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Nominal Values (nominal + value)
Selected AbstractsChronic urticaria , which clinical parameters are pathogenetically relevant?JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 1 2007A retrospective investigation of 339 patients Summary Background: Urticaria is a clinical reaction pattern triggered by many factors causing liberation of vasoactive substances such as histamine, prostaglandins and kinins. It presents as transient itching wheals which are either limited to the local stimulus area or more widespread. Urticaria is classified according to its duration into acute (duration , 6 weeks) and chronic (duration 6 weeks) forms. Various clinical investigations may be initiated to diagnose the cause. This study critically evaluates the relevance of frequently performed laboratory investigations and searches for infectious foci, as well as the results of physical provocation testing and oral provocation with food additives. Patients and Methods: The laboratory and clinical data of 339 patients who had been treated for urticaria at the Christian-Albrechts-University in Kiel over a period of four years were collected in a data entry form and statistically evaluated. Nominal values were analyzed by their relative and absolute quantities, quantitative parameters with the help of statistical data such as minimum, maximum, median and 25th and 75th percentiles. Results: Chronic recurrent urticaria was most common, accounting for 52% of cases. Women were affected 1.8 times more often than men. One-third of the patients also had angioedema. The medians of all laboratory parameters evaluated were within normal values. Only rarely were elevated antinuclear antibody titers, abnormal thyroid function tests or active infections such as hepatitis B or borreliosis detected. The search for infectious foci identified tonsillitis or sinusitis in almost 50% of analyzed patients. Positive reactions to physical testing occurred in 30% of patients and in 11% to oral provocation with various food additives. Conclusions: This study of a large patient group stresses the relevance of individually- tailored evaluations in patients affected with urticaria rather than an expensive initial broad diagnostic testing. More specific searches should be based on individual clues. [source] Scaling of spectral displacement ordinates with damping ratiosEARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 2 2005Julian J. Bommer Abstract The next generation of seismic design codes, especially those adopting the framework of performance-based design, will include the option of design based on displacements rather than forces. For direct displacement-based design using the substitute structure approach, the spectral ordinates of displacement need to be specified for a wide range of response periods and for several levels of damping. The code displacement spectra for damping values higher than the nominal value of 5% of critical will generally be obtained, as is the case in Eurocode 8 and other design codes, by applying scaling factors to the 5% damped ordinates. These scaling factors are defined as functions of the damping ratio and, in some cases, the response period, but are independent of the nature of the expected ground shaking. Using both predictive equations for spectral ordinates at several damping levels and stochastic simulations, it is shown that the scaling factors for different damping levels vary with magnitude and distance, reflecting a dependence of the scaling on the duration of shaking that increases with the damping ratio. The options for incorporating the influence of this factor into design code specifications of displacement response spectra are discussed. Copyright © 2004 John Wiley & Sons, Ltd. [source] Occupational exposure to methyl tertiary butyl ether in relation to key health symptom prevalence: the effect of measurement error correctionENVIRONMETRICS, Issue 6 2003Aparna P. Keshaviah Abstract In 1995, White et al. reported that methyl tertiary butyl ether (MTBE), an oxygenate added to gasoline, was significantly associated with key health symptoms, including headaches, eye irritation, and burning of the nose and throat, among 44 people occupationally exposed to the compound and for whom serum MTBE measurements were available (odds ratio (OR),=,8.9, 95% CI,=,[1.2, 75.6]). However, these serum MTBE measurements were available for only 29 per cent of the 150 subjects enrolled. Around the same time, Mannino et al. conducted a similar study among individuals occupationally exposed to low levels of MTBE and did not find a significant