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Sample records for antibodies measuring surrogates

  1. Neutron capture cross sections from Surrogate measurements

    OpenAIRE

    Scielzo N.D.; Dietrich F.S.; Escher J.E.

    2010-01-01

    The prospects for determining cross sections for compound-nuclear neutron-capture reactions from Surrogate measurements are investigated. Calculations as well as experimental results are presented that test the Weisskopf-Ewing approximation, which is employed in most analyses of Surrogate data. It is concluded that, in general, one has to go beyond this approximation in order to obtain (n,γ) cross sections of sufficient accuracy for most astrophysical and nuclear-energy applications.

  2. Neutron capture cross sections from Surrogate measurements

    Directory of Open Access Journals (Sweden)

    Scielzo N.D.

    2010-03-01

    Full Text Available The prospects for determining cross sections for compound-nuclear neutron-capture reactions from Surrogate measurements are investigated. Calculations as well as experimental results are presented that test the Weisskopf-Ewing approximation, which is employed in most analyses of Surrogate data. It is concluded that, in general, one has to go beyond this approximation in order to obtain (n,γ cross sections of sufficient accuracy for most astrophysical and nuclear-energy applications.

  3. Neutron capture cross sections from surrogate measurements

    International Nuclear Information System (INIS)

    The prospects for determining cross sections for compound-nuclear neutron-capture reactions from Surrogate measurements are investigated. Calculations as well as experimental results are presented that test the Weisskopf-Ewing approximation, which is employed in most analyses of Surrogate data. The method is applied to the 155Gd(n,γ) reaction. It is concluded that, in general, one has to go beyond this approximation in order to obtain (n,γ) cross sections of sufficient accuracy for most astrophysical and nuclear-energy applications. (authors)

  4. Surrogate cloud fields with measured cloud properties

    CERN Document Server

    Venema, V; Simmer, C; Venema, Victor; Crewell, Susanne; Simmer, Clemens

    2003-01-01

    This paper describes two new methods to generate 2D and 3D cloud fields based on 1D and 2D ground based profiler meas-urements. These cloud fields share desired statistical properties with real cloud fields. As they, however, are similar but not the same as real clouds, we call them surrogate clouds. One important advantage of the new methods is that the amplitude distribution of cloud liquid water is also exactly determined by the measurement: The surrogate clouds made with the classi-cal methods such as the Fourier method and the Bounded Cascade method are Gaussian and 'log-normal-like', respectively. Our first new method iteratively creates a time series with a measured amplitude distribution and power spectrum. Our sec-ond method uses an evolutionary search algorithm to generate cloud fields with practically arbitrary constraints. These clouds will be used to study the relation between radiation and cloud structure.

  5. Statistical characteristics of surrogate data based on geophysical measurements

    Directory of Open Access Journals (Sweden)

    V. Venema

    2006-01-01

    Full Text Available In this study, the statistical properties of a range of measurements are compared with those of their surrogate time series. Seven different records are studied, amongst others, historical time series of mean daily temperature, daily rain sums and runoff from two rivers, and cloud measurements. Seven different algorithms are used to generate the surrogate time series. The best-known method is the iterative amplitude adjusted Fourier transform (IAAFT algorithm, which is able to reproduce the measured distribution as well as the power spectrum. Using this setup, the measurements and their surrogates are compared with respect to their power spectrum, increment distribution, structure functions, annual percentiles and return values. It is found that the surrogates that reproduce the power spectrum and the distribution of the measurements are able to closely match the increment distributions and the structure functions of the measurements, but this often does not hold for surrogates that only mimic the power spectrum of the measurement. However, even the best performing surrogates do not have asymmetric increment distributions, i.e., they cannot reproduce nonlinear dynamical processes that are asymmetric in time. Furthermore, we have found deviations of the structure functions on small scales.

  6. Antibody detection in tear samples as a surrogate to monitor host immunity against papillomavirus infections in vaccinated and naturally infected hosts

    Science.gov (United States)

    Brendle, Sarah; Balogh, Karla; Bywaters, Stephanie

    2014-01-01

    Monitoring serum antibodies against natural infections or after immunizations has been a standard clinical diagnostic procedure. However, collecting blood samples requires trained personnel, and may cause discomfort and increase the risk of complications. In this study, we investigated whether tear samples could serve as a surrogate for serum samples to measure specific antibodies. A widely used preclinical cottontail rabbit papillomavirus (CRPV)/rabbit model has been a surrogate model for high-risk human papillomavirus (HPV) infections. New Zealand white rabbits, either naturally infected with CRPV or immunized with two clinically available HPV vaccines (Gardasil and Cervarix), were examined for antibody generation in both tear and serum samples. We demonstrated that antibodies were detectable in tears from both naturally infected as well as vaccinated animals. Overall, the antibody levels in tears were ~10-fold lower than those from the corresponding serum samples, but background noise was lower in tear samples. The isotypes of antibodies in tears were predominantly IgA and IgG. These findings showed clearly that tears could be a surrogate for serum samples for monitoring antibody responses. As collecting tears causes no discomfort and poses no risk to patients, it represents a novel and promising method for monitoring future HPV epidemiological studies as well as for use in clinical practice. PMID:24903329

  7. Overview of Surrogates to Measure Audit Quality

    Directory of Open Access Journals (Sweden)

    Fuad Elmahedi Hussein

    2013-08-01

    Full Text Available After the collapse of Arthur Andersen in 2002, the auditing profession has faced increasing pressure fromexternal parties to enhance and improve audit quality. These pressures led to a continued need to study thefactors that affect audit quality. Until present, there is no agreement among researchers about the definition andfactors of audit quality. To date, the issue of how audit quality is measured remains a matter of controversy anddisagreement. Previous studies used alternatives to measure audit quality. This paper reviews both thearguments for and against for these studies. Although, the importance of these alternatives and its potentialcontribution on audit quality have been emphasized, they are not a justification to ignore audit characteristicsthat could have significant impact on audit quality. This paper contributes to audit literature and represents abrief overview of reviews both the arguments for and against of using audit quality alternatives in previousstudies over the past 30 years. Thus it provides a basis for discussing several potentially rich factors for futureresearch on audit quality.

  8. Ganglioside GD2-specific trifunctional surrogate antibody Surek demonstrates therapeutic activity in a mouse melanoma model

    Directory of Open Access Journals (Sweden)

    Ruf Peter

    2012-11-01

    Full Text Available Abstract Background Trifunctional bispecific antibodies (trAb are a special class of bispecific molecules recruiting and activating T cells and accessory immune cells simultaneously at the targeted tumor. The new trAb Ektomab that targets the melanoma-associated ganglioside antigen GD2 and the signaling molecule human CD3 (hCD3 on T cells demonstrated potent T-cell activation and tumor cell destruction in vitro. However, the relatively low affinity for the GD2 antigen raised the question of its therapeutic capability. To further evaluate its efficacy in vivo it was necessary to establish a mouse model. Methods We generated the surrogate trAb Surek, which possesses the identical anti-GD2 binding arm as Ektomab, but targets mouse CD3 (mCD3 instead of hCD3, and evaluated its chemical and functional quality as a therapeutic antibody homologue. The therapeutic and immunizing potential of Surek was investigated using B78-D14, a B16 melanoma transfected with GD2 and GD3 synthases and showing strong GD2 surface expression. The induction of tumor-associated and autoreactive antibodies was evaluated. Results Despite its low affinity of approximately 107 M-1 for GD2, Surek exerted efficient tumor cell destruction in vitro at an EC50 of 70ng/ml [0.47nM]. Furthermore, Surek showed strong therapeutic efficacy in a dose-dependent manner and is superior to the parental GD2 mono-specific antibody, while the use of a control trAb with irrelevant target specificity had no effect. The therapeutic activity of Surek was strictly dependent on CD4+ and CD8+ T cells, and cured mice developed a long-term memory response against a second challenge even with GD2-negative B16 melanoma cells. Moreover, tumor protection was associated with humoral immune responses dominated by IgG2a and IgG3 tumor-reactive antibodies indicating a Th1-biased immune response. Autoreactive antibodies against the GD2 target antigen were not induced. Conclusion Our data suggest that Surek revealed

  9. Neural Networks as Surrogate Models for Measurements in Optimization Algorithms

    Czech Academy of Sciences Publication Activity Database

    Holeňa, Martin; Linke, D.; Rodemerck, U.; Bajer, Lukáš

    Berlin: Springer, 2010 - (Al-Begain, K.; Fiems, D.; Knottenbelt, W.), s. 351-366. (Lecture Notes in Computer Science. 6148). ISBN 978-3-642-13567-5. ISSN 0302-9743. [ASMTA 2010. International Conference /17./. Cardiff (GB), 14.06.2010-16.06.2010] R&D Projects: GA ČR GA201/08/0802 Institutional research plan: CEZ:AV0Z10300504 Keywords : functions evaluated via measurements * evolutionary optimization * surrogate modelling * neural networks * boosting Subject RIV: IN - Informatics, Computer Science

  10. Measurement of antibodies to tubulin by radioimmunoassay

    International Nuclear Information System (INIS)

    A solid-phase double antibody radioimmunoassay capable of measuring antibody to tubulin, the principal component of microtubules, is described. This assay is simple, combining sensitivity with specificity and also allowing determination of antibody subclasses. (Auth.)

  11. Hepatology may have problems with putative surrogate outcome measures

    DEFF Research Database (Denmark)

    Gluud, Christian; Brok, Jesper; Gong, Yan;

    2007-01-01

    faster or more often, are cheaper, and/or are less invasively achieved than the clinical outcome. In practice, validation is surprisingly often overlooked, especially if a biologic plausible rationale is proposed. Surrogate outcomes must be validated before use. The first step in validation is to...... predicts the intervention's effect on the clinical outcome. In hepatology a number of putative surrogate outcomes are used both in clinical research and in clinical practice without having been properly validated. Sustained virological response to interferons and ribavirin in patients with chronic...

  12. Surrogate measures: A proposed alternative in human factors assessment of operational measures of performance

    Science.gov (United States)

    Kennedy, Robert S.; Lane, Norman E.; Kuntz, Lois A.

    1987-01-01

    Surrogate measures are proposed as an alternative to direct assessment of operational performance for purposes of screening agents who may have to work under unusual stresses or in exotic environments. Such measures are particularly proposed when the surrogate can be empirically validated against the operational criterion. The focus is on cognitive (or throughput) performances in humans as opposed to sensory (input) or motor (output) measures, but the methods should be applicable for development of batteries which will tap input/output functions. A menu of performance tasks is under development for implementation on a battery-operated portable microcomputer, with 21 tests currently available. The tasks are reliable and become stable in minimum amounts of time; appear sensitive to some agents; comprise constructs related to actual job tasks; and are easily administered in most environments. Implications for human factors engineering studies in environmental stress are discussed.

  13. Regression calibration for classical exposure measurement error in environmental epidemiology studies using multiple local surrogate exposures.

    Science.gov (United States)

    Bateson, Thomas F; Wright, J Michael

    2010-08-01

    Environmental epidemiologic studies are often hierarchical in nature if they estimate individuals' personal exposures using ambient metrics. Local samples are indirect surrogate measures of true local pollutant concentrations which estimate true personal exposures. These ambient metrics include classical-type nondifferential measurement error. The authors simulated subjects' true exposures and their corresponding surrogate exposures as the mean of local samples and assessed the amount of bias attributable to classical and Berkson measurement error on odds ratios, assuming that the logit of risk depends on true individual-level exposure. The authors calibrated surrogate exposures using scalar transformation functions based on observed within- and between-locality variances and compared regression-calibrated results with naive results using surrogate exposures. The authors further assessed the performance of regression calibration in the presence of Berkson-type error. Following calibration, bias due to classical-type measurement error, resulting in as much as 50% attenuation in naive regression estimates, was eliminated. Berkson-type error appeared to attenuate logistic regression results less than 1%. This regression calibration method reduces effects of classical measurement error that are typical of epidemiologic studies using multiple local surrogate exposures as indirect surrogate exposures for unobserved individual exposures. Berkson-type error did not alter the performance of regression calibration. This regression calibration method does not require a supplemental validation study to compute an attenuation factor. PMID:20573838

  14. Surrogacy assessment using principal stratification when surrogate and outcome measures are multivariate normal

    OpenAIRE

    Conlon, Anna S. C.; Taylor, Jeremy M.G.; Elliott, Michael R.

    2013-01-01

    In clinical trials, a surrogate outcome variable (S) can be measured before the outcome of interest (T) and may provide early information regarding the treatment (Z) effect on T. Using the principal surrogacy framework introduced by Frangakis and Rubin (2002. Principal stratification in causal inference. Biometrics 58, 21–29), we consider an approach that has a causal interpretation and develop a Bayesian estimation strategy for surrogate validation when the joint distribution of potential...

  15. Facial recognition of heroin vaccine opiates: Type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine

    OpenAIRE

    Matyas, Gary R.; Rice, Kenner C.; Cheng, Kejun; Li, Fuying; Antoline, Joshua F. G.; Iyer, Malliga R.; Jacobson, Arthur E; Mayorov, Alexander V.; Beck, Zoltan; Torres, Oscar; Alving, Carl R.

    2014-01-01

    Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two...

  16. A new hybrid surrogate ratio method for neutron-induced fission cross section measurements of short-lived actinides

    International Nuclear Information System (INIS)

    We will present a brief review of various surrogate methods employed for compound nuclear cross-section measurements along with our recent results using the hybrid surrogate ratio approach for determination of neutron induced fission cross sections of 233Pa and 234Pa isotopes

  17. Chapter 1. Direct and surrogate measures of soil water content

    International Nuclear Information System (INIS)

    The purpose of this manual is to provide guidance for field scientists who are not instrumentation experts but who wish to determine soil water content as part of their work. This publication is targeted to help those setting up soil water monitoring projects in the developing countries where expertise in many technologies is not readily available. However, it also has value to anyone planning a project involving the determination of field soil water content. Most importantly, it will also give some guidance as to what corroborative measurements are needed to check the performance of water sensing technology being used. A substantial suite of soil water sensors and technologies are available today. Some are well understood as to their technical capability and are both mechanically and electronically reliable. However, some technologies that claim to measure soil water content are quite unsuited to some applications and produce results that have little, if any, relation to soil water content in the field. This manual sets out a decision making process and critical factors for matching various water measurement technologies to project objectives. The first factor is the accuracy required by the user. The second is the degree of water content variability across the field to be measured. The third is the presence of interferences to the measurement process. And the fourth consists of the capabilities of the available devices in light of the spatial variability of water content and the interferences that are present. A successful outcome can only be obtained if all four factors are considered. Because this manual is intended to be a practical guide, it cannot be a simple one. Only reliable measurements are practically useful. The techniques involved in obtaining reliable values of soil water content are not simple, nor are the potential problems, pitfalls, and sensor interferences that can prevent good values from being obtained. The manual is divided into chapters that

  18. Facial recognition of heroin vaccine opiates: type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine.

    Science.gov (United States)

    Matyas, Gary R; Rice, Kenner C; Cheng, Kejun; Li, Fuying; Antoline, Joshua F G; Iyer, Malliga R; Jacobson, Arthur E; Mayorov, Alexander V; Beck, Zoltan; Torres, Oscar B; Alving, Carl R

    2014-03-14

    Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two unique hydrolytically stable haptens were created based on presumed structural facial similarities to heroin or to its active metabolites. After conjugation of a heroin-like hapten (DiAmHap) to tetanus toxoid and mixing with liposomes containing monophosphoryl lipid A, high titers of antibodies after two injections in mice had complementary binding sites that exhibited strong type 1 ("true") specific cross-reactivity with heroin and with both of its physiologically active metabolites. Mice immunized with each surrogate hapten exhibited reduced antinociceptive effects caused by injection of heroin. This approach obviates the need to create hydrolytically unstable synthetic heroin-like compounds to induce independent immune responses to heroin and its active metabolites for vaccine development. Facial recognition of hydrolytically stable surrogate haptens by antibodies together with type 1 cross-reactivities with heroin and its metabolites can help to guide synthetic chemical strategies for efficient development of a heroin vaccine. PMID:24486371

  19. Critical dosimetry measures and surrogate tools that can facilitate clinical success in PDT (Conference Presentation)

    Science.gov (United States)

    Pogue, Brian W.; Davis, Scott C.; Kanick, Stephen C.; Maytin, Edward V.; Pereira, Stephen P.; Palanisami, Akilan; Hasan, Tayyaba

    2016-03-01

    Photodynamic therapy can be a highly complex treatment with more than one parameter to control, or in some cases it is easily implemented with little control other than prescribed drug and light values. The role of measured dosimetry as related to clinical adoption has not been as successful as it could have been, and part of this may be from the conflicting goals of advocating for as many measurements as possible for accurate control, versus companies and clinical adopters advocating for as few measurements as possible, to keep it simple. An organized approach to dosimetry selection is required, which shifts from mechanistic measurements in pre-clinical and early phase I trials, towards just those essential dose limiting measurements and a focus on possible surrogate measures in phase II/III trials. This essential and surrogate approach to dosimetry should help successful adoption of clinical PDT if successful. The examples of essential dosimetry points and surrogate dosimetry tools which might be implemented in phase II and higher trials are discussed for solid tissue PDT with verteporfin and skin lesion treatment with aminolevulinc acid.

