used for detection and screening of microalbuminuria in these patients. With consideration to the cost of an assay, methods such as ELISA and RIA are not suitable methods for screening purpose. Therefore, the aim of this work is to set a dot immunoblotting method for the measurement and screening of microalbumin in urine samples. The study was conducted during the period August 2001 to June 2003 at the National Research Center for Genetic Engineering and Biotechnology (NRCGEB) and Pars Hospital Laboratory of Tehran, Iran on 96 diabetic patients urine samples. First, anti human albumin antibodies (Abs) were produced in rabbit and immunoglobulin G (IgG) fraction was purified by protein-A affinity chromatography. Titer of Abs and optimum incubation conditions were tested by direct ELISA. Then different concentration of human albumin (0-300 mg/l) was loaded to nitrocellulose membranes and was assayed by dot immunoblotting method. The specificity and cross reactivity of Abs was tested by SDS-PAGE electrophoresis and western immunoblotting. The sensitivity of the method was calculated from human albumin calibration curve and compared with commercial immunoturbidimetric assays. Our results indicates that in using IgG with the concentrations 0.5-1 ug/ml (2 x 10-5 to 10-4 dilutions) the intensity of color directly increased with the increase of human albumin standards in blots. Western immunoblotting of urine samples did not show any cross reactivity with other urine proteins. Comparison of results of this method by commercial immunoturbidimetric methods indicates the correlation regression of approximately 0.979. The sensitivity of the method was approximately 5 mg/L of human albumin. This simple

  3. Estimating the Capacity of Urban Transportation Networks with an Improved Sensitivity Based Method

    Directory of Open Access Journals (Sweden)

    Muqing Du

    2015-01-01

    Full Text Available The throughput of a given transportation network is always of interest to the traffic administrative department, so as to evaluate the benefit of the transportation construction or expansion project before its implementation. The model of the transportation network capacity formulated as a mathematic programming with equilibrium constraint (MPEC well defines this problem. For practical applications, a modified sensitivity analysis based (SAB method is developed to estimate the solution of this bilevel model. The high-efficient origin-based (OB algorithm is extended for the precise solution of the combined model which is integrated in the network capacity model. The sensitivity analysis approach is also modified to simplify the inversion of the Jacobian matrix in large-scale problems. The solution produced in every iteration of SAB is restrained to be feasible to guarantee the success of the heuristic search. From the numerical experiments, the accuracy of the derivatives for the linear approximation could significantly affect the converging of the SAB method. The results also show that the proposed method could obtain good suboptimal solutions from different starting points in the test examples.

  4. An efficient computational method for global sensitivity analysis and its application to tree growth modelling

    International Nuclear Information System (INIS)

    Wu, Qiong-Li; Cournède, Paul-Henry; Mathieu, Amélie

    2012-01-01

    Global sensitivity analysis has a key role to play in the design and parameterisation of functional–structural plant growth models which combine the description of plant structural development (organogenesis and geometry) and functional growth (biomass accumulation and allocation). We are particularly interested in this study in Sobol's method which decomposes the variance of the output of interest into terms due to individual parameters but also to interactions between parameters. Such information is crucial for systems with potentially high levels of non-linearity and interactions between processes, like plant growth. However, the computation of Sobol's indices relies on Monte Carlo sampling and re-sampling, whose costs can be very high, especially when model evaluation is also expensive, as for tree models. In this paper, we thus propose a new method to compute Sobol's indices inspired by Homma–Saltelli, which improves slightly their use of model evaluations, and then derive for this generic type of computational methods an estimator of the error estimation of sensitivity indices with respect to the sampling size. It allows the detailed control of the balance between accuracy and computing time. Numerical tests on a simple non-linear model are convincing and the method is finally applied to a functional–structural model of tree growth, GreenLab, whose particularity is the strong level of interaction between plant functioning and organogenesis. - Highlights: ► We study global sensitivity analysis in the context of functional–structural plant modelling. ► A new estimator based on Homma–Saltelli method is proposed to compute Sobol indices, based on a more balanced re-sampling strategy. ► The estimation accuracy of sensitivity indices for a class of Sobol's estimators can be controlled by error analysis. ► The proposed algorithm is implemented efficiently to compute Sobol indices for a complex tree growth model.

  5. Testing the sensitivity of Nested PCR method to detect Aspergillus fumigates in experimentally infected Sputum samples

    International Nuclear Information System (INIS)

    Ramadan, A.; Soukkaria, S.

    2013-01-01

    Fungal infections caused by Aspergillus species generally are occupying a second place among invasive fungal infections in the world, especially A. fumigatus, which is considered the main cause of invasive Aspergillosis (IA). Although IA rarely infects immunocompetent individuals, however, it can lead to death in immunocompromised patients. Therefore, it is necessary to diagnose the infection early in order to treat the disease efficiently. However, the conventional diagnostic tools, currently used to detect infections, has low sensitivity and reliability. Polymerase chain reaction (PCR) technology distribution as a molecular and high sensitive technology has allowed us to make comparative study between sensitivity of traditional currently used diagnostic method and Nested-PCR, the result of the study of sputum samples that experimentally infected with different concentrations of A.fumigatus spores ramping from 10 to10 6 spore/ml, have high sensitivity and specificity of Nested-PCR in detecting the lower concentrations, comparing with traditional diagnostic method (culture on Sabouraud media) that were negative in all concetrations. (author)

  6. A rapid detection method for policy-sensitive amines real-time supervision.

    Science.gov (United States)

    Zhang, Haixu; Shu, Jinian; Yang, Bo; Zhang, Peng; Ma, Pengkun

    2018-02-01

    Many organic amines that comprise a benzene ring are policy-sensitive because of their toxicity and links to social harm. However, to date, detection of such compounds mainly relies on offline methods. This study proposes an online pptv (parts per trillion by volume) level of detection method for amines, using the recently-built vacuum ultraviolet photoionization mass spectrometer (VUV-PIMS) combined with a new doping technique. Thus, the dichloromethane doping-assisted photoionization mass spectra of aniline, benzylamine, phenethylamine, amphetamine, and their structural isomers were recorded. The dominant characteristic mass peaks for all amines are those afforded by protonated amines and the amino radical-loss. The signal intensities of the amines were enhanced by 60-130 times compared to those recorded without doping assistance. Under 10s detection time, the sensitivities of aniline and benzylamine in the gas phase were determined as 4.0 and 2.7 countspptv -1 , with limits of detection (LODs) of 36 and 22 pptv, respectively. Notably, the detection efficiency of this method can be tenfold better in future applications since the ion transmission efficiency of the mass spectrometer was intentionally reduced to ~ 10% in this study. Therefore, dichloromethane doping-assisted photoionization mass spectrometry has proven to be a highly promising on-line approach to amine detection in environmental and judicial supervision and shows great potential for application in the biological field. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Adjoint Parameter Sensitivity Analysis for the Hydrodynamic Lattice Boltzmann Method with Applications to Design Optimization

    DEFF Research Database (Denmark)

    Pingen, Georg; Evgrafov, Anton; Maute, Kurt

    2009-01-01

    We present an adjoint parameter sensitivity analysis formulation and solution strategy for the lattice Boltzmann method (LBM). The focus is on design optimization applications, in particular topology optimization. The lattice Boltzmann method is briefly described with an in-depth discussion...

  8. A simple, reproducible and sensitive spectrophotometric method to estimate microalgal lipids

    Energy Technology Data Exchange (ETDEWEB)

    Chen Yimin [ChELSI Institute, Department of Chemical and Biological Engineering, University of Sheffield, Sheffield S1 3JD (United Kingdom); Vaidyanathan, Seetharaman, E-mail: s.vaidyanathan@sheffield.ac.uk [ChELSI Institute, Department of Chemical and Biological Engineering, University of Sheffield, Sheffield S1 3JD (United Kingdom)

    2012-04-29

    Highlights: Black-Right-Pointing-Pointer FAs released from lipids form complex with Cu-TEA in chloroform. Black-Right-Pointing-Pointer The FA-Cu-TEA complex gives strong absorbance at 260 nm. Black-Right-Pointing-Pointer The absorbance is sensitive and independent of C-atom number in the FAs (10-18). Black-Right-Pointing-Pointer Microalgal lipid extract and pure FA (such as C16) can both be used as standards. - Abstract: Quantification of total lipids is a necessity for any study of lipid production by microalgae, especially given the current interest in microalgal carbon capture and biofuels. In this study, we employed a simple yet sensitive method to indirectly measure the lipids in microalgae by measuring the fatty acids (FA) after saponification. The fatty acids were reacted with triethanolamine-copper salts (TEA-Cu) and the ternary TEA-Cu-FA complex was detected at 260 nm using a UV-visible spectrometer without any colour developer. The results showed that this method could be used to analyse low levels of lipids in the range of nano-moles from as little as 1 mL of microalgal culture. Furthermore, the structure of the TEA-Cu-FA complex and related reaction process are proposed to better understand this assay. There is no special instrument required and the method is very reproducible. To the best of our knowledge, this is the first report of the use of UV absorbance of copper salts with FA as a method to estimate lipids in algal cultures. It will pave the way for a more convenient assay of lipids in microalgae and can readily be expanded for estimating lipids in other biological systems.

  9. A simple, reproducible and sensitive spectrophotometric method to estimate microalgal lipids

    International Nuclear Information System (INIS)

    Chen Yimin; Vaidyanathan, Seetharaman

    2012-01-01

    Highlights: ► FAs released from lipids form complex with Cu–TEA in chloroform. ► The FA–Cu–TEA complex gives strong absorbance at 260 nm. ► The absorbance is sensitive and independent of C-atom number in the FAs (10–18). ► Microalgal lipid extract and pure FA (such as C16) can both be used as standards. - Abstract: Quantification of total lipids is a necessity for any study of lipid production by microalgae, especially given the current interest in microalgal carbon capture and biofuels. In this study, we employed a simple yet sensitive method to indirectly measure the lipids in microalgae by measuring the fatty acids (FA) after saponification. The fatty acids were reacted with triethanolamine–copper salts (TEA–Cu) and the ternary TEA–Cu–FA complex was detected at 260 nm using a UV–visible spectrometer without any colour developer. The results showed that this method could be used to analyse low levels of lipids in the range of nano-moles from as little as 1 mL of microalgal culture. Furthermore, the structure of the TEA–Cu–FA complex and related reaction process are proposed to better understand this assay. There is no special instrument required and the method is very reproducible. To the best of our knowledge, this is the first report of the use of UV absorbance of copper salts with FA as a method to estimate lipids in algal cultures. It will pave the way for a more convenient assay of lipids in microalgae and can readily be expanded for estimating lipids in other biological systems.

  10. 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.

  11. Investigation of colistin sensitivity via three different methods in Acinetobacter baumannii isolates with multiple antibiotic resistance.

    Science.gov (United States)

    Sinirtaş, Melda; Akalin, Halis; Gedikoğlu, Suna

    2009-09-01

    In recent years there has been an increase in life-threatening infections caused by Acinetobacter baumannii with multiple antibiotic resistance, which has lead to the use of polymyxins, especially colistin, being reconsidered. The aim of this study was to investigate the colistin sensitivity of A. baumannii isolates with multiple antibiotic resistance via different methods, and to evaluate the disk diffusion method for colistin against multi-resistant Acinetobacter isolates, in comparison to the E-test and Phoenix system. The study was carried out on 100 strains of A. baumannii (colonization or infection) isolated from the microbiological samples of different patients followed in the clinics and intensive care units of Uludağ University Medical School between the years 2004 and 2005. Strains were identified and characterized for their antibiotic sensitivity by Phoenix system (Becton Dickinson, Sparks, MD, USA). In all studied A. baumannii strains, susceptibility to colistin was determined to be 100% with the disk diffusion, E-test, and broth microdilution methods. Results of the E-test and broth microdilution method, which are accepted as reference methods, were found to be 100% consistent with the results of the disk diffusion tests; no very major or major error was identified upon comparison of the tests. The sensitivity and the positive predictive value of the disk diffusion method were found to be 100%. Colistin resistance in A. baumannii was not detected in our region, and disk diffusion method results are in accordance with those of E-test and broth microdilution methods.

  12. LLNA variability: An essential ingredient for a comprehensive assessment of non-animal skin sensitization test methods and strategies.

    Science.gov (United States)

    Hoffmann, Sebastian

    2015-01-01

    The development of non-animal skin sensitization test methods and strategies is quickly progressing. Either individually or in combination, the predictive capacity is usually described in comparison to local lymph node assay (LLNA) results. In this process the important lesson from other endpoints, such as skin or eye irritation, to account for variability reference test results - here the LLNA - has not yet been fully acknowledged. In order to provide assessors as well as method and strategy developers with appropriate estimates, we investigated the variability of EC3 values from repeated substance testing using the publicly available NICEATM (NTP Interagency Center for the Evaluation of Alternative Toxicological Methods) LLNA database. Repeat experiments for more than 60 substances were analyzed - once taking the vehicle into account and once combining data over all vehicles. In general, variability was higher when different vehicles were used. In terms of skin sensitization potential, i.e., discriminating sensitizer from non-sensitizers, the false positive rate ranged from 14-20%, while the false negative rate was 4-5%. In terms of skin sensitization potency, the rate to assign a substance to the next higher or next lower potency class was approx.10-15%. In addition, general estimates for EC3 variability are provided that can be used for modelling purposes. With our analysis we stress the importance of considering the LLNA variability in the assessment of skin sensitization test methods and strategies and provide estimates thereof.

  13. Radioimmunoassay (RIA), a highly specific, extremely sensitive quantitative method of analysis

    Energy Technology Data Exchange (ETDEWEB)

    Strecker, H; Hachmann, H; Seidel, L [Farbwerke Hoechst A.G., Frankfurt am Main (Germany, F.R.). Radiochemisches Lab.

    1979-02-01

    Radioimmunoassay is an analytical method combining the sensitivity of radioactivity measurements and the specificity of the antigen-antibody-reaction. Thus, substances can be measured in concentrations as low as picograms per milliliter serum besides a millionfold excess of otherwise disturbing material (for example in serum). The method is simple to perform and is at present mainly used in the field of endocrinology. Further areas of possible application are in the diagnosis of infectious disease, drug research, environmental protection, forensic medicine as well as general analytics. Quantities of radioactivity, exclusively used in vitro, are in the nano-Curie range. Therefore the radiation dose is negligible.

  14. Study of the AISI 347 austenitic stainless steel sensitization through the potentiokinetic reactivation method

    International Nuclear Information System (INIS)

    Teodoro, Celso Antonio; Wolynec, Stephan

    1996-01-01

    The sensitization kinetics of AISI 347 austenitic stainless steel samples, removed from a forged bar, was investigated with an electrochemical potentiokinetic reactivation method. After the solution anneal at 1140 deg C, the steel was submitted to sensitization treatments at 550 deg C, 670 deg C, 790 deg C and 910 deg C during times that varied from 1 h to 62 h. It was found that samples treated at 550 deg C, 670 deg C and 790 deg C become sensitized. The activation energy was found to be 124 kJ/mol. The observed behaviour was discussed in terms of both carbon retention in solution after the solution anneal and kinetics of carbon combination with chromium and niobium. (author)

  15. Dye-Sensitized Solar Cells with Optimal Gel Electrolyte Using the Taguchi Design Method

    Directory of Open Access Journals (Sweden)

    Jenn-Kai Tsai

    2013-01-01

    Full Text Available The Taguchi method was adopted to determine the optimal gel electrolyte used in dye-sensitized solar cells (DSSCs. Since electrolyte is a very important factor in fabrication of high performance and long-term stability DSSCs, to find the optimal composition of gel electrolyte is desired. In this paper, the common ingredients used in the liquid electrolyte were chosen. The ingredients then mixed with cheap ionic liquids and poly(vinylidenefluoride-co-hexafluoropropylene (PVDF-HFP were added to form colloidal electrolyte (gel. The optimal composition of each materials in the gel electrolyte determined by Taguchi method consists of 0.03 M I2, 0.15 M KI, 0.6 M LiI, 0.5 M 4-tertbutylpyridine (TBP, and 10% PVDF-HFP dissolved in the acetonitrile and 3-methoxypropionitrile (MPN solution with volume ratio of 2 : 1. The short circuit current density of 14.11 mA/cm2, the conversion efficiency (η of 5.52%, and the lifetime of over 110 days were observed for the dye-sensitized solar cell assembled with optimal gel electrolyte. The lifetime increases 10 times when compared with the conventional dye-sensitized solar cell assembled with liquid electrolyte.

  16. Sensitivity and uncertainty analyses applied to criticality safety validation, methods development. Volume 1

    International Nuclear Information System (INIS)

    Broadhead, B.L.; Hopper, C.M.; Childs, R.L.; Parks, C.V.

    1999-01-01

    This report presents the application of sensitivity and uncertainty (S/U) analysis methodologies to the code/data validation tasks of a criticality safety computational study. Sensitivity and uncertainty analysis methods were first developed for application to fast reactor studies in the 1970s. This work has revitalized and updated the available S/U computational capabilities such that they can be used as prototypic modules of the SCALE code system, which contains criticality analysis tools currently used by criticality safety practitioners. After complete development, simplified tools are expected to be released for general use. The S/U methods that are presented in this volume are designed to provide a formal means of establishing the range (or area) of applicability for criticality safety data validation studies. The development of parameters that are analogous to the standard trending parameters forms the key to the technique. These parameters are the D parameters, which represent the differences by group of sensitivity profiles, and the ck parameters, which are the correlation coefficients for the calculational uncertainties between systems; each set of parameters gives information relative to the similarity between pairs of selected systems, e.g., a critical experiment and a specific real-world system (the application)

  17. An improved electrochemiluminescence polymerase chain reaction method for highly sensitive detection of plant viruses

    International Nuclear Information System (INIS)

    Tang Yabing; Xing Da; Zhu Debin; Liu Jinfeng

    2007-01-01

    Recently, we have reported an electrochemiluminescence polymerase chain reaction (ECL-PCR) method for detection of genetically modified organisms. The ECL-PCR method was further improved in the current study by introducing a multi-purpose nucleic acid sequence that was specific to the tris(bipyridine) ruthenium (TBR) labeled probe, into the 5' terminal of the primers. The method was applied to detect plant viruses. Conserved sequence of the plant viruses was amplified by PCR. The product was hybridized with a biotin labeled probe and a TBR labeled probe. The hybridization product was separated by streptavidin-coated magnetic beads, and detected by measuring the ECL signals of the TBR labeled. Under the optimized conditions, the experiment results show that the detection limit is 50 fmol of PCR products, and the signal-to-noise ratio is in excess of 14.6. The method was used to detect banana streak virus, banana bunchy top virus, and papaya leaf curl virus. The experiment results show that this method could reliably identity viruses infected plant samples. The improved ECL-PCR approach has higher sensitivity and lower cost than previous approach. It can effectively detect the plant viruses with simplicity, stability, and high sensitivity

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

    Directory of Open Access Journals (Sweden)

    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

  19. Rapid, sensitive and cost effective method for isolation of viral DNA from feacal samples of dogs

    Directory of Open Access Journals (Sweden)

    Savi.

    2010-06-01

    Full Text Available A simple method for viral DNA extraction using chelex resin was developed. The method used was eco-friendly and cost effective compared to other methods such as phenol chloroform method which use health hazardous organic reagents. Further, a polymerase chain reaction (PCR based detection of canine parvovirus (CPV using primers from conserved region of VP2 gene was developed. To increase the sensitivity and specificity of reaction, nested PCR was designed. PCR reaction was optimized to amplify 747bp product of VP2 gene. The assay can be completed in few hours and doesn’t need hazardous chemicals. Thus, the sample preparation using chelating resin along with nested PCR seems to be a sensitive, specific and practical method for the detection of CPV in diarrhoeal feacal samples. [Vet. World 2010; 3(3.000: 105-106

  20. Sensitive method for the determination of nitrated polycyclic aromatic hydrocarbons in the human diet

    Energy Technology Data Exchange (ETDEWEB)

    Siegmund, B.; Weiss, R.; Pfannhauser, W. [Graz Univ. of Technology (Austria). Inst. of Food Chemistry

    2003-01-01

    The presence of nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) as contaminants in foods is nowadays a legitimate cause of concern, as they are reported to be strong direct-acting mutagens and carcinogens that may pose a risk to human health. Nevertheless, their concentrations in foods are in the ultra-trace region. In this study, we present a very sensitive analytical method for the determination of this compound class in complex food matrices. Special emphasis was put on sample extraction and clean up. Recoveries of 75% could be obtained for 1- and 2-nitronaphthalene; for all other compounds investigated the recoveries were {>=}94%. The determination of the compounds was performed by gas chromatography-mass spectrometry. The results show that the use of negative chemical ionization (NCI) increases the sensitivity by one order of magnitude in comparison to electron impact ionization (EI) (limits of detection 0.07-0.25 {mu}g kg{sup -1} for EI and 0.01-0.02 {mu}g kg{sup -1} for NCI). The influence of the sample matrix on the sensitivity of the method is demonstrated with extracts of a sample from a duplicate diet study. Due to the lack of a certified reference material the suitability of the method is demonstrated with pumpkin seed oil that was spiked with nitro-PAHs at two different concentration levels. (orig.)

  1. A counterselection method for Lactococcus lactis genome editing based on class IIa bacteriocin sensitivity.

    Science.gov (United States)

    Wan, Xing; Usvalampi, Anne M; Saris, Per E J; Takala, Timo M

    2016-11-01

    In this paper, we present a new counterselection method for deleting fragments from Lactococcus lactis chromosome. The method uses a non-replicating plasmid vector, which integrates into the chromosome and makes the cell sensitive to bacteriocins. The integration vector carries pUC ori functional in Escherichia coli but not in L. lactis, an erythromycin resistance gene for selecting single crossover integrants, and two fragments from L. lactis chromosome for homologous recombinations. In addition, the integration vector is equipped with the Listeria monocytogenes gene mptC encoding the mannose-phosphotransferase system component IIC, the receptor for class IIa bacteriocins. Expression of mptC from the integration vector renders the naturally resistant L. lactis sensitive to class IIa bacteriocins. This sensitivity is then used to select the double crossover colonies on bacteriocin agar. Only the cells which have regained the endogenous bacteriocin resistance through the loss of the mptC plasmid will survive. The colonies carrying the desired deletion can then be distinguished from the wild-type revertants by PCR. By using the class IIa bacteriocins leucocin A, leucocin C or pediocin AcH as the counterselective agents, we deleted 22- and 33-kb chromosomal fragments from the wild-type nisin producing L. lactis strain N8. In conclusion, this counterselection method presented here is a convenient, efficient and inexpensive technique to generate successive deletions in L. lactis chromosome.

  2. 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

  3. 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.

  4. 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,.

  5. 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.

  6. Single-acquisition method for simultaneous determination of extrinsic gamma-camera sensitivity and spatial resolution

    Energy Technology Data Exchange (ETDEWEB)

    Santos, J.A.M. [Servico de Fisica Medica, Instituto Portugues de Oncologia Francisco Gentil do Porto, E.P.E., Rua Dr. Antonio Bernardino de Almeida, 4200-072 Porto (Portugal)], E-mail: a.miranda@portugalmail.pt; Sarmento, S. [Servico de Fisica Medica, Instituto Portugues de Oncologia Francisco Gentil do Porto, E.P.E., Rua Dr. Antonio Bernardino de Almeida, 4200-072 Porto (Portugal); Alves, P.; Torres, M.C. [Departamento de Fisica da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto (Portugal); Bastos, A.L. [Servico de Medicina Nuclear, Instituto Portugues de Oncologia Francisco Gentil do Porto, E.P.E., Rua Dr. Antonio Bernardino de Almeida, 4200-072 Porto (Portugal); Ponte, F. [Servico de Fisica Medica, Instituto Portugues de Oncologia Francisco Gentil do Porto, E.P.E., Rua Dr. Antonio Bernardino de Almeida, 4200-072 Porto (Portugal)

    2008-01-15

    A new method for measuring simultaneously both the extrinsic sensitivity and spatial resolution of a gamma-camera in a single planar acquisition was implemented. A dual-purpose phantom (SR phantom; sensitivity/resolution) was developed, tested and the results compared with other conventional methods used for separate determination of these two important image quality parameters. The SR phantom yielded reproducible and accurate results, allowing an immediate visual inspection of the spatial resolution as well as the quantitative determination of the contrast for six different spatial frequencies. It also proved to be useful in the estimation of the modulation transfer function (MTF) of the image formation collimator/detector system at six different frequencies and can be used to estimate the spatial resolution as function of the direction relative to the digital matrix of the detector.

  7. Single-acquisition method for simultaneous determination of extrinsic gamma-camera sensitivity and spatial resolution

    International Nuclear Information System (INIS)

    Santos, J.A.M.; Sarmento, S.; Alves, P.; Torres, M.C.; Bastos, A.L.; Ponte, F.

    2008-01-01

    A new method for measuring simultaneously both the extrinsic sensitivity and spatial resolution of a gamma-camera in a single planar acquisition was implemented. A dual-purpose phantom (SR phantom; sensitivity/resolution) was developed, tested and the results compared with other conventional methods used for separate determination of these two important image quality parameters. The SR phantom yielded reproducible and accurate results, allowing an immediate visual inspection of the spatial resolution as well as the quantitative determination of the contrast for six different spatial frequencies. It also proved to be useful in the estimation of the modulation transfer function (MTF) of the image formation collimator/detector system at six different frequencies and can be used to estimate the spatial resolution as function of the direction relative to the digital matrix of the detector

  8. State of the art in non-animal approaches for skin sensitization testing: from individual test methods towards testing strategies.

    Science.gov (United States)

    Ezendam, Janine; Braakhuis, Hedwig M; Vandebriel, Rob J

    2016-12-01

    The hazard assessment of skin sensitizers relies mainly on animal testing, but much progress is made in the development, validation and regulatory acceptance and implementation of non-animal predictive approaches. In this review, we provide an update on the available computational tools and animal-free test methods for the prediction of skin sensitization hazard. These individual test methods address mostly one mechanistic step of the process of skin sensitization induction. The adverse outcome pathway (AOP) for skin sensitization describes the key events (KEs) that lead to skin sensitization. In our review, we have clustered the available test methods according to the KE they inform: the molecular initiating event (MIE/KE1)-protein binding, KE2-keratinocyte activation, KE3-dendritic cell activation and KE4-T cell activation and proliferation. In recent years, most progress has been made in the development and validation of in vitro assays that address KE2 and KE3. No standardized in vitro assays for T cell activation are available; thus, KE4 cannot be measured in vitro. Three non-animal test methods, addressing either the MIE, KE2 or KE3, are accepted as OECD test guidelines, and this has accelerated the development of integrated or defined approaches for testing and assessment (e.g. testing strategies). The majority of these approaches are mechanism-based, since they combine results from multiple test methods and/or computational tools that address different KEs of the AOP to estimate skin sensitization potential and sometimes potency. Other approaches are based on statistical tools. Until now, eleven different testing strategies have been published, the majority using the same individual information sources. Our review shows that some of the defined approaches to testing and assessment are able to accurately predict skin sensitization hazard, sometimes even more accurate than the currently used animal test. A few defined approaches are developed to provide an

  9. Nickel contact sensitivity in the guinea pig. An efficient open application test method

    DEFF Research Database (Denmark)

    Nielsen, G D; Rohold, A E; Andersen, Klaus Ejner

    1992-01-01

    Nickel contact sensitivity was successfully induced in guinea pigs using an open epicutaneous application method. Immediately after pretreatment with 1% aqueous sodium lauryl sulfate, upper back skin was treated daily for 4 weeks with 0.3%-3% nickel sulfate in either a 1% lanolin cream (Vaseline, p...