association between exposure to MTBE and the presence of one or more key health symptoms among the 264 study participants (OR,=,0.60, 95% CI,=,[0.3, 1.21]). In this article, we evaluate the effect of MTBE on the prevalence of key health symptoms by applying a regression calibration method to White et al.'s and Mannino et al.'s data. Unlike White et al., who classified exposure using actual MTBE levels among a subset of the participants, and Mannino et al., who classified exposure based on job category among all participants, we use all of the available data to obtain an estimate of the effect of MTBE in units of serum concentration, adjusted for measurement error due to using job category instead of measured exposure. After adjusting for age, gender and smoking status, MTBE exposure was found to be significantly associated with a 50 per cent increase in the prevalence of one or more key health symptoms per order of magnitude increase in blood concentration on the log10 scale, using data from the 409 study participants with complete information on the covariates (95% CI,=,[1.00, 2.25]). Simulation results indicated that under conditions similar to those observed in these data, the estimator is unbiased and has a coverage probability close to the nominal value. The methodology illustrated in this article is advantageous because all of the available data were used in the analysis, obtaining a more precise estimate of exposure effect on health outcome, and the estimate is adjusted for measurement error due to using job category instead of measured exposure. Copyright © 2003 John Wiley & Sons, Ltd. [source] Three Secondary Reference Materials for Lithium Isotope Measurements: Li7-N, Li6-N and LiCl-N SolutionsGEOSTANDARDS & GEOANALYTICAL RESEARCH, Issue 1 2007Jean Carignan matériaux de référence; isotopes de Li; solutions de Li; QUAD-ICP-MS; MC-ICP-MS The CRPG (Nancy, France) has prepared secondary reference materials for Li isotope measurements by mixing 7Li or 6Li spikes and either L-SVEC or IRMM-016 certified reference materials to produce solutions having a known Li concentration and isotopic composition. The Li7-N and Li6-N solution samples (1.5 mol l,1 HNO3) have nominal ,7Li isotopic compositions of 30.1, and -9.7, respectively relative to L-SVEC and concentrations of 100 mg l,1. Repeated measurement of these samples using the QUAD-ICP-MS at the CRPG yielded ,7Li of 30.4 ± 1.1, (n = 13) and -8.9 ± 0.9, (n = 9) at the 2s level of confidence. An additional LiCl-N solution was measured and yielded a delta value of 9.5 ± 0.6, (n = 3). Identical results were obtained at the BRGM (Orléans, France) from determinations performed with a Neptune MC-ICP-MS (30.2 ± 0.3,, n = 89 for the Li7-N, -8.0 ± 0.3,, n = 38 for the Li6-N and 10.1 ± 0.2,, n = 46 for LiCl-N at the 2s level of confidence). The deviation of measured composition relative to the nominal value for the Li6-N solution might be explained by either contamination during preparation or an error during sample weighing. These secondary reference materials, previously passed through ion exchange resin or directly analysed, may be used for checking the accuracy of Li isotopic measurements over a range of almost 40, and will be available to the scientific community upon request to J. Carignan or N. Vigier, CRPG. Le CRPG (Nancy, France) a préparé des matériaux secondaires de référence pour l'analyse des isotopes du Li en mélangeant des spikes de 7Li ou 6Li avec les matériaux de référence certifiés L-SVEC ou IRMM-016, ceci afin de produire des solutions ayant des concentrations et compositions isotopiques de Li connues. Les solutions Li7-N et Li6-N (1.5 mol l,1 HNO3) ont des compositions isotopiques nominales de ,7Li, exprimées par rapport à L-SVEC, de 30.1, et de -9.7, respectivement, et des concentrations de 10 0 mg l,1. L'analyse répétée de ces solutions par QUAD-ICP-MS au CRPG donne des ,7Li de 30.4 ± 1.1, (n = 13) et -8.9 ± 0.9, (n = 9) avec une incertitude à 2s. Une solution additionnelle de LiCl-N a été analysée et a donné une valeur de delta de 9.5 ± 0.6, (n = 3). Des résultats identiques ont été obtenus au BRGM (Orléans, France) où les déterminations ont été effectuées sur le MC-ICP-MS Neptune (30.2 ± 0.3,, n = 89 pour Li7-N, -8.0 ± 0.3,, n = 38 pour Li6-N et 10.1 ± 0.2,, n = 46 pour LiCl-N, à 2s d'intervalle de confiance). Le biais entre les compositions mesurées et la valeur nominale, observé pour la solution Li6-N peut être expliqué par une contamination durant la préparation ou par une erreur durant la pesée. Ces matériaux secondaires de référence, préalablement passés sur résine échangeuse d'ions ou analysés directement, peuvent