  20. Comparison of Surrogate Markers as Measures of Uncomplicated Insulin Resistance in Korean Adults

    Science.gov (United States)

    Kim, Tae Jong; Kim, Hye Jung; Kim, Young Bae; Lee, Jee Yon; Lee, Hye Sun; Hong, Jung Hwa

    2016-01-01

    Background Metabolic syndrome (MS) is known to increase the risk of various cardiometabolic diseases and in-sulin resistance (IR) has known to have central role in the development of MS. Many surrogate indices of IR have been proposed and the detection of MS might be a suitable model for assessing the accuracy of surrogate indices. The aims of our study are to invest the most appropriate index by assessment of the diagnostic capacity of IR among each surrogate index and identifying cut-off values for discriminating uncomplicated MS in Korean adults. Methods A cross-sectional study was performed, assessing 294 Korean adults, 85 of whom were diagnosed with uncomplicated MS. The sensitivities and specificities of five surrogate IR indices were compared to discriminate MS from healthy subjects; these included fasting serum insulin, homeostasis model assessment–insulin resistance index, quantitative insulin sensitivity check index, McAuley index, and Disse index. Correlations between each index value were assessed using Pearson's and Spearman's correlation methods. Results The McAuley index showed the highest area under the curve (0.85), specificity (86.12%), accuracy (82.31%), positive predictive value (68.13%), and negative predictive value (88.67%) to distinguish MS, with a cut-off point of 5.3 defined. Correlation coefficients of the five indices showed that the McAuley index had the strongest correlation with IR. Conclusion The McAuley index showed the best accuracy in the detection of MS as a surrogate marker of IR. To establish more effective and accurate standards of measuring IR, comprehensive and multi-scaled studies are required.

  1. DNA methylation arrays as surrogate measures of cell mixture distribution

    Directory of Open Access Journals (Sweden)

    Houseman Eugene

    2012-05-01

    Full Text Available Abstract Background There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls. Results Here we present a method, similar to regression calibration, for inferring changes in the distribution of white blood cells between different subpopulations (e.g. cases and controls using DNA methylation signatures, in combination with a previously obtained external validation set consisting of signatures from purified leukocyte samples. We validate the fundamental idea in a cell mixture reconstruction experiment, then demonstrate our method on DNA methylation data sets from several studies, including data from a Head and Neck Squamous Cell Carcinoma (HNSCC study and an ovarian cancer study. Our method produces results consistent with prior biological findings, thereby validating the approach. Conclusions Our method, in combination with an appropriate external validation set, promises new opportunities for large-scale immunological studies of both disease states and noxious exposures.

  2. Cross sections for neutron capture from surrogate measurements: An examination of Weisskopf-Ewing and ratio approximations

    CERN Document Server

    Escher, Jutta E

    2010-01-01

    Motivated by the renewed interest in the surrogate nuclear reactions approach, an indirect method for determining compound-nuclear reaction cross sections, the prospects for determining (n, gamma) cross sections for deformed rare-earth and actinide nuclei are investigated. A nuclear-reaction model is employed to simulate physical quantities that are typically measured in surrogate experiments and used to assess the validity of the Weisskopf-Ewing and ratio approximations, which are typically employed in the analysis of surrogate reactions. The expected accuracy of (n,gamma) cross sections extracted from typical surrogate measurements is discussed and limitations of the approximate methods are illustrated. Suggestions for moving beyond presently-employed approximations are made.

  3. Cross sections for neutron capture from surrogate measurements: An examination of Weisskopf-Ewing and ratio approximations

    International Nuclear Information System (INIS)

    Motivated by the renewed interest in the surrogate nuclear reactions approach, an indirect method for determining compound-nuclear reaction cross sections, the prospects for determining (n,γ) cross sections for deformed rare-earth and actinide nuclei are investigated. A nuclear reaction model is employed to simulate physical quantities that are typically measured in surrogate experiments and used to assess the validity of the Weisskopf-Ewing and ratio approximations, which are typically employed in the analysis of surrogate reactions. The expected accuracy of (n,γ) cross sections extracted from typical surrogate measurements is discussed and limitations of the approximate methods are illustrated. Suggestions for moving beyond presently employed approximations are made.

  4. Investigation of surrogate method for 55Fe(n,p)55Mn reaction cross-section measurement

    International Nuclear Information System (INIS)

    In the present work the feasibility study of surrogate technique for the cross-section measurement of 55Fe(n, p)55Mn is done. This reaction is very important in fusion environment as 55Fe (t1/2=2.73 years) is produced via 56Fe(n,2n)55Fe nuclear reaction with fast neutrons. It will be first time that we use surrogate method in fusion applications in this mass region

  5. Cross sections for neutron capture from surrogate measurements: An examination of Weisskopf-Ewing and ratio approximations

    OpenAIRE

    Escher, Jutta E.; Dietrich, Frank S.

    2010-01-01

    Motivated by the renewed interest in the surrogate nuclear reactions approach, an indirect method for determining compound-nuclear reaction cross sections, the prospects for determining (n, gamma) cross sections for deformed rare-earth and actinide nuclei are investigated. A nuclear-reaction model is employed to simulate physical quantities that are typically measured in surrogate experiments and used to assess the validity of the Weisskopf-Ewing and ratio approximations, which are typically ...

  6. Surrogate biochemical markers: precise measurement for strategic drug and biologics development.

    Science.gov (United States)

    Lee, J W; Hulse, J D; Colburn, W A

    1995-05-01

    More efficient drug and biologics development is necessary for future success of pharmaceutical and biotechnology companies. One way to achieve this objective is to use rationally selected surrogate markers to improve the early decision-making process. Using typical clinical chemistry methods to measure biochemical markers may not ensure adequate precision and reproducibility. In contrast, using analytical methods that meet good laboratory practices along with rational selection and validation of biochemical markers can give those who use them a competitive advantage over those who do not by providing meaningful data for earlier decision making. PMID:7657845

  7. Determining neutron capture cross sections with the Surrogate Reaction Technique: Measuring decay probabilities with STARS

    International Nuclear Information System (INIS)

    Neutron-induced reaction cross sections are sometimes difficult to measure due to target or beam limitations. For two-step reactions proceeding through an equilibrated intermediate state, an alternate 'surrogate reaction' technique [J.D. Cramer and H.C. Britt, Nucl. Sci. Eng. 41, 177 (1970), H.C. Britt and J.B. Wilhelmy, Nucl. Sci. Eng. 72, 222 (1979), W.Younes and H.C. Britt, Phys. Rev. C 67, 024610 (2003)] can be applicable, and is currently undergoing investigation at LLNL. Measured decay probabilities for the intermediate nucleus formed in a light-ion reaction can be combined with optical-model calculations for the formation of the same intermediate nucleus via the neutron-induced reaction. The result is an estimation for overall (n,γ/n/2n) cross sections. As a bench-mark, the reaction 92Zr(α, α'), surrogate for n+91Zr, was studied at the A.W. Wright Nuclear Structure Laboratory at Yale. Particles were detected in the silicon telescope STARS (Silicon Telescope Array for Reaction Studies) and γ-ray energies measured with germanium clover detectors from the YRAST (Yale Rochester Array for SpecTroscopy) ball. The experiment and preliminary observations will be discussed

  8. Genetic and phenotypic correlations between surrogate measures of insulin release obtained from OGTT data

    DEFF Research Database (Denmark)

    Gjesing, Anette P; Ribel-Madsen, Rasmus; Harder, Marie N; Eiberg, Hans; Grarup, Niels; Jørgensen, Torben; Ekstrøm, Claus T; Pedersen, Oluf; Hansen, Torben

    2015-01-01

    closely related to fasting insulin with a genetic correlation of 0.85. The effects of 82 selected susceptibility single nucleotide polymorphisms on these insulin secretion indices supported our interpretation of the data and added insight into the biological differences between the examined traits......AIMS/HYPOTHESIS: We examined the extent to which surrogate measures of insulin release have shared genetic causes. METHODS: Genetic and phenotypic correlations were calculated in a family cohort (n = 315) in which beta cell indices were estimated based on fasting and oral glucose-stimulated plasma....... RESULTS: We found a notable difference between the phenotypic and genetic correlations for the traits, emphasising that the phenotypic correlation is an insufficient measure of the magnitude of shared genetic impact. In addition, we found that corrected insulin response, insulinogenic index and incAUC for...

  9. Surrogate measures for providing high frequency estimates of total phosphorus concentrations in urban watersheds.

    Science.gov (United States)

    Viviano, Gaetano; Salerno, Franco; Manfredi, Emanuela Chiara; Polesello, Stefano; Valsecchi, Sara; Tartari, Gianni

    2014-11-01

    Until robust in situ sensors for total phosphorus (TP) are developed, continuous water quality measurements have the potential to be used as surrogates for generating high frequency estimates. Their use has widespread implications for water quality monitoring programmes considering that TP, in particular, is generally recognised as the limiting factor in the process of eutrophication. Surrogate measures for TP concentration, such as turbidity, have proved useful within natural and agricultural contexts, but their predictive capability for urban watersheds is considered more difficult, due to the different sources of TP, though a strict relationship with turbidity/suspended matter has been clearly described even for these environments. In this context, we investigated this still unresolved problem for high frequency estimation of TP concentration in urban environments by monitoring a medium-sized (71 km(2)) urban watershed (Lambro River watershed, north Italy) in which we detected 60 active combined sewer overflows, and an its natural sub-basin for comparison. We found two different relationships between turbidity and TP concentration in the investigated urban watershed that differently describe the prevalence of TP from point sources (domestic wastewaters) or diffuse origin (surface runoff). In this regard, we first characterise the prevailing sources of TP by using a marker for detecting domestic wastewater contamination (caffeine), then we describe the mutual relationships amongst the continuously monitored variables (in our case the occurrence of the First Flush and the clockwise turbidity/discharge hysteresis). Afterwards we discriminate, by observing variables that are continuously monitored (in our case, the discharge and the turbidity), amongst the continuous surrogate records according to their sources. In conclusion, we are able to apply the relevant turbidity/TP regression equations to each turbidity record and, thus, estimate the respective TP

  10. Surrogate indicators of sensitivity in gynecologic cytology: Can they be used to improve the measurement of sensitivity in the laboratory?

    OpenAIRE

    Renshaw Andrew; Brimo Fadi; Auger Manon

    2009-01-01

    Background: Measuring the sensitivity of screening in gynecologic cytology in real life is problematic. However, other quality measures may correlate with sensitivity, including the atypical squamous cells (ASC)/squamous intraepithelial lesion (SIL) ratio. Whether these other measures can function as "surrogate indicators" for sensitivity and improve the assessment of sensitivity in the laboratory is not known. Materials and Methods: We compared multiple quality measures with true screenin...

  11. Surrogate Reaction Measurement of Angular Dependent 239Pu (n , f) Probabilities

    Science.gov (United States)

    Koglin, Johnathon; Burke, Jason; Casperson, Robert; Jovanovic, Igor

    2015-10-01

    The surrogate method has previously been used to measure (n , f) cross sections of difficult to produce actinide isotopes. These measurements have inaccuracies at excitation energies below 1.5 MeV where the distribution of angular momentum states populated in the compound nucleus created by neutron absorption significantly differs from that arising from direct reactions. A method to measure the fission probability of individual angular momentum states arising from 239Pu (d , pf) and 239Pu (α ,α' f) reactions has been developed. This experimental apparatus consists of charged particle detectors with 40 keV FWHM resolution at 13 angles up and downstream of the particle beam. A segmented array of photovoltaic (solar) cells is used to measure the angular distribution of fission fragments. This distribution uniquely identifies the populated angular momentum states. These are fit to expected distributions to determine the contribution of each state. The charged particle and fission rates matrix obtained from this analysis determines fission probabilities of specific angular momentum states in the transition nucleus. Development of this scheme and first results will be discussed.

  12. Measurement of 55Fe(n ,p ) cross sections by the surrogate-reaction method for fusion technology applications

    Science.gov (United States)

    Pandey, Bhawna; Desai, V. V.; Suryanarayana, S. V.; Nayak, B. K.; Saxena, A.; Mirgule, E. T.; Santra, S.; Mahata, K.; Makawana, R.; Abhangi, M.; Basu, T. K.; Rao, C. V. S.; Jakhar, S.; Vala, S.; Sarkar, B.; Agrawal, H. M.; Kaur, G.; Prajapati, P. M.; Pal, Asim; Sarkar, D.; Kundu, A.

    2016-02-01

    We have measured the proton decay probabilities of the *56Fe and *47Ti compound systems which are populated by the transfer reactions 52Cr(6Li,d ) *56Fe (surrogate of n +55Fe→*56Fe→p +55Mn ) and 45Sc(6Li,α ) *47Ti (surrogate of n +46Ti→47Ti*→p +46Sc ) reactions, respectively. The 55Fe(n ,p ) cross sections were then obtained in the equivalent neutron energy range of 7.9 to 20.1 MeV within the framework of the surrogate-reaction method. The measured results were compared with predictions of the empire-3.2.3 statistical model code and various recent evaluated data libraries. The experimental cross-section data on 55Fe(n ,p ) are in reasonable agreement with EAF-2010, while the TENDL-2014 and ROSFOND-2010 data show some discrepancies. This study demonstrates the possibility of determining neutron-induced charged particle emission cross sections for unstable radionuclides relevant to fusion technology applications by the surrogate-reaction method.

  13. Generating surrogate data for time series with several simultaneously measured variables

    CERN Document Server

    Prichard, D; Dean Prichard; James Theiler

    1994-01-01

    We propose an extension to multivariate time series of the phase-randomized Fourier-transform algorithm for generating surrogate data. Such surrogate data sets must mimic not only the autocorrelations of each of the variables in the original data set, they must mimic the cross-correlations {\\em between} all the variables as well. The method is applied both to a simulated example (the three components of the Lorenz equations) and to data from a multichannel electroencephalogram.

  14. Comparative assessment of trial-level surrogacy measures for candidate time-to-event surrogate endpoints in clinical trials

    OpenAIRE

    Shi, Qian; Renfro, Lindsay A.; Bot, Brian M; Burzykowski, Tomasz; Buyse, Marc; Sargent, Daniel J.

    2011-01-01

    Various meta-analytical approaches have been applied to evaluate putative surrogate endpoints (S) of primary clinical endpoints (T), however a systematic assessment of their performance is lacking. Existing methods in the meta-analytic framework can be grouped into two types conventional and model-based trial-level surrogacy (TLS) measures. Both conventional and model-based TLS measures assess the ability to predict the treatment effect on T based on an observed treatment effect on putative S...

  15. Mixed butanols addition to gasoline surrogates: Shock tube ignition delay time measurements and chemical kinetic modeling

    KAUST Repository

    AlRamadan, Abdullah S.

    2015-10-01

    The demand for fuels with high anti-knock quality has historically been rising, and will continue to increase with the development of downsized and turbocharged spark-ignition engines. Butanol isomers, such as 2-butanol and tert-butanol, have high octane ratings (RON of 105 and 107, respectively), and thus mixed butanols (68.8% by volume of 2-butanol and 31.2% by volume of tert-butanol) can be added to the conventional petroleum-derived gasoline fuels to improve octane performance. In the present work, the effect of mixed butanols addition to gasoline surrogates has been investigated in a high-pressure shock tube facility. The ignition delay times of mixed butanols stoichiometric mixtures were measured at 20 and 40bar over a temperature range of 800-1200K. Next, 10vol% and 20vol% of mixed butanols (MB) were blended with two different toluene/n-heptane/iso-octane (TPRF) fuel blends having octane ratings of RON 90/MON 81.7 and RON 84.6/MON 79.3. These MB/TPRF mixtures were investigated in the shock tube conditions similar to those mentioned above. A chemical kinetic model was developed to simulate the low- and high-temperature oxidation of mixed butanols and MB/TPRF blends. The proposed model is in good agreement with the experimental data with some deviations at low temperatures. The effect of mixed butanols addition to TPRFs is marginal when examining the ignition delay times at high temperatures. However, when extended to lower temperatures (T < 850K), the model shows that the mixed butanols addition to TPRFs causes the ignition delay times to increase and hence behaves like an octane booster at engine-like conditions. © 2015 The Combustion Institute.

  16. Measurement of tumour reactive antibody and antibody conjugate by competition, quantitated by flow cytofluorimetry.

    Science.gov (United States)

    Robins, R A; Laxton, R R; Garnett, M; Price, M R; Baldwin, R W

    1986-06-24

    Binding of unlabelled monoclonal antibody preparations has been assessed by competition at saturation with fluorochrome labelled homologous antibody for binding to antigen bearing target cells. The extent of competition was measured by quantitative flow cytofluorimetry, and simple mathematical procedures have been developed to allow the interpretation of competition data in terms of antibody binding activity. In the system studied, non-specific (non-competitive) fluorescence was minimal, but an iterative method to calculate its contribution to the measured signal is given. This approach has the advantage that the antibody preparation to be tested does not need to be labelled or modified; this is particularly important when evaluating the binding activity of therapeutic antibody conjugates. Comparison with a well characterized standard antibody preparation provides a rapid, sensitive and accurate quality control procedure. This test is also simple to perform, requiring only the mixing of labelled and unlabelled antibodies with target cells, a single incubation, followed by analysis without washing of the target cells. PMID:2424997

  17. Surrogate indicators of sensitivity in gynecologic cytology: Can they be used to improve the measurement of sensitivity in the laboratory?

    Directory of Open Access Journals (Sweden)

    Renshaw Andrew

    2009-01-01

    Full Text Available Background: Measuring the sensitivity of screening in gynecologic cytology in real life is problematic. However, other quality measures may correlate with sensitivity, including the atypical squamous cells (ASC/squamous intraepithelial lesion (SIL ratio. Whether these other measures can function as "surrogate indicators" for sensitivity and improve the assessment of sensitivity in the laboratory is not known. Materials and Methods: We compared multiple quality measures with true screening sensitivity in a variety of situations. Results: The abnormal rate, ASC rate, and ASC/SIL ratio were all highly correlated (r = .83 or greater with sensitivity when the overall laboratory sensitivity was low (85% but became less correlated (.64 or less or uncorrelated when the screening sensitivity was higher (88% or 95%, respectively. Sensitivity was more highly correlated with the abnormal rate than the ASC/SIL ratio at low screening sensitivity. While thresholds could be set that were highly sensitive and specific for suboptimal screening, these thresholds were often less than one standard deviation away from the mean. Conclusion: The correlation of the abnormal rate and the ASC/SIL ratio with sensitivity depends on overall sensitivity. Standards to define minimum screening sensitivity can be defined, but these standards are relatively narrow. These features may limit the utility of these quality measures as surrogates for sensitivity.