  10. Pyocin-sensitivity testing as a method of typing Pseudomonas aeruginosa: use of "phage-free" preparations of pyocin.

    Science.gov (United States)

    Rampling, A; Whitby, J L; Wildy, P

    1975-11-01

    A method for pyocin-sensitivity typing by means of "phage-free" preparations of pyocin is described. The method was tested on 227 isolates of P. aeruginosa, collected from 34 different foci of infection in hospitals in the British Isles and the results were compared with those for combined serological and phage typing of all strains and pyocin production of 105 of the isolates. It is concluded that pyocin-sensitivity typing is a simple and reliable method giving a high degree of discrimination, comparable to that of combined serological and phage typing, and it is suitable for use in routine hospital laboratories.

  11. Fast and Sensitive Method for Determination of Domoic Acid in Mussel Tissue

    Directory of Open Access Journals (Sweden)

    Elena Barbaro

    2016-01-01

    Full Text Available Domoic acid (DA, a neurotoxic amino acid produced by diatoms, is the main cause of amnesic shellfish poisoning (ASP. In this work, we propose a very simple and fast analytical method to determine DA in mussel tissue. The method consists of two consecutive extractions and requires no purification steps, due to a reduction of the extraction of the interfering species and the application of very sensitive and selective HILIC-MS/MS method. The procedural method was validated through the estimation of trueness, extract yield, precision, detection, and quantification limits of analytical method. The sample preparation was also evaluated through qualitative and quantitative evaluations of the matrix effect. These evaluations were conducted both on the DA-free matrix spiked with known DA concentration and on the reference certified material (RCM. We developed a very selective LC-MS/MS method with a very low value of method detection limit (9 ng g−1 without cleanup steps.

  12. A sensitive fluorescence quenching method for the detection of tartrazine with acriflavine in soft drinks.

    Science.gov (United States)

    Yang, Huan; Ran, Guihua; Yan, Jingjing; Zhang, Hui; Hu, Xiaoli

    2018-03-01

    In this work, a simple, rapid, sensitive, selective spectrofluorimetric method was applied to detect tartrazine. The fluorescence of acriflavine could be efficiently quenched by tartrazine. The method manifested real time response as well as presented satisfied linear relationship to tartrazine. The linear response range of tartrazine (R 2 = 0.9995) was from 0.056 to 5 μmol L -1 . The detection limit (3σ/k) was 0.017 μmol L -1 , indicating that this method could be applied to detect traces of tartrazine. The accuracy and precision of the method was further assured by recovery studies via a standard addition method, with percentage recoveries in the range of 96.0% to 103.0%. Moreover, a quenching mechanism was investigated systematically by the linear plots at varying temperatures based on the Stern-Volmer equation, fluorescence lifetime and UV-visible absorption spectra, all of which proved to be static quenching. This sensitive, selective assay possessed a great application prospect for the food industry owing to its simplicity and rapidity for the detection of tartrazine. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Boundary integral method to calculate the sensitivity temperature error of microstructured fibre plasmonic sensors

    International Nuclear Information System (INIS)

    Esmaeilzadeh, Hamid; Arzi, Ezatollah; Légaré, François; Hassani, Alireza

    2013-01-01

    In this paper, using the boundary integral method (BIM), we simulate the effect of temperature fluctuation on the sensitivity of microstructured optical fibre (MOF) surface plasmon resonance (SPR) sensors. The final results indicate that, as the temperature increases, the refractometry sensitivity of our sensor decreases from 1300 nm/RIU at 0 °C to 1200 nm/RIU at 50 °C, leading to ∼7.7% sensitivity reduction and the sensitivity temperature error of 0.15% °C −1 for this case. These results can be used for biosensing temperature-error adjustment in MOF SPR sensors, since biomaterials detection usually happens in this temperature range. Moreover, the signal-to-noise ratio (SNR) of our sensor decreases from 0.265 at 0 °C to 0.154 at 100 °C with the average reduction rate of ∼0.42% °C −1 . The results suggest that at lower temperatures the sensor has a higher SNR. (paper)

  14. A simple method to measure critical angles for high-sensitivity differential refractometry.

    Science.gov (United States)

    Zilio, S C

    2012-01-16

    A total internal reflection-based differencial refractometer, capable of measuring the real and imaginary parts of the complex refractive index in real time, is presented. The device takes advantage of the phase difference acquired by s- and p-polarized light to generate an easily detectable minimum at the reflected profile. The method allows to sensitively measuring transparent and turbid liquid samples.

  15. An approach of sensitivity and uncertainty analyses methods installation in a safety calculation

    International Nuclear Information System (INIS)

    Pepin, G.; Sallaberry, C.

    2003-01-01

    Simulation of the migration in deep geological formations leads to solve convection-diffusion equations in porous media, associated with the computation of hydrogeologic flow. Different time-scales (simulation during 1 million years), scales of space, contrasts of properties in the calculation domain, are taken into account. This document deals more particularly with uncertainties on the input data of the model. These uncertainties are taken into account in total analysis with the use of uncertainty and sensitivity analysis. ANDRA (French national agency for the management of radioactive wastes) carries out studies on the treatment of input data uncertainties and their propagation in the models of safety, in order to be able to quantify the influence of input data uncertainties of the models on the various indicators of safety selected. The step taken by ANDRA consists initially of 2 studies undertaken in parallel: - the first consists of an international review of the choices retained by ANDRA foreign counterparts to carry out their uncertainty and sensitivity analysis, - the second relates to a review of the various methods being able to be used in sensitivity and uncertainty analysis in the context of ANDRA's safety calculations. Then, these studies are supplemented by a comparison of the principal methods on a test case which gathers all the specific constraints (physical, numerical and data-processing) of the problem studied by ANDRA

  16. Determination of Some Cephalosporins in Pharmaceutical Formulations by a Simple and Sensitive Spectrofluorimetric Method

    Directory of Open Access Journals (Sweden)

    Ali Abdollahi, Ahad Bavili-Tabrizi

    2016-03-01

    Full Text Available Background: Cephalosporins are among the safest and the most effective broad-spectrum bactericidal antimicrobial agents which have been prescribed by the clinician as antibiotics. Thus, the developing of simple, sensitive and rapid analytical methods for their determination can be attractive and desirable. Methods: A simple, rapid and sensitive spectrofluorimetric method was developed for the determination of cefixime, cefalexin and ceftriaxone in pharmaceutical formulations. Proposed method is based on the oxidation of these cephalosporins with cerium (IV to produce cerium (III, and its fluorescence was monitored at 356 ± 3 nm after excitation at 254 ± 3 nm. Results: The variables effecting oxidation of each cephalosporin with cerum (IV were studied and optimized. Under the experimental conditions used, the calibration graphs were linear over the range 0.1-4 µg/mL. The limit of detection and limit of quantification were in the range 0.031-0.054 and 0.102-0.172 µg/mL, respectively. Intra- and inter-day assay precisions, expressed as the relative standard deviation (RSD, were lower than 5.6 and 6.8%, respectively. Conclusion: The proposed method was applied to the determination of studied cephalosporins in pharmaceutical formulations by good recoveries in the range 91-110%.

  17. A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference

    International Nuclear Information System (INIS)

    Namba, Hiroki; Nakagawa, Keiichi; Iyo, Masaomi; Fukushi, Kiyoshi; Irie, Toshiaki

    1994-01-01

    A simple method, without measurement of the plasma input function, to obtain semiquantitative values of glucose utilization in tissues other than the brain with radioactive deoxyglucose is reported. The brain, in which glucose utilization is essentially insensitive to plasma glucose and insulin concentrations, was used as an internal reference. The effects of graded doses of oral glucose loading (0.5, 1 and 2 mg/g body weight) on insulin-sensitive tissues (heart, muscle and fat tissue) were studied in the rat. By using the brain-reference method, dose-dependent increases in glucose utilization were clearly shown in all the insulin-sensitive tissues examined. The method seems to be of value for measurement of glucose utilization using radioactive deoxyglucose and positron emission tomography in the heart or other insulin-sensitive tissues, especially during glucose loading. (orig.)

  18. Measurement of radon in air by α track method enhancement detection sensitivity using a lamp

    International Nuclear Information System (INIS)

    Maki, Y.; Tanaka, F.

    1983-01-01

    A new α track method is proposed for the measurement of 222 Rn concentration in environmental levels. This involves collecting radon daughters on the surface of pilot lamp and detecting α-particles emitted from the nuclides ( 218 Po and 214 Po) by a detector (LR 115). The detection sensitivity of this method is 6 times greater than that of the conventional α track method. (author)

  19. Quantitative Evaluation of Aged AISI 316L Stainless Steel Sensitization to Intergranular Corrosion: Comparison Between Microstructural Electrochemical and Analytical Methods

    Science.gov (United States)

    Sidhom, H.; Amadou, T.; Sahlaoui, H.; Braham, C.

    2007-06-01

    The evaluation of the degree of sensitization (DOS) to intergranular corrosion (IGC) of a commercial AISI 316L austenitic stainless steel aged at temperatures ranging from 550 °C to 800 °C during 100 to 80,000 hours was carried out using three different assessment methods. (1) The microstructural method coupled with the Strauss standard test (ASTM A262). This method establishes the kinetics of the precipitation phenomenon under different aging conditions, by transmission electronic microscope (TEM) examination of thin foils and electron diffraction. The subsequent chromium-depleted zones are characterized by X-ray microanalysis using scanning transmission electronic microscope (STEM). The superimposition of microstructural time-temperature-precipitation (TTP) and ASTM A262 time-temperature-sensitization (TTS) diagrams provides the relationship between aged microstructure and IGC. Moreover, by considering the chromium-depleted zone characteristics, sensitization and desensitization criteria could be established. (2) The electrochemical method involving the double loop-electrochemical potentiokinetic reactivation (DL-EPR) test. The operating conditions of this test were initially optimized using the experimental design method on the bases of the reliability, the selectivity, and the reproducibility of test responses for both annealed and sensitized steels. The TTS diagram of the AISI 316L stainless steel was established using this method. This diagram offers a quantitative assessment of the DOS and a possibility to appreciate the time-temperature equivalence of the IGC sensitization and desensitization. (3) The analytical method based on the chromium diffusion models. Using the IGC sensitization and desensitization criteria established by the microstructural method, numerical solving of the chromium diffusion equations leads to a calculated AISI 316L TTS diagram. Comparison of these three methods gives a clear advantage to the nondestructive DL-EPR test when it is

  20. Doppler method leak detection for LMFBR steam generators. Pt. 3. Investigation of detection sensitivity and method

    International Nuclear Information System (INIS)

    Kumagai, Hiromichi; Kinoshita, Izumi

    2001-01-01

    To prevent the expansion of tube damage and to maintain structural integrity in the steam generators (SGs) of a fast breeder reactor (FBR), it is necessary to detect precisely and immediately any leakage of water from heat transfer tubes. Therefore, the Doppler method was developed. Previous studies have revealed that, in the SG full-sector model that simulates actual SGs, the Doppler method can detect bubbles of 0.4 l/s within a few seconds. However in consideration of the dissolution rate of hydrogen generated by a sodium-water reaction even from a small water leak, it is necessary to detect smaller leakages of water from the heat transfer tubes. The detection sensitivity of the Doppler method and the influence of background noise were experimentally investigated. In-water experiments were performed using the SG model. The results show that the Doppler method can detect bubbles of 0.01 l/s (equivalent to a water leak rate of about 0.01 g/s) within a few seconds and that the background noise has little effect on water leak detection performance. The Doppler method thus has great potential for the detection of water leakage in SGs. (author)

  1. 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.

  2. "Cork taint" responsible compounds. Determination of haloanisoles and halophenols in cork matrix: A review.

    Science.gov (United States)

    Tarasov, Andrii; Rauhut, Doris; Jung, Rainer

    2017-12-01

    Analytical methods of haloanisoles and halophenols quantification in cork matrix are summarized in the current review. Sample-preparation and sample-treatment techniques have been compared and discussed from the perspective of their efficiency, time- and extractant-optimization, easiness of performance. Primary interest of these analyses usually addresses to 2,4,6-trichloroanisole (TCA), which is a major wine contaminant among haloanisoles. Two concepts of TCA determination are described in the review: releasable TCA and total TCA analyses. Chromatographic, bioanalytical and sensorial methods were compared according to their application in the cork industry and in scientific investigations. Finally, it was shown that modern analytical techniques are able to provide required sensitivity, selectivity and repeatability for haloanisoles and halophenols determination. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. The use of graph theory in the sensitivity analysis of the model output: a second order screening method

    International Nuclear Information System (INIS)

    Campolongo, Francesca; Braddock, Roger

    1999-01-01

    Sensitivity analysis screening methods aim to isolate the most important factors in experiments involving a large number of significant factors and interactions. This paper extends the one-factor-at-a-time screening method proposed by Morris. The new method, in addition to the 'overall' sensitivity measures already provided by the traditional Morris method, offers estimates of the two-factor interaction effects. The number of model evaluations required is O(k 2 ), where k is the number of model input factors. The efficient sampling strategy in the parameter space is based on concepts of graph theory and on the solution of the 'handcuffed prisoner problem'

  4. On the sensitivity of FPPE - TWRC method in thermal effusivity investigations of solids

    International Nuclear Information System (INIS)

    Dadarlat, Dorin; Streza, Mihaela; Pop, Mircea N; Tosa, Valer

    2009-01-01

    The front detection configuration (FPPE) together with the thermal-wave-resonator-cavity (TWRC) method was used for direct measurement of the thermal effusivity of solid materials inserted as backings in the FPPE detection cell. It was demonstrated that the normalized phase of the FPPE signal has an oscillating dependence as a function of sample's thickness. The paper presents experimental results on solid materials, with various values of thermal effusivity (Cu, brass, steel, bakelite, wood). A study of the sensitivity of the technique for different liquid/backing effusivity ratios is performed. The highest sensitivity was obtained when investigating solids with values of thermal effusivity not far from the effusivity of the liquid layer of the detection cell.

  5. Sensitivity assessment of direct method for diagnosis of Trichomonas vaginalis in comparison with Dorset Culture media

    Directory of Open Access Journals (Sweden)

    ebrahim badparva

    2010-04-01

    Full Text Available Trichomonas vaginalis is a flagellate protozoan that lives in the genital tract and causes trichomoniasis in women. About 200 million people all over the world are infected with T. vaginalis. There are various methods with different sensitivity and specificity for detection of this parasite, that one of them is direct smear of vaginal secretions which is simpler, rapid and cheaper than other diagnostic methods. Materials and Methods: Demographic data was gathered by a questionnaire which contained different variables. Vaginal secretions samples were taken by spicolum and two swaps that maintained in glucose solution in separate tubes from 160 women referred to health centers of Khorramabad. One of the vaginal samples was examined by direct smear in saline solution and the other was cultured in Dorse medium. Results: Of 160 women suspected of trichomoniasis, 11.8% and 18.75% were positive by direct smear and culture respectively. The sensitivity of the direct method was 63.3%. Our findings indicated that 30% of the infected women belonged to the 31 – 35 age group, which had the most relative frequency of positive cases. Most of the patients (43% were illiterate or had elementary educational level. Conclussion: The sensivity of direct method is 63% in compare to culture ( as a Gold standard , which is ralatively low . Although the efficacy of this test could be imporved by shortening the elapsed time between sampling and examination , use of skilled microscopists , and different samples , but we recommend that more sensitive methods such as culture and PCR should be used .

  6. Sensitivity analysis and parameter estimation for distributed hydrological modeling: potential of variational methods

    Directory of Open Access Journals (Sweden)

    W. Castaings

    2009-04-01

    Full Text Available Variational methods are widely used for the analysis and control of computationally intensive spatially distributed systems. In particular, the adjoint state method enables a very efficient calculation of the derivatives of an objective function (response function to be analysed or cost function to be optimised with respect to model inputs.

    In this contribution, it is shown that the potential of variational methods for distributed catchment scale hydrology should be considered. A distributed flash flood model, coupling kinematic wave overland flow and Green Ampt infiltration, is applied to a small catchment of the Thoré basin and used as a relatively simple (synthetic observations but didactic application case.

    It is shown that forward and adjoint sensitivity analysis provide a local but extensive insight on the relation between the assigned model parameters and the simulated hydrological response. Spatially distributed parameter sensitivities can be obtained for a very modest calculation effort (~6 times the computing time of a single model run and the singular value decomposition (SVD of the Jacobian matrix provides an interesting perspective for the analysis of the rainfall-runoff relation.

    For the estimation of model parameters, adjoint-based derivatives were found exceedingly efficient in driving a bound-constrained quasi-Newton algorithm. The reference parameter set is retrieved independently from the optimization initial condition when the very common dimension reduction strategy (i.e. scalar multipliers is adopted.

    Furthermore, the sensitivity analysis results suggest that most of the variability in this high-dimensional parameter space can be captured with a few orthogonal directions. A parametrization based on the SVD leading singular vectors was found very promising but should be combined with another regularization strategy in order to prevent overfitting.

  7. Sensitive double-antibody method for simultaneous determination of insulin and growth hormone

    International Nuclear Information System (INIS)

    Koparanova, O.; Sotirov, G.; Tyrkolev, N.

    1982-01-01

    A method is described for simultaneous determination of insulin and growth hormone in one sample, using double-antibody technique. The method is characterized by appreciable sensitivity (2.5 μE/ml for insulin and a.2 ng/ml for growth hormone), exactness (variation quotient 6-16 per cent) and reproducibility (96.9-117 per cent). There was no statistically significant difference in the insulin and growth hormone values of the same sera, determined by the here suggested and the standard methods. The necessary test material for examination of either hormone is minimal (0.2 ml). One may thus extend the possibilities for radioimmunologic determination of insulin and growth hormone, when only minor amounts of serum or other biological fluid are available. The method is also less time consuming. Results are reported of statistical processing of an experimental model and different sera determined by the standard method and the one described by the authors. (author)

  8. A simple, rapid, cost-effective and sensitive method for detection of Salmonella in environmental and pecan samples.

    Science.gov (United States)

    Dobhal, S; Zhang, G; Rohla, C; Smith, M W; Ma, L M

    2014-10-01

    PCR is widely used in the routine detection of foodborne human pathogens; however, challenges remain in overcoming PCR inhibitors present in some sample matrices. The objective of this study was to develop a simple, sensitive, cost-effective and rapid method for processing large numbers of environmental and pecan samples for Salmonella detection. This study was also aimed at validation of a new protocol for the detection of Salmonella from in-shell pecans. Different DNA template preparation methods, including direct boiling, prespin, multiple washing and commercial DNA extraction kits, were evaluated with pure cultures of Salmonella Typhimurium and with enriched soil, cattle feces and in-shell pecan each spiked individually with Salmonella Typhimurium. PCR detection of Salmonella was conducted using invA and 16S rRNA gene (internal amplification control) specific primers. The effect of amplification facilitators, including bovine serum albumin (BSA), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG) and gelatin on PCR sensitivity, was also evaluated. Conducting a prespin of sample matrices in combination with the addition of 0·4% (w/v) BSA and 1% (w/v) PVP in PCR mix was the simplest, most rapid, cost-effective and sensitive method for PCR detection of Salmonella, with up to 40 CFU Salmonella per reaction detectable in the presence of over 10(9 ) CFU ml(-1) of background micro-organisms from enriched feces soil or pecan samples. The developed method is rapid, cost-effective and sensitive for detection of Salmonella from different matrices. This study provides a method with broad applicability for PCR detection of Salmonella in complex sample matrices. This method has a potential for its application in different research arenas and diagnostic laboratories. © 2014 The Society for Applied Microbiology.

  9. A new surface resistance measurement method with ultrahigh sensitivity

    International Nuclear Information System (INIS)

    Liang, Changnian.

    1993-01-01

    A superconducting niobium triaxial cavity has been designed and fabricated to study residual surface resistance of planar superconducting materials. The edge of a 25.4 mm or larger diameter sample in the triaxial cavity is located outside the strong field region. Therefore, the edge effects and possible losses between the thin film and the substrate have been minimized, ensuring that induced RF losses are intrinsic to the test material. The fundamental resonant frequency of the cavity is the same as the working frequency of CEBAF cavities. The cavity has a compact size compared to its TE 011 counterpart, which makes it more sensitive to the sample's loss. For even higher sensitivity, a calorimetry method has been used to measure the RF losses on the superconducting sample. At 2 K, a 2 μK temperature change can be resolved by using carbon resistor sensors. The temperature distribution caused by RF heating is measured by 16 carbon composition resistor sensors. A 0.05 μW heating power can be detected as such a resolution, which translates to a surface resistance of 0.02 nΩ at a surface magnetic field of 52 Oe. This is the most sensitive device for surface resistance measurements to date. In addition, losses due to the indium seal, coupling probes, field emission sites other than the sample, and all of the high field resonator surface, are excluded in the measurement. Surface resistance of both niobium and high-Tc superconducting thin films has been measured. A low R s of 35.2 μΩ was measured for a 25.4 mm diameter YBa 2 Cu 3 O 7 thin film at 1.5 GHz and at 2 K. The measurement result is the first result for a large area epitaxially grown thin film sample at such a low RF frequency. The abrupt disappearance of multipacting between two parallel plates has been observed and monitored with the 16 temperature mapping sensors. Field emission or some field dependent anomalous RF losses on the niobium plate have also been observed

  10. 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.

  11. A sensitivity analysis method for the body segment inertial parameters based on ground reaction and joint moment regressor matrices.

    Science.gov (United States)

    Futamure, Sumire; Bonnet, Vincent; Dumas, Raphael; Venture, Gentiane

    2017-11-07

    This paper presents a method allowing a simple and efficient sensitivity analysis of dynamics parameters of complex whole-body human model. The proposed method is based on the ground reaction and joint moment regressor matrices, developed initially in robotics system identification theory, and involved in the equations of motion of the human body. The regressor matrices are linear relatively to the segment inertial parameters allowing us to use simple sensitivity analysis methods. The sensitivity analysis method was applied over gait dynamics and kinematics data of nine subjects and with a 15 segments 3D model of the locomotor apparatus. According to the proposed sensitivity indices, 76 segments inertial parameters out the 150 of the mechanical model were considered as not influent for gait. The main findings were that the segment masses were influent and that, at the exception of the trunk, moment of inertia were not influent for the computation of the ground reaction forces and moments and the joint moments. The same method also shows numerically that at least 90% of the lower-limb joint moments during the stance phase can be estimated only from a force-plate and kinematics data without knowing any of the segment inertial parameters. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A DNA microarray-based methylation-sensitive (MS)-AFLP hybridization method for genetic and epigenetic analyses.

    Science.gov (United States)

    Yamamoto, F; Yamamoto, M

    2004-07-01

    We previously developed a PCR-based DNA fingerprinting technique named the Methylation Sensitive (MS)-AFLP method, which permits comparative genome-wide scanning of methylation status with a manageable number of fingerprinting experiments. The technique uses the methylation sensitive restriction enzyme NotI in the context of the existing Amplified Fragment Length Polymorphism (AFLP) method. Here we report the successful conversion of this gel electrophoresis-based DNA fingerprinting technique into a DNA microarray hybridization technique (DNA Microarray MS-AFLP). By performing a total of 30 (15 x 2 reciprocal labeling) DNA Microarray MS-AFLP hybridization experiments on genomic DNA from two breast and three prostate cancer cell lines in all pairwise combinations, and Southern hybridization experiments using more than 100 different probes, we have demonstrated that the DNA Microarray MS-AFLP is a reliable method for genetic and epigenetic analyses. No statistically significant differences were observed in the number of differences between the breast-prostate hybridization experiments and the breast-breast or prostate-prostate comparisons.

  13. Effect of cantilever geometry on the optical lever sensitivities and thermal noise method of the atomic force microscope.

    Science.gov (United States)

    Sader, John E; Lu, Jianing; Mulvaney, Paul

    2014-11-01

    Calibration of the optical lever sensitivities of atomic force microscope (AFM) cantilevers is especially important for determining the force in AFM measurements. These sensitivities depend critically on the cantilever mode used and are known to differ for static and dynamic measurements. Here, we calculate the ratio of the dynamic and static sensitivities for several common AFM cantilevers, whose shapes vary considerably, and experimentally verify these results. The dynamic-to-static optical lever sensitivity ratio is found to range from 1.09 to 1.41 for the cantilevers studied - in stark contrast to the constant value of 1.09 used widely in current calibration studies. This analysis shows that accuracy of the thermal noise method for the static spring constant is strongly dependent on cantilever geometry - neglect of these dynamic-to-static factors can induce errors exceeding 100%. We also discuss a simple experimental approach to non-invasively and simultaneously determine the dynamic and static spring constants and optical lever sensitivities of cantilevers of arbitrary shape, which is applicable to all AFM platforms that have the thermal noise method for spring constant calibration.

  14. Masonry fireplace emissions test method: Repeatability and sensitivity to fueling protocol.

    Science.gov (United States)

    Stern, C H; Jaasma, D R; Champion, M R

    1993-03-01

    A test method for masonry fireplaces has been evaluated during testing on six masonry fireplace configurations. The method determines carbon monoxide and particulate matter emission rates (g/h) and factors (g/kg) and does not require weighing of the appliance to determine the timing of fuel loading.The intralaboratory repeatability of the test method has been determined from multiple tests on the six fireplaces. For the tested fireplaces, the ratio of the highest to lowest measured PM rate averaged 1.17 and in no case was greater than 1.32. The data suggest that some of the variation is due to differences in fuel properties.The influence of fueling protocol on emissions has also been studied. A modified fueling protocol, tested in large and small fireplaces, reduced CO and PM emission factors by roughly 40% and reduced CO and PM rates from 0 to 30%. For both of these fireplaces, emission rates were less sensitive to fueling protocol than emission factors.

  15. Screening, sensitivity, and uncertainty for the CREAM method of Human Reliability Analysis

    International Nuclear Information System (INIS)

    Bedford, Tim; Bayley, Clare; Revie, Matthew

    2013-01-01

    This paper reports a sensitivity analysis of the Cognitive Reliability and Error Analysis Method for Human Reliability Analysis. We consider three different aspects: the difference between the outputs of the Basic and Extended methods, on the same HRA scenario; the variability in outputs through the choices made for common performance conditions (CPCs); and the variability in outputs through the assignment of choices for cognitive function failures (CFFs). We discuss the problem of interpreting categories when applying the method, compare its quantitative structure to that of first generation methods and discuss also how dependence is modelled with the approach. We show that the control mode intervals used in the Basic method are too narrow to be consistent with the Extended method. This motivates a new screening method that gives improved accuracy with respect to the Basic method, in the sense that (on average) halves the uncertainty associated with the Basic method. We make some observations on the design of a screening method that are generally applicable in Risk Analysis. Finally, we propose a new method of combining CPC weights with nominal probabilities so that the calculated probabilities are always in range (i.e. between 0 and 1), while satisfying sensible properties that are consistent with the overall CREAM method

  16. Methods and computer codes for probabilistic sensitivity and uncertainty analysis

    International Nuclear Information System (INIS)

    Vaurio, J.K.