être utilisés pour vérifier la justesse des analyses isotopiques de Li sur une gamme de presque 40% et sont à la disposition de la communauté scientifique sur demande auprès de J. Carignan ou N. Vigier, CRPG. [source] Computing eigenvalue bounds of structures with uncertain-but-non-random parameters by a method based on perturbation theoryINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING, Issue 11 2007Huinan Leng Abstract In this paper, an eigenvalue problem that involves uncertain-but-non-random parameters is discussed. A new method is developed to evaluate the reliable upper and lower bounds on frequencies of structures for these problems. In this method the matrix in the deviation amplitude interval is considered to be a perturbation around the nominal value of the interval matrix, and the upper and lower bounds to the maximum and minimum eigenvalues of this perturbation matrix are computed, respectively. Then based on the matrix perturbation theory, the eigenvalue bounds of the original interval eigenvalue problem can be obtained. Finally, two numerical examples are provided and the results show that the proposed method is reliable and efficient. Copyright © 2006 John Wiley & Sons, Ltd. [source] Stability analysis of the drive-train of a wind turbine with quadratic torque controlINTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL, Issue 17 2009Chen Wang Abstract This paper investigates the stability of a variable-speed wind turbine operating under low to medium wind speed. The turbine is controlled to capture as much wind energy as possible. We concentrate on the mechanical level of the turbine system, more precisely on the drive-train with the standard quadratic generator torque controller. We consider both the one-mass and the two-mass models for the drive-train, with the inputs being the deviation of the active torque from an arbitrary positive nominal value and the tracking error of the generator torque. We show that the turbine system is input-to-state stable for the one-mass model and integral input-to-state stable for the two-mass model. Copyright © 2008 John Wiley & Sons, Ltd. [source] Model predictive control with learning-type set-point: Application to artificial pancreatic ,-cellAICHE JOURNAL, Issue 6 2010Youqing Wang Abstract A novel combination of model predictive control (MPC) and iterative learning control (ILC), referred to learning-type MPC (L-MPC), is proposed for closed-loop control in an artificial pancreatic ,-cell. The main motivation for L-MPC is the repetitive nature of glucose-meal-insulin dynamics over a 24-h period. L-MPC learns from an individual's lifestyle, inducing the control performance to improve from day to day. The proposed method is first tested on the Adult Average subject presented in the UVa/Padova diabetes simulator. After 20 days, the blood glucose concentrations can be kept within 68,145 mg/dl when the meals are repetitive. L-MPC can produce superior control performance compared with that achieved under MPC. In addition, L-MPC is robust to random variations in meal sizes within ±75% of the nominal value or meal timings within ±60 min. Furthermore, the robustness of L-MPC to subject variability is validated on Adults 1,10 in the UVa/Padova simulator. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Design of electronic systems based on functional capabilityQUALITY AND RELIABILITY ENGINEERING INTERNATIONAL, Issue 1 2008James M. Gilbert Abstract An important measure of design quality is the extent to which a circuit design is able to meets its specification in the presence of component parameter variations. Of equal importance is knowing how to improve this capability most effectively. This paper presents an analysis technique and visualization method which give the designer information about design quality and possible routes to improved quality. The paper introduces two new measures of functional capability, based on the process capability measure Cpk, and shows how these may be linked to the statistical variations in individual component parameters. It then shows how this information may be used to assess the effectiveness of altering the nominal value and variability in each of the component parameters in order to improve circuit performance capability. The analysis required is straightforward and the information is presented in a clear manner which can readily be interpreted by the designer. The effectiveness of the technique has been evaluated through analysis of a number of printed circuit board level analogue and mixed signal circuits and the results of a case study are shown. Copyright © 2007 John