  18. Level Densities in the actinide region and indirect n,y cross section measurements using the surrogate method

    Directory of Open Access Journals (Sweden)

    Wiedeking M.

    2012-02-01

    Full Text Available Results from a program of measurements of level densities and gamma ray strength functions in the actinide region are presented. Experiments at the Oslo cyclotron involving the Cactus/Siri detectors and 232Th(d,x and 232Th(3He,x reactions were carried out to help answer the question of which level density model is the most appropriate for actinide nuclei, since it will have an impact on cross section calculations important for reactor physics simulations. A new technique for extracting level densities and gamma ray strength functions from particle-gamma coincidence data is proposed and results from the development of this technique are presented. In addition, simultaneous measurements of compound nuclear gamma decay probabilities have been performed for the key thorium cycle nuclei 233Th, 231Th and 232Pa up to around 1MeV above the neutron binding energy and have enabled extraction of indirect neutron induced capture cross sections for the 232Th, 231Pa and 230Th nuclei using the surrogate reaction method. Since the neutron capture cross section for 232Th is already well known from direct measurements a comparison provides a stringent test of the applicability of the surrogate technique in the actinide region.

  19. Level Densities in the actinide region and indirect n,y cross section measurements using the surrogate method

    Science.gov (United States)

    Wilson, J. N.; Gunsing, F.; Bernstein, L.; Bürger, A.; Görgen, A.; Thompson, I. J.; Guttormssen, M.; Larsen, A.-C.; Mansouri, P.; Renstrøm, T.; Rose, S. J.; Siem, S.; Wiedeking, M.; Wiborg, T.

    2012-02-01

    Results from a program of measurements of level densities and gamma ray strength functions in the actinide region are presented. Experiments at the Oslo cyclotron involving the Cactus/Siri detectors and 232Th(d,x) and 232Th(3He,x) reactions were carried out to help answer the question of which level density model is the most appropriate for actinide nuclei, since it will have an impact on cross section calculations important for reactor physics simulations. A new technique for extracting level densities and gamma ray strength functions from particle-gamma coincidence data is proposed and results from the development of this technique are presented. In addition, simultaneous measurements of compound nuclear gamma decay probabilities have been performed for the key thorium cycle nuclei 233Th, 231Th and 232Pa up to around 1MeV above the neutron binding energy and have enabled extraction of indirect neutron induced capture cross sections for the 232Th, 231Pa and 230Th nuclei using the surrogate reaction method. Since the neutron capture cross section for 232Th is already well known from direct measurements a comparison provides a stringent test of the applicability of the surrogate technique in the actinide region.

  20. Antibody

    Science.gov (United States)

    An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples ... microorganisms (bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produced when the immune system mistakenly ...

  1. Surrogate gas prediction model as a proxy for Δ14C-based measurements of fossil fuel CO2

    Science.gov (United States)

    Coakley, Kevin J.; Miller, John B.; Montzka, Stephen A.; Sweeney, Colm; Miller, Ben R.

    2016-06-01

    The measured 14C:12C isotopic ratio of atmospheric CO2 (and its associated derived Δ14C value) is an ideal tracer for determination of the fossil fuel derived CO2 enhancement contributing to any atmospheric CO2 measurement (Cff). Given enough such measurements, independent top-down estimation of U.S. fossil fuel CO2 emissions should be possible. However, the number of Δ14C measurements is presently constrained by cost, available sample volume, and availability of mass spectrometer measurement facilities. Δ14C is therefore measured in just a small fraction of samples obtained by flask air sampling networks around the world. Here we develop a projection pursuit regression (PPR) model to predict Cff as a function of multiple surrogate gases acquired within the NOAA/Earth System Research Laboratory (ESRL) Global Greenhouse Gas Reference Network (GGGRN). The surrogates consist of measured enhancements of various anthropogenic trace gases, including CO, SF6, and halocarbon and hydrocarbon acquired in vertical airborne sampling profiles near Cape May, NJ and Portsmouth, NH from 2005 to 2010. Model performance for these sites is quantified based on predicted values corresponding to test data excluded from the model building process. Chi-square hypothesis test analysis indicates that these predictions and corresponding observations are consistent given our uncertainty budget which accounts for random effects and one particular systematic effect. However, quantification of the combined uncertainty of the prediction due to all relevant systematic effects is difficult because of the limited range of the observations and their relatively high fractional uncertainties at the sampling sites considered here. To account for the possibility of additional systematic effects, we incorporate another component of uncertainty into our budget. Expanding the number of Δ14C measurements in the NOAA GGGRN and building new PPR models at additional sites would improve our understanding of

  2. Calculations of Compound Nucleus Spin-Parity Distributions Populated via the (p,t) Reaction in Support of Surrogate Neutron Capture Measurements

    Science.gov (United States)

    Benstead, J.; Tostevin, J. A.; Escher, J. E.; Burke, J. T.; Hughes, R. O.; Ota, S.; Casperson, R. J.; Thompson, I. J.

    2016-06-01

    The surrogate reaction method may be used to determine the cross section for neutron induced reactions not accessible through standard experimental techniques. This is achieved by creating the same compound nucleus as would be expected in the desired reaction, but through a different incident channel, generally a direct transfer reaction. So far, the surrogate technique has been applied with reasonable success to determine the fission cross section for a number of actinides, but has been less successful when applied to other reactions, e.g. neutron capture, due to a `spin-parity mismatch'. This mismatch, between the spin and parity distributions of the excited levels of the compound nucleus populated in the desired and surrogate channels, leads to differing decay probabilities and hence reduces the validity of using the surrogate method to infer the cross section in the desired channel. A greater theoretical understanding of the expected distribution of levels excited in both the desired and surrogate channels is therefore required in order to attempt to address this mismatch and allow the method to be utilised with greater confidence. Two neutron transfer reactions, e.g. (p,t), which allow the technique to be utilised for isotopes further removed from the line of stability, are the subject of this study. Results are presented for the calculated distribution of compound nucleus states populated in 90Zr, via the 90Zr(p,t)90Zr reaction, and are compared against measured data at an incident proton energy of 28.56 MeV.

  3. Non-HDL-cholesterol as valid surrogate to apolipoprotein B100 measurement in diabetes: Discriminant Ratio and unbiased equivalence

    Directory of Open Access Journals (Sweden)

    Ahn Sylvie A

    2011-02-01

    Full Text Available Abstract Background Apolipoprotein B100 (apoB is a superior indicator of CV risk than total or LDL-C. Non-HDL-C represents a simple surrogate for apoB in hypertriglyceridemic and/or T2DM patients. ApoB and non-HDL-C show high correlation, although the degree of mutual concordance remains debated in CV risk evaluation. Objectives We used the Discriminant Ratio (DR methodology to compare the performance of non-HDL-C with that of apoB to rank diabetic patients according to dyslipidemia and to establish the underlying relationship between these variables taking measurement noise and intra-/intersubject variation into account, and to derive an unbiased equivalence equation. Methods Fasting total C, HDL-C, apoB and triglycerides were measured in 45 diabetic patients. The DR of the underlying between-subject standard deviation (SD to the within-subject SD was calculated from duplicates. Correlation coefficients between pairs were adjusted to include an estimate of the underlying correlation. Results Mean values [day 1 (1SD] were 143 (36 mg/dl (non-HDL-C and 98 (24 mg/dl (apoB. The DR's of both parameters were similar (1.76 and 1.83 (p = 0.83. Pearson's product-moment correlation coefficient between tests was very high (0.94, reaching unity (1.00 after attenuation adjustment. The unbiased equation of equivalence relating apoB to non-HDL-C had a slope of 0.65 and an intercept of 6.3 mg/dl. Conclusions The discrimination power of non-HDL-C is similar to that of apoB to rank diabetic patients according to atherogenic cholesterol and lipoprotein burden. Since true correlation between variables reached unity, non-HDL-C may provide not only a metabolic surrogate but also a candidate biometrical equivalent to apoB, as non-HDL-C calculation is readily available.

  4. Surrogate motherhood.

    Science.gov (United States)

    Chang, Curtis Li-ming

    2004-03-01

    A "surrogate mother" is a woman who, for financial or other reasons, agrees to bear a child for another woman who is incapable to conceive herself. In other words, she is a "substitute mother" that conceives, gestates and delivers a baby on behalf of another woman who is subsequently to be seen as the "real" (social and legal) mother of the child. Though the practice of surrogacy has already become a big market in western countries, it has also generated countless challenges for the law because it adds a third dimension to the meaning of motherhood. Like adoption, surrogacy separates the role of rearing mother from what the law has called the natural mother, but gestational surrogacy breaks the latter down into the roles of genetic mother and birth mother, leaving two women with biological connections to the child. Because surrogacy tends to commodify and dehumanize people, and because of all its legal, social, and psychological complications, it is obviously not wise to accept surrogacy as an alternative way of procreation. PMID:15460596

  5. DEVELOPMENT OF MEASUREMENT AND VISUALIZATION TECHNIQUES FOR CHARACTERIZATION OF MIXING AND COMBUSTION PROCESSES WITH SURROGATE FUELS

    OpenAIRE

    Micó Reche, Carlos

    2015-01-01

    [EN] The development and optimization of new combustion modes is nowadays an important research field, to reduce the pollutant emissions of the reciprocating internal combustion engines. Their development requires the use of a wide variety of experimental and theoretical tools, which make it possible to know and understand their fundamentals. In this context the main objective of this Thesis is framed: the development and optimization of measuring and visualization techniques, to reach the l...

  6. A new framework for selecting environmental surrogates.

    Science.gov (United States)

    Lindenmayer, David; Pierson, Jennifer; Barton, Philip; Beger, Maria; Branquinho, Cristina; Calhoun, Aram; Caro, Tim; Greig, Hamish; Gross, John; Heino, Jani; Hunter, Malcolm; Lane, Peter; Longo, Catherine; Martin, Kathy; McDowell, William H; Mellin, Camille; Salo, Hanna; Tulloch, Ayesha; Westgate, Martin

    2015-12-15

    Surrogate concepts are used in all sub-disciplines of environmental science. However, controversy remains regarding the extent to which surrogates are useful for resolving environmental problems. Here, we argue that conflicts about the utility of surrogates (and the related concepts of indicators and proxies) often reflect context-specific differences in trade-offs between measurement accuracy and practical constraints. By examining different approaches for selecting and applying surrogates, we identify five trade-offs that correspond to key points of contention in the application of surrogates. We then present an 8-step Adaptive Surrogacy Framework that incorporates cross-disciplinary perspectives from a wide spectrum of the environmental sciences, aiming to unify surrogate concepts across disciplines and applications. Our synthesis of the science of surrogates is intended as a first step towards fully leveraging knowledge accumulated across disciplines, thus consolidating lessons learned so that they may be accessible to all those operating in different fields, yet facing similar hurdles. PMID:26298409

  7. DETECTION OF LOW BIRTH WEIGHT BABIES BY AN ANTHROPOMETRIC SURROGATE MEASURE: A HOSPITAL BASED STUDY

    Directory of Open Access Journals (Sweden)

    Anjali

    2014-05-01

    Full Text Available INTRODUCTION: Birth weight is an indicator of both neonatal morbidity and mortality, maternal health, nutrition and quality of antenatal services. OBJECTIVE: To find out important anthropometric parameter(s in the newborn as related to birth weight so that newborns with low birth weight can be identified. MATERIAL AND METHODS: A prospective cross sectional, analytical, hospital based study was conducted at Amritsar on 200 term low birth weight newborn babies(<2.5 kg born during a period of 10 months and their various anthropometric measurements (HC, CC, MAC, TC, CFC were taken according to standard techniques. RESULTS: The study showed a strong correlation (p <0.001 between mid-arm circumference (r=0.834 and birth weight, followed by head circumference (r=0.816 and birth weight. Other parameters were also strongly correlated (p < 0.001. A value of <9.2 cm and <7.6 cm for mid-arm circumference showed highest validity for picking up newborns weighing <2500 gm and <2000 gm respectively. CONCLUSION: Measurement of arm circumference is easier, convenient and statistically superior to other anthropometrical parameters in detection of low birth weight newborn babies. The researchers recommend designing of a simple 'Tri-colored tape' for early detection of 'At Risk' LBW newborns in rural communities for their timely management.

  8. Inductive plethysmography potential as a surrogate for ventilatory measurements during rest and moderate physical exercise

    Directory of Open Access Journals (Sweden)

    Ramona Cabiddu

    2016-01-01

    Full Text Available Background: Portable respiratory inductive plethysmography (RIP systems have been validated for ventilatory assessment during resting conditions and during incremental treadmill exercise. However, in clinical settings and during field-based exercise, intensity is usually constant and submaximal. A demonstration of the ability of RIP to detect respiratory measurements accurately during constant intensity conditions would promote and validate the routine use of portable RIP devices as an alternative to ergospirometry (ES, the current gold standard technique for ventilatory measures. Objective: To investigate the agreement between respiratory variables recorded by a portable RIP device and by ES during rest and constant intensity exercise. Method: Tidal volume (VT, respiratory rate (RR and minute ventilation (VE were concurrently acquired by portable RIP and ES in seven healthy male volunteers during standing rest position and constant intensity treadmill exercise. Results: Significant agreement was found between RIP and ES acquisitions during the standing rest position and constant intensity treadmill exercise for RR and during the standing rest position for VE. Conclusion: Our results suggest that portable RIP devices might represent a suitable alternative to ES during rest and during constant submaximal exercise.

  9. Surrogate motherhood

    Directory of Open Access Journals (Sweden)

    Arteta-Acosta Cindy

    2011-06-01

    Full Text Available Surrogate motherhood, also known as surrogacy, has recently become achance to exercise the right of paternity by some people. Surrogacy itself did notinvolve a disadvantaged idea, but when this is coupled with scientific experimentsand economic and personal interests, requires intervention of the State tolegislate about consequences arising from the unlimited execution of this practice. Since 70’s,developed countries have been creating laws, decrees and regulations to regulateassisted reproduction, while developing countries have no specific legislation in thisregard, and in particular case of Colombia, law projects are proposed but soon withdrawndue to lack of knowledge and dedication.RESUMEN:La maternidad subrogada, conocida en el lenguaje popular como el alquiler de vientres seha convertido en los últimos años en una posibilidad para ejercer el derecho de paternidadpor parte de algunas personas. En sí misma no encierra una idea desventajosa, perocuando a esto se suman intereses económicos, experimentos científicos e interesespersonales, es necesaria la intervención del Estado para legislar con respecto a lasconsecuencias que se derivan de la acción sin límites de esta potestad. Desde ladécada de los 70’s, países desarrollados han divulgado leyes, decretos y normas pararegular la reproducción asistida; mientras que países en vía de desarrollo no tienenlegislaciones específicas al respecto, y en el caso particular de Colombia los proyectosde ley propuestos poco tiempo después son retirados debido a la falta de conocimientoy esmero.

  10. Measurement of body composition as a surrogate evaluation of energy balance in obese patients.

    Science.gov (United States)

    Rotella, Carlo Maria; Dicembrini, Ilaria

    2015-03-26

    In clinical practice obesity is primarily diagnosed through the body mass index. In order to characterize patients affected by obesity the use of traditional anthropometric measures appears misleading. Beyond the body mass index, there are overwhelming evidences towards the relevance of a more detailed description of the individual phenotype by characterizing the main body components as free-fat mass, muscle mass, and fat mass. Among the numerous techniques actually available, bioelectrical impedance analysis seems to be the most suitable in a clinical setting because it is simple, inexpensive, noninvasive, and highly reproducible. To date, there is no consensus concerning the use of one preferred equation for the resting energy expenditure in overweight and/or obese population. Energy restriction alone is an effective strategy to achieve an early and significant weight loss, however it results in a reduction of both fat and lean mass therefore promoting or aggravating an unfavourable body composition (as sarcobesity) in terms of mortality and comorbidities. Therefore the implementation of daily levels of physical activity should be simultaneously promoted. The major role of muscle mass in the energy balance has been recently established by the rising prevalence of the combination of two condition as sarcopenia and obesity. Physical exercise stimulates energy expenditure, thereby directly improving energy balance, and also promotes adaptations such as fiber type, mitochondrial biogenesis, improvement of insulin resistance, and release of myokines, which may influence different tissues, including muscle. PMID:25825693

  11. Photoplethysmography pulse rate variability as a surrogate measurement of heart rate variability during non-stationary conditions

    International Nuclear Information System (INIS)

    In this paper we assessed the possibility of using the pulse rate variability (PRV) extracted from the photoplethysmography signal as an alternative measurement of the HRV signal in non-stationary conditions. The study is based on analysis of the changes observed during a tilt table test in the heart rate modulation of 17 young subjects. First, the classical indices of HRV analysis were compared to the indices from PRV in intervals where stationarity was assumed. Second, the time-varying spectral properties of both signals were compared by time-frequency (TF) and TF coherence analysis. Third, the effect of replacing PRV with HRV in the assessment of the changes of the autonomic modulation of the heart rate was considered. Time-invariant HRV and PRV indices showed no statistically significant differences (p > 0.05) and high correlation (>0.97). Time-frequency analysis revealed that the TF spectra of both signals were highly correlated (0.99 ± 0.01); the difference between the instantaneous power, in the LF and HF bands, obtained from HRV and PRV was small (<10−3 s−2) and their temporal patterns were highly correlated (0.98 ± 0.04 and 0.95 ± 0.06 in the LF and HF bands, respectively) and TF coherence in the LF and HF bands was high (0.97 ± 0.04 and 0.89 ± 0.08, respectively). Finally, the instantaneous power in the LF band was observed to significantly increase during head-up tilt by both HRV and PRV analysis. These results suggest that although some differences in the time-varying spectral indices extracted from HRV and PRV exist, mainly in the HF band associated with respiration, PRV could be used as a surrogate of HRV during non-stationary conditions, at least during the tilt table test

  12. Comparison between knife-edge and frisbee-shaped surrogate surfaces for making dry deposition measurements: Wind tunnel experiments and computational fluid dynamics (CFD) modeling

    Science.gov (United States)

    Huang, Jiaoyan; Liu, Ying; Holsen, Thomas M.