    1985-01-01

    This paper describes the methods and applications experience with two computer codes that are now available from the National Energy Software Center at Argonne National Laboratory. The purpose of the SCREEN code is to identify a group of most important input variables of a code that has many (tens, hundreds) input variables with uncertainties, and do this without relying on judgment or exhaustive sensitivity studies. Purpose of the PROSA-2 code is to propagate uncertainties and calculate the distributions of interesting output variable(s) of a safety analysis code using response surface techniques, based on the same runs used for screening. Several applications are discussed, but the codes are generic, not tailored to any specific safety application code. They are compatible in terms of input/output requirements but also independent of each other, e.g., PROSA-2 can be used without first using SCREEN if a set of important input variables has first been selected by other methods. Also, although SCREEN can select cases to be run (by random sampling), a user can select cases by other methods if he so prefers, and still use the rest of SCREEN for identifying important input variables

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Method of estimating the sensitivity of a calculated nuclide vector to deviations in initial data

    International Nuclear Information System (INIS)

    Ivanov, E.A.

    1998-12-01

    The application of perturbation theory algorithms in modelling of nuclides transmutation is considered. The perturbation theory is used to construct the analytical technique of sensitivity analysis. It is shown that such algorithms have to be used in modelling of lifetime performance of nuclear power installations with the Monte Carlo method. The present approach differs from others by consistent use of analytical methods. (author)

  19. 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.

  20. 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.

  1. Effect-based trigger values for in vitro bioassays: Reading across from existing water quality guideline values.

    Science.gov (United States)

    Escher, Beate I; Neale, Peta A; Leusch, Frederic D L

    2015-09-15

    Cell-based bioassays are becoming increasingly popular in water quality assessment. The new generations of reporter-gene assays are very sensitive and effects are often detected in very clean water types such as drinking water and recycled water. For monitoring applications it is therefore imperative to derive trigger values that differentiate between acceptable and unacceptable effect levels. In this proof-of-concept paper, we propose a statistical method to read directly across from chemical guideline values to trigger values without the need to perform in vitro to in vivo extrapolations. The derivation is based on matching effect concentrations with existing chemical guideline values and filtering out appropriate chemicals that are responsive in the given bioassays at concentrations in the range of the guideline values. To account for the mixture effects of many chemicals acting together in a complex water sample, we propose bioanalytical equivalents that integrate the effects of groups of chemicals with the same mode of action that act in a concentration-additive manner. Statistical distribution methods are proposed to derive a specific effect-based trigger bioanalytical equivalent concentration (EBT-BEQ) for each bioassay of environmental interest that targets receptor-mediated toxicity. Even bioassays that are indicative of the same mode of action have slightly different numeric trigger values due to differences in their inherent sensitivity. The algorithm was applied to 18 cell-based bioassays and 11 provisional effect-based trigger bioanalytical equivalents were derived as an illustrative example using the 349 chemical guideline values protective for human health of the Australian Guidelines for Water Recycling. We illustrate the applicability using the example of a diverse set of water samples including recycled water. Most recycled water samples were compliant with the proposed triggers while wastewater effluent would not have been compliant with a few

  2. Verification of intraspecimen method using constant stress tension test of sensitized alloy 600

    International Nuclear Information System (INIS)

    Lee, Seung Ki; Choi, Hoi Su; Hwang, Il Soon

    2005-01-01

    Stress corrosion cracking (SCC) occurring at the Nibase alloy 600 used in the nuclear power plant SG tubes and CRDM penetration nozzles had been reported after long-term operation in the harsh environment. Intraspecimen method was developed to predict the SCC initiation time statistically. [1] By dividing a test area into a number of smaller regions (intraspecimens) having homogeneous physical and chemical condition each SCC initiation in each intraspecimen could be counted as an independent outcome to provide enough number of statistical data. Earlier work of intraspecimen method had many problems in test method and didn't agree with Weibull statistics which is the theoretical base of intraspecimen method. The test method is improved in this intraspecimen test. To find out the root causes of the problems in earlier work and improve the accuracy of intraspecimen method, two kinds of materials are introduced, which are different in grain size but same in chemical composition. Ni-base alloy 600, heat no. J313 and J323 are used as test materials. Specimens of sensitized Alloy 600 are tested under the condition of constant tensile stress and well defined chemical environment therefore we can easily observe typical intergranular stress corrosion cracking (IGSCC). Material with finer grain (J323) showed the areadependence in agreement with theoretical prediction. But material with coarser grain (J313) did not show any significant area-dependence. While SCC initiates earlier at grain boundaries that are oriented close to normal to the stress axis, crack initiation time showed no correlation with grain boundary misorientation estimated by Electron Back Scattered Diffraction (EBSD). From the SCC initiation tests with two test materials, it is concluded that the number of grains in an intraspecimen, degree of sensitization and uniform stress distribution are important parameters to meet Weibull statistics

  3. A new method of removing the high value feedback resistor in the charge sensitive preamplifier

    International Nuclear Information System (INIS)

    Xi Deming

    1993-01-01

    A new method of removing the high value feedback resistor in the charge sensitive preamplifier is introduced. The circuit analysis of this novel design is described and the measured performances of a practical circuit are provided

  4. 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.

  5. Leakage localisation method in a water distribution system based on sensitivity matrix: methodology and real test

    OpenAIRE

    Pascual Pañach, Josep

    2010-01-01

    Leaks are present in all water distribution systems. In this paper a method for leakage detection and localisation is presented. It uses pressure measurements and simulation models. Leakage localisation methodology is based on pressure sensitivity matrix. Sensitivity is normalised and binarised using a common threshold for all nodes, so a signatures matrix is obtained. A pressure sensor optimal distribution methodology is developed too, but it is not used in the real test. To validate this...

  6. A fast and highly sensitive blood culture PCR method for clinical detection of Salmonella enterica serovar Typhi

    Directory of Open Access Journals (Sweden)

    Zhou Liqing

    2010-04-01

    Full Text Available Abstract Background Salmonella Typhi causes an estimated 21 million new cases of typhoid fever and 216,000 deaths every year. Blood culture is currently the gold standard for diagnosis of typhoid fever, but it is time-consuming and takes several days for isolation and identification of causative organisms. It is then too late to initiate proper antibiotic therapy. Serological tests have very low sensitivity and specificity, and no practical value in endemic areas. As early diagnosis of the disease and prompt treatment are essential for optimal management, especially in children, a rapid sensitive detection method for typhoid fever is urgently needed. Although PCR is sensitive and rapid, initial research indicated similar sensitivity to blood culture and lower specificity. We developed a fast and highly sensitive blood culture PCR method for detection of Salmonella Typhi, allowing same-day initiation of treatment after accurate diagnosis of typhoid. Methods An ox bile tryptone soy broth was optimized for blood culture, which allows the complete lysis of blood cells to release intracellular bacteria without inhibiting the growth of Salmonella Typhi. Using the optimised broth Salmonella Typhi bacteria in artificial blood samples were enriched in blood culture and then detected by a PCR targeting the fliC-d gene of Salmonella Typhi. Results Tests demonstrated that 2.4% ox bile in blood culture not only lyzes blood cells completely within 1.5 hours so that the intracellular bacteria could be released, but also has no inhibiting effect on the growth of Salmonella Typhi. Three hour enrichment of Salmonella Typhi in tryptone soya broth containing 2.4% ox bile could increase the bacterial number from 0.75 CFU per millilitre of blood which is similar to clinical typhoid samples to the level which regular PCR can detect. The whole blood culture PCR assay takes less than 8 hours to complete rather than several days for conventional blood culture

  7. 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.

  8. A combined HM-PCR/SNuPE method for high sensitive detection of rare DNA methylation

    Directory of Open Access Journals (Sweden)

    Tierling Sascha

    2010-06-01

    Full Text Available Abstract Background DNA methylation changes are widely used as early molecular markers in cancer detection. Sensitive detection and classification of rare methylation changes in DNA extracted from circulating body fluids or complex tissue samples is crucial for the understanding of tumor etiology, clinical diagnosis and treatment. In this paper, we describe a combined method to monitor the presence of methylated tumor DNA in an excess of unmethylated background DNA of non-tumorous cells. The method combines heavy methyl-PCR, which favors preferential amplification of methylated marker sequence from bisulfite-treated DNA with a methylation-specific single nucleotide primer extension monitored by ion-pair, reversed-phase, high-performance liquid chromatography separation. Results This combined method allows detection of 14 pg (that is, four to five genomic copies of methylated chromosomal DNA in a 2000-fold excess (that is, 50 ng of unmethylated chromosomal background, with an analytical sensitivity of > 90%. We outline a detailed protocol for the combined assay on two examples of known cancer markers (SEPT9 and TMEFF2 and discuss general aspects of assay design and data interpretation. Finally, we provide an application example for rapid testing on tumor methylation in plasma DNA derived from a small cohort of patients with colorectal cancer. Conclusion The method allows unambiguous detection of rare DNA methylation, for example in body fluid or DNA isolates from cells or tissues, with very high sensitivity and accuracy. The application combines standard technologies and can easily be adapted to any target region of interest. It does not require costly reagents and can be used for routine screening of many samples.

  9. Diagnostic sensitivity and specificity of a participatory disease surveillance method for highly pathogenic avian influenza in household chicken flocks in Indonesia.

    Science.gov (United States)

    Robyn, M; Priyono, W B; Kim, L M; Brum, E

    2012-06-01

    A study was conducted to assess the diagnostic sensitivity and specificity of a disease surveillance method for diagnosis of highly pathogenic avian influenza (HPAI) outbreaks in household chicken flocks used by participatory disease surveillance (PDS) teams in Yogyakarta Province, Indonesia. The Government of Indonesia, in partnership with the Food and Agriculture Organization of the United Nations, has implemented a PDS method for the detection of HPAI outbreaks in poultry since 2006. The PDS method in Indonesia utilizes both a clinical case definition (CD) and the result of a commercial rapid antigen test kit Yogyakarta 55611, to diagnose HPAI outbreaks, primarily in backyard chicken flocks. The following diagnostic sensitivities and specificities were obtained relative to real-time reverse transcription-PCR as the gold standard diagnostic test: 1) 89% sensitivity (CI95: 75%-97%) and 96% specificity (CI95: 89%-99%) for the PDS CD alone; 2) 86% sensitivity (CI95: 71%-95%) and 99% specificity (CI95: 94%-100%) for the rapid antigen test alone; and 3) 84% sensitivity (CI95: 68%-94%) and 100% specificity (CI95: 96%-100%) for the PDS CD result combined with the rapid antigen test result. Based on these results, HPAI outbreaks in extensively raised household chickens can be diagnosed with sufficient sensitivity and specificity using the PDS method as implemented in Indonesia. Subject to further field evaluation, data from this study suggest that the diagnostic sensitivity of the PDS method may be improved by expanding the PDS CD to include more possible clinical presentations of HPAI and by increasing the number of rapid antigen tests to three different birds with HPAI-compatible signs of same flock.

  10. PROMETHEE Method and Sensitivity Analysis in the Software Application for the Support of Decision-Making

    Directory of Open Access Journals (Sweden)

    Petr Moldrik

    2008-01-01

    Full Text Available PROMETHEE is one of methods, which fall into multi-criteria analysis (MCA. The MCA, as the name itself indicates, deals with the evaluation of particular variants according to several criteria. Developed software application (MCA8 for the support of multi-criteria decision-making was upgraded about PROMETHEE method and a graphic tool, which enables the execution of the sensitivity analysis. This analysis is used to ascertain how a given model output depends upon the input parameters. The MCA8 software application with mentioned graphic upgrade was developed for purposes of solving multi-criteria decision tasks. In the MCA8 is possible to perform sensitivity analysis by a simple form – through column graphs. We can change criteria significances (weights in these column graphs directly and watch the changes of the order of variants immediately.

  11. Using a non-invasive technique in nutrition: synchrotron radiation infrared microspectroscopy spectroscopic characterization of oil seeds treated with different processing conditions on molecular spectral factors influencing nutrient delivery.

    Science.gov (United States)

    Zhang, Xuewei; Yu, Peiqiang

    2014-07-02

    Non-invasive techniques are a key to study nutrition and structure interaction. Fourier transform infrared microspectroscopy coupled with a synchrotron radiation source (SR-IMS) is a rapid, non-invasive, and non-destructive bioanalytical technique. To understand internal structure changes in relation to nutrient availability in oil seed processing is vital to find optimal processing conditions. The objective of this study was to use a synchrotron-based bioanalytical technique SR-IMS as a non-invasive and non-destructive tool to study the effects of heat-processing methods and oil seed canola type on modeled protein structure based on spectral data within intact tissue that were randomly selected and quantify the relationship between the modeled protein structure and protein nutrient supply to ruminants. The results showed that the moisture heat-related processing significantly changed (pprocessing by dry heating. The moisture heating increased (p0.05) in the protein spectral profile between the raw and dry-heated canola tissue and between yellow- and brown-type canola tissue. The results indicated that different heat processing methods have different impacts on the protein inherent structure. The protein intrinsic structure in canola seed tissue was more sensitive and more response to the moisture heating in comparison to the dry heating. These changes are expected to be related to the nutritive value. However, the current study is based on limited samples, and more large-scale studies are needed to confirm our findings.

  12. 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.

  13. A rapid and sensitive method for measuring N-acetylglucosaminidase activity in cultured cells.

    Directory of Open Access Journals (Sweden)

    Victor Mauri

    Full Text Available A rapid and sensitive method to quantitatively assess N-acetylglucosaminidase (NAG activity in cultured cells is highly desirable for both basic research and clinical studies. NAG activity is deficient in cells from patients with Mucopolysaccharidosis type IIIB (MPS IIIB due to mutations in NAGLU, the gene that encodes NAG. Currently available techniques for measuring NAG activity in patient-derived cell lines include chromogenic and fluorogenic assays and provide a biochemical method for the diagnosis of MPS IIIB. However, standard protocols require large amounts of cells, cell disruption by sonication or freeze-thawing, and normalization to the cellular protein content, resulting in an error-prone procedure that is material- and time-consuming and that produces highly variable results. Here we report a new procedure for measuring NAG activity in cultured cells. This procedure is based on the use of the fluorogenic NAG substrate, 4-Methylumbelliferyl-2-acetamido-2-deoxy-alpha-D-glucopyranoside (MUG, in a one-step cell assay that does not require cell disruption or post-assay normalization and that employs a low number of cells in 96-well plate format. We show that the NAG one-step cell assay greatly discriminates between wild-type and MPS IIIB patient-derived fibroblasts, thus providing a rapid method for the detection of deficiencies in NAG activity. We also show that the assay is sensitive to changes in NAG activity due to increases in NAGLU expression achieved by either overexpressing the transcription factor EB (TFEB, a master regulator of lysosomal function, or by inducing TFEB activation chemically. Because of its small format, rapidity, sensitivity and reproducibility, the NAG one-step cell assay is suitable for multiple procedures, including the high-throughput screening of chemical libraries to identify modulators of NAG expression, folding and activity, and the investigation of candidate molecules and constructs for applications in

  14. 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.

  15. Accuracy and Sensitivity of a Method of Jump Detection, Evaluated by Simulated Time Series

    Czech Academy of Sciences Publication Activity Database

    Chapanov, Y.; Ron, Cyril; Vondrák, Jan

    2017-01-01

    Roč. 14, č. 1 (2017), s. 73-82 ISSN 1214-9705 R&D Projects: GA ČR GA13-15943S Institutional support: RVO:67985815 Keywords : time series * data jump detection * high-sensitive method Subject RIV: DE - Earth Magnetism, Geodesy, Geography OBOR OECD: Physical geography Impact factor: 0.699, year: 2016

  16. Change in Photosystem II Photochemistry During Algal Growth Phases of Chlorella vulgaris and Scenedesmus obliquus.

    Science.gov (United States)

    Oukarroum, Abdallah

    2016-06-01

    Sensitivity of photosynthetic processes towards environmental stress is used as a bioanalytical tool to evaluate the responses of aquatic plants to a changing environment. In this paper, change of biomass density, chlorophyll a fluorescence and photosynthetic parameters during growth phases of two microalgae Chlorella vulgaris and Scenedesmus obliquus were studied. The photosynthetic growth behaviour changed significantly with cell age and algae species. During the exponential phase of growth, the photosynthesis capacity reached its maximum and decreased in ageing algal culture during stationary phase. In conclusion, the chlorophyll a fluorescence OJIP method and the derived fluorescence parameters would be an accurate method for obtaining information on maximum photosynthetic capacities and monitoring algal cell growth. This will contribute to more understanding, for example, of toxic actions of pollutants in microalgae test.

  17. A Fault Alarm and Diagnosis Method Based on Sensitive Parameters and Support Vector Machine

    Science.gov (United States)

    Zhang, Jinjie; Yao, Ziyun; Lv, Zhiquan; Zhu, Qunxiong; Xu, Fengtian; Jiang, Zhinong

    2015-08-01

    Study on the extraction of fault feature and the diagnostic technique of reciprocating compressor is one of the hot research topics in the field of reciprocating machinery fault diagnosis at present. A large number of feature extraction and classification methods have been widely applied in the related research, but the practical fault alarm and the accuracy of diagnosis have not been effectively improved. Developing feature extraction and classification methods to meet the requirements of typical fault alarm and automatic diagnosis in practical engineering is urgent task. The typical mechanical faults of reciprocating compressor are presented in the paper, and the existing data of online monitoring system is used to extract fault feature parameters within 15 types in total; the inner sensitive connection between faults and the feature parameters has been made clear by using the distance evaluation technique, also sensitive characteristic parameters of different faults have been obtained. On this basis, a method based on fault feature parameters and support vector machine (SVM) is developed, which will be applied to practical fault diagnosis. A better ability of early fault warning has been proved by the experiment and the practical fault cases. Automatic classification by using the SVM to the data of fault alarm has obtained better diagnostic accuracy.

  18. Efficient estimation of sensitivities for counterparty credit risk with the finite difference Monte Carlo method

    NARCIS (Netherlands)

    C.S.L. de Graaf (Kees); B.D. Kandhai; P.M.A. Sloot

    2017-01-01

    htmlabstractAccording to Basel III, financial institutions have to charge a credit valuation adjustment (CVA) to account for a possible counterparty default. Calculating this measure and its sensitivities is one of the biggest challenges in risk management. Here, we introduce an efficient method

  19. Ultra-sensitive chemiluminescence imaging DNA hybridization method in the detection of mosquito-borne viruses and parasites.

    Science.gov (United States)

    Zhang, Yingjie; Liu, Qiqi; Zhou, Biao; Wang, Xiaobo; Chen, Suhong; Wang, Shengqi

    2017-01-25

    Mosquito-borne viruses (MBVs) and parasites (MBPs) are transmitted through hematophagous arthropods-mosquitoes to homoiothermous vertebrates. This study aims at developing a detection method to monitor the spread of mosquito-borne diseases to new areas and diagnose the infections caused by MBVs and MBPs. In this assay, an ultra-sensitive chemiluminescence (CL) detection method was developed and used to simultaneously detect 19 common MBVs and MBPs. In vitro transcript RNA, virus-like particles (VLPs), and plasmids were established as positive or limit of detection (LOD) reference materials. MBVs and MBPs could be genotyped with high sensitivity and specificity. The cut-off values of probes were calculated. The absolute LODs of this strategy to detect serially diluted in vitro transcribed RNAs of MBVs and serially diluted plasmids of MBPs were 10 2 -10 3 copies/μl and 10 1 -10 2 copies/μl, respectively. Further, the LOD of detecting a strain of pre-quantified JEV was 10 1.8 -10 0.8 PFU/ml, fitted well in a linear regression model (coefficient of determination = 0.9678). Ultra-sensitive CL imaging DNA hybridization was developed and could simultaneously detect various MBVs and MBPs. The method described here has the potential to provide considerable labor savings due to its ability to screen for 19 mosquito-borne pathogens simultaneously.

  20. Sobol method application in dimensional sensitivity analyses of different AFM cantilevers for biological particles

    Science.gov (United States)

    Korayem, M. H.; Taheri, M.; Ghahnaviyeh, S. D.

    2015-08-01

    Due to the more delicate nature of biological micro/nanoparticles, it is necessary to compute the critical force of manipulation. The modeling and simulation of reactions and nanomanipulator dynamics in a precise manipulation process require an exact modeling of cantilevers stiffness, especially the stiffness of dagger cantilevers because the previous model is not useful for this investigation. The stiffness values for V-shaped cantilevers can be obtained through several methods. One of them is the PBA method. In another approach, the cantilever is divided into two sections: a triangular head section and two slanted rectangular beams. Then, deformations along different directions are computed and used to obtain the stiffness values in different directions. The stiffness formulations of dagger cantilever are needed for this sensitivity analyses so the formulations have been driven first and then sensitivity analyses has been started. In examining the stiffness of the dagger-shaped cantilever, the micro-beam has been divided into two triangular and rectangular sections and by computing the displacements along different directions and using the existing relations, the stiffness values for dagger cantilever have been obtained. In this paper, after investigating the stiffness of common types of cantilevers, Sobol sensitivity analyses of the effects of various geometric parameters on the stiffness of these types of cantilevers have been carried out. Also, the effects of different cantilevers on the dynamic behavior of nanoparticles have been studied and the dagger-shaped cantilever has been deemed more suitable for the manipulation of biological particles.

  1. 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.

  2. Testing of the derivative method and Kruskal-Wallis technique for sensitivity analysis of SYVAC

    International Nuclear Information System (INIS)

    Prust, J.O.; Edwards, H.H.

    1985-04-01

    The Kruskal-Wallis method of one-way analysis of variance by ranks has proved successful in identifying input parameters which have an important influence on dose. This technique was extended to test for first order interactions between parameters. In view of a number of practical difficulties and the computing resources required to carry out a large number of runs, this test is not recommended for detecting interactions between parameters. The derivative method of sensitivity analysis examines the partial derivative values of each input parameter with dose at various points across the parameter range. Important input parameters are associated with high derivatives and the results agreed well with previous sensitivity studies. The derivative values also provided information on the data generation distributions to be used for the input parameters in order to concentrate sampling in the high dose region of the parameter space to improve the sampling efficiency. Furthermore, the derivative values provided information on parameter interactions, the feasibility of developing a high dose algorithm and formed the basis for developing a regression equation. (author)

  3. Radiation sensitive area detection device and method

    Science.gov (United States)

    Carter, Daniel C. (Inventor); Hecht, Diana L. (Inventor); Witherow, William K. (Inventor)

    1991-01-01

    A radiation sensitive area detection device for use in conjunction with an X ray, ultraviolet or other radiation source is provided which comprises a phosphor containing film which releases a stored diffraction pattern image in response to incoming light or other electromagnetic wave. A light source such as a helium-neon laser, an optical fiber capable of directing light from the laser source onto the phosphor film and also capable of channelling the fluoresced light from the phosphor film to an integrating sphere which directs the light to a signal processing means including a light receiving means such as a photomultiplier tube. The signal processing means allows translation of the fluoresced light in order to detect the original pattern caused by the diffraction of the radiation by the original sample. The optical fiber is retained directly in front of the phosphor screen by a thin metal holder which moves up and down across the phosphor screen and which features a replaceable pinhole which allows easy adjustment of the resolution of the light projected onto the phosphor film. The device produces near real time images with high spatial resolution and without the distortion that accompanies prior art devices employing photomultiplier tubes. A method is also provided for carrying out radiation area detection using the device of the invention.

  4. Development of a Tandem Repeat-Based Polymerase Chain Displacement Reaction Method for Highly Sensitive Detection of 'Candidatus Liberibacter asiaticus'.

    Science.gov (United States)

    Lou, Binghai; Song, Yaqin; RoyChowdhury, Moytri; Deng, Chongling; Niu, Ying; Fan, Qijun; Tang, Yan; Zhou, Changyong

    2018-02-01

    Huanglongbing (HLB) is one of the most destructive diseases in citrus production worldwide. Early detection of HLB pathogens can facilitate timely removal of infected citrus trees in the field. However, low titer and uneven distribution of HLB pathogens in host plants make reliable detection challenging. Therefore, the development of effective detection methods with high sensitivity is imperative. This study reports the development of a novel method, tandem repeat-based polymerase chain displacement reaction (TR-PCDR), for the detection of 'Candidatus Liberibacter asiaticus', a widely distributed HLB-associated bacterium. A uniquely designed primer set (TR2-PCDR-F/TR2-PCDR-1R) and a thermostable Taq DNA polymerase mutant with strand displacement activity were used for TR-PCDR amplification. Performed in a regular thermal cycler, TR-PCDR could produce more than two amplicons after each amplification cycle. Sensitivity of the developed TR-PCDR was 10 copies of target DNA fragment. The sensitive level was proven to be 100× higher than conventional PCR and similar to real-time PCR. Data from the detection of 'Ca. L. asiaticus' with filed samples using the above three methods also showed similar results. No false-positive TR-PCDR amplification was observed from healthy citrus samples and water controls. These results thereby illustrated that the developed TR-PCDR method can be applied to the reliable, highly sensitive, and cost-effective detection of 'Ca. L. asiaticus'.

  5. Sensitivity improvement of an immuno-detection method for azaspiracids based on the use of microspheres coupled to a flow-fluorimetry system

    Directory of Open Access Journals (Sweden)

    María Fraga Corral

    2014-06-01

    These results demonstrate the high capability in terms of sensitivity of the microsphere-based immuno-detection assay for AZAs. The immobilization of AZA-1 instead of the synthetic AZA-2 used in Rodríguez et al (Rodriguez et al., 2014, combined with a lower mAb 8F4 concentration provided a remarkable improvement of sensitivity. The ON protocol used in Rodríguez et al. (Rodriguez et al., 2014 displayed a similar IC50 than the new short assay (around 1 nM while the new ON protocol provided an IC50 5-fold more sensitive (0.3 nM. Therefore, the new short assay allows a reduction of the experimental time. Additionally, the increase of sensitivity could help to avoid shellfish matrix interferences. Previously published works using immunoassays for the detection of phycotoxins present in shellfish avoided matrix interference by further extract dilution in combination with an increase of assay sensitivity (Fraga et al., 2012;Fraga et al., 2013. The extraction protocol described by Rodríguez et al. (Rodriguez et al., 2014 will probably be suitable for this newly optimized AZA-detection method since many reagents are the same and the higher sensitivity will allow higher extract dilution. Considering the extraction protocol recovery, sensitivity of the current assay and the regulated limit, shellfish extracts could be diluted up to 1:30 or 1:150 (v/v for detection with the short or long protocols, respectively. Additionally, mAb 8F4 was demonstrated to recognize AZA-2 and AZA-3 with cross-reactivities of 42 and 138 %, respectively. Presumably, this optimized assay will detect these analogs with similar cross-reactivity. The sensitivity of the microsphere-based assay for AZAs is enough to detect these compounds at the regulated levels in shellfish. This microsphere-based multi-detection method provides an easy-to-perform, highly sensitive and rapid method for the detection of AZAs. It could be included in a multi-detection method, which would allow time and sample volume

  6. Multisite-multivariable sensitivity analysis of distributed watershed models: enhancing the perceptions from computationally frugal methods

    Science.gov (United States)

    This paper assesses the impact of different likelihood functions in identifying sensitive parameters of the highly parameterized, spatially distributed Soil and Water Assessment Tool (SWAT) watershed model for multiple variables at multiple sites. The global one-factor-at-a-time (OAT) method of Morr...