Wiley & Sons, Ltd. [source] A direct injection high-throughput liquid chromatography tandem mass spectrometry method for the determination of a new orally active ,v,3 antagonist in human urine and dialysateRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 22 2003Wei Zeng A generic high-throughput liquid chromatography (HTLC) tandem mass spectrometry (MS/MS) assay for the determination of compound I in human urine and dialysate (hemodialysis) was developed and validated. By using the HTLC on-line extraction technique, sample pretreatment was not necessary. The sample was directly injected onto a narrow bore large particle size extraction column (50,×,1.0,mm, 60,,m) where the sample matrix was rapidly washed away using a high flow rate (5,mL/min) aqueous mobile phase while analytes were retained. The analytes were subsequently eluted from the extraction column onto an analytical column using an organic-enriched mobile phase prior to mass spectrometric detection. The analytes were then eluted from the analytical column to the mass spectrometer for the determination. The linear dynamic range was 2.0,6000,ng/mL for the urine assay and 0.1,300,ng/mL for the dialysate assay. Intraday accuracy and precision were evaluated by analyzing five replicates of calibration standards at all concentrations used to construct the standard curve. For the urine assay, the precision (RSD%, n,=,5) ranged from 1.9 to 8.0% and the accuracy ranged from 87.8 to 105.2% of nominal value. For the dialysate assay, the precision (RSD%, n,=,5) ranged from 1.1 to 10.0% and the accuracy from 94.5 to 105.2% of nominal value. In-source fragmentation of the acyl glucuronide metabolite (compound III) did not interfere with the determination of parent compound I. The developed HTLC/MS/MS methodology was specific for compound I in the presence of compound III. Column life-time is increased and sample analysis time is decreased over traditional reversed-phase methods when direct injection assays for urine and dialysate are coupled with the technology of HTLC. Copyright © 2003 John Wiley & Sons, Ltd. [source] Modeling the Korean Chonsei Lease ContractREAL ESTATE ECONOMICS, Issue 1 2003Brent W. Ambrose Chonsei is a unique Korean lease contract in which the tenant pays an up,front deposit, typically about 40 to 80% of the value of the property, with no requirement for periodic rent payments. At the contract maturation, the landlord then returns the nominal value of the deposit. Since there is no legal obligation on the part of the landlord to deposit the money in an escrow account, the principal default risk associated with the chonsei contract falls on the tenant. We discuss the development and popularity of this contractual agreement in the context of the public policy initiatives, historical and institutional settings surrounding the Korean housing and housing finance market. We develop a contingent,claims model that recognizes the compound options embedded in the chonsei contract. Theoretical predictions are confirmed by an empirical analysis using monthly data from 1986 to 2000. Our analysis shows that the chonsei contract is an indigenous market response to economic conditions prevalent in Korea. [source] Controlled release experiments with nonylphenol in aquatic microcosmsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2003Gerd Pfister Abstract A method of controlled release of technical nonylphenol (tNP) was developed to simulate realistic exposure in ecotoxicological studies on aquatic organisms. The direct addition of tNP from an aqueous stock solution into 50 ml of water led to a concentration decrease of 80 to 90% weight/volume (w/v) from nominal values within 48 h. The inclusion of tNP in semipermeable low-density polyethylene (LDPE) lay-flat tubing (controlled-release devices [CRDs]) of different length allowed a continuous release into pure water at a rate of about 30 ,g/cm2/d. Using CRDs in aquaria containing 15 L of 63-,m-filtered lake water, eight different concentrations with maxima between 38.1 and 326.7 ,g/L were maintained for 11 d. During a second experiment in 15-L aquaria, five replicates of three concentrations were maintained using CRDs of the same length. Concentrations after 38 d varied between 0.1 and 6.7, 26.1 and 41.9, and 49.9 and 76.0 ,g/L. In aquatic microcosms containing 230 L of lake water, a natural plankton community, 50 L of sediment, and macrophytes, seven different tNP concentrations (maxima 11,120.1 ,g/L) were maintained over 45 d using CRDs of different length. They were replaced after 14 and 25 d because release of tNP was slower than predicted from laboratory