    2011-08-01

    Dry deposition is a major pathway for atmospheric contaminant movement from the atmosphere to the earth surface. Despite its importance, there is no generally accepted direct method to measure dry deposition. Recently, the interest in using surrogate surfaces to measure dry deposition is growing, primarily because of their ease of use. However, a problem with these surfaces is extrapolating the results obtained to natural surfaces. There are two popular surrogate plates used to measure dry deposition. One had a sharp leading edge (knife-edge) (KSS), and the other has a smooth-edge (frisbee-shaped) (FSS). In this study, the performances of these two surrogate surfaces to directly measure gas dry deposition were explored using wind tunnel experiments and two-dimensional (2D) computational fluid dynamic (CFD) models. Although the fluid fields above these two plates were different, both created laminar boundary layers (distance above the surface where the velocity gradient is constant) with a constant thickness after approximately five cm. In the wind tunnel, gaseous elemental mercury (GEM) deposition to gold-coated filters was used to measure deposition velocities ( Vd) in part because for this combination deposition is air-side controlled. The GEM Vd to both surfaces increased with increasing wind speeds. Based on both measurements and CFD simulations, the Vds to the FSS were approximately 30% higher and more variable than to the KSS when the wind flow was parallel to the surfaces. However, when the angle between the surfaces and the wind was varied the Vds to the FSS were less dependent on the incident angle than to the KSS.

  13. Cutoff Values of Surrogate Measures of Insulin Resistance for Metabolic Syndrome in Korean Non-diabetic Adults

    OpenAIRE

    Lee, Sihoon; Choi, Sunghee; Kim, Hae Jin; Chung, Yoon-Sok; Lee, Kwan Woo; Lee, Hyun Chul; Huh, Kap Bum; Kim, Dae Jung

    2006-01-01

    We investigated the cutoff values of surrogate of insulin resistance for diagnosing metabolic syndrome in Korean adults. The data from 976 non-diabetic individuals (484 men and 492 women) aged 30-79 yr were analyzed. We determined the odds ratios for the prevalence of metabolic syndrome according to the quartiles of fasting insulin, homeostasis model for insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) as independent variables, while adjusting for age, s...

  14. Heat capacity measurement of synthetic CaCe(IV)(PO4)2: a surrogate study for plutonium

    International Nuclear Information System (INIS)

    Pu has several isotopes starting from 238Pu to 242Pu and 244Pu where latter is the most stable isotope (half-life is 82 million years). Except 241Pu, all of its isotopes are α-active. Pu is harmful for human being due to its radioactivity and the heavy metal poison effects. The reprocessing of irradiated fuel (U-Pu cycle) from nuclear power plants contains high level waste containing Pu, U along with fission products. Disposal of radioactive wastes is a serious environmental problem for which complete satisfactory solution is not available. In order to store the high level radioactive waste in long-term geological repositories, specific waste forms need to be used which will allow the radioactivity to decay away while the matrix retain their integrity for thousands of years. The mineral analogues of the ceramic waste forms provide evidence for long term durability. Monazite-like compounds would seem to be ideal hosts for actinides. U and Pu could exist with two stabilized oxidation states (III and IV) in the phosphate matrix where, Pu in the trivalent oxidation state appears as the most stable state in the monazite structure and Pu(IV) could exist in brabantite CaTh(PO4)2 by replacing Th. Due to radio toxicity of Pu, experiments were first carried out with Ce as surrogate, since Ce has similar properties with Pu in terms of ionic size and redox properties (oxidation states III and IV). Hence, thermophysical properties of CaCe(IV)(PO4)2(s) were studied instead of CaPu(IV)(PO4)2. In order to prevent heat up of actinide storage matrix due to decay heat of the actinides, the material with high specific heat is desirable. In this study, heat capacity measurements of CaCe(IV)(PO4)2(s) has been carried out using Differential Scanning Calorimeter (DSC) in the temperature range 298-773 K and the results were compared with that of reported component phosphates in monazite and brabantite structures

  15. Measuring the sequence-affinity landscape of antibodies with massively parallel titration curves

    OpenAIRE

    Adams, Rhys M.; Kinney, Justin B.; Mora, Thierry; Walczak, Aleksandra M.

    2016-01-01

    Despite the central role that antibodies play in the adaptive immune system and in biotechnology, much remains unknown about the quantitative relationship between an antibody's amino acid sequence and its antigen binding affinity. Here we describe a new experimental approach, called Tite-Seq, that is capable of measuring binding titration curves and corresponding affinities for thousands of variant antibodies in parallel. The measurement of titration curves eliminates the confounding effects ...

  16. A comparison of lung motion measured using implanted electromagnetic transponders and motion algorithmically predicted using external surrogates as an alternative to respiratory correlated CT imaging

    Science.gov (United States)

    Lechleiter, Kristen M.; Low, Daniel A.; Chaudhari, Amir; Lu, Wei; Hubenschmidt, James P.; Mayse, Martin L.; Dimmer, Steven C.; Bradley, Jeffrey D.; Parikh, Parag J.

    2007-03-01

    Three-dimensional volumetric imaging correlated with respiration (4DCT) typically utilizes external breathing surrogates and phase-based models to determine lung tissue motion. However, 4DCT requires time consuming post-processing and the relationship between external breathing surrogates and lung tissue motion is not clearly defined. This study compares algorithms using external respiratory motion surrogates as predictors of internal lung motion tracked in real-time by electromagnetic transponders (Calypso® Medical Technologies) implanted in a canine model. Simultaneous spirometry, bellows, and transponder positions measurements were acquired during free breathing and variable ventilation respiratory patterns. Functions of phase, amplitude, tidal volume, and airflow were examined by least-squares regression analysis to determine which algorithm provided the best estimate of internal motion. The cosine phase model performed the worst of all models analyzed (R2 = 31.6%, free breathing, and R2 = 14.9%, variable ventilation). All algorithms performed better during free breathing than during variable ventilation measurements. The 5D model of tidal volume and airflow predicted transponder location better than amplitude or either of the two phasebased models analyzed, with correlation coefficients of 66.1% and 64.4% for free breathing and variable ventilation respectively. Real-time implanted transponder based measurements provide a direct method for determining lung tissue location. Current phase-based or amplitude-based respiratory motion algorithms cannot as accurately predict lung tissue motion in an irregularly breathing subject as a model including tidal volume and airflow. Further work is necessary to quantify the long term stability of prediction capabilities using amplitude and phase based algorithms for multiple lung tumor positions over time.

  17. Association of indoor nitrogen dioxide with respiratory symptoms in children: application of measurement error correction techniques to utilize data from multiple surrogates.

    Science.gov (United States)

    Li, Ruifeng; Weller, Edie; Dockery, Douglas W; Neas, Lucas M; Spiegelman, Donna

    2006-07-01

    In 1991, Neas et al. reported that indoor nitrogen dioxide (NO(2)), a byproduct of high-temperature combustion, was significantly associated with lower respiratory symptoms among a cohort of 1,159 white children aged 7-11 years in six US cities studied from 1983 to 1988. For each 15 p.p.b. increment of NO(2), the multivariate adjusted odds ratio (OR) was 1.4 (95% confidence interval (CI)=[1.1, 1.7]). Although indoor NO(2) concentration in the ambient air was assessed only in a subset of the children, the prevalence of lower respiratory symptoms and surrogate exposure variables were available in all of the children at the time of the indoor monitoring program. This paper evaluates the effect of indoor NO(2) exposure on the annual risk of lower respiratory symptoms by applying a regression calibration method to the 2,891 children in the overall study with complete covariate and outcome data, 1,137 of whom had NO(2) directly measured and 1,754 of whom only surrogate exposure data were available. An estimate of the indoor annual NO(2) exposure effect (p.p.b.) is obtained, which is adjusted for measurement error induced by the use of surrogate NO(2) sources among the 1,754. These sources include the presence of a gas stove with or without a pilot light, the presence of a kerosene space heater, the presence of a wood stove, and the usage of a stove for heating, and residential characteristics, including fan usage for kitchen ventilation and the total number of rooms in the home. After adjusting for age, gender, city, parental history of respiratory diseases, and smoking inside the children's home (packs/day), a 15-p.p.b. increment in NO(2) exposure was found to be associated with a significant 50% increased annual risk of lower respiratory symptoms (OR=1.5, 95% CI=[1.2, 1.8]). 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. Using the

  18. Improving food and agricultural production. Thailand. Application on monoclonal antibodies for progesterone measurement

    International Nuclear Information System (INIS)

    The duties of the mission were to provide instructions on the maintenance of hybridoma cell lines and their culture and the harvesting of monoclonal antibodies; to assist the counterparts in Thailand to develop work plans for the use of monoclonal antibodies in radioimmunoassay measurements of progesterone; and to assess the need for and feasibility of establishing a laboratory for producing monoclonal antibodies directed against progesterone. The report contains a summary of the activities performed in fulfillment of these duties

  19. Study of the 238U(d,p) surrogate reaction via the simultaneous measurement of gamma-decay and fission probabilities

    CERN Document Server

    Ducasse, Q; Aïche, M; Marini, P; Mathieu, L; Görgen, A; Guttormsen, M; Larsen, A C; Tornyi, T; Wilson, J N; Barreau, G; Boutoux, G; Czajkowski, S; Giacoppo, F; Gunsing, F; Hagen, T W; Lebois, M; Lei, J; Méot, V; Morillon, B; Moro, A; Renstrøm, T; Roig, O; Rose, S J; Sérot, O; Siem, S; Tsekhanovich, I; Tveten, G M; Wiedeking, M

    2015-01-01

    We investigated the 238U(d,p) reaction as a surrogate for the n + 238U reaction. For this purpose we measured for the first time the gamma-decay and fission probabilities of 239U* simultaneously and compared them to the corresponding neutron-induced data. We present the details of the procedure to infer the decay probabilities, as well as a thorough uncertainty analysis, including parameter correlations. Calculations based on the continuum-discretized coupled-channels and distorted-wave Born approximations were used to correct our data from detected protons originating from elastic and inelastic deuteron breakup. The corrected fission probability is in agreement with neutron-induced data, whereas the gamma-decay probability is much higher than the neutron-induced data. The performed statistical-model calculations are not able to explain these results.

  20. Surrogate waveform models

    Science.gov (United States)

    Blackman, Jonathan; Field, Scott; Galley, Chad; Scheel, Mark; Szilagyi, Bela; Tiglio, Manuel

    2015-04-01

    With the advanced detector era just around the corner, there is a strong need for fast and accurate models of gravitational waveforms from compact binary coalescence. Fast surrogate models can be built out of an accurate but slow waveform model with minimal to no loss in accuracy, but may require a large number of evaluations of the underlying model. This may be prohibitively expensive if the underlying is extremely slow, for example if we wish to build a surrogate for numerical relativity. We examine alternate choices to building surrogate models which allow for a more sparse set of input waveforms. Research supported in part by NSERC.

  1. Measurement of cross linked fibrin derivatives in plasma: an immunoassay using monoclonal antibodies.

    OpenAIRE

    Whitaker, A. N.; Elms, M J; Masci, P P; Bundesen, P G; Rylatt, D B; Webber, A J; Bunce, I H

    1984-01-01

    Fibrinogen degradation, fibrin polymerisation, and the insertion of cross links into fibrin by fibrin stabilising factor lead to the appearance of new antigenic determinants. Antibodies against these antigenic sites may react specifically with the derivatives but not with the parent molecules. We have utilised a monoclonal antibody, which interacts with the cross linked fragment D dimer and related high molecular weight fibrin derivatives, to develop an enzyme immunoassay which measures cross...

  2. Measurement of anti-enzyme antibodies using an active-site directed radiolabel

    International Nuclear Information System (INIS)

    A new technique is described for measuring antibodies to an enzyme which is not available in pure form. The secretions of the rat parasitic nematode, Nippostrongylus brasiliensis, were treated with tritiated diisopropylfluorophosphate. Only one component, an acetylcholinesterase, was radiolabelled. Antibodies to this enzyme in rat antisera were estimated by the Farr technique using the labelled enzyme as antigen. The acetylcholinesterase secreted by Necator Americanus, the human hookworm, was similarly specifically labelled

  3. Measurement and evaluation of the relationships between capillary pressure, relative permeability, and saturation for surrogate fluids for laboratory study of geological carbon sequestration

    Science.gov (United States)

    Mori, H.; Trevisan, L.; Sakaki, T.; Cihan, A.; Smits, K. M.; Illangasekare, T. H.

    2013-12-01

    Multiphase flow models can be used to improve our understanding of the complex behavior of supercritical CO2 (scCO2) in deep saline aquifers to make predictions for the stable storage strategies. These models rely on constitutive relationships such as capillary pressure (Pc) - saturation (Sw) and relative permeability (kr) - saturation (Sw) as input parameters. However, for practical application of these models, such relationships for scCO2 and brine system are not readily available for geological formations. This is due to the complicated and expensive traditional methods often used to obtain these relationships in the laboratory through high pressure and/or high-temperature controls. A method that has the potential to overcome the difficulty in conducting such experiments is to replicate scCO2 and brine with surrogate fluids that capture the density and viscosity effects to obtain the constitutive relationships under ambient conditions. This study presents an investigation conducted to evaluate this method. An assessment of the method allows us to evaluate the prediction accuracy of multiphase models using the constitutive relationships developed from this approach. With this as a goal, the study reports multiple laboratory column experiments conducted to measure these relationships. The obtained relationships were then used in the multiphase flow simulator TOUGH2 T2VOC to explore capillary trapping mechanisms of scCO2. A comparison of the model simulation to experimental observation was used to assess the accuracy of the measured constitutive relationships. Experimental data confirmed, as expected, that the scaling method cannot be used to obtain the residual and irreducible saturations. The results also showed that the van Genuchten - Mualem model was not able to match the independently measured kr data obtained from column experiments. Simulated results of fluid saturations were compared with saturation measurements obtained using x-ray attenuations. This

  4. Measurement of salivary cortisol--effects of replacing polyester with cotton and switching antibody

    DEFF Research Database (Denmark)

    Hansen, Ase Marie; Garde, Anne Helene; Persson, Roger;

    2008-01-01

    measurements in our laboratory were affected by: 1) changes in the tampon material and 2) changes in the antibody of the analytical kit. In study 1, saliva from healthy subjects (n = 19) was split and spiked to Salivette polyester and cotton tampons, respectively, and treated as ordinary samples before being...... analysed for cortisol using a Spectria RIA kit for cortisol. In study 2, 68 anonymous saliva samples were analysed with the Spectria Cortisol RIA kit both before and after the manufacturer changed the antibody. The change from polyester to cotton tampons reduced the measured concentration of salivary...

  5. Is 18F-FDG a surrogate tracer to measure tumor hypoxia? Comparison with the hypoxic tracer 14C-EF3 in animal tumor models

    International Nuclear Information System (INIS)

    Introduction: Fluorodeoxyglucose (FDG) has been reported as a surrogate tracer to measure tumor hypoxia with positron emission tomography (PET). The hypothesis is that there is an increased uptake of FDG under hypoxic conditions secondary to enhanced glycolysis, compensating the hypoxia-induced loss of cellular energy production. Several studies have already addressed this issue, some with conflicting results. This study aimed to compare the tracers 14C-EF3 and 18F-FDG to detect hypoxia in mouse tumor models. Materials and methods: C3H, tumor-bearing mice (FSAII and SCCVII tumors) were injected iv with 14C-EF3, and 1 h later with 18F-FDG. Using a specifically designed immobilization device with fiducial markers, PET (Mosaic (registered) , Philips) images were acquired 1 h after the FDG injection. After imaging, the device containing mouse was frozen, transversally sliced and imaged with autoradiography (AR) (FLA-5100, Fujifilm) to obtain high resolution images of the 18F-FDG distribution within the tumor area. After a 48-h delay allowing for 18F decay a second AR was performed to image 14C-EF3 distribution. AR images were aligned to reconstruct the full 3D tumor volume, and were compared with the PET images. Image segmentation with threshold-based methods was applied on both AR and PET images to derive various tracer activity volumes. The matching index DSI (dice similarity index) was then computed. The comparison was performed under normoxic (ambient air, FSAII: n = 4, SCCVII, n = 5) and under hypoxic conditions (10% O2 breathing, SCCVII: n = 4). Results: On AR, under both ambient air and hypoxic conditions, there was a decreasing similarity between 14C-EF3 and FDG with higher activity sub-volumes. Under normoxic conditions, when comparing the 10% of tumor voxels with the highest 18F-FDG or 14C-EF3 activity, a DSI of 0.24 and 0.20 was found for FSAII and SCCVII, respectively. Under hypoxic conditions, a DSI of 0.36 was observed for SCCVII tumors. When comparing

  6. A new method for measuring antibody using radiolabeled protein A in a solid-phase radioimmunoassay

    International Nuclear Information System (INIS)

    A micro solid-phase radioimmunoassay was developed which utilizes radiolabeled staphylococcal Protein A ([125I] Protein A) in place of radiolabeled anti-immunoglobulin ([125I]anti-IgG) for the measurement of antibody. For the assay, antigen is adsorbed to the wells of a microtiter plate followed by dilutions of serum and [125I]-Protein A in subsequent steps. It was found that this assay can be used to measure antibody (Ab) against a variety of antigens in human and rabbit but not goat immune serum. Binding of [125I]-Protein A and [125I]anti-IgG to human and rabbit IgG was comparable. It was possible to quantify this amount of Ab in human serum by reference to immune rabbit serum. The sensitivity of this assay for rabbit antibody was 1 ng/ml. (Auth.)