  7. Efficient Estimation of Sensitivities for Counterparty Credit Risk with the Finite Difference Monte Carlo Method

    NARCIS (Netherlands)

    de Graaf, C.S.L.; Kandhai, D.; Sloot, P.M.A.

    According to Basel III, financial institutions have to charge a credit valuation adjustment (CVA) to account for a possible counterparty default. Calculating this measure and its sensitivities is one of the biggest challenges in risk management. Here, we introduce an efficient method for the

  8. 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.

  9. Vector method for strain estimation in phase-sensitive optical coherence elastography

    Science.gov (United States)

    Matveyev, A. L.; Matveev, L. A.; Sovetsky, A. A.; Gelikonov, G. V.; Moiseev, A. A.; Zaitsev, V. Y.

    2018-06-01

    A noise-tolerant approach to strain estimation in phase-sensitive optical coherence elastography, robust to decorrelation distortions, is discussed. The method is based on evaluation of interframe phase-variation gradient, but its main feature is that the phase is singled out at the very last step of the gradient estimation. All intermediate steps operate with complex-valued optical coherence tomography (OCT) signals represented as vectors in the complex plane (hence, we call this approach the ‘vector’ method). In comparison with such a popular method as least-square fitting of the phase-difference slope over a selected region (even in the improved variant with amplitude weighting for suppressing small-amplitude noisy pixels), the vector approach demonstrates superior tolerance to both additive noise in the receiving system and speckle-decorrelation caused by tissue straining. Another advantage of the vector approach is that it obviates the usual necessity of error-prone phase unwrapping. Here, special attention is paid to modifications of the vector method that make it especially suitable for processing deformations with significant lateral inhomogeneity, which often occur in real situations. The method’s advantages are demonstrated using both simulated and real OCT scans obtained during reshaping of a collagenous tissue sample irradiated by an IR laser beam producing complex spatially inhomogeneous deformations.

  10. Radiation-sensitive material and method of recording information upon radiation-sensitive material

    International Nuclear Information System (INIS)

    Petrov, V.V.; Krjuchin, A.A.

    1981-01-01

    The invention can be employed for recording binary information in memory units of electronic computers, in video-recording equipment, laser recording devices and other recording means. The proposed radiation-sensitive material comprises a metallic layer made of silver, or copper, or nickel, or thallium, or alloy thereof, an inorganic material layer made of arsenic chalcogenide, or antimony chalcogenide, or bismuth chalcogenide, and a separation layer disposed between the metallic layer and the inorganic material layer made of a material which is inert relative to said layers, which separation layer has a thickness sufficient for preventing interaction between the metallic layer and the inorganic material layer when the radiation-sensitive materials is exposed to electromagnetic or corpuscular radiation having a power density lower than a threshold value required for the breakdown of the separation layer in the area exposed to radiation. The separation layer can be made from As, Sb, Si or Ge or their oxides, metallic oxides of e.g. Al, Ti, V or Fe, or from polyorganosiloxane films. (author)

  11. Sensitivity and Interaction Analysis Based on Sobol’ Method and Its Application in a Distributed Flood Forecasting Model

    Directory of Open Access Journals (Sweden)

    Hui Wan

    2015-06-01

    Full Text Available Sensitivity analysis is a fundamental approach to identify the most significant and sensitive parameters, helping us to understand complex hydrological models, particularly for time-consuming distributed flood forecasting models based on complicated theory with numerous parameters. Based on Sobol’ method, this study compared the sensitivity and interactions of distributed flood forecasting model parameters with and without accounting for correlation. Four objective functions: (1 Nash–Sutcliffe efficiency (ENS; (2 water balance coefficient (WB; (3 peak discharge efficiency (EP; and (4 time to peak efficiency (ETP were implemented to the Liuxihe model with hourly rainfall-runoff data collected in the Nanhua Creek catchment, Pearl River, China. Contrastive results for the sensitivity and interaction analysis were also illustrated among small, medium, and large flood magnitudes. Results demonstrated that the choice of objective functions had no effect on the sensitivity classification, while it had great influence on the sensitivity ranking for both uncorrelated and correlated cases. The Liuxihe model behaved and responded uniquely to various flood conditions. The results also indicated that the pairwise parameters interactions revealed a non-ignorable contribution to the model output variance. Parameters with high first or total order sensitivity indices presented a corresponding high second order sensitivity indices and correlation coefficients with other parameters. Without considering parameter correlations, the variance contributions of highly sensitive parameters might be underestimated and those of normally sensitive parameters might be overestimated. This research laid a basic foundation to improve the understanding of complex model behavior.

  12. Chemical kinetic functional sensitivity analysis: Elementary sensitivities

    International Nuclear Information System (INIS)

    Demiralp, M.; Rabitz, H.

    1981-01-01

    Sensitivity analysis is considered for kinetics problems defined in the space--time domain. This extends an earlier temporal Green's function method to handle calculations of elementary functional sensitivities deltau/sub i//deltaα/sub j/ where u/sub i/ is the ith species concentration and α/sub j/ is the jth system parameter. The system parameters include rate constants, diffusion coefficients, initial conditions, boundary conditions, or any other well-defined variables in the kinetic equations. These parameters are generally considered to be functions of position and/or time. Derivation of the governing equations for the sensitivities and the Green's funciton are presented. The physical interpretation of the Green's function and sensitivities is given along with a discussion of the relation of this work to earlier research

  13. Preliminary Structural Sensitivity Study of Hypersonic Inflatable Aerodynamic Decelerator Using Probabilistic Methods

    Science.gov (United States)

    Lyle, Karen H.

    2014-01-01

    Acceptance of new spacecraft structural architectures and concepts requires validated design methods to minimize the expense involved with technology validation via flighttesting. This paper explores the implementation of probabilistic methods in the sensitivity analysis of the structural response of a Hypersonic Inflatable Aerodynamic Decelerator (HIAD). HIAD architectures are attractive for spacecraft deceleration because they are lightweight, store compactly, and utilize the atmosphere to decelerate a spacecraft during re-entry. However, designers are hesitant to include these inflatable approaches for large payloads or spacecraft because of the lack of flight validation. In the example presented here, the structural parameters of an existing HIAD model have been varied to illustrate the design approach utilizing uncertainty-based methods. Surrogate models have been used to reduce computational expense several orders of magnitude. The suitability of the design is based on assessing variation in the resulting cone angle. The acceptable cone angle variation would rely on the aerodynamic requirements.

  14. Developing cultural sensitivity

    DEFF Research Database (Denmark)

    Ruddock, Heidi; Turner, deSalle

    2007-01-01

    . Background. Many countries are becoming culturally diverse, but healthcare systems and nursing education often remain mono-cultural and focused on the norms and needs of the majority culture. To meet the needs of all members of multicultural societies, nurses need to develop cultural sensitivity......Title. Developing cultural sensitivity: nursing students’ experiences of a study abroad programme Aim. This paper is a report of a study to explore whether having an international learning experience as part of a nursing education programme promoted cultural sensitivity in nursing students...... and incorporate this into caregiving. Method. A Gadamerian hermeneutic phenomenological approach was adopted. Data were collected in 2004 by using in-depth conversational interviews and analysed using the Turner method. Findings. Developing cultural sensitivity involves a complex interplay between becoming...

  15. LSHSIM: A Locality Sensitive Hashing based method for multiple-point geostatistics

    Science.gov (United States)

    Moura, Pedro; Laber, Eduardo; Lopes, Hélio; Mesejo, Daniel; Pavanelli, Lucas; Jardim, João; Thiesen, Francisco; Pujol, Gabriel

    2017-10-01

    Reservoir modeling is a very important task that permits the representation of a geological region of interest, so as to generate a considerable number of possible scenarios. Since its inception, many methodologies have been proposed and, in the last two decades, multiple-point geostatistics (MPS) has been the dominant one. This methodology is strongly based on the concept of training image (TI) and the use of its characteristics, which are called patterns. In this paper, we propose a new MPS method that combines the application of a technique called Locality Sensitive Hashing (LSH), which permits to accelerate the search for patterns similar to a target one, with a Run-Length Encoding (RLE) compression technique that speeds up the calculation of the Hamming similarity. Experiments with both categorical and continuous images show that LSHSIM is computationally efficient and produce good quality realizations. In particular, for categorical data, the results suggest that LSHSIM is faster than MS-CCSIM, one of the state-of-the-art methods.

  16. Privacy Protection Method for Multiple Sensitive Attributes Based on Strong Rule

    Directory of Open Access Journals (Sweden)

    Tong Yi

    2015-01-01

    Full Text Available At present, most studies on data publishing only considered single sensitive attribute, and the works on multiple sensitive attributes are still few. And almost all the existing studies on multiple sensitive attributes had not taken the inherent relationship between sensitive attributes into account, so that adversary can use the background knowledge about this relationship to attack the privacy of users. This paper presents an attack model with the association rules between the sensitive attributes and, accordingly, presents a data publication for multiple sensitive attributes. Through proof and analysis, the new model can prevent adversary from using the background knowledge about association rules to attack privacy, and it is able to get high-quality released information. At last, this paper verifies the above conclusion with experiments.

  17. Biosensing strategies based on enzymatic reactions and nanoparticles.

    Science.gov (United States)

    Díez-Buitrago, Beatriz; Briz, Nerea; Liz-Marzán, Luis M; Pavlov, Valeri

    2018-04-16

    Enzymes are pivotal elements in bioanalysis due to their specificity and extremely high catalytic activity. The sensitivity of bioanalytical assays depends mainly on the capacity of an observer to detect the product(s) of a biocatalytic reaction. Both natural and artificial compounds have been traditionally used to evaluate enzymatic activities. The drawbacks of chromogenic and fluorogenic organic enzymatic substrates are their high cost and low stability, resulting in high background signals. We review here state of the art assays in the detection of enzymatic activities using recent advances in nanoscience. Novel methods based on the use of nanoparticles lead to increased sensitivity and decreased costs for bioanalysis based on enzymes as recognition elements and signal amplifiers in Enzyme-Linked Immunosorbent Assays (ELISA). Novel approaches toward the detection of enzymatic activities are based on biocatalytic synthesis, modulation, etching, and aggregation of nanoparticles under physiological conditions.

  18. A Sensitivity Analysis Method to Study the Behavior of Complex Process-based Models

    Science.gov (United States)

    Brugnach, M.; Neilson, R.; Bolte, J.

    2001-12-01

    The use of process-based models as a tool for scientific inquiry is becoming increasingly relevant in ecosystem studies. Process-based models are artificial constructs that simulate the system by mechanistically mimicking the functioning of its component processes. Structurally, a process-based model can be characterized, in terms of its processes and the relationships established among them. Each process comprises a set of functional relationships among several model components (e.g., state variables, parameters and input data). While not encoded explicitly, the dynamics of the model emerge from this set of components and interactions organized in terms of processes. It is the task of the modeler to guarantee that the dynamics generated are appropriate and semantically equivalent to the phenomena being modeled. Despite the availability of techniques to characterize and understand model behavior, they do not suffice to completely and easily understand how a complex process-based model operates. For example, sensitivity analysis studies model behavior by determining the rate of change in model output as parameters or input data are varied. One of the problems with this approach is that it considers the model as a "black box", and it focuses on explaining model behavior by analyzing the relationship input-output. Since, these models have a high degree of non-linearity, understanding how the input affects an output can be an extremely difficult task. Operationally, the application of this technique may constitute a challenging task because complex process-based models are generally characterized by a large parameter space. In order to overcome some of these difficulties, we propose a method of sensitivity analysis to be applicable to complex process-based models. This method focuses sensitivity analysis at the process level, and it aims to determine how sensitive the model output is to variations in the processes. Once the processes that exert the major influence in

  19. [Sensitivity analysis of AnnAGNPS model's hydrology and water quality parameters based on the perturbation analysis method].

    Science.gov (United States)

    Xi, Qing; Li, Zhao-Fu; Luo, Chuan

    2014-05-01

    Sensitivity analysis of hydrology and water quality parameters has a great significance for integrated model's construction and application. Based on AnnAGNPS model's mechanism, terrain, hydrology and meteorology, field management, soil and other four major categories of 31 parameters were selected for the sensitivity analysis in Zhongtian river watershed which is a typical small watershed of hilly region in the Taihu Lake, and then used the perturbation method to evaluate the sensitivity of the parameters to the model's simulation results. The results showed that: in the 11 terrain parameters, LS was sensitive to all the model results, RMN, RS and RVC were generally sensitive and less sensitive to the output of sediment but insensitive to the remaining results. For hydrometeorological parameters, CN was more sensitive to runoff and sediment and relatively sensitive for the rest results. In field management, fertilizer and vegetation parameters, CCC, CRM and RR were less sensitive to sediment and particulate pollutants, the six fertilizer parameters (FR, FD, FID, FOD, FIP, FOP) were particularly sensitive for nitrogen and phosphorus nutrients. For soil parameters, K is quite sensitive to all the results except the runoff, the four parameters of the soil's nitrogen and phosphorus ratio (SONR, SINR, SOPR, SIPR) were less sensitive to the corresponding results. The simulation and verification results of runoff in Zhongtian watershed show a good accuracy with the deviation less than 10% during 2005- 2010. Research results have a direct reference value on AnnAGNPS model's parameter selection and calibration adjustment. The runoff simulation results of the study area also proved that the sensitivity analysis was practicable to the parameter's adjustment and showed the adaptability to the hydrology simulation in the Taihu Lake basin's hilly region and provide reference for the model's promotion in China.

  20. Near-infrared dyes and upconverting phosphors as biomolecule labels and probes

    Science.gov (United States)

    Patonay, Gabor; Strekowski, Lucjan; Nguyen, Diem-Ngoc; Seok, Kim Jun

    2007-02-01

    Near-Infrared (NIR) absorbing chromophores have been used in analytical and bioanalytical chemistry extensively, including for determination of properties of biomolecules, DNA sequencing, immunoassays, capillary electrophoresis (CE) separations, etc. The major analytical advantages of these dyes are low background interference and high molar absorptivities. NIR dyes have additional advantages due to their sensitivity to microenvironmental changes. Spectral changes induced by the microenvironment are not desirable if the labels are used as a simple reporting group, e.g., during a biorecognition reaction. For these applications upconverting phosphors seem to be a better choice. There are several difficulties in utilizing upconverting phosphors as reporting labels. These are: large physical size, no reactive groups and insolubility in aqueous systems. This presentation will discuss how these difficulties can be overcome for bioanalytical and forensic applications. During these studies we also have investigated how to reduce physical size of the phosphor by simple grinding without losing activity and how to attach reactive moiety to the phosphor to covalently bind to the biomolecule of interest. It has to be emphasized that the described approach is not suitable for medical applications and the results of this research are not applicable in medical applications. For bioanalytical and forensic applications upconverting phosphors used as reporting labels have several advantages. They are excited with lasers that are red shifted respective to phosphorescence, resulting in no light scatter issues during detection. Also some phosphors are excited using eye safe lasers. In addition energy transfer to NIR dyes is possible, allowing detection schemes using donor-acceptor pairs. Data is presented to illustrate the feasibility of this phenomenon. If microenvironmental sensitivity is required, then specially designed NIR dyes can be used as acceptor labels. Several novel dyes

  1. Contrast sensitivity measured by two different test methods in healthy, young adults with normal visual acuity.

    Science.gov (United States)

    Koefoed, Vilhelm F; Baste, Valborg; Roumes, Corinne; Høvding, Gunnar

    2015-03-01

    This study reports contrast sensitivity (CS) reference values obtained by two different test methods in a strictly selected population of healthy, young adults with normal uncorrected visual acuity. Based on these results, the index of contrast sensitivity (ICS) is calculated, aiming to establish ICS reference values for this population and to evaluate the possible usefulness of ICS as a tool to compare the degree of agreement between different CS test methods. Military recruits with best eye uncorrected visual acuity 0.00 LogMAR or better, normal colour vision and age 18-25 years were included in a study to record contrast sensitivity using Optec 6500 (FACT) at spatial frequencies of 1.5, 3, 6, 12 and 18 cpd in photopic and mesopic light and CSV-1000E at spatial frequencies of 3, 6, 12 and 18 cpd in photopic light. Index of contrast sensitivity was calculated based on data from the three tests, and the Bland-Altman technique was used to analyse the agreement between ICS obtained by the different test methods. A total of 180 recruits were included. Contrast sensitivity frequency data for all tests were highly skewed with a marked ceiling effect for the photopic tests. The median ICS for Optec 6500 at 85 cd/m2 was -0.15 (95% percentile 0.45), compared with -0.00 (95% percentile 1.62) for Optec at 3 cd/m2 and 0.30 (95% percentile 1.20) FOR CSV-1000E. The mean difference between ICSFACT 85 and ICSCSV was -0.43 (95% CI -0.56 to -0.30, p<0.00) with limits of agreement (LoA) within -2.10 and 1.22. The regression line on the difference of average was near to zero (R2=0.03). The results provide reference CS and ICS values in a young, adult population with normal visual acuity. The agreement between the photopic tests indicated that they may be used interchangeably. There was little agreement between the mesopic and photopic tests. The mesopic test seemed best suited to differentiate between candidates and may therefore possibly be useful for medical selection purposes.

  2. 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 ...

  3. A TOUCH-SENSITIVE DEVICE

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to an optical touch-sensitive device and a method of determining a position and determining a position change of an object contacting an optical touch sensitive device. In particular, the present invention relates to an optical touch pad and a method of determining...... a position and determining a position change of an object contacting an optical touch pad. A touch-sensitive device, according to the present invention may comprise a light source, a touch- sensitive waveguide, a detector array, and a first light redirecting member, wherein at least a part of the light...... propagating towards a specific point of the detector array is prevented from being incident upon the specific point of the detector array when an object contacts a touch-sensitive surface of the touch-sensitive waveguide at a corresponding specific contact point....

  4. Sensitive method for the quantitative determination of bromocriptine in human plasma by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Salvador, Arnaud; Dubreuil, Didier; Denouel, Jannick; Millerioux, L

    2005-06-25

    A sensitive LC-MS-MS assay for the quantitative determination of bromocriptine has been developed and validated and is described in this work. The assay involved the extraction of the analyte from 1 ml of human plasma using a solid phase extraction on Oasis MCX cartridges. Chromatography was performed on a Symmetry C18 (2.1 mm x 100 mm, 3.5 microm) column using a mobile phase consisting of 25:75:01 acetonitrile-water-formic acid with a flow rate of 250 microl/min. The linearity was within the concentration range of 2-500 pg/ml. The lower limit of quantification was 2 pg/ml. This method has been demonstrated to be an improvement over existing methods due to its greater sensitivity and specificity.

  5. A laboratory measurement method for pressure sensitive adhesives in agglomeration deinking of mixed office waste paper: The high-low scanning contrast method

    OpenAIRE

    Guolin Tong; Shuang Sun; Cuixia Wang; Kecheng Fu; Yungchang F. Chin

    2012-01-01

    A simple measurement method for pressure sensitive adhesives (PSA) in an agglomeration deinking system of mixed office waste paper was studied. This method was based on the different scanning performance of ink and PSA specks in hot-pressed and oven-dried handsheets with the change of contrast values that had been selected and set in the image analysis software. The numbers of ink specks per square meter (NPM) were well recognized at both low and high contrast values and exhibited a very good...

  6. Comparative Method for Indirect Sensitivity Measurement of UHF RFID Reader with Respect to Interoperability and Conformance Requirements

    Directory of Open Access Journals (Sweden)

    Lukas Kypus

    2014-01-01

    Full Text Available There is never-ending race for the competitive advantage that forces RFID technology service integrators to focus more on used technology qualitative aspects and theirs impacts inside RFID ecosystem. This paper contributes to UHF RFID reader qualitative parameters evaluation and assessment problematic. It presents and describes in details indirect method and procedure of sensitivity measurement created for UHF RFID readers. We applied this method on RFID readers within prepared test environment and confirmed long term intention and recognized trend. Due to regulations limitations, there is not possible to increase output power over defined limits, but there are possibilities to influence reader sensitivity. Our proposal is to use customized comparative measurement method with insertion loss compensation for return link. Beside the main goal achievement, results show as well the qualitative status of development snapshot of reader. Method and following experiment helped us to gain an external view, current values of important parameters and motivation we want to follow up on as well as compared developed reader with its commercial competitors.

  7. SuBSENSE: a universal change detection method with local adaptive sensitivity.

    Science.gov (United States)

    St-Charles, Pierre-Luc; Bilodeau, Guillaume-Alexandre; Bergevin, Robert

    2015-01-01

    Foreground/background segmentation via change detection in video sequences is often used as a stepping stone in high-level analytics and applications. Despite the wide variety of methods that have been proposed for this problem, none has been able to fully address the complex nature of dynamic scenes in real surveillance tasks. In this paper, we present a universal pixel-level segmentation method that relies on spatiotemporal binary features as well as color information to detect changes. This allows camouflaged foreground objects to be detected more easily while most illumination variations are ignored. Besides, instead of using manually set, frame-wide constants to dictate model sensitivity and adaptation speed, we use pixel-level feedback loops to dynamically adjust our method's internal parameters without user intervention. These adjustments are based on the continuous monitoring of model fidelity and local segmentation noise levels. This new approach enables us to outperform all 32 previously tested state-of-the-art methods on the 2012 and 2014 versions of the ChangeDetection.net dataset in terms of overall F-Measure. The use of local binary image descriptors for pixel-level modeling also facilitates high-speed parallel implementations: our own version, which used no low-level or architecture-specific instruction, reached real-time processing speed on a midlevel desktop CPU. A complete C++ implementation based on OpenCV is available online.

  8. Hamiltonian Markov Chain Monte Carlo Methods for the CUORE Neutrinoless Double Beta Decay Sensitivity

    Science.gov (United States)

    Graham, Eleanor; Cuore Collaboration

    2017-09-01

    The CUORE experiment is a large-scale bolometric detector seeking to observe the never-before-seen process of neutrinoless double beta decay. Predictions for CUORE's sensitivity to neutrinoless double beta decay allow for an understanding of the half-life ranges that the detector can probe, and also to evaluate the relative importance of different detector parameters. Currently, CUORE uses a Bayesian analysis based in BAT, which uses Metropolis-Hastings Markov Chain Monte Carlo, for its sensitivity studies. My work evaluates the viability and potential improvements of switching the Bayesian analysis to Hamiltonian Monte Carlo, realized through the program Stan and its Morpho interface. I demonstrate that the BAT study can be successfully recreated in Stan, and perform a detailed comparison between the results and computation times of the two methods.

  9. In vitro bioassays for detecting dioxin-like activity--application potentials and limits of detection, a review.

    Science.gov (United States)

    Eichbaum, Kathrin; Brinkmann, Markus; Buchinger, Sebastian; Reifferscheid, Georg; Hecker, Markus; Giesy, John P; Engwall, Magnus; van Bavel, Bert; Hollert, Henner

    2014-07-15

    Use of in vitro assays as screening tool to characterize contamination of a variety of environmental matrices has become an increasingly popular and powerful toolbox in the field of environmental toxicology. While bioassays cannot entirely substitute analytical methods such as gas chromatography-mass spectrometry (GC-MS), the increasing improvement of cell lines and standardization of bioassay procedures enhance their utility as bioanalytical pre-screening tests prior to more targeted chemical analytical investigations. Dioxin-receptor-based assays provide a holistic characterization of exposure to dioxin-like compounds (DLCs) by integrating their overall toxic potential, including potentials of unknown DLCs not detectable via e.g. GC-MS. Hence, they provide important additional information with respect to environmental risk assessment of DLCs. This review summarizes different in vitro bioassay applications for detection of DLCs and considers the comparability of bioassay and chemical analytically derived toxicity equivalents (TEQs) of different approaches and various matrices. These range from complex samples such as sediments through single reference to compound mixtures. A summary of bioassay derived detection limits (LODs) showed a number of current bioassays to be equally sensitive as chemical methodologies, but moreover revealed that most of the bioanalytical studies conducted to date did not report their LODs, which represents a limitation with regard to low potency samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. 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...

  11. 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.

  12. Correlation of radiation sensitivity and nitrofurantoin sensitivity of Escherichia coli K-12

    International Nuclear Information System (INIS)

    Kloeck, K.

    1981-01-01

    The Uvr- and rec-mutants of E.coli K-12 have been tested with a view to their radiation- and nitrofuration sensitivity. The tests showed that all mutants tested were more radiation- and NF-sensitive than the wild type AB 1157. When the NF-sensitivity had been compared to the UV- and X-ray sensitivity it became obvious that the NF-sensitivity is correlated to the UV-sensitivity. Studies carried out with regard to the time dependence of the NF-effect on E.coli showed that the effect of NF on E. Coli became weaker after about 1 1/2 to 2 hours. That is possibly caused by the fact that the E. coli bacteria succeed in reducing the NF to an inactive form. By means of nitrosoguanidine mutants of E-coli AB 1157 had been induced and by means of the Replicite Plating Method, NF-sensible mutants had been isolated from the plutonium mixture. Among the mutants which had been isolated by this method, 74% had been more UV-sensitive than the wild type and 55% more X-ray sensitive. Thus NF-sensitive mutants have not necessarily to be considered as rec-mutants as there are also uvr-mutants in the mixture. (orig.) [de

  13. Determining the sensitivity of Data Envelopment Analysis method used in airport benchmarking

    Directory of Open Access Journals (Sweden)

    Mircea BOSCOIANU

    2013-03-01

    Full Text Available In the last decade there were some important changes in the airport industry, caused by the liberalization of the air transportation market. Until recently airports were considered infrastructure elements, and they were evaluated only by traffic values or their maximum capacity. Gradual orientation towards commercial led to the need of finding another ways of evaluation, more efficiency oriented. The existing methods for assessing efficiency used for other production units were not suitable to be used in case of airports due to specific features and high complexity of airport operations. In the last years there were some papers that proposed the Data Envelopment Analysis as a method for assessing the operational efficiency in order to conduct the benchmarking. This method offers the possibility of dealing with a large number of variables of different types, which represents the main advantage of this method and also recommends it as a good benchmarking tool for the airports management. This paper goal is to determine the sensitivity of this method in relation with its inputs and outputs. A Data Envelopment Analysis is conducted for 128 airports worldwide, in both input- and output-oriented measures, and the results are analysed against some inputs and outputs variations. Possible weaknesses of using DEA for assessing airports performance are revealed and analysed against this method advantages.

  14. Sensitive enumeration of Listeria monocytogenes and other Listeria species in various naturally contaminated matrices using a membrane filtration method.