experiments. Concentrations in the top 1-cm sediment layer were on average 19 times higher during the dosing period than concentrations in the water at the same time. In the sediments, different levels of applications led to concentrations that differed less distinctly than in the water. This method is suitable for exposing aquatic organisms continuously to constant, ecologically relevant concentrations of NP and represents an improvement over previous dosing methods in which exposure varied. [source] Preparation of a Synthetic Titanite Glass Calibration Material for In Situ Microanalysis by Direct Fusion in Graphite Electrodes: A Preliminary Characterisation by EPMA and LA-ICP-MSGEOSTANDARDS & GEOANALYTICAL RESEARCH, Issue 2 2005Magne Ødegård matériaux de calibration; microanalyse; fusion directe; électrodes de graphite; verre de titanite This paper describes a technique for the preparation of a titanite (CaTiSiO5) glass calibration material for use in in situ microanalysis of major, minor, and trace elements in geological materials. The starting composition was a titanite matrix doped with minor and trace elements at , 200 ,g g -1. The elements Sc, Y, REEs, Th and U were added in the form of nitrates in solution, and the elements V, Cr, Mn, Fe, Co, Ni, Zr, Nb, Hf and W were added as solid oxides. The synthetic titanite glass was produced by direct fusion by resistance heating in graphite electrodes at 1600-1700 °C, and quenched in air. Backscattered electron images indicate good homogeneity, with no signs of separate phases or vesicles, and analysis of the major elements Ca, Ti and Si by electron microprobe showed relative standard deviations between 0.5 and 0.7%, based on six independent measurements. Deviations from nominal concentrations for Ca, Si and Ti were measured to -1.2, -3.3 and -0.8%, respectively. The homogeneity of the trace elements in the glass was assessed by LA-ICP-MS analyses, using NIST SRM 610, 612 and 616 as external calibrators, and Ca as the internal standard element. Determinations were made both with a quadrupole mass spectrometer and a sector field instrument, and both raster and spot modes of analysis were used. For the majority of doped elements, precision was better than 10%, and relative deviations from nominal values were, with few exceptions, between 5 and 10%. Cet article décrit une technique de préparation d'un verre de composition CaTiSiO5 (titanite) pour l'utiliser comme matériau de calibration lors de microanalyses in situ des éléments majeurs, mineurs et en trace dans des matériaux géologiques. La composition de départ a une matrice de titanite, dopée avec des éléments mineurs et en trace à une concentration de , 200 ,g g-1. Les éléments Sc, Y, REE, Th et U ont été ajoutés sous forme de nitrates en solution et les éléments V, Cr, Mn, Fe, Co, Ni, Zr, Nb, Hf et W sous forme d'oxydes solides. Le verre synthétique de titanite a été produit par fusion directe avec un chauffage par des résistances dans des électrodes de graphite à 1600-1700 °C suivi d'un refroidissement rapide à l'air. Les images obtenues par électrons rétrodiffusés montrent que le verre présente une bonne homogénéité, sans aucun signe de phases individualisées ou de vésicules, et l'analyse des éléments majeurs Ca, Ti et Si par microsonde électronique a des déviations standard relatives (RSD) entre 0.5 et 0.7% provenant de six mesures indépendantes. Les déviations par rapport aux concentrations calculées, pour Ca, Si et Ti, sont de -1.2, -3.3 et -0.8% respectivement. L'homogénéité de répartition des éléments en trace dans le verre a été vérifiée par des analyses LA-ICP-MS, en utilisant les matériaux de référence NIST SRM 610, 612 et 616 pour la calibration externe et Ca comme élément standard interne. Les déterminations ont été faites avec un spectromètre de masse de type quadrupôle et un autre de type secteur magnétique, par des analyses à la fois en mode balayage et en mode ponctuel. Pour la majorité des éléments dopés, la précision est meilleure que 10% et les déviations standard relatives par rapport aux valeurs calculées sont, à quelques exceptions près, entre 5 et 10%. [source] Rapid and accurate quantitative phase analysis using a fast detectorJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 1 2004A. F. Gualtieri The accuracy of the weight fractions calculated with the Rietveld method for various polycrystalline systems using data collected for very short times (5,45,min) with an RTMS (real-time multiple strip) detector was verified. The weight estimates were compared with those obtained using the same conventional Bragg,Brentano geometry, a gas proportional detector