  7. Stationarization via surrogates

    International Nuclear Information System (INIS)

    The surrogate data method, classically used for non-linearity tests, amounts to the use of some constrained noise providing a reference for statistical testing. It is revisited here as a method for stationarization and this feature is put forward in the context of non-stationarity testing. The stationarization property of surrogates is first explored in a time–frequency perspective and used for devising a test of stationarity relative to an observation time. Then, more general forms of surrogates are developed, directly in time–frequency or mixed domains of representation (ambiguity and time-lag domains included), and it is shown how they allow for other tests of non-stationary features: detection of the existence of a transient in some noise; assessment of non-stationary cross-correlations

  8. Birds as biodiversity surrogates

    DEFF Research Database (Denmark)

    Larsen, Frank Wugt; Bladt, Jesper Stentoft; Balmford, Andrew;

    2012-01-01

    1. Most biodiversity is still unknown, and therefore, priority areas for conservation typically are identified based on the presence of surrogates, or indicator groups. Birds are commonly used as surrogates of biodiversity owing to the wide availability of relevant data and their broad popular...... appeal. However, some studies have found birds to perform relatively poorly as indicators. We therefore ask how the effectiveness of this approach can be improved by supplementing data on birds with information on other taxa. 2. Here, we explore two strategies using (i) species data for other taxa...... areas identified on the basis of birds alone performed well in representing overall species diversity where birds were relatively speciose compared to the other taxa in the data sets. Adding species data for one taxon increased surrogate effectiveness better than adding genus- and family-level data...

  9. Immunogenicity of anti-tumor necrosis factor antibodies-toward improved methods of anti-antibody measurement.

    Science.gov (United States)

    Aarden, Lucien; Ruuls, Sigrid R; Wolbink, Gertjan

    2008-08-01

    To date, millions of people have been treated with therapeutic monoclonal antibodies (TmAbs) for various indications. It is becoming increasingly clear that TmAbs can be immunogenic, which may reduce efficacy or induce adverse effects. Over the years, the importance of antibody formation has been questioned and sometimes minimized, as few antibody responses to TmAbs (HACA or HAHA) were reported. However, the methods to detect and quantify such antibodies used in the past have been problematic. Only recently, methods have been developed that have adequate sensitivity and are not seriously disturbed by false-positive reactions caused by rheumatoid factors, natural antibodies to Fab or F(ab')2 fragments, or Fc interactions of IgG4. The large number of treated patients, in combination with these new assays, presents a unique opportunity to study the anti-antibody immune response in man, possibly allowing us to manipulate immunogenicity in the future. PMID:18619538

  10. Plutonium radiation surrogate

    Science.gov (United States)

    Frank, Michael I.

    2010-02-02

    A self-contained source of gamma-ray and neutron radiation suitable for use as a radiation surrogate for weapons-grade plutonium is described. The source generates a radiation spectrum similar to that of weapons-grade plutonium at 5% energy resolution between 59 and 2614 keV, but contains no special nuclear material and emits little .alpha.-particle radiation. The weapons-grade plutonium radiation surrogate also emits neutrons having fluxes commensurate with the gamma-radiation intensities employed.

  11. Surrogate reaction methods for neutron induced cross-sections

    International Nuclear Information System (INIS)

    A brief discussion on surrogate reaction methods and some of the recent results on neutron induced fission cross-section measurements carried out by our group and the possibility of extending the measurements for determining (n,g), (n,2n) and (n,p) reaction cross-sections by surrogate reaction method are presented

  12. Measurement of 55Fe(n,p)55Mn reaction cross-section by Surrogate Reaction Method for fusion technology

    International Nuclear Information System (INIS)

    Developing Fusion technology is a dream project for cheap, abundant and green energy source for future generations. Efforts are underway to build a International Thermonuclear Experimental Reactor (ITER project) using D-T fusion reaction releasing 14-MeV neutrons. It is needed to perform detailed neutronics study to qualify materials for component design for the fusion reactors, as presently done for fission reactors. Generally stainless steel (SS) is used as a structural material having Fe, Ni, Cr, Mn, Co, Nb as main constituents (in SS316 content of Fe and 65%). Interaction of 14-MeV neutrons with structural material produces various long-lived radio nuclides. The assessment of the radiological hazard showed that the main contribution to activation comes from 54Mn, 56Mn, 55Fe, 57Co, 58Co, 60Co, 57Ni, 51Cr and 94Nb that originate from transmutation reactions of neutrons with the elements in the initial SS composition. Fusion neutronics studies have been done during many years considering only the stable isotopes of Cr, Fe, Ni. But in the development of D-T fusion reactor, large amount radio nuclides will be produced during reactor operation as well as after shutdown of the reactor. 55Fe is a primary dominant nuclide produced by neutron induced reaction on Fe, Co and Ni elements by 56Fe(n,2n), 54Fe(n, γ), 59Co(n, α) 56Mn(β-) 56Fe(n,2n), and 58Ni(n, α) reactions. As of today, there is no experimental measurement of the 55Fe(n,p) cross-section

  13. Developments in Surrogating Methods

    Directory of Open Access Journals (Sweden)

    Hans van Dormolen

    2005-11-01

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

  14. Triglyceride glucose index as a surrogate measure of insulin sensitivity in obese adolescents with normoglycemia, prediabetes, and type 2 diabetes mellitus: Comparison with the hyperinsulinemic–euglycemic clamp

    Science.gov (United States)

    There is a need for simple surrogate estimates of insulin sensitivity in epidemiological studies of obese youth because the hyperinsulinemic-euglycemic clamp is not feasible on a large scale. Objectives: (i) To examine the triglyceride glucose (TyG) index (Ln[fasting triglycerides (mg/dL)'×'fasting ...

  15. Compound-nuclear reaction cross sections via surrogate reactions

    International Nuclear Information System (INIS)

    The surrogate reaction method is an indirect technique for determining cross sections for nuclear reactions that proceed through a well-defined compound nucleus. In this method, the same compound nucleus is produced by an alternate ('surrogate') reaction and its decay products measured. The assumptions underlying the method are examined for the special case of 235U(n, f)

  16. Creation of a retrospective job-exposure matrix using surrogate measures of exposure for a cohort of US career firefighters from San Francisco, Chicago and Philadelphia

    Science.gov (United States)

    Dahm, Matthew M; Bertke, Stephen; Allee, Steve; Daniels, Robert D

    2015-01-01

    Objectives To construct a cohort-specific job-exposure matrix (JEM) using surrogate metrics of exposure for a cancer study on career firefighters from the Chicago, Philadelphia and San Francisco Fire Departments. Methods Departmental work history records, along with data on historical annual fire-runs and hours, were collected from 1950 to 2009 and coded into separate databases. These data were used to create a JEM based on standardised job titles and fire apparatus assignments using several surrogate exposure metrics to estimate firefighters’ exposure to the combustion byproducts of fire. The metrics included duration of exposure (cumulative time with a standardised exposed job title and assignment), fire-runs (cumulative events of potential fire exposure) and time at fire (cumulative hours of potential fire exposure). Results The JEM consisted of 2298 unique job titles alongside 16 174 fire apparatus assignments from the three departments, which were collapsed into 15 standardised job titles and 15 standardised job assignments. Correlations were found between fire-runs and time at fires (Pearson coefficient=0.92), duration of exposure and time at fires (Pearson coefficient=0.85), and duration of exposure and fire-runs (Pearson coefficient=0.82). Total misclassification rates were found to be between 16–30% when using duration of employment as an exposure surrogate, which has been traditionally used in most epidemiological studies, compared with using the duration of exposure surrogate metric. Conclusions The constructed JEM successfully differentiated firefighters based on gradient levels of potential exposure to the combustion byproducts of fire using multiple surrogate exposure metrics. PMID:26163543

  17. Measurement of antibody titer to fowl pox virus by enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Iritani, Y; Sawaguchi, K

    1994-12-01

    The usefulness of the measurement of antibody titer to fowl pox virus (FPV) by enzyme-linked immunosorbent assay (ELISA) was evaluated in SPF chickens with or without inoculation with FPV. The optimum concentration of purified antigen was 10 micrograms/ml of protein. The absorbance at 492 nm was less than 0.10 in the chickens negative to FPV from 1 to 63 days old. By contrast, a higher titer was detected in SPF chickens with various FPVs inoculated into the wing web than in non-inoculated chickens. Moreover, there was no cross response to chicken sera immunized with Haemophilus paragallinarum, Marek's disease virus, Newcastle disease virus or infectious bronchitis virus. The titers increased after vaccination were not increased after subsequent challenge with virulent FPV. These findings suggested the usefulness of the measurement of the antibody response to FPV vaccine by ELISA. PMID:7696418

  18. Use and Clinical Interpretation of Pneumococcal Antibody Measurements in the Evaluation of Humoral Immune Function

    OpenAIRE

    Daly, Thomas M.; Hill, Harry R.

    2014-01-01

    Pneumococcal vaccination is a commonly used technique for assessing the humoral immune status of a patient suspected of having immunodeficiency. Interpretation of what constitutes an adequate response, however, can be challenging. This is due to the complexity of the data generated from serotype-specific assays, historical variations in the assays used to measure pneumococcal antibodies, and varying recommendations on the relevant cut points that define response. In this review, we summarize ...

  19. A nylon ball solid-phase radioimmunoassay for specific antibodies in human sera. Application to measurement of IgG antibodies to pollen allergens

    International Nuclear Information System (INIS)

    The principle of the radioallergosorbent test (RAST) has been used to measure IgG antibodies to timothy grass pollen allergens in sera from desensitized allergic subjects. 125I-labeled goat anti-human IgG was used as detector protein. Non-specific binding was eliminated by use of a non-porous nylon ball an antigen carrier and by use of a special buffer with high ionic strength and pH, containing 1% bovine gamma globulin and 5% normal rabbit serum as 'balance proteins'. At dilution 1:80 non-specific binding was only 0.28% and the binding ratio for a high-titer serum was about 10. By inhibition experiments the assay was demonstrated to be specific for IgG antibodies to timothy grass pollen. The results obtained with this assay correlated statistically significantly with those found with a double-antibody method. Serum dilution curves were parallel, indicating that the assay is in allergen excess. The within-assay coefficient of variation ranged from 3.9 to 7.6%; the between-assay coefficient of variation from 8.4 to 19.5%. The assay is very simple to perform, requiring no centrifugation. The allergen-coated balls are stable for at least 3 months. The assay should be applicable to measurement of IgG antibodies and IgG subclass antibodies to any protein antigen of interest. (Auth.)

  20. Introduction of surrogate approach for determining nuclear reaction cross sections

    International Nuclear Information System (INIS)

    The surrogate nuclear reaction approach plays an important role in the determination of nuclear reaction cross sections that are difficult to be measured directly. In this paper, we investigate its basis, factors affecting its accuracy, and its three variants: the external surrogate ratio method (ESRM), the internal surrogate ratio method (ISRM) and the hybrid surrogate ratio method (HSRM). Each method was described, and their applications or experimental tests were given, from which we could see their respective advantages and disadvantages. And it is found that the spin-parity mismatch, or the (weak) Weisskopf-Ewing limit equivalently, is an inherent limitation of the approach. It is also seen that the surrogate approach can reach a high accuracy, so it is a good indirect approach when the nuclear reaction cross sections are unavailable to be measured directly. (authors)

  1. Diagnosis of hypersensitivity pneumonitis by measurement of antibodies against environmental antigens

    International Nuclear Information System (INIS)

    Hypersensitivity pneumonitis (HP), an immunologically mediated chronic pulmonary disease, is the result of an inflammatory response of the lung initiated by the inhalation of environmental organic dusts. These organic dusts usually contain substances (antigens) capable of eliciting immune responses in humans. The symptoms of HP generally present as recurrent flu-like episodes which makes it difficult to establish the proper diagnosis. However, detection in patients' sera of high-titer antibodies against the environmental antigens could be of great help in identifying those materials causing the disease and which must be avoided. A highly specific and sensitive serodiagnostic test, a radioimmuno assay (RIA), was developed for measurement of antibodies against antigens relevant to Farmer's Lung Disease (FLD), a type of HP affecting farmers

  2. Meet the surrogate fish

    International Nuclear Information System (INIS)

    This article gives details of the US Department of Energy's innovative research into the development of a sensor system that will work as a surrogate fish to provide information to aid the design of fish-friendly turbines for hydroelectric power plants. The selection of the dams for the testing of sensor fish, the release and recovery of the sensor fish, the recording of the physical forces exerted on fish as they pass through the turbines, and use of the information gathered to build more sensor fish are discussed. Fish investigations conducted at the Pacific Northwest National Laboratory are briefly described. (UK)

  3. Surrogate time series

    CERN Document Server

    Schreiber, T; Schreiber, Thomas; Schmitz, Andreas

    1999-01-01

    Before we apply nonlinear techniques, for example those inspired by chaos theory, to dynamical phenomena occurring in nature, it is necessary to first ask if the use of such advanced techniques is justified "by the data". While many processes in nature seem very unlikely a priori to be linear, the possible nonlinear nature might not be evident in specific aspects of their dynamics. The method of surrogate data has become a very popular tool to address such a question. However, while it was meant to provide a statistically rigorous, foolproof framework, some limitations and caveats have shown up in its practical use. In this paper, recent efforts to understand the caveats, avoid the pitfalls, and to overcome some of the limitations, are reviewed and augmented by new material. In particular, we will discuss specific as well as more general approaches to constrained randomisation, providing a full range of examples. New algorithms will be introduced for unevenly sampled and multivariate data and for surrogate sp...

  4. Determining vaccination frequency in farmed rainbow trout using Vibrio anguillarum O1 specific serum antibody measurements.

    Directory of Open Access Journals (Sweden)

    Lars Holten-Andersen

    Full Text Available BACKGROUND: Despite vaccination with a commercial vaccine with a documented protective effect against Vibrio anguillarum O1 disease outbreaks caused by this bacterium have been registered among rainbow trout at Danish fish farms. The present study examined specific serum antibody levels as a valid marker for assessing vaccination status in a fish population. For this purpose a highly sensitive enzyme-linked immunosorbent assay (ELISA was developed and used to evaluate sera from farmed rainbow trout vaccinated against V. anguillarum O1. STUDY DESIGN: Immune sera from rainbow trout immunised with an experimental vaccine based on inactivated V. anguillarum O1 bacterin in Freund's incomplete adjuvant were used for ELISA optimisation. Subsequently, sera from farmed rainbow trout vaccinated with a commercial vaccine against V. anguillarum were analysed with the ELISA. The measured serum antibody levels were compared with the vaccine status of the fish (vaccinated/unvaccinated as evaluated through visual examination. RESULTS: Repeated immunisation with the experimental vaccine lead to increasing levels of specific serum antibodies in the vaccinated rainbow trout. The farmed rainbow trout responded with high antibody levels to a single injection with the commercial vaccine. However, the diversity in responses was more pronounced in the farmed fish. Primary visual examinations for vaccine status in rainbow trout from the commercial farm revealed a large pool of unvaccinated specimens (vaccination failure rate=20% among the otherwise vaccinated fish. Through serum analyses using the ELISA in a blinded set-up it was possible to separate samples collected from the farmed rainbow trout into vaccinated and unvaccinated fish. CONCLUSIONS: Much attention has been devoted to development of new and more effective vaccines. Here we present a case from a Danish rainbow trout farm indicating that attention should also be directed to the vaccination procedure in

  5. Surrogate Endpoints in Suicide Research

    Science.gov (United States)

    Wortzel, Hal S.; Gutierrez, Peter M.; Homaifar, Beeta Y.; Breshears, Ryan E.; Harwood, Jeri E.

    2010-01-01

    Surrogate endpoints frequently substitute for rare outcomes in research. The ability to learn about completed suicides by investigating more readily available and proximate outcomes, such as suicide attempts, has obvious appeal. However, concerns with surrogates from the statistical science perspective exist, and mounting evidence from…

  6. Surrogate Modeling for Geometry Optimization

    DEFF Research Database (Denmark)

    Rojas Larrazabal, Marielba de la Caridad; Abraham, Yonas; Holzwarth, Natalie; Plemmons, Robert

    2009-01-01

    A new approach for optimizing the nuclear geometry of an atomic system is described. Instead of the original expensive objective function (energy functional), a small number of simpler surrogates is used.......A new approach for optimizing the nuclear geometry of an atomic system is described. Instead of the original expensive objective function (energy functional), a small number of simpler surrogates is used....

  7. HAHA--nothing to laugh about. Measuring the immunogenicity (human anti-human antibody response) induced by humanized monoclonal antibodies applying ELISA and SPR technology.

    Science.gov (United States)

    Nechansky, Andreas

    2010-01-01

    Immunogenicity induced by passively applied proteins is a serious issue because it is directly related to the patient's safety. The out-come of an immune reaction to a therapeutic protein can range from transient appearance of antibodies without any clinical significance to severe life threatening conditions. Within this article, enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) methodology to measure immunogenicity are compared and the pros and cons are discussed. PMID:19679421

  8. Surrogate mothers: the legal issues.

    Science.gov (United States)

    Mady, T M

    1981-01-01

    Increasing numbers of couples have benefitted from, or may be considering use of, the surrogate mother procedure. In this procedure, a couple, usually a husband and wife, enters into a contract with a surrogate mother. Under the terms of the contract, the surrogate mother is artificially inseminated, bears a child, and relinquishes all rights regarding that child to the semen donor and his wife. In exchange for bearing a child, the surrogate mother often receives a fee. In light of such increased use of the procedure, the issue of whether or not the arrangement is legal has particular importance. Questions of legality involve possible violations of criminal baby-selling statutes. Issues of whether adoption is necessary and whether the child is legitimate also are inherent in the surrogate mother arrangement. This Note argues that these questions should be resolved in favor of finding no impediment to the use of the surrogate mother procedure, at least within certain guidelines. However, even in the absence of legal impediment, detailed contracts and thorough medical screening for genetic, physical and psychological problems would further eliminate ambiguities regarding liability. In addition, the Note concludes that legislation should be enacted to deal with the legal ambiguities of the surrogate mother arrangement. This legislation should regulate the parties that enter into such an arrangement and the rights and responsibilities of these parties. PMID:7332012

  9. Measuring and evaluating interferon beta-induced antibodies in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Ross, C; Clemmesen, K M; Sørensen, P S;

    2006-01-01

    Administration of interferons (IFNs) may induce antibodies that interfere with therapeutic efficacy. We have optimized and validated methods for large-scale economic screening. Sera from patients with relapsing-remitting multiple sclerosis (MS) were investigated for binding antibody (BAb) by prot......Administration of interferons (IFNs) may induce antibodies that interfere with therapeutic efficacy. We have optimized and validated methods for large-scale economic screening. Sera from patients with relapsing-remitting multiple sclerosis (MS) were investigated for binding antibody (BAb...