    Science.gov (United States)

    Barre, Léna; Brasseur, Emilie; Doux, Camille; Lombard, Bertrand; Besse, Nathalie Gnanou

    2015-06-01

    For the enumeration of Listeria monocytogenes (L. monocytogenes) in food, a sensitive enumeration method has been recently developed. This method is based on a membrane filtration of the food suspension followed by transfer of the filter on a selective medium to enumerate L. monocytogenes. An evaluation of this method was performed with several categories of foods naturally contaminated with L. monocytogenes. The results obtained with this technique were compared with those obtained from the modified reference EN ISO 11290-2 method for the enumeration of L. monocytogenes in food, and are found to provide more precise results. In most cases, the filtration method enabled to examine a greater quantity of food thus greatly improving the sensitivity of the enumeration. However, it was hardly applicable to some food categories because of filtration problems and background microbiota interference. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. [Influence of Sex and Age on Contrast Sensitivity Subject to the Applied Method].

    Science.gov (United States)

    Darius, Sabine; Bergmann, Lisa; Blaschke, Saskia; Böckelmann, Irina

    2018-02-01

    The aim of the study was to detect gender and age differences in both photopic and mesopic contrast sensitivity with different methods in relation to German driver's license regulations (Fahrerlaubnisverordnung; FeV). We examined 134 healthy volunteers (53 men, 81 women) with an age between 18 and 76 years, that had been divided into two groups (AG I Mars charts under standardized illumination were applied for photopic contrast sensitivity. We could not find any gender differences. When evaluating age, there were no differences between the two groups for the Mars charts nor in the Rodatest. In all other tests, the younger volunteers achieved significantly better results. For contrast vision, there exists age-adapted cut-off-values. Concerning the driving safety of traffic participants, sufficient photopic and mesopic contrast vision should be focused on, independent of age. Therefore, there is a need to reconsider the age-adapted cut-off-values. Georg Thieme Verlag KG Stuttgart · New York.

  16. 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%.

  17. 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.

  18. Direct comparison of phase-sensitive vibrational sum frequency generation with maximum entropy method: case study of water.

    Science.gov (United States)

    de Beer, Alex G F; Samson, Jean-Sebastièn; Hua, Wei; Huang, Zishuai; Chen, Xiangke; Allen, Heather C; Roke, Sylvie

    2011-12-14

    We present a direct comparison of phase sensitive sum-frequency generation experiments with phase reconstruction obtained by the maximum entropy method. We show that both methods lead to the same complex spectrum. Furthermore, we discuss the strengths and weaknesses of each of these methods, analyzing possible sources of experimental and analytical errors. A simulation program for maximum entropy phase reconstruction is available at: http://lbp.epfl.ch/. © 2011 American Institute of Physics

  19. [The modified method registration of kinesthetic evoked potentials and its application for research of proprioceptive sensitivity disorders at spondylogenic cervical myelopathy].

    Science.gov (United States)

    Gordeev, S A; Voronin, S G

    2016-01-01

    To analyze the efficacy of modified (passive radiocarpal articulation flexion/extension) and «standard» (passive radiocarpal articulation flexion) methods of kinesthetic evoked potentials for proprioceptive sensitivity assessment in healthy subjects and patients with spondylotic cervical myelopathy. The study included 14 healthy subjects (4 women and 10 men, mean age 54.1±10.5 years) and 8 patients (2 women and 6 men, mean age 55.8±10.9 years) with spondylotic cervical myelopathy. Muscle-joint sensation was examined during the clinical study. A modified method of kinesthetic evoked potentials was developed. This method differed from the "standard" one by the organization of a cycle including several passive movements,where each new movement differed from the preceding one by the direction. The modified method of kinesthetic evoked potentials ensures more reliable kinesthetic sensitivity assessment due to movement variability. Asignificant increaseof the latent periods of the early components of the response was found in patients compared to healthy subjects. The modified method of kinesthetic evoked potentials can be used for objective diagnosis of proprioceptive sensitivity disorders in patients with spondylotic cervical myelopathy.

  20. A probabilistic method for species sensitivity distributions taking into account the inherent uncertainty and variability of effects to estimate environmental risk.

    Science.gov (United States)

    Gottschalk, Fadri; Nowack, Bernd

    2013-01-01

    This article presents a method of probabilistically computing species sensitivity distributions (SSD) that is well-suited to cope with distinct data scarcity and variability. First, a probability distribution that reflects the uncertainty and variability of sensitivity is modeled for each species considered. These single species sensitivity distributions are then combined to create an SSD for a particular ecosystem. A probabilistic estimation of the risk is carried out by combining the probability of critical environmental concentrations with the probability of organisms being impacted negatively by these concentrations. To evaluate the performance of the method, we developed SSD and risk calculations for the aquatic environment exposed to triclosan. The case studies showed that the probabilistic results reflect the empirical information well, and the method provides a valuable alternative or supplement to more traditional methods for calculating SSDs based on averaging raw data and/or on using theoretical distributional forms. A comparison and evaluation with single SSD values (5th-percentile [HC5]) revealed the robustness of the proposed method. Copyright © 2012 SETAC.

  1. 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.

  2. Method of shaping of direction-characterization of sensitivity of ionizing radiation detection probe

    International Nuclear Information System (INIS)

    Czarnecki, J.; Jaszczuk, J.; Kruczyk, M.; Slapa, M.; Wroblewski, T.

    1986-01-01

    A method of shaping of direction-characterization of sensitivity of the ionizing radiation detection probe, especially equipped with small gamma detectors is described. Two detectors are placed coaxially in the bases of the cylindrical shield. One of them is uncovered in the highest degree and the second is not covered to a maximum. The signals from them are processed on the standarized sequences of electrical impulses (taking into account the heights and the widths of the amplitude). 2 figs., 1 tab. (A.S.)

  3. Development of a new, rapid and sensitive HPTLC method for estimation of Milnacipran in bulk, formulation and compatibility study

    Directory of Open Access Journals (Sweden)

    Gautam Singhvi

    2017-05-01

    Full Text Available A simple, sensitive and rapid high performance thin layer chromatographic (HPTLC method has been developed and validated for quantitative determination of Milnacipran Hydrochloride (MIL in bulk and formulations. The chromatographic development was carried out on HPTLC plates precoated with silica gel 60 F254 using a mixture of acetonitrile, water and ammonia (6:0.6:1.6 (v/v/v as mobile phase. Detection was carried out densitometrically at 220 nm. The Rf value of drug was found to be 0.63 ± 0.02. The method was validated as per ICH guideline with respect to linearity, accuracy, precision, robustness etc. The calibration curve was found to be linear over a range of 100–1000 ng μL−1 with a regression coefficient of 0.999. The accuracy was found to be very high (99.12–100.87%. %RSD values for intra-day and inter-day variation were not more than 1.43. The method has demonstrated high sensitivity and specificity. The method was applied for compatibility studies also. The method is new, simple and economic for routine estimation of MIL in bulk, preformulation studies and pharmaceutical formulation to help the industries as well as researchers for their sensitive determination of MIL rapidly at low cost in routine analysis.

  4. [Improvement of sensitivity in the second generation HCV core antigen assay by a novel concentration method using polyethylene glycol (PEG)].

    Science.gov (United States)

    Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Syundou, Hiromi; Saito, Hidetsugu

    2007-11-01

    A HCV core antigen (Ag) detection assay system, Lumipulse Ortho HCV Ag has been developed and is commercially available in Japan with a lower detection level limit of 50 fmol/l, which is equivalent to 20 KIU/ml in PCR quantitative assay. HCV core Ag assay has an advantage of broader dynamic range compared with PCR assay, however the sensitivity is lower than PCR. We developed a novel HCV core Ag concentration method using polyethylene glycol (PEG), which can improve the sensitivity five times better than the original assay. The reproducibility was examined by consecutive five-time measurement of HCV patients serum, in which the results of HCV core Ag original and concentrated method were 56.8 +/- 8.1 fmol/l (mean +/- SD), CV 14.2% and 322.9 +/- 45.5 fmol/l CV 14.0%, respectively. The assay results of HCV negative samples in original HCV core Ag were all 0.1 fmol/l and the results were same even in the concentration method. The results of concentration method were 5.7 times higher than original assay, which was almost equal to theoretical rate as expected. The assay results of serially diluted samples were also as same as expected data in both original and concentration assay. We confirmed that the sensitivity of HCV core Ag concentration method had almost as same sensitivity as PCR high range assay in the competitive assay study using the serially monitored samples of five HCV patients during interferon therapy. A novel concentration method using PEG in HCV core Ag assay system seems to be useful for assessing and monitoring interferon treatment for HCV.

  5. Prediction of clamp-derived insulin sensitivity from the oral glucose insulin sensitivity index

    DEFF Research Database (Denmark)

    Tura, Andrea; Chemello, Gaetano; Szendroedi, Julia

    2018-01-01

    that underwent both a clamp and an OGTT or meal test, thereby allowing calculation of both the M value and OGIS. The population was divided into a training and a validation cohort (n = 359 and n = 154, respectively). After a stepwise selection approach, the best model for M value prediction was applied......AIMS/HYPOTHESIS: The euglycaemic-hyperinsulinaemic clamp is the gold-standard method for measuring insulin sensitivity, but is less suitable for large clinical trials. Thus, several indices have been developed for evaluating insulin sensitivity from the oral glucose tolerance test (OGTT). However......, most of them yield values different from those obtained by the clamp method. The aim of this study was to develop a new index to predict clamp-derived insulin sensitivity (M value) from the OGTT-derived oral glucose insulin sensitivity index (OGIS). METHODS: We analysed datasets of people...

  6. Variation of strain rate sensitivity index of a superplastic aluminum alloy in different testing methods

    Science.gov (United States)

    Majidi, Omid; Jahazi, Mohammad; Bombardier, Nicolas; Samuel, Ehab

    2017-10-01

    The strain rate sensitivity index, m-value, is being applied as a common tool to evaluate the impact of the strain rate on the viscoplastic behaviour of materials. The m-value, as a constant number, has been frequently taken into consideration for modeling material behaviour in the numerical simulation of superplastic forming processes. However, the impact of the testing variables on the measured m-values has not been investigated comprehensively. In this study, the m-value for a superplastic grade of an aluminum alloy (i.e., AA5083) has been investigated. The conditions and the parameters that influence the strain rate sensitivity for the material are compared with three different testing methods, i.e., monotonic uniaxial tension test, strain rate jump test and stress relaxation test. All tests were conducted at elevated temperature (470°C) and at strain rates up to 0.1 s-1. The results show that the m-value is not constant and is highly dependent on the applied strain rate, strain level and testing method.

  7. Sensitivity study with respect to direction of ADI method during re-flooding in AHWR

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, M.; Mukhopadhyay, D. [Bhabha Atomic Research Centre, Mumbai (India). Reactor Safety Div.; Ghosh, A.K. [Bhabha Atomic Research Centre, Mumbai (India). Raja Ramanna Fellow; Kumar, R. [Indian Institute of Technology, Roorkee (India)

    2015-05-15

    The Advanced Heavy water Reactor (AHWR) is a natural circulation vertical pressure tube type boiling light water cooled and heavy water moderated reactor. As the AHWR fuel bundle quenching under accident condition is designed primarily with radial jets at several axial locations, bottom re-flooding still remain open as another option. Radial direction injection of emergency core cooling leads to rewetting of AHWR fuel cluster in circumferential direction. A 3D fuel pin model has been developed by using Finite Difference Method (FDM) of transient heat conduction equation. Alternating Direction Implicit technique of Finite Difference Method (FDM) has been used for discretisation of numerical equation in different time step at different direction. Sensitivity numerical study with respect to direction of ADI method has been carried out to optimize the time step during the transient as well as steady state and is found that it is insensitivity with direction of solution. Further, to assess influence of circumferential rewetting vis-a-vis axial rewetting. Both the analyses are carried out with same fluid temperature and heat transfer coefficients as boundary conditions. It has been found from the analyses that for radial jet, the circumferential conduction is significant and overall the fuel temperature falls in the quench plane with the initiation of quenching event. The paper discusses the sensitivity study with respect to direction of ADI solution and comparison of numerical results for circumferential and axial rewetting for single pin.

  8. 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.

  9. Risk Assessment Method for Offshore Structure Based on Global Sensitivity Analysis

    Directory of Open Access Journals (Sweden)

    Zou Tao

    2012-01-01

    Full Text Available Based on global sensitivity analysis (GSA, this paper proposes a new risk assessment method for an offshore structure design. This method quantifies all the significances among random variables and their parameters at first. And by comparing the degree of importance, all minor factors would be negligible. Then, the global uncertainty analysis work would be simplified. Global uncertainty analysis (GUA is an effective way to study the complexity and randomness of natural events. Since field measured data and statistical results often have inevitable errors and uncertainties which lead to inaccurate prediction and analysis, the risk in the design stage of offshore structures caused by uncertainties in environmental loads, sea level, and marine corrosion must be taken into account. In this paper, the multivariate compound extreme value distribution model (MCEVD is applied to predict the extreme sea state of wave, current, and wind. The maximum structural stress and deformation of a Jacket platform are analyzed and compared with different design standards. The calculation result sufficiently demonstrates the new risk assessment method’s rationality and security.

  10. Fast and sensitive method for detecting volatile species in liquids

    Science.gov (United States)

    Trimarco, Daniel B.; Pedersen, Thomas; Hansen, Ole; Chorkendorff, Ib; Vesborg, Peter C. K.

    2015-07-01

    This paper presents a novel apparatus for extracting volatile species from liquids using a "sniffer-chip." By ultrafast transfer of the volatile species through a perforated and hydrophobic membrane into an inert carrier gas stream, the sniffer-chip is able to transport the species directly to a mass spectrometer through a narrow capillary without the use of differential pumping. This method inherits features from differential electrochemical mass spectrometry (DEMS) and membrane inlet mass spectrometry (MIMS), but brings the best of both worlds, i.e., the fast time-response of a DEMS system and the high sensitivity of a MIMS system. In this paper, the concept of the sniffer-chip is thoroughly explained and it is shown how it can be used to quantify hydrogen and oxygen evolution on a polycrystalline platinum thin film in situ at absolute faradaic currents down to ˜30 nA. To benchmark the capabilities of this method, a CO-stripping experiment is performed on a polycrystalline platinum thin film, illustrating how the sniffer-chip system is capable of making a quantitative in situ measurement of <1 % of a monolayer of surface adsorbed CO being electrochemically stripped off an electrode at a potential scan-rate of 50 mV s-1.

  11. 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.

  12. High Temperature and High Sensitive NOx Gas Sensor with Hetero-Junction Structure using Laser Ablation Method

    Science.gov (United States)

    Gao, Wei; Shi, Liqin; Hasegawa, Yuki; Katsube, Teruaki

    In order to develop a high temperature (200°C˜400°C) and high sensitive NOx gas sensor, we developed a new structure of SiC-based hetero-junction device Pt/SnO2/SiC/Ni, Pt/In2O3/SiC/Ni and Pt/WO3/SiC/Ni using a laser ablation method for the preparation of both metal (Pt) electrode and metal-oxide film. It was found that Pt/In2O3/SiC/Ni sensor shows higher sensitivity to NO2 gas compared with the Pt/SnO2/SiC/Ni and Pt/WO3/SiC/Ni sensor, whereas the Pt/WO3/SiC/Ni sensor had better sensitivity to NO gas. These results suggest that selective detection of NO and NO2 gases may be obtained by choosing different metal oxide films.

  13. Progress in the development of phase-sensitive neutron reflectometry methods

    International Nuclear Information System (INIS)

    Majkrzak, C.F.; Berk, N.F.; Kienzle, P.; Perez-Salas, U.

    2009-01-01

    It has been a number of years since phase-sensitive specular neutron reflectometry (PSNR) methods employing reference layers were first introduced to help remove the ambiguity inherent in the reconstruction of scattering length density (SLD) depth profiles (Majkrzak, C. F.; Berk, N. F. Physica B 2003, 336, 27) from specular reflectivity measurements. Although a number of scientific applications of PSNR techniques have now been successfully realized (Majkrzak, C. F.; Berk, N. F.; Perez-Salas, U. A. Langmuir 2003, 19, 7796 and references therein), in certain cases practical difficulties remain. In this article, we describe possible solutions to two specific problems: (1) the need for explicit, detailed knowledge of the SLD profile of a given reference layer of finite thickness; and (2) for a reference layer of finite thickness in which only two density variations are possible, how to identify which of two mathematical solutions corresponds to the true physical structure.

  14. Progress in the development of phase-sensitive neutron reflectometry methods.

    Energy Technology Data Exchange (ETDEWEB)

    Majkrzak, C. F.; Berk, N. F.; Kienzle, P.; Perez-Salas, U. (Materials Science Division); (NIST Center for Neutron Research)

    2009-01-01

    It has been a number of years since phase-sensitive specular neutron reflectometry (PSNR) methods employing reference layers were first introduced to help remove the ambiguity inherent in the reconstruction of scattering length density (SLD) depth profiles (Majkrzak, C. F.; Berk, N. F. Physica B 2003, 336, 27) from specular reflectivity measurements. Although a number of scientific applications of PSNR techniques have now been successfully realized (Majkrzak, C. F.; Berk, N. F.; Perez-Salas, U. A. Langmuir 2003, 19, 7796 and references therein), in certain cases practical difficulties remain. In this article, we describe possible solutions to two specific problems: (1) the need for explicit, detailed knowledge of the SLD profile of a given reference layer of finite thickness; and (2) for a reference layer of finite thickness in which only two density variations are possible, how to identify which of two mathematical solutions corresponds to the true physical structure.

  15. Sensitive method for the analysis of carbohydrates by gas chromatography of 3H-labeled alditol acetates

    International Nuclear Information System (INIS)

    Prehm, P.; Scheid, A.

    1978-01-01

    A highly sensitive method has been developed for the analysis of carbohydrates from glycoproteins or lipopolysaccharides. The method is based on labeling the carbohydrates with [ 3 H] sodium borohydride, acetylating the resulting alditols and separating them by gas chromatography. The gas effluent is fractionated by trapping on silicone-coated glass beads and the amount of radioactivity is determined. This permits the quantitation of as little as 0.2 nmoles monosaccharide with an accuracy of 10 to 15%. (Auth)

  16. Sensitivity analysis of a coupled hydrodynamic-vegetation model using the effectively subsampled quadratures method (ESQM v5.2)

    Science.gov (United States)

    Kalra, Tarandeep S.; Aretxabaleta, Alfredo; Seshadri, Pranay; Ganju, Neil K.; Beudin, Alexis

    2017-12-01

    Coastal hydrodynamics can be greatly affected by the presence of submerged aquatic vegetation. The effect of vegetation has been incorporated into the Coupled Ocean-Atmosphere-Wave-Sediment Transport (COAWST) modeling system. The vegetation implementation includes the plant-induced three-dimensional drag, in-canopy wave-induced streaming, and the production of turbulent kinetic energy by the presence of vegetation. In this study, we evaluate the sensitivity of the flow and wave dynamics to vegetation parameters using Sobol' indices and a least squares polynomial approach referred to as the Effective Quadratures method. This method reduces the number of simulations needed for evaluating Sobol' indices and provides a robust, practical, and efficient approach for the parameter sensitivity analysis. The evaluation of Sobol' indices shows that kinetic energy, turbulent kinetic energy, and water level changes are affected by plant stem density, height, and, to a lesser degree, diameter. Wave dissipation is mostly dependent on the variation in plant stem density. Performing sensitivity analyses for the vegetation module in COAWST provides guidance to optimize efforts and reduce exploration of parameter space for future observational and modeling work.

  17. Global and Local Sensitivity Analysis Methods for a Physical System

    Science.gov (United States)

    Morio, Jerome

    2011-01-01

    Sensitivity analysis is the study of how the different input variations of a mathematical model influence the variability of its output. In this paper, we review the principle of global and local sensitivity analyses of a complex black-box system. A simulated case of application is given at the end of this paper to compare both approaches.…

  18. Highly sensitive electrochemical detection of human telomerase activity based on bio-barcode method.

    Science.gov (United States)

    Li, Ying; Liu, Bangwei; Li, Xia; Wei, Qingli

    2010-07-15

    In the present study, an electrochemical method for highly sensitive detection of human telomerase activity was developed based on bio-barcode amplification assay. Telomerase was extracted from HeLa cells, then the extract was mixed with telomerase substrate (TS) primer to perform extension reaction. The extension product was hybridized with the capture DNA immobilized on the Au electrode and then reacted with the signal DNA on Au nanoparticles to form a sandwich hybridization mode. Electrochemical signals were generated by chronocoulometric interrogation of [Ru(NH(3))(6)](3+) that quantitatively binds to the DNA on Au nanoparticles via electrostatic interaction. This method can detect the telomerase activity from as little as 10 cultured cancer cells without the polymerase chain reaction (PCR) amplification of telomerase extension product. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  19. Photoelectrochemical enzymatic biosensors.

    Science.gov (United States)

    Zhao, Wei-Wei; Xu, Jing-Juan; Chen, Hong-Yuan

    2017-06-15

    Enzymatic biosensors have been valuable bioanalytical devices for analysis of diverse targets in disease diagnosis, biological and biomedical research, etc. Photoelectrochemical (PEC) bioanalysis is a recently emerged method that promptly becoming a subject of new research interests due to its attractive potential for future bioanalysis with high sensitivity and specificity. PEC enzymatic biosensors integrate the inherent sensitivities of PEC bioanalysis and the selectivity of enzymes and thus share their both advantages. Currently, PEC enzymatic biosensors have become a hot topic of significant research and the recent impetus has grown rapidly as demonstrated by increased research papers. Given the pace of advances in this area, this review will make a thorough discussion and survey on the fundamentals, sensing strategies, applications and the state of the art in PEC enzymatic biosensors, followed by future prospects based on our own opinions. We hope this work could provide an accessible introduction to PEC enzymatic biosensors for any scientist. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. New sensitive high-performance liquid chromatography-tandem mass spectrometry method for the detection of horse and pork in halal beef.

    Science.gov (United States)

    von Bargen, Christoph; Dojahn, Jörg; Waidelich, Dietmar; Humpf, Hans-Ulrich; Brockmeyer, Jens

    2013-12-11

    The accidental or fraudulent blending of meat from different species is a highly relevant aspect for food product quality control, especially for consumers with ethical concerns against species, such as horse or pork. In this study, we present a sensitive mass spectrometrical approach for the detection of trace contaminations of horse meat and pork and demonstrate the specificity of the identified biomarker peptides against chicken, lamb, and beef. Biomarker peptides were identified by a shotgun proteomic approach using tryptic digests of protein extracts and were verified by the analysis of 21 different meat samples from the 5 species included in this study. For the most sensitive peptides, a multiple reaction monitoring (MRM) method was developed that allows for the detection of 0.55% horse or pork in a beef matrix. To enhance sensitivity, we applied MRM(3) experiments and were able to detect down to 0.13% pork contamination in beef. To the best of our knowledge, we present here the first rapid and sensitive mass spectrometrical method for the detection of horse and pork by use of MRM and MRM(3).

  1. Calibration of the pressure sensitivity of microphones by a free-field method at frequencies up to 80 khz.

    Science.gov (United States)

    Zuckerwar, Allan J; Herring, G C; Elbing, Brian R

    2006-01-01

    A free-field (FF) substitution method for calibrating the pressure sensitivity of microphones at frequencies up to 80 kHz is demonstrated with both grazing and normal-incidence geometries. The substitution-based method, as opposed to a simultaneous method, avoids problems associated with the nonuniformity of the sound field and, as applied here, uses a 1/4-in. air-condenser pressure microphone as a known reference. Best results were obtained with a centrifugal fan, which is used as a random, broadband sound source. A broadband source minimizes reflection-related interferences that can plague FF measurements. Calibrations were performed on 1/4-in. FF air-condenser, electret, and microelectromechanical systems (MEMS) microphones in an anechoic chamber. The uncertainty of this FF method is estimated by comparing the pressure sensitivity of an air-condenser FF microphone, as derived from the FF measurement, with that of an electrostatic actuator calibration. The root-mean-square difference is found to be +/- 0.3 dB over the range 1-80 kHz, and the combined standard uncertainty of the FF method, including other significant contributions, is +/- 0.41 dB.

  2. High-Sensitivity Spectrophotometry.

    Science.gov (United States)

    Harris, T. D.

    1982-01-01

    Selected high-sensitivity spectrophotometric methods are examined, and comparisons are made of their relative strengths and weaknesses and the circumstances for which each can best be applied. Methods include long path cells, noise reduction, laser intracavity absorption, thermocouple calorimetry, photoacoustic methods, and thermo-optical methods.…

  3. The sensitivity of clinical diagnostic methods in the diagnosis of diabetic neuropathy.

    Science.gov (United States)

    Onde, M E; Ozge, A; Senol, M G; Togrol, E; Ozdag, F; Saracoglu, M; Misirli, H

    2008-01-01

    This study assessed the sensitivity of various methods for the clinical diagnosis of diabetic peripheral neuropathy. A total of 147 randomly selected patients with diabetes mellitus and 65 age- and sex-matched healthy controls were evaluated by various clinical (the neuropathy symptom score [NSS], the neuropathy disability score [NDS], vibration perception thresholds [VPTs], Tinel's sign and Phalen's sign), laboratory (fasting plasma glucose and glycosylated haemoglobin levels) and electro-physiological (nerve conduction studies, H-reflex and F-wave measurements) methods. In the patient group, 8.2% had an abnormal NSS, 28.5% had a positive Phalen's sign, 32.6% had a positive Tinel's sign, 42.8% had an abnormal VPT and 57.1% had an abnormal NDS. Significant correlations were found between electro-physiologically confirmed neuropathy and the two provocation tests and abnormal VPTs. In conclusion, assessment with a complete neurological examination and standard electrophysiological tests is very important for the diagnosis of diabetic peripheral neuropathy and the prevention of morbidity in patients with or without symptoms.

  4. 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

  5. A Method for Rapid Measurement of Contrast Sensitivity on Mobile Touch-Screens

    Science.gov (United States)

    Mulligan, Jeffrey B.

    2016-01-01

    Touch-screen displays in cell phones and tablet computers are now pervasive, making them an attractive option for vision testing outside of the laboratory or clinic. Here we de- scribe a novel method in which subjects use a finger swipe to indicate the transition from visible to invisible on a grating which is swept in both contrast and frequency. Because a single image can be swiped in about a second, it is practical to use a series of images to zoom in on particular ranges of contrast or frequency, both to increase the accuracy of the measurements and to obtain an estimate of the reliability of the subject. Sensitivities to chromatic and spatio-temporal modulations are easily measured using the same method. A proto- type has been developed for Apple Computer's iPad/iPod/iPhone family of devices, implemented using an open-source scripting environment known as QuIP (QUick Image Processing, http://hsi.arc.nasa.gov/groups/scanpath/research.php). Preliminary data show good agreement with estimates obtained from traditional psychophysical methods as well as newer rapid estimation techniques. Issues relating to device calibration are also discussed.

  6. A non-contact, thermal noise based method for the calibration of lateral deflection sensitivity in atomic force microscopy

    International Nuclear Information System (INIS)

    Mullin, Nic; Hobbs, Jamie K.