and a 13,h data acquisition. The analysed samples were monophasic and polyphasic mixtures with different degrees of complexity: the standard corundum NIST 676; a sample (labelled 1g) provided as a standard sample for the IUCr CPD Quantitative Phase Analysis Round Robin; a natural pyroclastic rock from Riano (Rome, Italy) containing zeolitic minerals and a glass phase; and a hydraulic lime. The results of the refinements show estimated weights consistent with both those obtained with a gas proportional detector and with the nominal values, indicating a very good accuracy. Only when variable slits are used, the accuracy of the estimated weights slightly decreases. The outcome of this work is a very important step forward towards fast and accurate QPA for production control and quality management, obtained by combining the use of a rapid detector and existing user-friendly software. [source] Defibrillation Depends on Conductivity Fluctuations and the Degree of Disorganization in Reentry PatternsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2005GERNOT PLANK Ph.D. Introduction: Cardiac fibrillation is the deterioration of the heart's normally well-organized activity into one or more meandering spiral waves, which subsequently break up into many meandering wave fronts. Delivery of an electric shock (defibrillation) is the only effective way of restoring the normal rhythm. This study focuses on examining whether higher degrees of disorganization requires higher shock strengths to defibrillate and whether microscopic conductivity fluctuations favor shock success. Methods and Results: We developed a three-dimensional computer bidomain model of a block of cardiac tissue with straight fibers immersed in a conductive bath. The membrane behavior was described by the Courtemanche human atrial action potential model incorporating electroporation and an acetylcholine- (ACh) dependent potassium current. Intracellular conductivities were varied stochastically around nominal values with variations of up to 50%. A single rotor reentry was initiated and, by adjusting the spatial ACh variation, the level of organization could be controlled. The single rotor could be stabilized or spiral wave breakup could be provoked leading to fibrillatory-like activity. For each level of organization, multiple shock timings and strengths were applied to compute the probability of shock success as a function of shock strength. Conclusions: Our results suggest that the level of the small-scale conductivity fluctuations is a very important factor in defibrillation. A higher variation significantly lowers the required shock strength. Further, we demonstrated that success also heavily depends on the level of organization of the fibrillatory episode. In general, higher levels of disorganization require higher shock strengths to defibrillate. [source] Upper limits on X-ray emission from two rotating radio transientsMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 3 2009D. L. Kaplan ABSTRACT X-ray emission from the enigmatic rotating radio transients (RRATs) offers a vital clue to understanding these objects and how they relate to the greater neutron star population. An X-ray counterpart to RRAT J1819,1458 is known, and its properties are similar to those of other middle-aged (0.1 Myr) neutron stars. We have searched for X-ray emission with Chandra/Advanced CCD Imaging Spectrometer at the positions of two RRATs with arcsecond (or better) localization, J0847,4316 and J1846,0257. Despite deep searches (especially for RRAT J1846,0257) we did not detect any emission with 0.3,8 keV count-rate limits of 1 and 0.068 counts ks,1, respectively, at 3, confidence. Assuming thermal emission similar to that seen from RRAT J1819,1458 (a blackbody with radius ,20 km), we derive effective temperature limits of 77 and 91 eV for the nominal values of the distances and column densities to both sources, although both of those quantities are highly uncertain and correlated. If we instead fix the temperature of the emission (a blackbody with kT= 0.14 keV), we derive unabsorbed luminosity limits in the 0.3,8 keV range of 1 × 1032 and 3 × 1032 erg s,1. These limits are considerably below the luminosity of RRAT J1819,1458(4 × 1033 erg s,1), suggesting that RRATs J0847,4316 and J1846,0257 have cooled beyond the point of visibility (plausible given the differences in characteristic age). However, as we have not detected X-ray emission, it may also be that the emission from RRATs J0847,4316 and J1846,0257 has a different character from that of RRAT J1819,1458. The two non-detections may prove a counterpoint to RRAT J1819,1458, but more