  10. Neutron-induced cross-sections via the surrogate method

    International Nuclear Information System (INIS)

    The surrogate reaction method is an indirect way of determining neutron-induced cross sections through transfer or inelastic scattering reactions. This method presents the advantage that in some cases the target material is stable or less radioactive than the material required for a neutron-induced measurement. The method is based on the hypothesis that the excited nucleus is a compound nucleus whose decay depends essentially on its excitation energy and on the spin and parity state of the populated compound state. Nevertheless, the spin and parity population differences between the compound-nuclei produced in the neutron and transfer-induced reactions may be different. This work reviews the surrogate method and its validity. Neutron-induced fission cross sections obtained with the surrogate method are in general good agreement. However, it is not yet clear to what extent the surrogate method can be applied to infer radiative capture cross sections. We performed an experiment to determine the gamma decay probabilities for 176Lu and 173Yb by using the surrogate reactions 174Yb(3He,pγ)176Lu* and 174Yb(3He,αγ)173Yb*, respectively, and compare them with the well-known corresponding probabilities obtained in the 175Lu(n,γ) and 172Yb(n,γ) reactions. This experiment provides answers to understand why, in the case of gamma-decay, the surrogate method gives significant deviations compared to the corresponding neutron-induced reaction. In this work, we have also assessed whether the surrogate method can be applied to extract capture probabilities in the actinide region. Previous experiments on fission have also been reinterpreted. Thus, this work provides new insights into the surrogate method. This work is organised in the following way: in chapter 1, the theoretical aspects related to the surrogate method will be introduced. The validity of the surrogate method will be investigated by means of statistical model calculations. In chapter 2, a review on experiments based

  11. Evolving issues in surrogate motherhood.

    Science.gov (United States)

    Erlen, J A; Holzman, I R

    1990-01-01

    Surrogate mothering is an arrangement whereby a woman who gives birth to an infant intends--through a contractual agreement--to give that baby to another couple. The recent Baby M case in the United States has raised numerous legal concerns causing many legislative bodies to consider possible statutes to regulate or prohibit surrogacy. The competing interests among and between the individuals involved in this relationship (i.e., the surrogate mother, the couple, the baby, and society) suggest various ethical issues related to benefits, risks, and autonomy. Legal and ethical concerns surrounding the technologically possible procedure of surrogate motherhood are discussed. PMID:2391288

  12. New aspects of radioimmunochemical measurement of human parathyroid hormone using the labelled antibody technique

    International Nuclear Information System (INIS)

    Two forms of heterogeneity of parathyroid hormone (PTH) have given rise to conflicting results: one due to the heterogeneity of the secreted species from the gland and their peripheral metabolism and the other representing the immunochemical heterogeneity of the available antibodies. We have developed sequence specific assays using the technique of labelled antibodies. Therefore, results of assays measuring the C-terminal part and the (1-34)-N-terminal part of the molecule could be compared to those of an assay for hormone bearing both N- and C-terminal antigenic determinants. This assay is supposed to detect predominantly (1-84)-intact hormone. The immunoradiometric assay of (1-34)-PTH has a sensitivity of 0.04 ng/ml. This technique avoids the critical iodination of the hormone fragment containing no tyrosine. There is the expected overlap between normal subjects and patients with primary and secondary hyperparathyroidism. The most important finding are results from patients undergoing neck catheterization. We demonstrated nonuniform secretion of different species of PTH by parathyroid adenomata and normal glands. This supports the hypothesis of cleavage of the (1-84)-molecule in the gland. (orig.)

  13. IgE antibody responses in schistosomiasis measured by a radioallergosorbent test

    International Nuclear Information System (INIS)

    Helminth infections are associated with the production of unusually high concentrations of circulating IgE antibody. Assays for IgE antibodies should provide useful approaches for the study of protective immunity and may also be of use in serodiagnosis of diseases induced by helminths. The radioallergosorbent test is carried out by attaching the antigen or allergen to an insoluble supportive material, allowing the IgE antibodies in the test serum to react with excess bound antigen, and then estimating the IgE antibody bound by its reaction with 125I-labelled goat anti-human IgE antibody

  14. LEGAL DISCUSSIONS ON SURROGATE MOTHERHOOD

    OpenAIRE

    FİDAN, Yılmaz

    2015-01-01

     The surrogate motherhood and IVF (test-tube baby) practice has currently reached an advanced level and people who are not allowed to pregnancy for medical reasons, look at positively the surrogate motherhood. The surrogacy is permitted worlwide in many countries like  USA except in New Jersey, Michigan and Arizona states). Georgia, Thailand, India, Belgium, England,  Brazil, some countries of Africa. It is banned in Germany, Sweden, Italy and Norway. In Turkey, The Presidency of Religious Af...

  15. A microbiological surrogate for evaluating treatment efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Rice, E.W.; Fox, K.W.; Miltner, R.J. [Environmental Protection Agency, Cincinnati, OH (United States)] [and others

    1995-10-01

    In this study we report on the use of a microbial surrogate system which can be used to evaluate the efficiency of various unit processes used in drinking water treatment for the removal of microbial contaminants. The proposed procedure uses Gram-positive, mesophilic, aerobic spore-forming bacteria as the surrogate organisms. These bacteria do not pose a public health threat and are naturally occurring in most surface water supplies. The aerobic spore-formers are easy to culture and are present throughout the treatment train. This group of organisms consists primarily of species of the genus Bacillus. These organisms form endospores which are ellipsoidal to spherical in shape and measure on average approximately 0.5 X 1.0 X 1.5 micrometers, and are environmentally resistant. Like pathogenic Giardia cysts and Cryptosporidium oocysts endospores of aerobic bacilli may be found far into the treatment train.

  16. Post-pellet-digestion precipitation and solid phase extraction: A practical and efficient workflow to extract surrogate peptides for ultra-high performance liquid chromatography--tandem mass spectrometry bioanalysis of a therapeutic antibody in the low ng/mL range.

    Science.gov (United States)

    Gong, Chao; Zheng, Naiyu; Zeng, Jianing; Aubry, Anne-Françoise; Arnold, Mark E

    2015-12-11

    The current LC-MS/MS approach for bioanalysis of protein therapeutics requires generating peptides from protein molecules via trypsin digestion, followed by sensitive detection of these surrogate peptides by multiple reaction monitoring (MRM). However, the presence of huge amount of matrix-related interference peptides generated from trypsin digestion often causes substantial matrix effect or isobaric interferences during LC-MS/MS analysis. Solid phase extraction (SPE) exhibits great potential in sample extraction to overcome these challenges due to its characteristic features of high selectivity, reproducibility, cost-effectiveness and potential to be automated. Here, we report an effective SPE methodology for the bioanalysis of protein therapeutics involving post-pellet-digestion precipitation and SPE cleanup prior to UHPLC-MS/MS analysis. Specifically, proteins in serum samples were first precipitated with methanol to enrich the protein analyte in the pellet prior to trypsin digestion of the pellet (pellet-digestion). The trypsin digest was further processed by a post-pellet-digestion precipitation (second precipitation) to remove matrix-related clog-causing components prior to SPE on OASIS™ MAX (Mixed-Mode Anion-Exchange) SPE plate. This methodology successfully overcame SPE clogging issue and enabled extraction of 100μL of monkey serum on SPE with significant sensitivity improvement to achieve a lower limit of quantitation (LLOQ) of 50ng/mL for a human monoclonal antibody of the IgG4 subclass. This UHPLC-MS/MS assay was validated in a concentration range of 50-5000ng/mL with intra- and inter-assay precisions of within 9.6% CV, and assay accuracy of within ±2.9% Dev of their nominal concentrations. To our best knowledge, this is the pellet digestion with SPE method for LC-MS/MS bioanalysis of a monoclonal antibody for the first time to achieve a LLOQ in the low ng/mL concentration range. PMID:26525666

  17. Development of a Coxsackievirus A16 neutralization assay based on pseudoviruses for measurement of neutralizing antibody titer in human serum.

    Science.gov (United States)

    Jin, Jun; Ma, Hongxia; Xu, Lin; An, Dong; Sun, Shiyang; Huang, Xueyong; Kong, Wei; Jiang, Chunlai

    2013-02-01

    Serum neutralizing antibody titers are indicative of protective immunity against Coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV71), the two main etiological agents of hand, foot and mouth disease (HFMD), and provide the basis for evaluating vaccine efficacy. The current CV-A16 neutralization assay based on inhibition of cytopathic effects requires manual microscopic examination, which is time-consuming and labor-intensive. In this study, a high-throughput neutralization assay was developed by employing CV-A16 pseudoviruses expressing luciferase for detecting infectivity in rhabdomyosarcoma (RD) cells and measuring serum viral neutralizing antibodies. Without the need to use infectious CV-A16 strains, the neutralizing antibody titer against CV-A16 could be determined within 15h by measuring luciferase signals by this assay. The pseudovirus CV-A16 neutralization assay (pCNA) was validated by comparison with a conventional CV-A16 neutralization assay (cCNA) in testing 174 human serum samples collected from children (age <5 years). The neutralizing antibody titers determined by these two assays were well correlated (R(2)=0.7689). These results suggest that the pCNA can serve as a rapid and objective procedure for the measurement of neutralizing antibodies against CV-A16. PMID:23178532

  18. Bioaccessibility of metals in alloys: Evaluation of three surrogate biofluids

    International Nuclear Information System (INIS)

    Bioaccessibility in vitro tests measure the solubility of materials in surrogate biofluids. However, the lack of uniform methods and the effects of variable test parameters on material solubility limit interpretation. One aim of this study was to measure and compare bioaccessibility of selected economically important alloys and metals in surrogate physiologically based biofluids representing oral, inhalation and dermal exposures. A second aim was to experimentally test different biofluid formulations and residence times in vitro. A third aim was evaluation of dissolution behavior of alloys with in vitro lung and dermal biofluid surrogates. This study evaluated the bioaccessibility of sixteen elements in six alloys and 3 elemental/metal powders. We found that the alloys/metals, the chemical properties of the surrogate fluid, and residence time all had major impacts on metal solubility. The large variability of bioaccessibility indicates the relevancy of assessing alloys as toxicologically distinct relative to individual metals. -- Highlights: • All alloy grades, independent of biofluid, revealed time-dependent release. • Different alloy materials are useful for testing of bioaccessibility parameters. • Minor changes in biofluid formulations have effects on bioaccessibility. • Dissolution studies illustrated effects of alloy and media on metal dissolution. • Metal solubility is compared in a series of alloys in various surrogate biofluids. -- We illustrate in vitro bioaccessibility tests of alloys for health characterization purposes; bio-surrogate formulations, and residence times have a major impact on bioaccessibility

  19. A novel technique, using radioluminography, for the measurement of uniformity of radiolabelled antibody distribution in a colorectal cancer xenograft model

    International Nuclear Information System (INIS)

    Purpose: Radioimmunotherapy of cancer employs an antitumour antibody to carry a radionuclide selectively to deposits of cancer. Conventional dose estimates, based on the Medical Internal Radiation Dose (MIRD) formulation, assume uniform distribution of radiolabelled antitumour antibody within tissue source regions. This assumption has been tested by using a statistical model to predict the pixel value distribution obtained from the digitised radioluminographs of a known radioactive source. The model uses the statistical nature of the detection of radiation where any uniform source distribution can be expected to have a detected histogram of pixel counts that is normal or Gaussian. Therefore, any test for the degree of normality in the detected distribution is also a measure of the degree of uniformity in the source. Methods and Materials: Three statistical techniques have been used to test the normality of the histogram of pixel values produced from the antibody distribution in a tissue section. Kurtosis, skew, and Lilliefor's are tests for normality and have statistically defined critical values for a normal distribution. After administration of 125I-labelled F(ab)2 antibody to nude mice bearing the LS174T colorectal cancer xenograft, the uniformity of antibody distribution in tumour and healthy tissues is measured using the radioluminographs of formalin-fixed paraffin sections. The test statistic for kurtosis, skew, and Lilliefor's is calculated for each tissue and is compared to critical values from statistical tables. Results: The radiolabelled antibody is distributed uniformly in liver, spleen, muscle, lung, and colon and, therefore, conforms to conventional use of the MIRD formulation. The study showed that the kidney cortex and medulla should be considered separately in macroscopic absorbed-dose calculations, as should bone marrow and hard bone. Antibody heterogeneity in the tumour necessitates the incorporation of a microdosimetric tumour model into a

  20. Urethral and periurethral dosimetry in prostate brachytherapy: is there a convenient surrogate?

    International Nuclear Information System (INIS)

    Purpose: To assess and compare two models for a surrogate urethra to be used for postimplant dosimetry in prostate brachytherapy. Methods and Materials: Twenty men with a urinary catheter present at the time of postimplant computed tomographic imaging were studied. Urethral and periurethral volumes were defined as 5-mm and 10-mm diameter volumes, respectively. Three contours of each were used: one contour of the true urethra (and periurethra), and two surrogate models. The true volumes were centered on the catheter center. One surrogate model used volumes centered on the geometrical center of each prostate contour (centered surrogate). The other surrogate model was based on the average deviation of the true urethra from a reference line through the geometrical center of the axial midplane of the prostate (deviated surrogate). Maximum point doses and the D10, D25, D50, D90, V100, V120, and V150 of the true and surrogate volumes were measured and compared (Dn is the minimum dose [Gy] received by n% of the structure, and Vm is the volume [%] of the structure that received m% of the prescribed dose) as well as the distances between the surrogate urethras and the true urethra. Results: Doses determined from both surrogate urethral and periurethral volumes were in good agreement with the true urethral and periurethral doses except in the superior third of the gland. The deviated surrogate provided a physically superior likeness to the true urethra. Certain dose-volume histogram (DVH)-based parameters could also be predicted reasonably well on the basis of the surrogates. Correlation coefficients ≥0.85 were seen for D25, D50, V100, V120, and V150 for both models. All the other parameters had correlation coefficients in the range of 0.73 - 0.85. Conclusions: Both surrogate models predicted true urethral dosimetry reasonably well. It is recommended that the simpler deviated surrogate would be a more suitable surrogate for routine clinical practice

  1. Chlamydia pneumoniae antibody levels before coronary events in the Helsinki Heart Study as measured by different methods.

    Science.gov (United States)

    Paldanius, Mika; Leinonen, Maija; Virkkunen, Hanna; Tenkanen, Leena; Sävykoski, Tiina; Mänttäri, Matti; Saikku, Pekka

    2006-11-01

    The lack of specific tests for the diagnosis of chronic Chlamydia pneumoniae infection has led to the use of enzyme immunoassay (EIA) instead of the gold standard, that is, microimmunofluorescence (MIF), in the measurement of C. pneumoniae antibodies. We assessed the predictive values of C. pneumoniae antibody levels and seroconversions measured by MIF and EIA for coronary events in the prospective Helsinki Heart Study. Sera from 239 cases with coronary events and 239 controls were available at the baseline and data from 210 cases and 211 controls before and after the event. The agreement between MIF and EIA antibody levels was best in high antibody titers. In conditional logistic regression analysis, only high IgA MIF titers (>/=40) at the baseline predicted future coronary events, and the participants with MIF seroconversion between consecutive sera had a higher (nonsignificant) risk for coronary events than the controls. The difference in the kinetics of EIA and MIF antibodies demonstrated that MIF should remain the gold standard. PMID:16757141

  2. Psychosocial aspects of surrogate motherhood.

    Science.gov (United States)

    van den Akker, Olga B A

    2007-01-01

    This review addresses the psychosocial research carried out on surrogacy triads (surrogate mothers, commissioning mothers and offspring) and shows that research has focused on a number of specific issues: attachment and disclosure to surrogate offspring; experiences, characteristics and motivations of surrogate mothers; and changes in profiles of the commissioning/intended mothers. Virtually all studies have used highly selected samples making generalizations difficult. There have been a notable lack of theory, no interventions and only a handful of longitudinal studies or studies comparing different populations. Few studies have specifically questioned the meaning of and need for a family or the influence and impact that professionals, treatment availability and financial factors have on the choices made for surrogate and intended mothers. Societal attitudes have changed somewhat; however, according to public opinion, women giving up babies still fall outside the acceptable remit. Surrogate and intended mothers appear to reconcile their unusual choice through a process of cognitive restructuring, and the success or failure of this cognitive appraisal affects people's willingness to be open and honest about their choices. Normal population surveys, on the contrary, are less accepting of third party reproduction; they have no personal need to reconsider and hence maintain their original normative cognitively consonant state. PMID:16936307

  3. Methods of assessing the functional status of patients with left ventricular systolic dysfunction in interventional studies: can brain natriuretic peptide measurement be used as surrogate for the traditional methods?