    2014-01-01

    Calibration of lateral forces and displacements has been a long standing problem in lateral force microscopies. Recently, it was shown by Wagner et al. that the thermal noise spectrum of the first torsional mode may be used to calibrate the deflection sensitivity of the detector. This method is quick, non-destructive and may be performed in situ in air or liquid. Here we make a full quantitative comparison of the lateral inverse optical lever sensitivity obtained by the lateral thermal noise method and the shape independent method developed by Anderson et al. We find that the thermal method provides accurate results for a wide variety of rectangular cantilevers, provided that the geometry of the cantilever is suitable for torsional stiffness calibration by the torsional Sader method, in-plane bending of the cantilever may be eliminated or accounted for and that any scaling of the lateral deflection signal between the measurement of the lateral thermal noise and the measurement of the lateral deflection is eliminated or corrected for. We also demonstrate that the thermal method may be used to characterize the linearity of the detector signal as a function of position, and find a deviation of less than 8% for the instrument used

  7. Sensitivity analysis and comparison of two methods of using heart rate to represent energy expenditure during walking.

    Science.gov (United States)

    Karimi, Mohammad Taghi

    2015-01-01

    Heart rate is an accurate and easy to use method to represent the energy expenditure during walking, based on physiological cost index (PCI). However, in some conditions the heart rate during walking does not reach to a steady state. Therefore, it is not possible to determine the energy expenditure by use of the PCI index. The total heart beat index (THBI) is a new method to solve the aforementioned problem. The aim of this research project was to find the sensitivity of both the physiological cost index (PCI) and total heart beat index (THBI). Fifteen normal subjects and ten patients with flatfoot disorder and two subjects with spinal cord injury were recruited in this research project. The PCI and THBI indexes were determined by use of heart beats with respect to walking speed and total distance walked, respectively. The sensitivity of PCI was more than that of THBI index in the three groups of subjects. Although the PCI and THBI indexes are easy to use and reliable parameters to represent the energy expenditure during walking, their sensitivity is not high to detect the influence of some orthotic interventions, such as use of insoles or using shoes on energy expenditure during walking.

  8. 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

  9. The use of carbon black-TiO2 composite prepared using solid state method as counter electrode and E. conferta as sensitizer for dye-sensitized solar cell (DSSC) applications

    Science.gov (United States)

    Jaafar, Hidayani; Ahmad, Zainal Arifin; Ain, Mohd Fadzil

    2018-05-01

    In this paper, counter electrodes based on carbon black (CB)-TiO2 composite are proposed as a cost-effective alternative to conventional Pt counter electrodes used in dye-sensitized solar cell (DSSC) applications. CB-TiO2 composite counter electrodes with different weight percentages of CB were prepared using the solid state method and coated onto fluorine-doped tin oxide (FTO) glass using doctor blade method while Eleiodoxa conferta (E. conferta) and Nb-doped TiO2 were used as sensitizer and photoanode, respectively, with electrolyte containing I-/I-3 redox couple. The experimental results revealed that the CB-TiO2 composite influenced the photovoltaic performance by enhancing the electrocatalytic activity. As the amount of CB increased, the catalytic activity improved due to the increase in surface area which then led to low charge-transfer resistance (RCT) at the electrolyte/CB electrode interface. Due to the use of the modified photoanode together with natural dye sensitizers, the counter electrode based on 15 wt% CB-TiO2 composite was able to produce the highest energy conversion efficiency (2.5%) making it a viable alternative counter electrode.

  10. The pointillism method for creating stimuli suitable for use in computer-based visual contrast sensitivity testing.

    Science.gov (United States)

    Turner, Travis H

    2005-03-30

    An increasingly large corpus of clinical and experimental neuropsychological research has demonstrated the utility of measuring visual contrast sensitivity. Unfortunately, existing means of measuring contrast sensitivity can be prohibitively expensive, difficult to standardize, or lack reliability. Additionally, most existing tests do not allow full control over important characteristics, such as off-angle rotations, waveform, contrast, and spatial frequency. Ideally, researchers could manipulate characteristics and display stimuli in a computerized task designed to meet experimental needs. Thus far, 256-bit color limitation in standard cathode ray tube (CRT) monitors has been preclusive. To this end, the pointillism method (PM) was developed. Using MATLAB software, stimuli are created based on both mathematical and stochastic components, such that differences in regional luminance values of the gradient field closely approximate the desired contrast. This paper describes the method and examines its performance in sine and square-wave image sets from a range of contrast values. Results suggest the utility of the method for most experimental applications. Weaknesses in the current version, the need for validation and reliability studies, and considerations regarding applications are discussed. Syntax for the program is provided in an appendix, and a version of the program independent of MATLAB is available from the author.

  11. Uncertainty and sensitivity assessments of an agricultural-hydrological model (RZWQM2) using the GLUE method

    Science.gov (United States)

    Sun, Mei; Zhang, Xiaolin; Huo, Zailin; Feng, Shaoyuan; Huang, Guanhua; Mao, Xiaomin

    2016-03-01

    Quantitatively ascertaining and analyzing the effects of model uncertainty on model reliability is a focal point for agricultural-hydrological models due to more uncertainties of inputs and processes. In this study, the generalized likelihood uncertainty estimation (GLUE) method with Latin hypercube sampling (LHS) was used to evaluate the uncertainty of the RZWQM-DSSAT (RZWQM2) model outputs responses and the sensitivity of 25 parameters related to soil properties, nutrient transport and crop genetics. To avoid the one-sided risk of model prediction caused by using a single calibration criterion, the combined likelihood (CL) function integrated information concerning water, nitrogen, and crop production was introduced in GLUE analysis for the predictions of the following four model output responses: the total amount of water content (T-SWC) and the nitrate nitrogen (T-NIT) within the 1-m soil profile, the seed yields of waxy maize (Y-Maize) and winter wheat (Y-Wheat). In the process of evaluating RZWQM2, measurements and meteorological data were obtained from a field experiment that involved a winter wheat and waxy maize crop rotation system conducted from 2003 to 2004 in southern Beijing. The calibration and validation results indicated that RZWQM2 model can be used to simulate the crop growth and water-nitrogen migration and transformation in wheat-maize crop rotation planting system. The results of uncertainty analysis using of GLUE method showed T-NIT was sensitive to parameters relative to nitrification coefficient, maize growth characteristics on seedling period, wheat vernalization period, and wheat photoperiod. Parameters on soil saturated hydraulic conductivity, nitrogen nitrification and denitrification, and urea hydrolysis played an important role in crop yield component. The prediction errors for RZWQM2 outputs with CL function were relatively lower and uniform compared with other likelihood functions composed of individual calibration criterion. This

  12. A high-sensitive and quantitative in-line monitoring method for transplutonium elements separation processes

    International Nuclear Information System (INIS)

    Zhu Rongbao; Wang Shiju; Xu Yingpu; Zhang Zengrui

    1986-04-01

    A high-sensitive monitoring device and a quantitative analys technigue for transplutonium elements separation processes are described. X-ray and low energy γ-ray are measured by means of a scintillation monitor with two NaI(Tl) thin crystals. The α spectra of the fluents of ion-exchange column is measured by means of Si(Au) surface barrier in-line monitor. The construction of the monitors, auxiliary electronics, investigation result for the α spectra character of thick source and the calibration method were described. The determination results for extracting process of 243 Am and 244 Cm by ion-exchange chromatography were given. The sensitivity of total adding amount for 243 Am using the 4π scintillation monitor is better than 0.1 μCi. The precision of 243 Am and 244 Cm concentration determination using Si(Au) monitor is +- 5%. The precision of the two metals contents in containers is about +- 10%

  13. 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.

  14. Sensitive silicon PIN-diode dosimeter for fast neutrons and method to control and increase its sensitivity

    International Nuclear Information System (INIS)

    Swinehart, P.R.; Swartz, J.M.

    1978-01-01

    With the personnel dosimeter, applicable e.g. in medicine, a dose of 0.1 rad for neutrons with an energy greater than 10 keV can be detected. In the range between 0.1 and 20 rad sensitivity is increased to 5 mV/rad. This sensitivity can be achieved by distributing the mass of the semiconductor material of the diode or equal to four times the reciprocal base width. Appropriate dimensions are 750 μm for the edge length of the end surface resp. diameter and 750 μm up to 5000 μm for the base width. (DG) [de

  15. Radiation-sensitive compounds and methods of using same

    International Nuclear Information System (INIS)

    DeMajistre, R.

    1977-01-01

    Novel diacrylates are prepared by reacting a monohydroxylated acrylic monomer with a polyisocyanate. The reaction product may be polymerized by subjecting to ionizing irradiation, actinic light or to free radical catalysis to form a useful coating material. The diacrylates may also be copolymerized with other radiation sensitive materials

  16. Sensitivity analysis of a coupled hydrodynamic-vegetation model using the effectively subsampled quadratures method (ESQM v5.2

    Directory of Open Access Journals (Sweden)

    T. S. Kalra

    2017-12-01

    Full Text Available Coastal hydrodynamics can be greatly affected by the presence of submerged aquatic vegetation. The effect of vegetation has been incorporated into the Coupled Ocean–Atmosphere–Wave–Sediment Transport (COAWST modeling system. The vegetation implementation includes the plant-induced three-dimensional drag, in-canopy wave-induced streaming, and the production of turbulent kinetic energy by the presence of vegetation. In this study, we evaluate the sensitivity of the flow and wave dynamics to vegetation parameters using Sobol' indices and a least squares polynomial approach referred to as the Effective Quadratures method. This method reduces the number of simulations needed for evaluating Sobol' indices and provides a robust, practical, and efficient approach for the parameter sensitivity analysis. The evaluation of Sobol' indices shows that kinetic energy, turbulent kinetic energy, and water level changes are affected by plant stem density, height, and, to a lesser degree, diameter. Wave dissipation is mostly dependent on the variation in plant stem density. Performing sensitivity analyses for the vegetation module in COAWST provides guidance to optimize efforts and reduce exploration of parameter space for future observational and modeling work.

  17. Simultaneous determination of zolazepam and tiletamine in dog plasma by liquid chromatography coupled to a tandem mass spectrometry.

    Science.gov (United States)

    Noh, Kyeumhan; Kim, Kil-Soo; Ahn, Byoungki; Archimbault, Pillippe; Oh, Tae-Ho; Kang, Wonku

    2012-10-01

    A mixture of tiletamine, a dissociative anesthetic, and zolazepam, a minor tranquilizer, has been widely used as an anesthetic or an immobilizing agent in a variety of animal species. However, interestingly, their pharmacokinetic behaviors have been published only in polar bears and pigs. In this study, we introduce a sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for determining the two drugs in dog plasma. After simple protein precipitation with acetonitrile including midazolam (internal standard), the analytes were chromatographed on a reversed-phase column with a mobile phase of 10 m m ammonium acetate aqueous solution and acetonitrile (1:4, v/v). The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This method was used to measure the concentrations of zolazepam and tiletamine in plasma after a single intramuscular 10 mg dose of each in beagle dogs. Copyright © 2012 John Wiley & Sons, Ltd.

  18. A practical sensitivity analysis method for ranking sources of uncertainty in thermal–hydraulics applications

    Energy Technology Data Exchange (ETDEWEB)

    Pourgol-Mohammad, Mohammad, E-mail: pourgolmohammad@sut.ac.ir [Department of Mechanical Engineering, Sahand University of Technology, Tabriz (Iran, Islamic Republic of); Hoseyni, Seyed Mohsen [Department of Basic Sciences, East Tehran Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Hoseyni, Seyed Mojtaba [Building & Housing Research Center, Tehran (Iran, Islamic Republic of); Sepanloo, Kamran [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of)

    2016-08-15

    Highlights: • Existing uncertainty ranking methods prove inconsistent for TH applications. • Introduction of a new method for ranking sources of uncertainty in TH codes. • Modified PIRT qualitatively identifies and ranks uncertainty sources more precisely. • The importance of parameters is calculated by a limited number of TH code executions. • Methodology is applied successfully on LOFT-LB1 test facility. - Abstract: In application to thermal–hydraulic calculations by system codes, sensitivity analysis plays an important role for managing the uncertainties of code output and risk analysis. Sensitivity analysis is also used to confirm the results of qualitative Phenomena Identification and Ranking Table (PIRT). Several methodologies have been developed to address uncertainty importance assessment. Generally, uncertainty importance measures, mainly devised for the Probabilistic Risk Assessment (PRA) applications, are not affordable for computationally demanding calculations of the complex thermal–hydraulics (TH) system codes. In other words, for effective quantification of the degree of the contribution of each phenomenon to the total uncertainty of the output, a practical approach is needed by considering high computational burden of TH calculations. This study aims primarily to show the inefficiency of the existing approaches and then introduces a solution to cope with the challenges in this area by modification of variance-based uncertainty importance method. Important parameters are identified by the modified PIRT approach qualitatively then their uncertainty importance is quantified by a local derivative index. The proposed index is attractive from its practicality point of view on TH applications. It is capable of calculating the importance of parameters by a limited number of TH code executions. Application of the proposed methodology is demonstrated on LOFT-LB1 test facility.

  19. A practical sensitivity analysis method for ranking sources of uncertainty in thermal–hydraulics applications

    International Nuclear Information System (INIS)

    Pourgol-Mohammad, Mohammad; Hoseyni, Seyed Mohsen; Hoseyni, Seyed Mojtaba; Sepanloo, Kamran

    2016-01-01

    Highlights: • Existing uncertainty ranking methods prove inconsistent for TH applications. • Introduction of a new method for ranking sources of uncertainty in TH codes. • Modified PIRT qualitatively identifies and ranks uncertainty sources more precisely. • The importance of parameters is calculated by a limited number of TH code executions. • Methodology is applied successfully on LOFT-LB1 test facility. - Abstract: In application to thermal–hydraulic calculations by system codes, sensitivity analysis plays an important role for managing the uncertainties of code output and risk analysis. Sensitivity analysis is also used to confirm the results of qualitative Phenomena Identification and Ranking Table (PIRT). Several methodologies have been developed to address uncertainty importance assessment. Generally, uncertainty importance measures, mainly devised for the Probabilistic Risk Assessment (PRA) applications, are not affordable for computationally demanding calculations of the complex thermal–hydraulics (TH) system codes. In other words, for effective quantification of the degree of the contribution of each phenomenon to the total uncertainty of the output, a practical approach is needed by considering high computational burden of TH calculations. This study aims primarily to show the inefficiency of the existing approaches and then introduces a solution to cope with the challenges in this area by modification of variance-based uncertainty importance method. Important parameters are identified by the modified PIRT approach qualitatively then their uncertainty importance is quantified by a local derivative index. The proposed index is attractive from its practicality point of view on TH applications. It is capable of calculating the importance of parameters by a limited number of TH code executions. Application of the proposed methodology is demonstrated on LOFT-LB1 test facility.

  20. Acquisition and processing method for human sensorial, sensitive, motory and phonatory circuits reaction times

    International Nuclear Information System (INIS)

    Doche, Claude

    1972-01-01

    This work describes a storage and acquisition device and a method for human sensorial and sensitive motory and phonatory reaction times. The considered circuits are those made with the visual, auditory and sensory receptor organs and the motory or phonatory effector organs. The anatomo-physiological localization of these circuits allows us to appreciate the possibilities of the central nervous system for different angles. The experimental population is made of normal and pathological individuals (individuals having tumoral or vascular, localized or diffused cerebral lesions or parkinsonian individuals). The parameter processing method is based on the multivariate analysis results and allows us to position each individual compared to a normal individual and to appreciate the weight of each circuit in this positioning. Clinical exploitation results give to this method a prognosis and therapeutic interest. It seems though untimely to talk about its diagnosis value. (author) [fr

  1. Sensitivity and uncertainty analysis

    CERN Document Server

    Cacuci, Dan G; Navon, Ionel Michael

    2005-01-01

    As computer-assisted modeling and analysis of physical processes have continued to grow and diversify, sensitivity and uncertainty analyses have become indispensable scientific tools. Sensitivity and Uncertainty Analysis. Volume I: Theory focused on the mathematical underpinnings of two important methods for such analyses: the Adjoint Sensitivity Analysis Procedure and the Global Adjoint Sensitivity Analysis Procedure. This volume concentrates on the practical aspects of performing these analyses for large-scale systems. The applications addressed include two-phase flow problems, a radiative c

  2. Sensitivity study of a method for updating a finite element model of a nuclear power station cooling tower

    International Nuclear Information System (INIS)

    Billet, L.

    1994-01-01

    The Research and Development Division of Electricite de France is developing a surveillance method of cooling towers involving on-site wind-induced measurements. The method is supposed to detect structural damage in the tower. The damage is identified by tuning a finite element model of the tower on experimental mode shapes and eigenfrequencies. The sensitivity of the method was evaluated through numerical tests. First, the dynamic response of a damaged tower was simulated by varying the stiffness of some area of the model shell (from 1 % to 24 % of the total shell area). Second, the structural parameters of the undamaged cooling tower model were updated in order to make the output of the undamaged model as close as possible to the synthetic experimental data. The updating method, based on the minimization of the differences between experimental modal energies and modal energies calculated by the model, did not detect a stiffness change over less than 3 % of the shell area. Such a sensitivity is thought to be insufficient to detect tower cracks which behave like highly localized defaults. (author). 8 refs., 9 figs., 6 tabs

  3. An Adjoint Sensitivity Method Applied to Time Reverse Imaging of Tsunami Source for the 2009 Samoa Earthquake

    Science.gov (United States)

    Hossen, M. Jakir; Gusman, Aditya; Satake, Kenji; Cummins, Phil R.

    2018-01-01

    We have previously developed a tsunami source inversion method based on "Time Reverse Imaging" and demonstrated that it is computationally very efficient and has the ability to reproduce the tsunami source model with good accuracy using tsunami data of the 2011 Tohoku earthquake tsunami. In this paper, we implemented this approach in the 2009 Samoa earthquake tsunami triggered by a doublet earthquake consisting of both normal and thrust faulting. Our result showed that the method is quite capable of recovering the source model associated with normal and thrust faulting. We found that the inversion result is highly sensitive to some stations that must be removed from the inversion. We applied an adjoint sensitivity method to find the optimal set of stations in order to estimate a realistic source model. We found that the inversion result is improved significantly once the optimal set of stations is used. In addition, from the reconstructed source model we estimated the slip distribution of the fault from which we successfully determined the dipping orientation of the fault plane for the normal fault earthquake. Our result suggests that the fault plane dip toward the northeast.

  4. Sensitivity in risk analyses with uncertain numbers.

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, W. Troy; Ferson, Scott

    2006-06-01

    Sensitivity analysis is a study of how changes in the inputs to a model influence the results of the model. Many techniques have recently been proposed for use when the model is probabilistic. This report considers the related problem of sensitivity analysis when the model includes uncertain numbers that can involve both aleatory and epistemic uncertainty and the method of calculation is Dempster-Shafer evidence theory or probability bounds analysis. Some traditional methods for sensitivity analysis generalize directly for use with uncertain numbers, but, in some respects, sensitivity analysis for these analyses differs from traditional deterministic or probabilistic sensitivity analyses. A case study of a dike reliability assessment illustrates several methods of sensitivity analysis, including traditional probabilistic assessment, local derivatives, and a ''pinching'' strategy that hypothetically reduces the epistemic uncertainty or aleatory uncertainty, or both, in an input variable to estimate the reduction of uncertainty in the outputs. The prospects for applying the methods to black box models are also considered.

  5. 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.

  6. Mehar Methods for Fuzzy Optimal Solution and Sensitivity Analysis of Fuzzy Linear Programming with Symmetric Trapezoidal Fuzzy Numbers

    Directory of Open Access Journals (Sweden)

    Sukhpreet Kaur Sidhu

    2014-01-01

    Full Text Available The drawbacks of the existing methods to obtain the fuzzy optimal solution of such linear programming problems, in which coefficients of the constraints are represented by real numbers and all the other parameters as well as variables are represented by symmetric trapezoidal fuzzy numbers, are pointed out, and to resolve these drawbacks, a new method (named as Mehar method is proposed for the same linear programming problems. Also, with the help of proposed Mehar method, a new method, much easy as compared to the existing methods, is proposed to deal with the sensitivity analysis of the same type of linear programming problems.

  7. Standard test method for electrochemical reactivation (EPR) for detecting sensitization of AISI type 304 and 304L stainless steels

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    1994-01-01

    1.1 This test method covers a laboratory procedure for conducting an electrochemical reactivation (EPR) test on AISI Type 304 and 304L (UNS No. S30400 and S30403, respectively) stainless steels. This test method can provide a nondestructive means of quantifying the degree of sensitization in these steels (1, 2, 3). This test method has found wide acceptance in studies of the effects of sensitization on intergranular corrosion and intergranular stress corrosion cracking behavior (see Terminology G15). The EPR technique has been successfully used to evaluate other stainless steels and nickel base alloys (4), but the test conditions and evaluation criteria used were modified in each case from those cited in this test method. 1.2 The values stated in SI units are to be regarded as the standard. The inch-pound units given in parentheses are for information only. 1.3 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this...

  8. 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.

  9. 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.

  10. Sensitivity analysis of an environmental model: an application of different analysis methods

    International Nuclear Information System (INIS)

    Campolongo, Francesca; Saltelli, Andrea

    1997-01-01

    A parametric sensitivity analysis (SA) was conducted on a well known model for the production of a key sulphur bearing compound from algal biota. The model is of interest because of the climatic relevance of the gas (dimethylsulphide, DMS), an initiator of cloud particles. A screening test at low sample size is applied first (Morris method) followed by a computationally intensive variance based measure. Standardised regression coefficients are also computed. The various SA measures are compared with each other, and the use of bootstrap is suggested to extract empirical confidence bounds on the SA estimators. For some of the input factors, investigators guess about the parameters relevance was confirmed; for some others, the results shed new light on the system mechanism and on the data parametrisation

  11. Determination of paraquat in water samples using a sensitive fluorescent probe titration method.

    Science.gov (United States)

    Yao, Feihu; Liu, Hailong; Wang, Guangquan; Du, Liming; Yin, Xiaofen; Fu, Yunlong

    2013-06-01

    Paraquat (PQ), a nonselective herbicide, is non-fluorescent in aqueous solutions. Thus, its determination through direct fluorescent methods is not feasible. The supramolecular inclusion interaction of PQ with cucurbit[7]uril was studied by a fluorescent probe titration method. Significant quenching of the fluorescence intensity of the cucurbit[7]uril-coptisine fluorescent probe was observed with the addition of PQ. A new fluorescent probe titration method with high selectivity and sensitivity at the ng/mL level was developed to determine PQ in aqueous solutions with good precision and accuracy based on the significant quenching of the supramolecular complex fluorescence intensity. The proposed method was successfully used in the determination of PQ in lake water, tap water, well water, and ditch water in an agricultural area, with recoveries of 96.73% to 105.77%. The fluorescence quenching values (deltaF) showed a good linear relationship with PQ concentrations from 1.0 x 10(-8) to 1.2 x 10(-5) mol/L with a detection limit of 3.35 x 10(-9) mol/L. In addition, the interaction models of the supramolecular complexes formed between the host and the guest were established using theoretical calculations. The interaction mechanism between the cucurbit[7]uril and PQ was confirmed by 1H NMR spectroscopy.

  12. Sensitivity analysis of the use of Life Cycle Impact Assessment methods: a case study on building materials

    DEFF Research Database (Denmark)

    Bueno, Cristiane; Hauschild, Michael Zwicky; Rossignolo, Joao Adriano

    2016-01-01

    The main aim of this research is to perform a sensitivity analysis of a Life Cycle Assessment (LCA) case study to understand if the use of different Life Cycle Impact Assessment (LCIA) methods may lead to different conclusions by decision makers and stakeholders. A complete LCA was applied to non...

  13. Radiation and thermal characteristics of L5178Y-sensitive cells and usefulness of eosin staining method to detect heat-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Nishioka, Yasuji (Hiroshima Univ. (Japan). School of Medicine)

    1990-08-01

    Radiosensitivity, thermosensitivity, drug sensitivity and their combined effects were investigated in mouse L5178Y-wild cells (LY-W) and L5178Y-sensitive cells (LY-S). The following results were obtained: LY-S were more radiosensitive than LY-W but were similar in their thermosensitivity. Thermotolerance induction was similar but the decay was faster in LY-W which had a shorter doubling time. The radiosensitizing effect of heating was similar in both cell lines. The thermal enhancement ratio was higher for a longer duration of heating at 42degC than for a shorter duration at 44degC, both of which exhibited a similar level of survival when applied alone. The eosin staining method was useful to detect heat-induced interphase death and thermal sensitizing effects of drugs. In LY-W, interphase death was the main mode of hyperthermic cell killing and was independent of the hyperthermic temperature, whereas in LY-S, the percentage of interphase death increased with the hyperthermic temperature. Procaine and bleomycin sensitized both cells to heat. Survival estimated by the eosin staining method shifted towards that obtained by colony forming method in heated LY-S after procaine. Sensitization to heat by procaine suggests that interphase death after hyperthermia is probably due to membrane damage. Comparison of the present work with previous ones, further suggests that with an increase in thermosensitivity, there is an increase in heat-induced interphase death. (author) 67 refs.

  14. Radiation and thermal characteristics of L5178Y-sensitive cells and usefulness of eosin staining method to detect heat-induced cell death

    International Nuclear Information System (INIS)

    Nishioka, Yasuji

    1990-01-01

    Radiosensitivity, thermosensitivity, drug sensitivity and their combined effects were investigated in mouse L5178Y-wild cells (LY-W) and L5178Y-sensitive cells (LY-S). The following results were obtained: LY-S were more radiosensitive than LY-W but were similar in their thermosensitivity. Thermotolerance induction was similar but the decay was faster in LY-W which had a shorter doubling time. The radiosensitizing effect of heating was similar in both cell lines. The thermal enhancement ratio was higher for a longer duration of heating at 42degC than for a shorter duration at 44degC, both of which exhibited a similar level of survival when applied alone. The eosin staining method was useful to detect heat-induced interphase death and thermal sensitizing effects of drugs. In LY-W, interphase death was the main mode of hyperthermic cell killing and was independent of the hyperthermic temperature, whereas in LY-S, the percentage of interphase death increased with the hyperthermic temperature. Procaine and bleomycin sensitized both cells to heat. Survival estimated by the eosin staining method shifted towards that obtained by colony forming method in heated LY-S after procaine. Sensitization to heat by procaine suggests that interphase death after hyperthermia is probably due to membrane damage. Comparison of the present work with previous ones, further suggests that with an increase in thermosensitivity, there is an increase in heat-induced interphase death. (author) 67 refs

  15. Current status and bioanalytical challenges in the detection of unknown anabolic androgenic steroids in doping control analysis.