detections are certainly needed before we can begin to derive general X-ray emission properties for the RRAT populations. [source] Variation mode and effect analysis: an application to fatigue life predictionQUALITY AND RELIABILITY ENGINEERING INTERNATIONAL, Issue 2 2009Pär Johannesson Abstract We present an application of the probabilistic branch of variation mode and effect analysis (VMEA) implemented as a first-order, second-moment reliability method. First order means that the failure function is approximated to be linear around the nominal values with respect to the main influencing variables, while second moment means that only means and variances are taken into account in the statistical procedure. We study the fatigue life of a jet engine component and aim at a safety margin that takes all sources of prediction uncertainties into account. Scatter is defined as random variation due to natural causes, such as non-homogeneous material, geometry variation within tolerances, load variation in usage, and other uncontrolled variations. Other uncertainties are unknown systematic errors, such as model errors in the numerical calculation of fatigue life, statistical errors in estimates of parameters, and unknown usage profile. By treating also systematic errors as random variables, the whole safety margin problem is put into a common framework of second-order statistics. The final estimated prediction variance of the logarithmic life is obtained by summing the variance contributions of all sources of scatter and other uncertainties, and it represents the total uncertainty in the life prediction. Motivated by the central limit theorem, this logarithmic life random variable may be regarded as normally distributed, which gives possibilities to calculate relevant safety margins. Copyright © 2008 John Wiley & Sons, Ltd. [source] Validation of a simple HPLC method for DRF-4848, a novel COX-2 inhibitor suitable for pharmacokinetic application in rats,BIOMEDICAL CHROMATOGRAPHY, Issue 12 2006Raja Reddy Kallem Abstract For pharmacokinetic and toxicokinetic purpose a simple HPLC-UV method has been developed and validated for the estimation of DRF-4848, a novel COX-2 inhibitor in rat plasma. A liquid,liquid extraction was used to extract DRF-4848 and internal standard (IS, DRF-4367) from rat plasma. The analysis was performed on a C18 column with UV detection at 285 nm. The isocratic mobile phase, 0.01 m potassium dihydrogen ortho phosphate (pH 3.2) and acetonitrile (50:50, v/v) was run at a flow rate of 1 mL/min. The retention times of DRF-4848 and IS were 6.8 and 11.2 min, respectively. Absolute recovery for analyte and IS was >80% from rat plasma. A linear response was observed over a concentration range 0.1,20 mg/mL. The lower limit of quantification (LLOQ) of DRF-4848 was 0.1 mg/mL. The inter- and intra-day precisions in the measurement of quality control (QC) samples, 0.1, 0.3, 8.0 and 15.0 mg/mL, were in the range 1.74,8.70% relative standard deviation (RSD) and 0.75,8.43% RSD, respectively. Accuracy in the measurement of QC samples was in the range 93.29,116.51% of the nominal values. Analyte and IS were stable in the battery of stability studies viz., benchtop, autosampler, long-term and freeze/thaw cycles. Copyright © 2006 John Wiley & Sons, Ltd. [source] Development and validation of a sensitive ELISA for quantitation of Grastim® (rhG-CSF) in rat plasma: application to a pharmacokinetic study,BIOMEDICAL CHROMATOGRAPHY, Issue 9 2006Chandrasekar Nirmala Abstract Grastim® is bacterially produced recombinant counterpart of human granulocyte colony stimulating factor (G-CSF). It has biological activity similar to that of endogenous G-CSF. In the present work a sensitive, accurate, precise and enzyme-linked immunosorbent assay (ELISA) for the quantitation of G-CSF in rat plasma was developed and validated. The ELISA method employed a technique in which anti-human-G-CSF was adsorbed onto 96-well maxisorp plates and used to capture the G-CSF in rat plasma samples. The captured G-CSF was then detected using streptavidin-HRP amplification system. Absolute recovery was >90% from rat plasma. The validation includes assessments of method accuracy and precision, range of reliable response, lower limit of quantitation (LLOQ), storage stability (30 days) in rat plasma and assay specificity. The standard curve for G-CSF was linear (R2 > 0.996) in the concentration range 4.88,625 pg/mL. The LLOQ was established at 4.88 pg/mL. The inter- and intra-day precisions in the measurement of quality control (QC) samples, 15, 250 and 500 pg/mL, were in the range 3.00,8.66% relative standard deviation (RSD) and 1.03,4.69% RSD, respectively. Accuracy in the measurement of QC samples was in the range 87.28,110.79% of the nominal values. The assay shows dilutional linearity and specificity. Stability of G-CSF was established for 30 days at ,80°C and through three freeze,thaw cycles. The validated assay was successfully employed for the assessment of pharmacokinetic disposition of G-CSF in rats. Copyright © 2006 John Wiley & Sons, Ltd. [source] HPLC method for determination of DRF-4367 in rat plasma: validation and its application to pharmacokinetics in Wistar rats,BIOMEDICAL CHROMATOGRAPHY, Issue 8 2004Ramesh Mullangi Abstract A speci,c, accurate, precise and reproducible high-performance liquid chromatography (HPLC) method was developed for the estimation of DRF-4367, a novel cyclooxygenase-2 inhibitor in rat plasma. The assay procedure involved simple liquid/liquid extraction of DRF-4367 and internal standard (IS, celecoxib) from plasma into dichloromethane. The organic layer was separated and evaporated under a gentle stream of nitrogen at 40°C. The residue was reconstituted in the mobile phase and injected onto a Kromasil KR 100-5C18 column (4.6 × 250 mm, 5 µm). The mobile phase consisting of 0.01 m potassium dihydrogen ortho -phosphate (pH 3.2) and acetonitrile (40:60, v/v) was used at a ,ow rate of 1.0 mL/min. The eluate was monitored using an UV detector set at 247 nm. The ratio of peak area of analyte to IS was used for quanti,cation of plasma samples. Nominal retention times of DRF-4367 and IS were 6.6 and 11.2 min, respectively. The standard curve for DRF-4367 was linear (r2 > 0.999) in the concentration range 0.1,20 µg/mL. Absolute recovery was >86% from rat plasma for both analyte and IS. The lower limit of quanti,cation of DRF-4367 was 0.1 µg/mL. The inter- and intra-day precisions in the measurement of quality control samples, 0.1, 0.3, 8.0 and 15.0 µg/mL, were in the range 6.93,9.34% relative standard deviation (RSD) and 0.48,6.59% RSD, respectively. Accuracy in the measurement of QC samples was in the range 91.24,109.36% of the nominal values. Analyte and IS were stable in the battery of stability studies, viz. benchtop, autosampler and freeze,thaw cycles. Stability of DRF-4367 was established for 1 month at ,80°C. The application of the assay to a pharmacokinetic study in rats is described. Copyright © 2004 John Wiley & Sons, Ltd. [source] High performance liquid chromatographic,mass spectrometric assay for the quantitation of BMS-204352 in dog K3EDTA plasmaBIOMEDICAL CHROMATOGRAPHY, Issue 3 2002Ming Yao A high performance liquid chromatographic-mass spectrometric (LC/MS) assay was developed and validated for the determination of BMS-204352 in dog K3EDTA plasma. A 0.5,mL aliquot of control plasma was spiked with BMS-204352 and internal standard (IS) and buffered with 1,mL of 5,mM ammonium acetate. The mixture was then extracted with 3,mL of toluene. After separation and evaporation of the organic phase to dryness using nitrogen at 40°C, the residue was reconstituted in the mobile phase and 25,µL of the sample were injected onto a Hypersil C18 column (2,×,50,mm; 3,µm) at a flow rate of 0.5,mL/min. The mobile phase was consisted of two solvent mixtures (A and B). Solvent A was composed of 5,mM ammonium acetate and 0.1% triethylamine in 75:25 v/v water:methanol, pH adjusted to 5.5 with glacial acetic acid, and solvent B was 5,mM ammonium acetate in methanol. A linear gradient system was used to elute the analytes. The mass spectrometer was programmed to admit the de-protonated molecules at m/z 352.7 (IS) and m/z 357.9 (BMS-204352). Standard curves of BMS-204352 were linear (r2,,,0.998) over the concentration range of 0.5,1000,ng/mL. The mean predicted quality control (QC) concentrations deviated less than 5.1% from the corresponding nominal values (ie 4, 80, 400 and 2000,ng/mL); the within- and between-assay precision of the assay were within 5.5% relative standard deviation. Stability of BMS-204352 was confirmed after at least three freeze/thaw cycles and BMS-204532 was stable in dog plasma when stored frozen at or below ,20°C for at least 16 weeks in spiked QC samples and for at least 4 1/2 weeks for in vivo study samples. BMS-204352 and IS were stable in the injection solvent at room temperature for at least 24,h. The assay was applied to delineate the pharmacokinetic disposition of BMS-204352 in dogs following a single intravenous dose administration. In conclusion, the assay is accurate, precise, specific, sensitive and reproducible for the pharmacokinetic analysis of BMS-204532 in dog plasma. Copyright © 2002 John Wiley & Sons, Ltd. [source] | ||||||||||||||||