    DEFF Research Database (Denmark)

    Abdulla, Jawdat; Køber, Lars; Torp-Pedersen, Christian

    2004-01-01

    AIM: To review whether brain natriuretic peptides (BNP) can be used as a surrogate for the traditional methods of assessing functional status in interventional studies of patients with left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: The traditional methods for assessing...... functional status including New York Heart Association (NYHA) class, exercise intolerance and quality of life were reviewed in relation to BNP measurements in patients with LVSD. A meta-analysis of four studies evaluating BNP levels versus exercise peak oxygen uptake or 6-minute walking distance showed...... a significant correlation, but a low R-value of -0.59. Studies using BNP levels for optimisation of heart failure therapy showed conflicting results concerning the correlation between the functional improvement and changes in BNP levels. Conflicting results were also found concerning the utility of BNP levels...

  4. Generation of anti-idiotype scFv for pharmacokinetic measurement in lymphoma patients treated with chimera anti-CD22 antibody SM03.

    Directory of Open Access Journals (Sweden)

    Qi Zhao

    Full Text Available Pre-clinical and clinical studies of therapeutic antibodies require highly specific reagents to examine their immune responses, bio-distributions, immunogenicity, and pharmacodynamics in patients. Selective antigen-mimicking anti-idiotype antibody facilitates the assessment of therapeutic antibody in the detection, quantitation and characterization of antibody immune responses. Using mouse specific degenerate primer pairs and splenocytic RNA, we generated an idiotype antibody-immunized phage-displayed scFv library in which an anti-idiotype antibody against the therapeutic chimera anti-CD22 antibody SM03 was isolated. The anti-idiotype scFv recognized the idiotype of anti-CD22 antibody and inhibited binding of SM03 to CD22 on Raji cell surface. The anti-idiotype scFv was subsequently classified as Ab2γ type. Moreover, our results also demonstrated firstly that the anti-idiotype scFv could be used for pharmacokinetic measurement of circulating residual antibody in lymphoma patients treated with chimera anti-CD22 monoclonal antibody SM03. Of important, the present approach could be easily adopted to generate anti-idiotype antibodies for therapeutic antibodies targeting membrane proteins, saving the cost and time for producing a soluble antigen.

  5. Antibody responses measured by various serologic tests in pigs orally inoculated with low numbers of Toxoplasma gondii oocysts

    DEFF Research Database (Denmark)

    Dubey, J. P.; Andrews, C.D.; Lind, Peter; Kwok, O.C.H.; Thulliez, P.; Lunney, J.K.

    1996-01-01

    Objective-To follow antibody responses measured by various serologic tests in pigs orally inoculated with low (less than or equal to 10 oocysts) numbers of Toxoplasma gondii oocysts. Animals-24, 2- to 3-month-old pigs. Procedure-Pigs (n = 42) were inoculated orally with 10 (14 pigs) or 1 (28 pigs...

  6. Surrogates with random Fourier Phases

    CERN Document Server

    Raeth, Christoph

    2008-01-01

    The method of surrogates is widely used in the field of nonlinear data analysis for testing for weak nonlinearities. The two most commonly used algorithms for generating surrogates are the amplitude adjusted Fourier transform (AAFT) and the iterated amplitude adjusted Fourier transfom (IAAFT) algorithm. Both the AAFT and IAAFT algorithm conserve the amplitude distribution in real space and reproduce the power spectrum (PS) of the original data set very accurately. The basic assumption in both algorithms is that higher-order correlations can be wiped out using a Fourier phase randomization procedure. In both cases, however, the randomness of the Fourier phases is only imposed before the (first) Fourier back tranformation. Until now, it has not been studied how the subsequent remapping and iteration steps may affect the randomness of the phases. Using the Lorenz system as an example, we show that both algorithms may create surrogate realizations containing Fourier phase correlations. We present two new iterativ...

  7. Use of recombinant RNP peptides 70K and A in an ELISA for measurement of antibodies in mixed connective tissue disease: a longitudinal follow up of 18 patients.

    OpenAIRE

    de Rooij, D J; Habets, W J; van de Putte, L B; Hoet, M H; Verbeek, A L; van Venrooij, W J

    1990-01-01

    In a three year prospective study disease activity variables and levels of antibody against the RNP-peptides 70K and A were measured in 18 patients with mixed connective tissue disease. Antibody measurement entailed use of cloned autoantigens in an enzyme linked immunosorbent assay (ELISA). Fluctuations in antibody levels against 70K and A were most commonly noted in patients who also had changes in disease activity, but these changes in serology and disease activity were synchronous in only ...

  8. Simultaneous measurements of auto-immune and infectious disease specific antibodies using a high throughput multiplexing tool.

    Directory of Open Access Journals (Sweden)

    Atul Asati

    Full Text Available Considering importance of ganglioside antibodies as biomarkers in various immune-mediated neuropathies and neurological disorders, we developed a high throughput multiplexing tool for the assessment of gangliosides-specific antibodies based on Biolpex/Luminex platform. In this report, we demonstrate that the ganglioside high throughput multiplexing tool is robust, highly specific and demonstrating ∼100-fold higher concentration sensitivity for IgG detection than ELISA. In addition to the ganglioside-coated array, the high throughput multiplexing tool contains beads coated with influenza hemagglutinins derived from H1N1 A/Brisbane/59/07 and H1N1 A/California/07/09 strains. Influenza beads provided an added advantage of simultaneous detection of ganglioside- and influenza-specific antibodies, a capacity important for the assay of both infectious antigen-specific and autoimmune antibodies following vaccination or disease. Taken together, these results support the potential adoption of the ganglioside high throughput multiplexing tool for measuring ganglioside antibodies in various neuropathic and neurological disorders.

  9. Solid-phase radioimmunoassay for measurement of circulating antibody titres to wheat gliadin and its subfractions in patients with adult coeliac disease

    Energy Technology Data Exchange (ETDEWEB)

    Ciclitira, P.J.; Ellis, H.J. (Guy' s Hospital, London (UK)); Evans, D.J. (Hammersmith Hospital, London (UK))

    1983-08-26

    A solid-phase radioimmunoassay for the measurement of circulating antibody titres to wheat gliadin is described. Using this assay, the authors have measured antibody titres to unfractionated gliadin in normal healthy controls, in coeliac patients on a gluten-free or a normal diet, and in patients with ulcerative colitis and Crohn's disease. High titres of antibodies to unfractionated gliadin were observed only in the patients with untreated coeliac disease. Antibody titres to ..cap alpha.., ..beta.., ..gamma.. and ..omega.. gliadin subfractions were measured in patients with untreated coeliac disease and compared with titres in normal controls. Patients with untreated coeliac disease had higher antibody titres to the gliadin subfractions. No specific pattern of circulating antibody titres to gliadin subfractions was observed in the untreated coeliac patients which would provide a diagnostic profile. These results suggest shared antigenicity between the gliadin subfractions.

  10. A solid-phase radioimmunoassay for measurement of circulating antibody titres to wheat gliadin and its subfractions in patients with adult coeliac disease

    International Nuclear Information System (INIS)

    A solid-phase radioimmunoassay for the measurement of circulating antibody titres to wheat gliadin is described. Using this assay, the authors have measured antibody titres to unfractionated gliadin in normal healthy controls, in coeliac patients on a gluten-free or a normal diet, and in patients with ulcerative colitis and Crohn's disease. High titres of antibodies to unfractionated gliadin were observed only in the patients with untreated coeliac disease. Antibody titres to α, #betta#, #betta# and #betta# gliadin subfractions were measured in patients with untreated coeliac disease and compared with titres in normal controls. Patients with untreated coeliac disease had higher antibody titres to the gliadin subfractions. No specific pattern of circulating antibody titres to gliadin subfractions was observed in the untreated coeliac patients which would provide a diagnostic profile. These results suggest shared antigenicity between the gliadin subfractions. (Auth.)

  11. In vitro molecular magnetic resonance imaging detection and measurement of apoptosis using superparamagnetic iron oxide + antibody as ligands for nucleosomes

    International Nuclear Information System (INIS)

    Recent research in cell biology as well as oncology research has focused on apoptosis or programmed cell death as a means of quantifying the induced effects of treatment. A hallmark of late-stage apoptosis is nuclear fragmentation in which DNA is degraded to release nucleosomes with their associated histones. In this work, a method was developed for detecting and measuring nucleosome concentration in vitro with magnetic resonance imaging (MRI). The indirect procedure used a commercially available secondary antibody-superparamagnetic iron oxide (SPIO) particle complex as a contrast agent that bound to primary antibodies against nucleosomal histones H4, H2A and H2B. Using a multiple-echo spin-echo sequence on a 1.5 T clinical MRI scanner, significant T2 relaxation enhancement as a function of in vitro nucleosomal concentration was measured. In addition, clustering or aggregation of the contrast agent was demonstrated with its associated enhancement in T2 effects. The T2 clustering enhancement showed a complex dependence on relative concentrations of nucleosomes, primary antibody and secondary antibody + SPIO. The technique supports the feasibility of using MRI measurements of nucleosome concentration in blood as a diagnostic, prognostic and predictive tool in the management of cancer. (paper)

  12. Enzyme-linked immunosorbent assay for measurement of antibody to type III group B streptococci.

    OpenAIRE

    Polin, R.A.; Douglas, S D; Kasper, D L; Baker, C J

    1982-01-01

    Neonates at risk for fulminant type III, group B streptococcal (III GBS) infection are those who lack antibody to the capsular polysaccharide. A newly developed enzyme-linked immunosorbent assay (ELISA) was compared with a standard radioactive antigen-binding assay (RABA) for quantitation of III GBS antibody in human sera. Although there was a significant correlation between the ELISA and RABA (r = 0.81; P less than 0.001) in general, the ELISA detected antibody both to core and native antige...

  13. Determination of neutron induced fission cross sections by surrogate reaction methods for nuclear energy applications

    International Nuclear Information System (INIS)

    In this talk, surrogate reaction methods are briefly discussed and presented. Some of the recent results on neutron induced fission cross section measurements carried out and the possibility of extending the measurements for determining (n,γ), (n,2n) and (n,p) reaction cross-sections by surrogate reaction method are also discussed

  14. Flow cytometric measurement of RNA synthesis using bromouridine labelling and bromodeoxyuridine antibodies

    DEFF Research Database (Denmark)

    Jensen, P O; Larsen, J; Christiansen, J;

    1993-01-01

    Nuclear RNA synthesis can be analysed by flow cytometry of cells labelled with 5-bromouridine (BrUrd) and stained with anti-bromodeoxyuridine (BrdUrd) antibody and FITC-conjugated secondary antibody. A panel of 5 different commercially available anti-BrdUrd antibodies was tested on cells of a HL-60...... human leukemia cell line, stained as a methanol-fixed nuclear suspension. The BrUrd-induced fluorescence signals were highest with the antibody ABDM (Partec), moderate but reproducible with B-44 (Becton Dickinson), variable or low with BR-3 and IU-4 (Caltag), and not detectable with Bu20a (DAKO...... variation of RNA synthesis during the cell cycle. The BrUrd incorporation was high in the S and G2 phase, variable in G1, and negligible in mitosis. Similar results were obtained using other cell types....

  15. Solid phase measurements of antibody and lectin binding to xenogenic carbohydrate antigens

    DEFF Research Database (Denmark)

    Kirkeby, Svend; André, Sabine; Gabius, Hans-Joachim

    2004-01-01

    naturally occurring subfraction from human serum, to Galalpha containing neoglycoproteins and mouse laminin that were immobilized on microtiter plates. RESULTS: Galalpha reactive antibodies with similar monosaccharide specificity have distinct structural preference for sugar ligands. Laminin and......-Galalpha1 antibodies that both have been raised against glycans on rabbit red blood cells may recognize Galalpha-antigens with varying specificities. Binding results obtained after digestion with alpha-galactosidase indicate that some xenoreactive Galalpha groups are not directly accessible for removal by...

  16. Gating treatment delivery QA based on a surrogate motion analysis

    International Nuclear Information System (INIS)

    Full text: To develop a methodology to estimate intrafractional target position error during a phase-based gated treatment. Westmead Cancer Care Centre is using respiratory correlated phase-based gated beam delivery in the treatment of lung cancer. The gating technique is managed by the Varian Real-time Position Management (RPM) system, version 1.7.5. A 6-dot block is placed on the abdomen of the patient and acts as a surrogate for the target motion. During a treatment session, the motion of the surrogate can be recorded by RPM application. Analysis of the surrogate motion file by in-house developed software allows the intrafractional error of the treatment session to be computed. To validate the computed error, a simple test that involves the introduction of deliberate errors is performed. Errors of up to 1.1 cm are introduced to a metal marker placed on a surrogate using the Varian Breathing Phantom. The moving marker was scanned in prospective mode using a GE Lightspeed 16 CT scanner. Using the CT images, a difference of the marker position with and without introduced errors is compared to the calculated errors based on the surrogate motion. The average and standard deviation of a difference between calculated target position errors and measured introduced artificial errors of the marker position is 0.02 cm and 0.07 cm respectively. Conclusion The calculated target positional error based on surrogate motion analysis provides a quantitative measure of intrafractional target positional errors during treatment. Routine QA for gated treatment using surrogate motion analysis is relatively quick and simple.

  17. Polyclonal antibodies to tropoelastin and the specific detection and measurement of tropoelastin in vitro.

    Science.gov (United States)

    Prosser, I W; Whitehouse, L A; Parks, W C; Stahle-Bäckdahl, M; Hinek, A; Park, P W; Mecham, R P

    1991-01-01

    Because tropoelastin is difficult to purify, most antibodies to elastin are raised against the insoluble form of the molecule. While these antibodies cross-react with tropoelastin, antigenic differences between insoluble and soluble elastin suggest that antibodies raised directly against tropoelastin might provide a more sensitive and specific reagent for evaluating tropoelastin production in elastin-producing systems. Using an improved method for purifying tropoelastin from tissue culture explants, we describe the generation and characterization of an antibody to bovine tropoelastin. This antibody was used to develop a sensitive, direct-binding immunoassay capable of quantifying small levels of tropoelastin in conditioned medium from cultured cells. This assay takes advantage of the propensity of tropoelastin to adsorb to vinyl microtiter plates, even in the presence of serum proteins. This property, in combination with the increased sensitivity obtained using antibodies to tropoelastin, provides for a direct-binding immunoassay that detects nanogram quantities of tropoelastin directly in cell culture medium, avoiding sample preparation steps that result in extensive loss of tropoelastin. In addition, this direct-binding assay is ten- to 30-fold more sensitive than the existing competitive ELISA assays. PMID:2060302

  18. Measurement of thyrotropin receptor antibodies (TRAK) with a second generation assay in patients with Graves' disease

    International Nuclear Information System (INIS)

    Aim: The detection of TSH-receptor-antibodies (TRAb) in patients (pts) with Graves' disease (GD) is routinely used in nuclear medicine laboratories. It is performed by commercial, porcine radioreceptorassays (RRA) measuring TSH binding inhibitory activity. A second generation assay using the human, recombinant TSH-receptor was developed during the last years. The manufacturer composed this new assay as a coated tube RRA (CT RRA) and claimed a higher sensitivity for GD. Methods: TRAb was measured in 207 pts with various thyroid disorders and 205 healthy controls using the new coated tube RRA (Fa. B.R.A.H.M.S. Diagnostica GmbH, Berlin, Germany) as well as a conventional RRA (Fa. Medipan Diagnostica GmbH, Selchow, Germany): 60 pts suffering from GD showing a relapse after anti-thyroid drug treatment and before radioiodine therapy, 109 pts with disseminated autonomia (DA) and 38 pts suffering from Hashimoto's thyroiditis. A ROC-analysis was performed to find the optimal decision threshold level for positivity. Results: We found 42/60 TRAb-positive pts with GD in the established RRA (threshold 6 U/L) and 52/60 in the CT RRA, respectively. The sensitivity increased from 70% (RRA) to 86,7% (CT RRA). The CT RRA found 2 false positives (one Hashimoto's and one healthy control) and the RRA detected 3 Hashimoto's and 2 healthy controls as false positive. Conclusion: The increased sensitivity of CT RRA for GD provides an advantage compared to conventional RRA, especially in GD-patients relapsing afte antithyroid drug treatment. Functional sensitivity and Interassayvariation of CT RRA are very precisely compared to conventional RRA. Handling of the new assay is also improved. (orig.)

  19. Revisiting algorithms for generating surrogate time series

    CERN Document Server

    Raeth, C; Papadakis, I E; Brinkmann, W

    2011-01-01

    The method of surrogates is one of the key concepts of nonlinear data analysis. Here, we demonstrate that commonly used algorithms for generating surrogates often fail to generate truly linear time series. Rather, they create surrogate realizations with Fourier phase correlations leading to non-detections of nonlinearities. We argue that reliable surrogates can only be generated, if one tests separately for static and dynamic nonlinearities.

  20. Surrogate nuclear reaction methods for astrophysics

    International Nuclear Information System (INIS)

    A brief outline of the Surrogate reaction method, an indirect approach for determining compound-nuclear reaction cross sections, is given. The assumptions introduced in the analysis of a typical Surrogate experiment are discussed and prospects for using the Surrogate method to obtain cross sections relevant to the astrophysical s-process are considered

  1. Surrogate Model Development for Fuels for Advanced Combustion Engines

    Energy Technology Data Exchange (ETDEWEB)

    Anand, Krishnasamy [University of Wisconsin, Madison; Ra, youngchul [University of Wisconsin, Madison; Reitz, Rolf [University of Wisconsin; Bunting, Bruce G [ORNL

    2011-01-01

    The fuels used in internal-combustion engines are complex mixtures of a multitude of different types of hydrocarbon species. Attempting numerical simulations of combustion of real fuels with all of the hydrocarbon species included is highly unrealistic. Thus, a surrogate model approach is generally adopted, which involves choosing a few representative hydrocarbon species whose overall behavior mimics the characteristics of the target fuel. The present study proposes surrogate models for the nine fuels for advanced combustion engines (FACE) that have been developed for studying low-emission, high-efficiency advanced diesel engine concepts. The surrogate compositions for the fuels are arrived at by simulating their distillation profiles to within a maximum absolute error of 4% using a discrete multi-component (DMC) fuel model that has been incorporated in the multi-dimensional computational fluid dynamics (CFD) code, KIVA-ERC-CHEMKIN. The simulated surrogate compositions cover the range and measured concentrations of the various hydrocarbon classes present in the fuels. The fidelity of the surrogate fuel models is judged on the basis of matching their specific gravity, lower heating value, hydrogen/carbon (H/C) ratio, cetane number, and cetane index with the measured data for all nine FACE fuels.