    Science.gov (United States)

    Pozo, Oscar J; De Brabanter, Nik; Fabregat, Andreu; Segura, Jordi; Ventura, Rosa; Van Eenoo, Peter; Deventer, Koen

    2013-11-01

    Androgenic anabolic steroids (AAS) are prohibited in sports due to their anabolic effects. Doping control laboratories usually face the screening of AAS misuse by target methods based on MS detection. Although these methods allow for the sensitive and specific detection of targeted compounds and metabolites, the rest remain undetectable. This fact opens a door for cheaters, since different AAS can be synthesized in order to evade doping control tests. This situation was evidenced in 2003 with the discovery of the designer steroid tetrahydrogestrinone. One decade after this discovery, the detection of unknown AAS still remains one of the main analytical challenges in the doping control field. In this manuscript, the current situation in the detection of unknown AAS is reviewed. Although important steps have been made in order to minimize this analytical problem and different analytical strategies have been proposed, there are still some drawbacks related to each approach.

  16. A Sensitive and Specific PCR Based Method for Identification of Cryptosporidium Sp. Using New Primers from 18S Ribosomal RNA

    Directory of Open Access Journals (Sweden)

    M Heydarnezhadi

    2011-09-01

    Full Text Available Background: The main goal of the present study was to develop a new sensitive and specific PCR based method for Identification of Cryptosporidium sp. using novel primers from 18S ribosomal RNA. Cryptosporidi­osis in high-risk host groups particularly in neonates and immuno-compromised individuals may result in death. To the best of our knowledge this is the first study regarding develop a new PCR based method to diagnose the cryptosporidiosis in Iran.Methods: A total of 850 human fecal samples from patients clinically suspected to cryptosporidiosis and 100 healthy and diarrheic cattle stool specimens were collected. The simplified formol-ether concentration method was carried out for all samples. They were then examined microscopically by modified Ziehl-Neel­sen staining method. Total DNA was extracted by QIA amp DNA stool mini kit was carried out by using designed prim­ers.Results: Twenty nine cases of cryptosporidiosis infection in human and 30 samples from cattle microscopi­cally were posi­tive. The described primary and nested PCR method could detect all Cryptospori­dium positive samples from human and cattle. Regards to suspected negative samples in pri­mary PCR examination, the Nested PCR could ap­prove two more positive results. Furthermore, Nested PCR analysis was able to detect one more case which was nega­tive in both microscopically examination and primary PCR. Specificity of the test was 100%. Sensitivity of Nested PCR in comparison to our gold standard; microscopy after Ridley concentration modified ziehl-Neelsen, was 100 %.Conclusion: Our developed PCR based method by using new primers devised from 18S ribosomal RNA revealed the ability for identification of the Cryptosporidium species such as C. parvum and C. huminis with high specificity and sensitivity.

  17. Development of a rapid, simple and sensitive HPLC-FLD method for determination of rhodamine B in chili-containing products.

    Science.gov (United States)

    Qi, Ping; Lin, Zhihao; Li, Jiaxu; Wang, ChengLong; Meng, WeiWei; Hong, Hong; Zhang, Xuewu

    2014-12-01

    In this work, a simple, rapid and sensitive analytical method for the determination of rhodamine B in chili-containing foodstuffs is described. The dye is extracted from samples with methanol and analysed without further cleanup procedure by high-performance liquid chromatography (HPLC) coupled to fluorescence detection (FLD). The influence of matrix fluorescent compounds (capsaicin and dihydrocapsaicin) on the analysis was overcome by the optimisation of mobile-phase composition. The limit of determination (LOD) and limit of quantification (LOQ) were 3.7 and 10 μg/kg, respectively. Validation data show a good repeatability and within-lab reproducibility with relative standard deviations rhodamine B in foodstuffs. This method is suitable for the routine analysis of rhodamine B due to its sensitivity, simplicity, reasonable time and cost. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Parallel replica dynamics method for bistable stochastic reaction networks: Simulation and sensitivity analysis

    Science.gov (United States)

    Wang, Ting; Plecháč, Petr

    2017-12-01

    Stochastic reaction networks that exhibit bistable behavior are common in systems biology, materials science, and catalysis. Sampling of stationary distributions is crucial for understanding and characterizing the long-time dynamics of bistable stochastic dynamical systems. However, simulations are often hindered by the insufficient sampling of rare transitions between the two metastable regions. In this paper, we apply the parallel replica method for a continuous time Markov chain in order to improve sampling of the stationary distribution in bistable stochastic reaction networks. The proposed method uses parallel computing to accelerate the sampling of rare transitions. Furthermore, it can be combined with the path-space information bounds for parametric sensitivity analysis. With the proposed methodology, we study three bistable biological networks: the Schlögl model, the genetic switch network, and the enzymatic futile cycle network. We demonstrate the algorithmic speedup achieved in these numerical benchmarks. More significant acceleration is expected when multi-core or graphics processing unit computer architectures and programming tools such as CUDA are employed.

  19. Parallel replica dynamics method for bistable stochastic reaction networks: Simulation and sensitivity analysis.

    Science.gov (United States)

    Wang, Ting; Plecháč, Petr

    2017-12-21

    Stochastic reaction networks that exhibit bistable behavior are common in systems biology, materials science, and catalysis. Sampling of stationary distributions is crucial for understanding and characterizing the long-time dynamics of bistable stochastic dynamical systems. However, simulations are often hindered by the insufficient sampling of rare transitions between the two metastable regions. In this paper, we apply the parallel replica method for a continuous time Markov chain in order to improve sampling of the stationary distribution in bistable stochastic reaction networks. The proposed method uses parallel computing to accelerate the sampling of rare transitions. Furthermore, it can be combined with the path-space information bounds for parametric sensitivity analysis. With the proposed methodology, we study three bistable biological networks: the Schlögl model, the genetic switch network, and the enzymatic futile cycle network. We demonstrate the algorithmic speedup achieved in these numerical benchmarks. More significant acceleration is expected when multi-core or graphics processing unit computer architectures and programming tools such as CUDA are employed.

  20. Determination of IgE antibodies to the benzylpenicilloyl determinant: a comparison of the sensitivity and specificity of three radio allergo sorbent test methods.

    Science.gov (United States)

    Garcia, J J; Blanca, M; Moreno, F; Vega, J M; Mayorga, C; Fernandez, J; Juarez, C; Romano, A; de Ramon, E

    1997-01-01

    The quantitation of in vitro IgE antibodies to the benzylpenicilloyl determinant (BPO) is a useful tool for evaluating suspected penicillin allergic subjects. Although many different methods have been employed, few studies have compared their diagnostic specificity and sensitivity. In this study, the sensitivity and specificity of three different radio allergo sorbent test (RAST) methods for quantitating specific IgE antibodies to the BPO determinant were compared. Thirty positive control sera (serum samples from penicillin allergic subjects with a positive clinical history and a positive penicillin skin test) and 30 negative control sera (sera from subjects with no history of penicillin allergy and negative skin tests) were tested for BPO-specific IgE antibodies by RAST using three different conjugates coupled to the solid phase: benzylpenicillin conjugated to polylysine (BPO-PLL), benzylpenicillin conjugated to human serum albumin (BPO-HSA), and benzylpenicillin conjugated to an aminospacer (BPO-SP). Receiver operator control curves (ROC analysis) were carried out by determining different cut-off points between positive and negative values. Contingence tables were constructed and sensitivity, specificity, negative predictive values (PV-), and positive predictive values (PV+) were calculated. Pearson correlation coefficients (r) and intraclass correlation coefficients (ICC) were determined and the differences between methods were compared by chi 2 analysis. Analysis of the areas defined by the ROC curves showed statistical differences among the three methods. When cut-off points for optimal sensitivity and specificity were chosen, the BPO-HSA assay was less sensitive and less specific and had a lower PV- and PV+ than the BPO-PLL and BPO-SP assays. Assessment of r and ICC indicated that the correlation was very high, but the concordance between the PLL and SP methods was higher than between the PLL and HSA or SP and HSA methods. We conclude that for quantitating Ig

  1. A rule based method for context sensitive threshold segmentation in SPECT using simulation

    International Nuclear Information System (INIS)

    Fleming, John S.; Alaamer, Abdulaziz S.

    1998-01-01

    Robust techniques for automatic or semi-automatic segmentation of objects in single photon emission computed tomography (SPECT) are still the subject of development. This paper describes a threshold based method which uses empirical rules derived from analysis of computer simulated images of a large number of objects. The use of simulation allowed the factors affecting the threshold which correctly segmented objects to be investigated systematically. Rules could then be derived from these data to define the threshold in any particular context. The technique operated iteratively and calculated local context sensitive thresholds along radial profiles from the centre of gravity of the object. It was evaluated in a further series of simulated objects and in human studies, and compared to the use of a global fixed threshold. The method was capable of improving accuracy of segmentation and volume assessment compared to the global threshold technique. The improvements were greater for small volumes, shapes with large surface area to volume ratio, variable surrounding activity and non-uniform distributions. The method was applied successfully to simulated objects and human studies and is considered to be a significant advance on global fixed threshold techniques. (author)

  2. Sensitivity analysis approaches applied to systems biology models.

    Science.gov (United States)

    Zi, Z

    2011-11-01

    With the rising application of systems biology, sensitivity analysis methods have been widely applied to study the biological systems, including metabolic networks, signalling pathways and genetic circuits. Sensitivity analysis can provide valuable insights about how robust the biological responses are with respect to the changes of biological parameters and which model inputs are the key factors that affect the model outputs. In addition, sensitivity analysis is valuable for guiding experimental analysis, model reduction and parameter estimation. Local and global sensitivity analysis approaches are the two types of sensitivity analysis that are commonly applied in systems biology. Local sensitivity analysis is a classic method that studies the impact of small perturbations on the model outputs. On the other hand, global sensitivity analysis approaches have been applied to understand how the model outputs are affected by large variations of the model input parameters. In this review, the author introduces the basic concepts of sensitivity analysis approaches applied to systems biology models. Moreover, the author discusses the advantages and disadvantages of different sensitivity analysis methods, how to choose a proper sensitivity analysis approach, the available sensitivity analysis tools for systems biology models and the caveats in the interpretation of sensitivity analysis results.

  3. 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.

  4. High order depletion sensitivity analysis

    International Nuclear Information System (INIS)

    Naguib, K.; Adib, M.; Morcos, H.N.

    2002-01-01

    A high order depletion sensitivity method was applied to calculate the sensitivities of build-up of actinides in the irradiated fuel due to cross-section uncertainties. An iteration method based on Taylor series expansion was applied to construct stationary principle, from which all orders of perturbations were calculated. The irradiated EK-10 and MTR-20 fuels at their maximum burn-up of 25% and 65% respectively were considered for sensitivity analysis. The results of calculation show that, in case of EK-10 fuel (low burn-up), the first order sensitivity was found to be enough to perform an accuracy of 1%. While in case of MTR-20 (high burn-up) the fifth order was found to provide 3% accuracy. A computer code SENS was developed to provide the required calculations

  5. Applicability of the two-angle differential method to response measurement of neutron-sensitive devices at the RCNP high-energy neutron facility

    Energy Technology Data Exchange (ETDEWEB)

    Masuda, Akihiko, E-mail: aki-masuda@aist.go.jp [National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568 (Japan); Matsumoto, Tetsuro [National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568 (Japan); Iwamoto, Yosuke [Japan Atomic Energy Agency (JAEA), 2-4 Shirakata, Tokai, Naka, Ibaraki 319-1195 (Japan); Hagiwara, Masayuki [High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Satoh, Daiki; Sato, Tatsuhiko [Japan Atomic Energy Agency (JAEA), 2-4 Shirakata, Tokai, Naka, Ibaraki 319-1195 (Japan); Iwase, Hiroshi [High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Yashima, Hiroshi [Research Reactor Institute, Kyoto University, 2-1010 Asashiro-nishi, Kumatori, Sennan, Osaka 590-0494 (Japan); Nakane, Yoshihiro [Japan Atomic Energy Agency (JAEA), 2-4 Shirakata, Tokai, Naka, Ibaraki 319-1195 (Japan); Nishiyama, Jun [Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8550 (Japan); Shima, Tatsushi; Tamii, Atsushi; Hatanaka, Kichiji [Research Center for Nuclear Physics (RCNP), Osaka University, 10-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan); Harano, Hideki [National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568 (Japan); Nakamura, Takashi [Cyclotron and Radioisotope Center (CYRIC), Tohoku University, 6-3 Aramaki, Aoba, Sendai, Miyagi 980-8578 (Japan)

    2017-03-21

    Quasi-monoenergetic high-energy neutron fields induced by {sup 7}Li(p,n) reactions are used for the response evaluation of neutron-sensitive devices. The quasi-monoenergetic high-energy field consists of high-energy monoenergetic peak neutrons and unwanted continuum neutrons down to the low-energy region. A two-angle differential method has been developed to compensate for the effect of the continuum neutrons in the response measurements. In this study, the two-angle differential method was demonstrated for Bonner sphere detectors, which are typical examples of moderator-based neutron-sensitive detectors, to investigate the method's applicability and its dependence on detector characteristics. Experiments were performed under 96–387 MeV quasi-monoenergetic high-energy neutron fields at the Research Center for Nuclear Physics (RCNP), Osaka University. The measurement results for large high-density polyethylene (HDPE) sphere detectors agreed well with Monte Carlo calculations, which verified the adequacy of the two-angle differential method. By contrast, discrepancies were observed in the results for small HDPE sphere detectors and metal-induced sphere detectors. The former indicated that detectors that are particularly sensitive to low-energy neutrons may be affected by penetrating neutrons owing to the geometrical features of the RCNP facility. The latter discrepancy could be consistently explained by a problem in the evaluated cross-section data for the metals used in the calculation. Through those discussions, the adequacy of the two-angle differential method was experimentally verified, and practical suggestions were made pertaining to this method.

  6. Simple and sensitive detection method for diprophylline using glutathione-capped CdTe quantum dots as fluorescence probes

    Energy Technology Data Exchange (ETDEWEB)

    Ying, Suyan; Cui, Shumin [College of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004 (China); Wang, Weiping, E-mail: wangwp@zjnu.edu.cn [College of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004 (China); Feng, Jiuju [College of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004 (China); Chen, Jianrong [College of Geography and Environmental Science, Zhejiang Normal University, Jinhua 321004 (China)

    2014-01-15

    A simple and sensitive method for detecting diprophylline (DPP) was developed based on the fluorescence quenching of glutathione-capped CdTe quantum dots (GSH–CdTe QDs) by using diprophylline in a KH{sub 2}PO{sub 4}–Na{sub 2}HPO{sub 4} medium. Parameters affecting the quenching efficiency, including types and pH of buffer solutions as well as temperature, reaction time, adding sequence, and interfering substances, were investigated and optimized. In optimum conditions, the calibration plot of the quenched fluorescence intensity F{sub 0}/F with a DPP concentration range of 1.67×10{sup –6} mol L{sup −1} to 1.33×10{sup –5} mol L{sup −1} was linear. The detection limit (with signal to noise ratio of 3) for DPP was 2.24×10{sup –7} mol L{sup −1}. The proposed method was successfully applied for detecting DPP in human serum. The recovery of the method was in the range of 87.41% to 117.94%. Finally, the possible quenching mechanism of GSH–CdTe QDs and DPP was also discussed. -- Highlights: • Fluorescence of GSH/CdTe QDs was quenched by diprophylline in phosphate medium. • A simple and sensitive detection method for diprophylline based on fluorescence quenching was developed. • Quenching mechanism of GSH-capped CdTe QDs with diprophylline was discussed.

  7. Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.

    Directory of Open Access Journals (Sweden)

    Heewon Park

    Full Text Available The personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and perform personalized anti-cancer therapy. Although the existing methods for patient-specific analysis have successfully uncovered crucial biomarkers, their performance takes a sudden turn for the worst in the presence of outliers, since the methods are based on non-robust manners. In practice, clinical and genomic alterations datasets usually contain outliers from various sources (e.g., experiment error, coding error, etc. and the outliers may significantly affect the result of patient-specific analysis. We propose a robust methodology for patient-specific analysis in line with the NetwrokProfiler. In the proposed method, outliers in high dimensional gene expression levels and drug response datasets are simultaneously controlled by robust Mahalanobis distance in robust principal component space. Thus, we can effectively perform for predicting anti-cancer drug sensitivity and identifying sensitivity-specific biomarkers for individual patients. We observe through Monte Carlo simulations that the proposed robust method produces outstanding performances for predicting response variable in the presence of outliers. We also apply the proposed methodology to the Sanger dataset in order to uncover cancer biomarkers and predict anti-cancer drug sensitivity, and show the effectiveness of our method.

  8. Global sensitivity analysis by polynomial dimensional decomposition

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, Sharif, E-mail: rahman@engineering.uiowa.ed [College of Engineering, The University of Iowa, Iowa City, IA 52242 (United States)

    2011-07-15

    This paper presents a polynomial dimensional decomposition (PDD) method for global sensitivity analysis of stochastic systems subject to independent random input following arbitrary probability distributions. The method involves Fourier-polynomial expansions of lower-variate component functions of a stochastic response by measure-consistent orthonormal polynomial bases, analytical formulae for calculating the global sensitivity indices in terms of the expansion coefficients, and dimension-reduction integration for estimating the expansion coefficients. Due to identical dimensional structures of PDD and analysis-of-variance decomposition, the proposed method facilitates simple and direct calculation of the global sensitivity indices. Numerical results of the global sensitivity indices computed for smooth systems reveal significantly higher convergence rates of the PDD approximation than those from existing methods, including polynomial chaos expansion, random balance design, state-dependent parameter, improved Sobol's method, and sampling-based methods. However, for non-smooth functions, the convergence properties of the PDD solution deteriorate to a great extent, warranting further improvements. The computational complexity of the PDD method is polynomial, as opposed to exponential, thereby alleviating the curse of dimensionality to some extent.

  9. A simple and sensitive method for L-cysteine detection based on the fluorescence intensity increment of quantum dots

    International Nuclear Information System (INIS)

    Huang Shan; Xiao Qi; Li Ran; Guan Hongliang; Liu Jing; Liu Xiaorong; He Zhike; Liu Yi

    2009-01-01

    In this contribution, a simple and sensitive method for L-cysteine detection was established based on the increment of the fluorescence intensity of mercaptoacetic acid-capped CdSe/ZnS quantum dots (QDs) in aqueous solution. Meanwhile, the fluorescence characteristics and the optimal conditions were investigated in detail. Under the optimized conditions, the linear range of QDs fluorescence intensity versus the concentration of L-cysteine was 10-800 nmol L -1 , with a correlation coefficient (R) of 0.9969 and a limit of detection (3σ black) of 3.8 nmol L -1 . The relative standard deviation (R.S.D.) for 0.5 μmol L -1 L-cysteine was 1.1% (n = 5). There was no interference to coexisting foreign substances including common ions, carbohydrates, nucleotide acids and other 19 amino acids. The proposed method possessed the advantages of simplicity, rapidity and sensitivity. Synthetic amino acid samples, medicine sample together with human urine samples were analyzed by the methodology and the results were satisfying.

  10. Highly sensitive methanol chemical sensor based on undoped silver oxide nanoparticles prepared by a solution method

    International Nuclear Information System (INIS)

    Rahman, M.M.; Khan, S.B.; Asiri, A.M.; Jamal, A.; Faisal, M.

    2012-01-01

    We have prepared silver oxide nanoparticles (NPs) by a simple solution method using reducing agents in alkaline medium. The resulting NPs were characterized by UV-vis and FT-IR spectroscopy, X-ray powder diffraction, and field-emission scanning electron microscopy. They were deposited on a glassy carbon electrode to give a sensor with a fast response towards methanol in liquid phase. The sensor also displays good sensitivity and long-term stability, and enhanced electrochemical response. The calibration plot is linear (r 2 = 0.8294) over the 0.12 mM to 0.12 M methanol concentration range. The sensitivity is ∼ 2.65 μAcm -2 mM -1 , and the detection limit is 36.0 μM (at a SNR of 3). We also discuss possible future prospective uses of this metal oxide semiconductor nanomaterial in terms of chemical sensing. (author)

  11. Dye-Sensitized Solar Cells with Anatase TiO2 Nanorods Prepared by Hydrothermal Method

    Directory of Open Access Journals (Sweden)

    Ming-Jer Jeng

    2013-01-01

    Full Text Available The hydrothermal method provides an effective reaction environment for the synthesis of nanocrystalline materials with high purity and well-controlled crystallinity. In this work, we started with various sizes of commercial TiO2 powders and used the hydrothermal method to prepare TiO2 thin films. We found that the synthesized TiO2 nanorods were thin and long when smaller TiO2 particles were used, while larger TiO2 particles produced thicker and shorter nanorods. We also found that TiO2 films prepared by TiO2 nanorods exhibited larger surface roughness than those prepared by the commercial TiO2 particles. It was found that a pure anatase phase of TiO2 nanorods can be obtained from the hydrothermal method. The dye-sensitized solar cells fabricated with TiO2 nanorods exhibited a higher solar efficiency than those fabricated with commercial TiO2 nanoparticles directly. Further, triple-layer structures of TiO2 thin films with different particle sizes were investigated to improve the solar efficiency.

  12. A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment.

    Science.gov (United States)

    Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang

    2015-08-04

    Digital PCR has developed rapidly since it was first reported in the 1990 s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products.

  13. Application of the Tikhonov regularization method to wind retrieval from scatterometer data I. Sensitivity analysis and simulation experiments

    International Nuclear Information System (INIS)

    Zhong Jian; Huang Si-Xun; Du Hua-Dong; Zhang Liang

    2011-01-01

    Scatterometer is an instrument which provides all-day and large-scale wind field information, and its application especially to wind retrieval always attracts meteorologists. Certain reasons cause large direction error, so it is important to find where the error mainly comes. Does it mainly result from the background field, the normalized radar cross-section (NRCS) or the method of wind retrieval? It is valuable to research. First, depending on SDP2.0, the simulated ‘true’ NRCS is calculated from the simulated ‘true’ wind through the geophysical model function NSCAT2. The simulated background field is configured by adding a noise to the simulated ‘true’ wind with the non-divergence constraint. Also, the simulated ‘measured’ NRCS is formed by adding a noise to the simulated ‘true’ NRCS. Then, the sensitivity experiments are taken, and the new method of regularization is used to improve the ambiguity removal with simulation experiments. The results show that the accuracy of wind retrieval is more sensitive to the noise in the background than in the measured NRCS; compared with the two-dimensional variational (2DVAR) ambiguity removal method, the accuracy of wind retrieval can be improved with the new method of Tikhonov regularization through choosing an appropriate regularization parameter, especially for the case of large error in the background. The work will provide important information and a new method for the wind retrieval with real data. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

  14. Extended forward sensitivity analysis of one-dimensional isothermal flow

    International Nuclear Information System (INIS)

    Johnson, M.; Zhao, H.

    2013-01-01

    Sensitivity analysis and uncertainty quantification is an important part of nuclear safety analysis. In this work, forward sensitivity analysis is used to compute solution sensitivities on 1-D fluid flow equations typical of those found in system level codes. Time step sensitivity analysis is included as a method for determining the accumulated error from time discretization. The ability to quantify numerical error arising from the time discretization is a unique and important feature of this method. By knowing the relative sensitivity of time step with other physical parameters, the simulation is allowed to run at optimized time steps without affecting the confidence of the physical parameter sensitivity results. The time step forward sensitivity analysis method can also replace the traditional time step convergence studies that are a key part of code verification with much less computational cost. One well-defined benchmark problem with manufactured solutions is utilized to verify the method; another test isothermal flow problem is used to demonstrate the extended forward sensitivity analysis process. Through these sample problems, the paper shows the feasibility and potential of using the forward sensitivity analysis method to quantify uncertainty in input parameters and time step size for a 1-D system-level thermal-hydraulic safety code. (authors)

  15. Rapid determination of recent cocaine use with magnetic particles-based enzyme immunoassays in serum, saliva, and urine fluids.

    Science.gov (United States)

    Vidal, Juan C; Bertolín, Juan R; Bonel, Laura; Asturias, Laura; Arcos-Martínez, M Julia; Castillo, Juan R

    2016-06-05

    Cocaine is one of the most worldwide used illicit drugs. We report a magnetic particles-based enzyme-linked immunoassay (mpEIA) method for the rapid and sensitive determination of cocaine (COC) in saliva, urine and serum samples. Under optimized conditions, the limits of detections were 0.09ngmL(-1) (urine), 0.15ngmL(-1) (saliva), and 0.06ngmL(-1) COC (human serum). Sensitivities were in the range EC50=0.6-2.5ngmL(-1) COC. The cross-reactivity with the principal metabolite benzoylecgonine (BZE) was only 1.6%. Recovering percentages of doped samples (0, 10, 50, and 100ngmL(-1) of COC) ranged from about 86-111%. Some advantages of the developed mpEIA over conventional ELISA kits are faster incubations, improved reproducibility, and consumption of lower amounts of antibody and enzyme conjugates due to the use of magnetic beads. The reported method was validated following the guidelines on bioanalytical methods of the European Medicines Agency (2011). Unmetabolized COC detection has a great interest in pharmacological, pharmacokinetics, and toxicokinetics studies, and can be used to detect a very recent COC use (1-6h). Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Methods for global sensitivity analysis in life cycle assessment

    NARCIS (Netherlands)

    Groen, Evelyne A.; Bokkers, Eddy; Heijungs, Reinout; Boer, de Imke J.M.

    2017-01-01

    Purpose: Input parameters required to quantify environmental impact in life cycle assessment (LCA) can be uncertain due to e.g. temporal variability or unknowns about the true value of emission factors. Uncertainty of environmental impact can be analysed by means of a global sensitivity analysis to

  17. Extreme Thermal Sensitivity and Pain-Induced Sensitization in a Fibromyalgia Patient

    Directory of Open Access Journals (Sweden)

    Fong Wong

    2010-01-01

    Full Text Available During the course of a psychophysical study of fibromyalgia syndrome (FMS, one of the subjects with a long history of headache and facial pain displayed an extraordinarily severe thermal allodynia. Her stimulus-response function for ratings of cutaneous heat pain revealed a sensitivity clearly beyond that of normal controls and most FMS subjects. Specially designed psychophysical methods showed that heat sensitivity sometimes increased dramatically within a series of stimuli. Prior exposure to moderate heat pain served as a trigger for allodynic ratings of series of normally neutral thermal stimulation. These observations document a case of breakthrough pain sensitivity with implications for mechanisms of FMS pain.

  18. A highly sensitive kinetic spectrophotometric method for the determination of ascorbic Acid in pharmaceutical samples.

    Science.gov (United States)

    Shishehbore, Masoud Reza; Aghamiri, Zahra

    2014-01-01

    In this study, a new reaction system for quantitative determination of ascorbic acid was introduced. The developed method is based on inhibitory effect of ascorbic acid on the Orange G-bromate system. The change in absorbance was followed spectrophotometrically at 478 nm. The dependence of sensitivity on the reaction variables including reagents concentration, temperature and time was investigated. Under optimum experimental conditions, calibration curve was linear over the range 0.7 - 33.5 μg mL(-1) of ascorbic acid including two linear segments and the relative standard deviations (n = 6) for 5.0 and 20.0 μg mL(-1) of ascorbic acid were 1.08 and 1.02%, respectively. The limit of detection was 0.21 μg mL(-) (1) of ascorbic acid. The effect of diverse species was also investigated. The developed method was successfully applied for the determination of ascorbic acid in pharmaceutical samples. The results were in a good agreement with those of reference method.

  19. 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

  20. Self-powered wireless carbohydrate/oxygen sensitive biodevice based on radio signal transmission.

    Science.gov (United States)

    Falk, Magnus; Alcalde, Miguel; Bartlett, Philip N; De Lacey, Antonio L; Gorton, Lo; Gutierrez-Sanchez, Cristina; Haddad, Raoudha; Kilburn, Jeremy; Leech, Dónal; Ludwig, Roland; Magner, Edmond; Mate, Diana M; Conghaile, Peter Ó; Ortiz, Roberto; Pita, Marcos; Pöller, Sascha; Ruzgas, Tautgirdas; Salaj-Kosla, Urszula; Schuhmann, Wolfgang; Sebelius, Fredrik; Shao, Minling; Stoica, Leonard; Sygmund, Cristoph; Tilly, Jonas; Toscano, Miguel D; Vivekananthan, Jeevanthi; Wright, Emma; Shleev, Sergey

    2014-01-01

    Here for the first time, we detail self-contained (wireless and self-powered) biodevices with wireless signal transmission. Specifically, we demonstrate the operation of self-sustained carbohydrate and oxygen sensitive biodevices, consisting of a wireless electronic unit, radio transmitter and separate sensing bioelectrodes, supplied with electrical energy from a combined multi-enzyme fuel cell generating sufficient current at required voltage to power the electronics. A carbohydrate/oxygen enzymatic fuel cell was assembled by comparing the performance of a range of different bioelectrodes followed by selection of the most suitable, stable combination. Carbohydrates (viz. lactose for the demonstration) and oxygen were also chosen as bioanalytes, being important biomarkers, to demonstrate the operation of the self-contained biosensing device, employing enzyme-modified bioelectrodes to enable the actual sensing. A wireless electronic unit, consisting of a micropotentiostat, an energy harvesting module (voltage amplifier together with a capacitor), and a radio microchip, were designed to enable the biofuel cell to be used as a power supply for managing the sensing devices and for wireless data transmission. The electronic system used required current and voltages greater than 44 µA and 0.57 V, respectively to operate; which the biofuel cell was capable of providing, when placed in a carbohydrate and oxygen containing buffer. In addition, a USB based receiver and computer software were employed for proof-of concept tests of the developed biodevices. Operation of bench-top prototypes was demonstrated in buffers containing different concentrations of the analytes, showcasing that the variation in response of both carbohydrate and oxygen biosensors could be monitored wirelessly in real-time as analyte concentrations in buffers were changed, using only an enzymatic fuel cell as a power supply.

  1. Self-powered wireless carbohydrate/oxygen sensitive biodevice based on radio signal transmission.

    Directory of Open Access Journals (Sweden)

    Magnus Falk

    Full Text Available Here for the first time, we detail self-contained (wireless and self-powered biodevices with wireless signal transmission. Specifically, we demonstrate the operation of self-sustained carbohydrate and oxygen sensitive biodevices, consisting of a wireless electronic unit, radio transmitter and separate sensing bioelectrodes, supplied with electrical energy from a combined multi-enzyme fuel cell generating sufficient current at required voltage to power the electronics. A carbohydrate/oxygen enzymatic fuel cell was assembled by comparing the performance of a range of different bioelectrodes followed by selection of the most suitable, stable combination. Carbohydrates (viz. lactose for the demonstration and oxygen were also chosen as bioanalytes, being important biomarkers, to demonstrate the operation of the self-contained biosensing device, employing enzyme-modified bioelectrodes to enable the actual sensing. A wireless electronic unit, consisting of a micropotentiostat, an energy harvesting module (voltage amplifier together with a capacitor, and a radio microchip, were designed to enable the biofuel cell to be used as a power supply for managing the sensing devices and for wireless data transmission. The electronic system used required current and voltages greater than 44 µA and 0.57 V, respectively to operate; which the biofuel cell was capable of providing, when placed in a carbohydrate and oxygen containing buffer. In addition, a USB based receiver and computer software were employed for proof-of concept tests of the developed biodevices. Operation of bench-top prototypes was demonstrated in buffers containing different concentrations of the analytes, showcasing that the variation in response of both carbohydrate and oxygen biosensors could be monitored wirelessly in real-time as analyte concentrations in buffers were changed, using only an enzymatic fuel cell as a power supply.

  2. Low-Cost and Rapid Fabrication of Metallic Nanostructures for Sensitive Biosensors Using Hot-Embossing and Dielectric-Heating Nanoimprint Methods

    Directory of Open Access Journals (Sweden)

    Kuang-Li Lee

    2017-07-01

    Full Text Available We propose two approaches—hot-embossing and dielectric-heating nanoimprinting methods—for low-cost and rapid fabrication of periodic nanostructures. Each nanofabrication process for the imprinted plastic nanostructures is completed within several seconds without the use of release agents and epoxy. Low-cost, large-area, and highly sensitive aluminum nanostructures on A4 size plastic films are fabricated by evaporating aluminum film on hot-embossing nanostructures. The narrowest bandwidth of the Fano resonance is only 2.7 nm in the visible light region. The periodic aluminum nanostructure achieves a figure of merit of 150, and an intensity sensitivity of 29,345%/RIU (refractive index unit. The rapid fabrication is also achieved by using radio-frequency (RF sensitive plastic films and a commercial RF welding machine. The dielectric-heating, using RF power, takes advantage of the rapid heating/cooling process and lower electric power consumption. The fabricated capped aluminum nanoslit array has a 5 nm Fano linewidth and 490.46 nm/RIU wavelength sensitivity. The biosensing capabilities of the metallic nanostructures are further verified by measuring antigen–antibody interactions using bovine serum albumin (BSA and anti-BSA. These rapid and high-throughput fabrication methods can benefit low-cost, highly sensitive biosensors and other sensing applications.

  3. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

  4. Near-infrared responsive PbS-sensitized photovoltaic photodetectors fabricated by the spin-assisted successive ionic layer adsorption and reaction method

    International Nuclear Information System (INIS)

    Im, Sang Hyuk; Kim, Hi-jung; Seok, Sang Il

    2011-01-01

    A PbS-sensitized photovoltaic photodetector responsive to near-infrared (NIR) light was fabricated by depositing monolayered PbS nanoparticles on a mesoporous TiO 2 (mp-TiO 2 ) film via the spin-assisted successive ionic layer adsorption and reaction (SILAR) method. By adjusting the size and morphology of the PbS nanoparticles through repeated spin-assisted SILAR cycles, the PbS-sensitized photovoltaic photodetector achieved an external quantum efficiency of 9.3% at 1140 nm wavelength and could process signals up to 1 kHz.

  5. A novel method of sensitivity analysis testing by applying the DRASTIC and fuzzy optimization methods to assess groundwater vulnerability to pollution: the case of the Senegal River basin in Mali

    Science.gov (United States)

    Souleymane, Keita; Zhonghua, Tang

    2017-08-01

    Vulnerability to groundwater pollution in the Senegal River basin was studied by two different but complementary methods: the DRASTIC method (which evaluates the intrinsic vulnerability) and the fuzzy method (which assesses the specific vulnerability by taking into account the continuity of the parameters). The validation of this application has been tested by comparing the connection in groundwater and distribution of different established classes of vulnerabilities as well as the nitrate distribution in the study area. Three vulnerability classes (low, medium and high) have been identified by both the DRASTIC method and the fuzzy method (between which the normalized model was used). An integrated analysis reveals that high classes with 14.64 % (for the DRASTIC method), 21.68 % (for the normalized DRASTIC method) and 18.92 % (for the fuzzy method) are not the most dominant. In addition, a new method for sensitivity analysis was used to identify (and confirm) the main parameters which impact the vulnerability to pollution with fuzzy membership. The results showed that the vadose zone is the main parameter which impacts groundwater vulnerability to pollution while net recharge contributes least to pollution in the study area. It was also found that the fuzzy method better assesses the vulnerability to pollution with a coincidence rate of 81.13 % versus that of 77.35 % for the DRASTIC method. These results serve as a guide for policymakers to identify areas sensitive to pollution before such sites are used for socioeconomic infrastructures.

  6. Sensitivity Weaknesses in Application of some Statistical Distribution in First Order Reliability Methods

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Enevoldsen, I.

    1993-01-01

    It has been observed and shown that in some examples a sensitivity analysis of the first order reliability index results in increasing reliability index, when the standard deviation for a stochastic variable is increased while the expected value is fixed. This unfortunate behaviour can occur when...... a stochastic variable is modelled by an asymmetrical density function. For lognormally, Gumbel and Weibull distributed stochastic variables it is shown for which combinations of the/3-point, the expected value and standard deviation the weakness can occur. In relation to practical application the behaviour...... is probably rather infrequent. A simple example is shown as illustration and to exemplify that for second order reliability methods and for exact calculations of the probability of failure this behaviour is much more infrequent....

  7. A Modified LC/MS/MS Method with Enhanced Sensitivity for the Determination of Scopolamine in Human Plasma

    Science.gov (United States)

    Wang, Zuwei; Vaksman, Zalman; Putcha, Lakshmi

    2008-01-01

    Intranasal scopolamine is a choice drug for the treatment of motion sickness during space flight because of its quick onset of action, short half-life and favorable sideeffects profile. The dose administered usually ranges between 0.1 and 0.4 mg. Such small doses make it difficult to detect concentrations of scopolamine in biological fluids using existing sensitive LC/MS/MS method, especially when the biological sample volumes are limited. To measure scopolamine in human plasma to facilitate pharmacokinetic evaluation of the drug, we developed a sensitive LC/MS/MS method using 96 well micro elution plates for solid phase extraction (SPE) of scopolamine in human plasma. Human plasma (100-250 micro L) were loaded onto Waters Oasis HLB 96 well micro elution plate and eluted with 50 L of organic solvent without evaporation and reconstitution. HPLC separation of the eluted sample was performed using an Agilent Zorbax SB-CN column (50 x 2.1 mm) at a flow rate of 0.2 mL/min for 3 minutes. The mobile phase for separation was 80:20 (v/v) methanol: ammonium acetate (30 mM) in water. Concentrations of scopolamine were determined using a Micromass Quattro Micro(TM) mass spectrometer with electrospray ionization (ESI). ESI mass spectra were acquired in positive ion mode with multiple reaction monitoring for the determination of scopolamine m/z = 304.2 right arrow 138.1 and internal standard hyoscyamine m/z = 290.2 right arrow 124.1. The method is rapid, reproducible, specific and has the following parameters: scopolamine and the IS are eluted at about 1.1 and 1.7 min respectively. The linear range is 25-10000 pg/mL for scopolamine in human plasma with correlation coefficients greater than 0.99 and CV less than 0.5%. The intra-day and inter-day CVs are less than 15% for quality control samples with concentrations of 75,300, and 750 pg/mL of scopolamine in human plasma. SPE using 96 well micro elution plates allows rapid sample preparation and enhanced sensitivity for the LC

  8. Developing a Method for Resolving NOx Emission Inventory Biases Using Discrete Kalman Filter Inversion, Direct Sensitivities, and Satellite-Based Columns

    Science.gov (United States)

    An inverse method was developed to integrate satellite observations of atmospheric pollutant column concentrations and direct sensitivities predicted by a regional air quality model in order to discern biases in the emissions of the pollutant precursors.

  9. Highly sensitive detection of influenza virus in saliva by real-time PCR method using sugar chain-immobilized gold nanoparticles; application to clinical studies

    Directory of Open Access Journals (Sweden)

    Yasuo Suda

    2015-09-01

    Full Text Available A highly sensitive and convenient method for detecting influenza virus was developed using modified end-point melt curve analysis of a RT-qPCR SYBR Green method and influenza virus-binding sugar chain-immobilized gold-nanoparticles (SGNP. Because SGNPs capture influenza viruses, the virus-SGNP complex was separated easily by centrifugation. Viral RNA was detected at very low concentrations, suggesting that SGNP increased sensitivity compared with standard methods. This method was applied to clinical studies. Influenza viruses were detected in saliva of patients or inpatients who had been considered influenza-free by a rapid diagnostic assay of nasal swabs. Furthermore, the method was applied to a human trial of prophylactic anti-influenza properties of yogurt containing Lactobacillus acidophilus L-92. The incidence of influenza viruses in saliva of the L-92 group was found to be significantly lower compared to the control group. Thus, this method was useful for monitoring the course of anti-influenza treatment or preventive measures against nosocomial infection.

  10. Sensitivity and specificity of various beta-lactam antibiotics and phenotypical methods for detection of TEM, SHV and CTX-M extended-spectrum beta-lactamases.

    Science.gov (United States)

    Bedenic, B; Vranes, J; Mihaljevic, Lj; Tonkic, M; Sviben, M; Plecko, V; Kalenic, S

    2007-04-01

    The aim of this study was to compare the sensitivity and specificity of six different beta-lactam antibiotics using five phenotypical tests for detection of extended spectrum beta-lactamases (ESBLs) based on synergism of beta-lactam antibiotics and clavulanate. Experiments were performed on a set of 80 Klebsiella pneumoniae strains and 105 Escherichia coli strains with previously characterized ESBLs (SHV, TEM and CTX-M). ESBLs were detected by five different phenotypical methods: MIC (minimum inhibitory concentration) determination of beta-lactam antibiotics with and without clavulanate, double-disk synergy test (DDST), inhibitor-potentiated disk-diffusion test (IPDDT), CLSI-Clinical and Laboratory Standard Institution (former NCCLS) combined-disk-test, and modified MAST-disk-diffusion test (MAST-DD-test). Seven antibiotics were tested as indicators of ESBL production: ceftazidime, cefotaxime, ceftriaxone, aztreonam, ceftibuten, cefpodoxime and cefepime. Ceftazidime and aztreonam were the best indicators for SHV-5, SHV-12 and TEM beta-lactamases whereas cefotaxime and ceftriaxone were the most sensitive in detection of SHV-2 and CTX-M beta-lactamases in DDST, IPDDT and CLSI test. MIC determination of beta-lactam antibiotics with and without clavulanate was the most sensitive method. DDST was the least sensitive test. Double-disk synergy test, which is the most frequently used test for detection of ESBLs in routine laboratories, was the least sensitive independently of the indicator antibiotic. Since MIC determination is a very laborious and time consuming method, we would recommend the NCCLS combined disk test or IPDD test for detection of ESBLs in routine laboratories with 5 mm zone augmentation breakpoint.

  11. Accelerated Sensitivity Analysis in High-Dimensional Stochastic Reaction Networks.

    Science.gov (United States)

    Arampatzis, Georgios; Katsoulakis, Markos A; Pantazis, Yannis

    2015-01-01

    Existing sensitivity analysis approaches are not able to handle efficiently stochastic reaction networks with a large number of parameters and species, which are typical in the modeling and simulation of complex biochemical phenomena. In this paper, a two-step strategy for parametric sensitivity analysis for such systems is proposed, exploiting advantages and synergies between two recently proposed sensitivity analysis methodologies for stochastic dynamics. The first method performs sensitivity analysis of the stochastic dynamics by means of the Fisher Information Matrix on the underlying distribution of the trajectories; the second method is a reduced-variance, finite-difference, gradient-type sensitivity approach relying on stochastic coupling techniques for variance reduction. Here we demonstrate that these two methods can be combined and deployed together by means of a new sensitivity bound which incorporates the variance of the quantity of interest as well as the Fisher Information Matrix estimated from the first method. The first step of the proposed strategy labels sensitivities using the bound and screens out the insensitive parameters in a controlled manner. In the second step of the proposed strategy, a finite-difference method is applied only for the sensitivity estimation of the (potentially) sensitive parameters that have not been screened out in the first step. Results on an epidermal growth factor network with fifty parameters and on a protein homeostasis with eighty parameters demonstrate that the proposed strategy is able to quickly discover and discard the insensitive parameters and in the remaining potentially sensitive parameters it accurately estimates the sensitivities. The new sensitivity strategy can be several times faster than current state-of-the-art approaches that test all parameters, especially in "sloppy" systems. In particular, the computational acceleration is quantified by the ratio between the total number of parameters over the

  12. Accelerated Sensitivity Analysis in High-Dimensional Stochastic Reaction Networks.

    Directory of Open Access Journals (Sweden)

    Georgios Arampatzis

    Full Text Available Existing sensitivity analysis approaches are not able to handle efficiently stochastic reaction networks with a large number of parameters and species, which are typical in the modeling and simulation of complex biochemical phenomena. In this paper, a two-step strategy for parametric sensitivity analysis for such systems is proposed, exploiting advantages and synergies between two recently proposed sensitivity analysis methodologies for stochastic dynamics. The first method performs sensitivity analysis of the stochastic dynamics by means of the Fisher Information Matrix on the underlying distribution of the trajectories; the second method is a reduced-variance, finite-difference, gradient-type sensitivity approach relying on stochastic coupling techniques for variance reduction. Here we demonstrate that these two methods can be combined and deployed together by means of a new sensitivity bound which incorporates the variance of the quantity of interest as well as the Fisher Information Matrix estimated from the first method. The first step of the proposed strategy labels sensitivities using the bound and screens out the insensitive parameters in a controlled manner. In the second step of the proposed strategy, a finite-difference method is applied only for the sensitivity estimation of the (potentially sensitive parameters that have not been screened out in the first step. Results on an epidermal growth factor network with fifty parameters and on a protein homeostasis with eighty parameters demonstrate that the proposed strategy is able to quickly discover and discard the insensitive parameters and in the remaining potentially sensitive parameters it accurately estimates the sensitivities. The new sensitivity strategy can be several times faster than current state-of-the-art approaches that test all parameters, especially in "sloppy" systems. In particular, the computational acceleration is quantified by the ratio between the total number of

  13. 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...

  14. Advances in bioanalytical techniques to measure steroid hormones in serum.

    Science.gov (United States)

    French, Deborah

    2016-06-01

    Steroid hormones are measured clinically to determine if a patient has a pathological process occurring in the adrenal gland, or other hormone responsive organs. They are very similar in structure making them analytically challenging to measure. Additionally, these hormones have vast concentration differences in human serum adding to the measurement complexity. GC-MS was the gold standard methodology used to measure steroid hormones clinically, followed by radioimmunoassay, but that was replaced by immunoassay due to ease of use. LC-MS/MS has now become a popular alternative owing to simplified sample preparation than for GC-MS and increased specificity and sensitivity over immunoassay. This review will discuss these methodologies and some new developments that could simplify and improve steroid hormone analysis in serum.

  15. Electrophysiological measurements of spectral sensitivities: a review

    Directory of Open Access Journals (Sweden)

    R.D. DeVoe

    1997-02-01

    Full Text Available Spectral sensitivities of visual systems are specified as the reciprocals of the intensities of light (quantum fluxes needed at each wavelength to elicit the same criterion amplitude of responses. This review primarily considers the methods that have been developed for electrophysiological determinations of criterion amplitudes of slow-wave responses from single retinal cells. Traditional flash methods can require tedious dark adaptations and may yield erroneous spectral sensitivity curves which are not seen in such modifications as ramp methods. Linear response methods involve interferometry, while constant response methods involve manual or automatic adjustments of continuous illumination to keep response amplitudes constant during spectral scans. In DC or AC computerized constant response methods, feedback to determine intensities at each wavelength is derived from the response amplitudes themselves. Although all but traditional flash methods have greater or lesser abilities to provide on-line determinations of spectral sensitivities, computerized constant response methods are the most satisfactory due to flexibility, speed and maintenance of a constant adaptation level

  16. 1HNMR-Based metabolomic profiling method to develop plasma biomarkers for sensitivity to chronic heat stress in growing pigs.

    Directory of Open Access Journals (Sweden)

    Samir Dou

    Full Text Available The negative impact of heat stress (HS on the production performances in pig faming is of particular concern. Novel diagnostic methods are needed to predict the robustness of pigs to HS. Our study aimed to assess the reliability of blood metabolome to predict the sensitivity to chronic HS of 10 F1 (Large White × Creole sire families (SF reared in temperate (TEMP and in tropical (TROP regions (n = 56±5 offsprings/region/SF. Live body weight (BW and rectal temperature (RT were recorded at 23 weeks of age. Average daily feed intake (AFDI and average daily gain were calculated from weeks 11 to 23 of age, together with feed conversion ratio. Plasma blood metabolome profiles were obtained by Nuclear Magnetic Resonance spectroscopy (1HNMR from blood samples collected at week 23 in TEMP. The sensitivity to hot climatic conditions of each SF was estimated by computing a composite index of sensitivity (Isens derived from a linear combination of t statistics applied to familial BW, ADFI and RT in TEMP and TROP climates. A model of prediction of sensitivity was established with sparse Partial Least Square Discriminant Analysis (sPLS-DA between the two most robust SF (n = 102 and the two most sensitive ones (n = 121 using individual metabolomic profiles measured in TEMP. The sPLS-DA selected 29 buckets that enabled 78% of prediction accuracy by cross-validation. On the basis of this training, we predicted the proportion of sensitive pigs within the 6 remaining families (n = 337. This proportion was defined as the predicted membership of families to the sensitive category. The positive correlation between this proportion and Isens (r = 0.97, P < 0.01 suggests that plasma metabolome can be used to predict the sensitivity of pigs to hot climate.

  17. Enhanced Sensitivity to Detection Nanomolar Level of Cu2 + Compared to Spectrophotometry Method by Functionalized Gold Nanoparticles: Design of Sensor Assisted by Exploiting First-order Data with Chemometrics

    Science.gov (United States)

    Rasouli, Zolaikha; Ghavami, Raouf

    2018-02-01

    A simple, sensitive and efficient colorimetric assay platform for the determination of Cu2 + was proposed with the aim of developing sensitive detection based on the aggregation of AuNPs in presence of a histamine H2-receptor antagonist (famotidine, FAM) as recognition site. This study is the first to demonstrate that the molar extinction coefficients of the complexes formed by FAM and Cu2 + are very low (by analyzing the chemometrics methods on the first order data arising from different metal to ligand ratio method), leading to the undesirable sensitivity of FAM-based assays. To resolve the problem of low sensitivity, the colorimetry method based on the Cu2 +-induced aggregation of AuNPs functionalized with FAM was introduced. This procedure is accompanied by a color change from bright red to blue which can be observed with the naked eyes. Detection sensitivity obtained by the developed method increased about 100 fold compared with the spectrophotometry method. This sensor exhibited a good linear relation between the absorbance ratios at 670 to 520 nm (A670/520) and the concentration in the range 2-110 nM with LOD = 0.76 nM. The satisfactory analytical performance of the proposed sensor facilitates the development of simple and affordable UV-Vis chemosensors for environmental applications.

  18. An overview of the environmental applicability of vermicompost: from wastewater treatment to the development of sensitive analytical methods.

    Science.gov (United States)

    Pereira, Madson de Godoi; Neta, Lourdes Cardoso de Souza; Fontes, Maurício Paulo Ferreira; Souza, Adriana Nascimento; Matos, Thaionara Carvalho; Sachdev, Raquel de Lima; dos Santos, Arnaud Victor; da Guarda Souza, Marluce Oliveira; de Andrade, Marta Valéria Almeida Santana; Paulo, Gabriela Marinho Maciel; Ribeiro, Joselito Nardy; Ribeiro, Araceli Verónica Flores Nardy

    2014-01-01

    The use of vermicompost (humified material) for treating wastewaters, remediating polluted soils, improving agricultural productivity, protecting crop production, and developing sensitive analytical methods is reviewed here, covering the past 17 years. The main advantages of vermicompost, considering all applications covered in this paper, comprise (i) easy acquisition, (ii) low costs, (iii) structural, chemical, and biological characteristics responsible for exceptional adsorptive capacities as well as pollutant degradation, and (iv) the promotion of biocontrol. Specifically, for wastewater decontamination, a considerable number of works have verified the adsorption of toxic metals, but the application of vermicompost is still scarce for the retention of organic compounds. Problems related to the final disposal of enriched vermicompost (after treatment steps) are often found, in spite of some successful destinations such as organic fertilizer. For decontaminating soils, the use of vermicompost is quite scarce, mainly for inorganic pollutants. In agricultural productivity and biocontrol, vermicompost imparts remarkable benefits regarding soil aggregation, plant nutrition, and the development of beneficial microorganisms against phytopathogens. Finally, the use of vermicompost in sensitive analytical methods for quantifying toxic metals is the newest application of this adsorbent.

  19. Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles.

    Science.gov (United States)

    Aiba, Toshiki; Saito, Toshiyuki; Hayashi, Akiko; Sato, Shinji; Yunokawa, Harunobu; Maruyama, Toru; Fujibuchi, Wataru; Kurita, Hisaka; Tohyama, Chiharu; Ohsako, Seiichiroh

    2017-03-09

    It has been pointed out that environmental factors or chemicals can cause diseases that are developmental in origin. To detect abnormal epigenetic alterations in DNA methylation, convenient and cost-effective methods are required for such research, in which multiple samples are processed simultaneously. We here present methylated site display (MSD), a unique technique for the preparation of DNA libraries. By combining it with amplified fragment length polymorphism (AFLP) analysis, we developed a new method, MSD-AFLP. Methylated site display libraries consist of only DNAs derived from DNA fragments that are CpG methylated at the 5' end in the original genomic DNA sample. To test the effectiveness of this method, CpG methylation levels in liver, kidney, and hippocampal tissues of mice were compared to examine if MSD-AFLP can detect subtle differences in the levels of tissue-specific differentially methylated CpGs. As a result, many CpG sites suspected to be tissue-specific differentially methylated were detected. Nucleotide sequences adjacent to these methyl-CpG sites were identified and we determined the methylation level by methylation-sensitive restriction endonuclease (MSRE)-PCR analysis to confirm the accuracy of AFLP analysis. The differences of the methylation level among tissues were almost identical among these methods. By MSD-AFLP analysis, we detected many CpGs showing less than 5% statistically significant tissue-specific difference and less than 10% degree of variability. Additionally, MSD-AFLP analysis could be used to identify CpG methylation sites in other organisms including humans. MSD-AFLP analysis can potentially be used to measure slight changes in CpG methylation level. Regarding the remarkable precision, sensitivity, and throughput of MSD-AFLP analysis studies, this method will be advantageous in a variety of epigenetics-based research.

  20. Near-infrared responsive PbS-sensitized photovoltaic photodetectors fabricated by the spin-assisted successive ionic layer adsorption and reaction method

    Energy Technology Data Exchange (ETDEWEB)

    Im, Sang Hyuk; Kim, Hi-jung; Seok, Sang Il, E-mail: seoksi@krict.re.kr [KRICT-EPFL Global Research Laboratory, Advanced Materials Division, Korea Research Institute of Chemical Technology, 19 Sinseongno, Yuseong, Daejeon 305-600 (Korea, Republic of)

    2011-09-30

    A PbS-sensitized photovoltaic photodetector responsive to near-infrared (NIR) light was fabricated by depositing monolayered PbS nanoparticles on a mesoporous TiO{sub 2} (mp-TiO{sub 2}) film via the spin-assisted successive ionic layer adsorption and reaction (SILAR) method. By adjusting the size and morphology of the PbS nanoparticles through repeated spin-assisted SILAR cycles, the PbS-sensitized photovoltaic photodetector achieved an external quantum efficiency of 9.3% at 1140 nm wavelength and could process signals up to 1 kHz.