  2. Pseudo-plaque reduction neutralization test (PPRNT for the measurement of neutralizing antibodies to Crimean-Congo hemorrhagic fever virus

    Directory of Open Access Journals (Sweden)

    Canakoglu Nurettin

    2013-01-01

    Full Text Available Abstract Background Crimean-Congo hemorrhagic fever virus (CCHFV is a tick-borne virus of the genus Nairovirus family Bunyaviridae, which are enveloped viruses containing tripartite, negative polarity, single-stranded RNA. CCHF is characterized by high case mortality, occurring in Asia, Africa, the Middle East and Europe. Currently, there are no specific treatments or licensed vaccines available for CCHFV. Recently, two research groups have found adult mice with defective interferon responses allowed to lethal CCHFV infection. These mouse models could provide invaluable information for further studies. Efforts to develop a vaccine against CCHFV are being made. To determine the efficacy of vaccine candidates it is important to conduct serological studies that can accurately measure levels of protective antibodies. In the present study, a pseudo-plaque reduction neutralization test (PPRNT based on enzyme-catalyzed color development of infected cells probed with anti-CCHFV antibodies was used to measure neutralization antibody of CCHFV. Methods Sixty-nine human serum samples (20 acute and 49 convalescent were tested. The presence of CCHFV antibodies was determined and confirmed by a commercial ELISA kit. CCHFV RNA was determined by RT-PCR. All the samples were analyzed by PPRNT and fluorescent focus reduction neutralization test (FFRNT to measure of CCHFV-neutralizing antibodies. Results Pseudo-plaque reduction neutralization test showed a high sensitivity (98%, specificity (100% and agreement (96,6% in qualitative comparison with those of the FFRNT. There was a high correlation between the titers obtained in PPRNT and FFRNT (R2 = 0.92. The inter- and intra-assay variation of PPRNT revealed good reproducibility and positive cut-off of PPRNT was defined as 1:4 by the geometric mean titers for the individual samples distributed. Conclusion The pseudo-plaque reduction neutralization test described in this study is a fast, reproducible and sensitive

  3. Measurement of Antibodies to Infectious Bronchitis Virus in Indigenous Chicken Flocks Around Maharlou Lake in Iran

    Directory of Open Access Journals (Sweden)

    M.M. Hadipour

    2011-06-01

    Full Text Available To evaluate the seroprevalence of Infectious Bronchitis Virus (IBV in indigenous chicken flocks, serum samples from 200 mature indigenous chickens in villages around Maharlou Lake in Southwest of Iran were tested for IBV antibodies using commercial IBV Enzyme-Linked Immunosorbent Assay (ELISA. The studied indigenous chickens had not been previously vaccinated and showed no clinical signs of disease. The overall ELISA titer and seroprevalence of IBV antibodies revealed in this study were 1427 and 68%, respectively. The results indicate a relatively high prevalence of IBV in indigenous chicken flocks in Southwest of Iran and necessitate the regular vaccination programme against IB in native flocks.

  4. Statistical evaluation of surrogate endpoints with examples from cancer clinical trials.

    Science.gov (United States)

    Buyse, Marc; Molenberghs, Geert; Paoletti, Xavier; Oba, Koji; Alonso, Ariel; Van der Elst, Wim; Burzykowski, Tomasz

    2016-01-01

    A surrogate endpoint is intended to replace a clinical endpoint for the evaluation of new treatments when it can be measured more cheaply, more conveniently, more frequently, or earlier than that clinical endpoint. A surrogate endpoint is expected to predict clinical benefit, harm, or lack of these. Besides the biological plausibility of a surrogate, a quantitative assessment of the strength of evidence for surrogacy requires the demonstration of the prognostic value of the surrogate for the clinical outcome, and evidence that treatment effects on the surrogate reliably predict treatment effects on the clinical outcome. We focus on these two conditions, and outline the statistical approaches that have been proposed to assess the extent to which these conditions are fulfilled. When data are available from a single trial, one can assess the "individual level association" between the surrogate and the true endpoint. When data are available from several trials, one can additionally assess the "trial level association" between the treatment effect on the surrogate and the treatment effect on the true endpoint. In the latter case, the "surrogate threshold effect" can be estimated as the minimum effect on the surrogate endpoint that predicts a statistically significant effect on the clinical endpoint. All these concepts are discussed in the context of randomized clinical trials in oncology, and illustrated with two meta-analyses in gastric cancer. PMID:25682941

  5. Someone to Lean on: Assessment and Implications of Social Surrogate Use in Childhood

    Science.gov (United States)

    Arbeau, Kimberley A.; Coplan, Robert J.; Matheson, Adrienne

    2012-01-01

    A social surrogate is a person who helps a shy individual deal with the stresses of a social situation. Previous research has only investigated social surrogate use in adults. The purpose of the current study was to develop and evaluate a new self-report measure of social surrogacy in middle childhood and to explore the implications of this…

  6. Development of an infectious surrogate hepatitis C virus based on a recombinant vesicular stomatitis virus expressing hepatitis C virus envelope glycoproteins and green fluorescent protein.

    Science.gov (United States)

    Okuma, Kazu; Fukagawa, Koji; Tateyama, Seiji; Kohma, Takuya; Mochida, Keiko; Hiyoshi, Masateru; Takahama, Youichi; Hamaguchi, Yukio; Hirose, Kunitaka; Buonocore, Linda; Rose, John K; Mizuochi, Toshiaki; Hamaguchi, Isao

    2015-01-01

    To develop surrogate viruses for hepatitis C virus (HCV), we previously produced recombinant vesicular stomatitis viruses (rVSVs) lacking glycoprotein G but instead expressing chimeric HCV E1/E2 fused to G. These rVSVs were not infectious in HCV-susceptible hepatoma cells. In this study, to develop an infectious surrogate HCV based on an rVSV (vesicular stomatitis virus [VSV]/HCV), we generated a novel rVSV encoding the native E1/E2 (H77 strain) and green fluorescent protein (GFP) instead of G. Here, we showed that this VSV/HCV efficiently infected human hepatoma cells, including Huh7 human hepatoma cells, expressed GFP in these cells, and propagated, but did not do so in nonsusceptible BHK-21 cells. The infectivity of VSV/HCV, measured as the number of foci of GFP-positive cells, was specifically reduced by the addition of chimpanzee anti-HCV serum, anti-E2 antibody, or anti-CD81 antibody to the cultures. When sera obtained from HCV-infected or uninfected patients were added, infection was selectively inhibited only by the sera of HCV-infected patients. These data together suggest that this infectious GFP-expressing VSV/HCV could be a useful tool for studying the mechanisms of HCV entry into cells and for assessing potential inhibitors of viral entry, including neutralizing antibodies. PMID:25672345

  7. Determining Vaccination Frequency in Farmed Rainbow Trout Using Vibrio anguillarum O1 Specific Serum Antibody Measurements

    DEFF Research Database (Denmark)

    Holten-Andersen, Lars; Dalsgaard, Inger; Nylén, Jørgen;

    2012-01-01

    Background Despite vaccination with a commercial vaccine with a documented protective effect against Vibrio anguillarum O1 disease outbreaks caused by this bacterium have been registered among rainbow trout at Danish fish farms. The present study examined specific serum antibody levels as a valid...

  8. (d,pγ) Reactions and the surrogate reaction technique

    International Nuclear Information System (INIS)

    Neutron-capture reactions on neutron-rich nuclei are important to understand r-process nucleosynthesis, as well as applied needs such as stewardship science and nuclear energy. Because of the short half-lives of these species, it is not possible to measure these reactions directly with neutron beams on unstable targets. The (d,pγ) reaction with radioactive ion beams has been proposed as a surrogate reaction for (n,γ). Experiments to develop (d,pγ) techniques with radioactive ion beams and to demonstrate the efficacy of the (d,pγ) reaction as a surrogate for (n,γ) are discussed

  9. Bedload-surrogate monitoring technologies

    Science.gov (United States)

    Gray, John R.; Laronne, Jonathan B.; Marr, Jeffrey D.G.

    2010-01-01

    Advances in technologies for quantifying bedload fluxes and in some cases bedload size distributions in rivers show promise toward supplanting traditional physical samplers and sampling methods predicated on the collection and analysis of physical bedload samples. Four workshops held from 2002 to 2007 directly or peripherally addressed bedload-surrogate technologies, and results from these workshops have been compiled to evaluate the state-of-the-art in bedload monitoring. Papers from the 2007 workshop are published for the first time with this report. Selected research and publications since the 2007 workshop also are presented. Traditional samplers used for some or all of the last eight decades include box or basket samplers, pan or tray samplers, pressure-difference samplers, and trough or pit samplers. Although still useful, the future niche of these devices may be as a means for calibrating bedload-surrogate technologies operating with active- and passive-type sensors, in many cases continuously and automatically at a river site. Active sensors include acoustic Doppler current profilers (ADCPs), sonar, radar, and smart sensors. Passive sensors include geophones (pipes or plates) in direct contact with the streambed, hydrophones deployed in the water column, impact columns, and magnetic detection. The ADCP for sand and geophones for gravel are currently the most developed techniques, several of which have been calibrated under both laboratory and field conditions. Although none of the bedload-surrogate technologies described herein are broadly accepted for use in large-scale monitoring programs, several are under evaluation. The benefits of verifying and operationally deploying selected bedload-surrogate monitoring technologies could be considerable, providing for more frequent and consistent, less expensive, and arguably more accurate bedload data obtained with reduced personal risk for use in managing the world's sedimentary resources. Twenty-six papers are

  10. Total Cross Sections as a Surrogate for Neutron Capture: An Opportunity to Accurately Constrain (n,γ) Cross Sections for Nuclides Beyond the Reach of Direct Measurements

    Energy Technology Data Exchange (ETDEWEB)

    Koehler, Paul E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-03-05

    There are many (n,γ) cross sections of great interest to radiochemical diagnostics and to nuclear astrophysics which are beyond the reach of current measurement techniques, and likely to remain so for the foreseeable future. In contrast, total neutron cross sections currently are feasible for many of these nuclides and provide almost all the information needed to accurately calculate the (n,γ) cross sections via the nuclear statistical model (NSM). I demonstrate this for the case of 151Sm; NSM calculations constrained using average resonance parameters obtained from total cross section measurements made in 1975, are in excellent agreement with recent 151Sm (n,γ) measurements across a wide range of energy. Furthermore, I demonstrate through simulations that total cross section measurements can be made at the Manuel Lujan Jr. Neutron Scattering Center at the Los Alamos Neutron Science Center for samples as small as 10μg. Samples of this size should be attainable for many nuclides of interest. Finally, I estimate that over half of the radionuclides identified ∼20 years ago as having (n,γ) cross sections of importance to s-process nucleosynthesis studies (24/43) and radiochemical diagnostics (11/19), almost none of which have been measured, can be constrained using this technique.

  11. Improved Performance of Dynamic Measures of Insulin Response Over Surrogate Indices to Identify Genetic Contributors of Type 2 Diabetes: The GUARDIAN Consortium.

    Science.gov (United States)

    Palmer, Nicholette D; Wagenknecht, Lynne E; Langefeld, Carl D; Wang, Nan; Buchanan, Thomas A; Xiang, Anny H; Allayee, Hooman; Bergman, Richard N; Raffel, Leslie J; Chen, Yii-Der Ida; Haritunians, Talin; Fingerlin, Tasha; Goodarzi, Mark O; Taylor, Kent D; Rotter, Jerome I; Watanabe, Richard M; Bowden, Donald W

    2016-07-01

    Type 2 diabetes (T2D) is a heterogeneous disorder with contributions from peripheral insulin resistance and β-cell dysfunction. For minimization of phenotypic heterogeneity, quantitative intermediate phenotypes characterizing basal glucose homeostasis (insulin resistance and HOMA of insulin resistance [HOMAIR] and of β-cell function [HOMAB]) have shown promise in relatively large samples. We investigated the utility of dynamic measures of glucose homeostasis (insulin sensitivity [SI] and acute insulin response [AIRg]) evaluating T2D-susceptibility variants (n = 57) in Hispanic Americans from the GUARDIAN Consortium (n = 2,560). Basal and dynamic measures were genetically correlated (HOMAB-AIRg: ρG = 0.28-0.73; HOMAIR-SI: ρG = -0.73 to -0.83) with increased heritability for the dynamic measure AIRg Significant association of variants with dynamic measures (P discrete elements of glucose homeostasis. Although more costly to obtain, dynamic measures yield significant results that could be considered physiologically "closer" to causal pathways and provide insight into the discrete mechanisms of action. PMID:27207554

  12. An empirical assessment and comparison of species-based and habitat-based surrogates: a case study of forest vertebrates and large old trees.

    Science.gov (United States)

    Lindenmayer, David B; Barton, Philip S; Lane, Peter W; Westgate, Martin J; McBurney, Lachlan; Blair, David; Gibbons, Philip; Likens, Gene E

    2014-01-01

    A holy grail of conservation is to find simple but reliable measures of environmental change to guide management. For example, particular species or particular habitat attributes are often used as proxies for the abundance or diversity of a subset of other taxa. However, the efficacy of such kinds of species-based surrogates and habitat-based surrogates is rarely assessed, nor are different kinds of surrogates compared in terms of their relative effectiveness. We use 30-year datasets on arboreal marsupials and vegetation structure to quantify the effectiveness of: (1) the abundance of a particular species of arboreal marsupial as a species-based surrogate for other arboreal marsupial taxa, (2) hollow-bearing tree abundance as a habitat-based surrogate for arboreal marsupial abundance, and (3) a combination of species- and habitat-based surrogates. We also quantify the robustness of species-based and habitat-based surrogates over time. We then use the same approach to model overall species richness of arboreal marsupials. We show that a species-based surrogate can appear to be a valid surrogate until a habitat-based surrogate is co-examined, after which the effectiveness of the former is lost. The addition of a species-based surrogate to a habitat-based surrogate made little difference in explaining arboreal marsupial abundance, but altered the co-occurrence relationship between species. Hence, there was limited value in simultaneously using a combination of kinds of surrogates. The habitat-based surrogate also generally performed significantly better and was easier and less costly to gather than the species-based surrogate. We found that over 30 years of study, the relationships which underpinned the habitat-based surrogate generally remained positive but variable over time. Our work highlights why it is important to compare the effectiveness of different broad classes of surrogates and identify situations when either species- or habitat-based surrogates are likely

  13. An empirical assessment and comparison of species-based and habitat-based surrogates: a case study of forest vertebrates and large old trees.

    Directory of Open Access Journals (Sweden)

    David B Lindenmayer

    Full Text Available A holy grail of conservation is to find simple but reliable measures of environmental change to guide management. For example, particular species or particular habitat attributes are often used as proxies for the abundance or diversity of a subset of other taxa. However, the efficacy of such kinds of species-based surrogates and habitat-based surrogates is rarely assessed, nor are different kinds of surrogates compared in terms of their relative effectiveness. We use 30-year datasets on arboreal marsupials and vegetation structure to quantify the effectiveness of: (1 the abundance of a particular species of arboreal marsupial as a species-based surrogate for other arboreal marsupial taxa, (2 hollow-bearing tree abundance as a habitat-based surrogate for arboreal marsupial abundance, and (3 a combination of species- and habitat-based surrogates. We also quantify the robustness of species-based and habitat-based surrogates over time. We then use the same approach to model overall species richness of arboreal marsupials. We show that a species-based surrogate can appear to be a valid surrogate until a habitat-based surrogate is co-examined, after which the effectiveness of the former is lost. The addition of a species-based surrogate to a habitat-based surrogate made little difference in explaining arboreal marsupial abundance, but altered the co-occurrence relationship between species. Hence, there was limited value in simultaneously using a combination of kinds of surrogates. The habitat-based surrogate also generally performed significantly better and was easier and less costly to gather than the species-based surrogate. We found that over 30 years of study, the relationships which underpinned the habitat-based surrogate generally remained positive but variable over time. Our work highlights why it is important to compare the effectiveness of different broad classes of surrogates and identify situations when either species- or habitat

  14. Thyroid Antibodies

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Thyroid Antibodies Share this page: Was this page helpful? Also known as: Thyroid Autoantibodies; Antithyroid Antibodies; Antimicrosomal Antibody; Thyroid Microsomal Antibody; ...

  15. Spot Sampling and Exposure Surrogate Selection as Sources of Bias in Environmental Epidemiology Studies

    Science.gov (United States)

    Spot measurements of chemical biomarkers are often used as quantitative exposure surrogates in environmental epidemiology studies. These measures can be expressed a number of different ways – for example, urinary biomarkers can be expressed in units of concentration (&micr...

  16. Multicenter comparison of levels of antibody to the Neisseria meningitidis group A capsular polysaccharide measured by using an enzyme-linked immunosorbent assay.

    OpenAIRE

    Carlone, G M; Frasch, C E; Siber, G R; Quataert, S; Gheesling, L L; Turner, S H; Plikaytis, B D; Helsel, L O; Dewitt, W. E.; Bibb, W F

    1992-01-01

    There is no standard immunoassay for evaluating immune responses to meningococcal vaccines. We developed an enzyme-linked immunosorbent assay to measure total levels of antibody to Neisseria meningitidis group A capsular polysaccharide. Five laboratories measured the antibody levels in six paired pre- and postvaccination serum samples by using the enzyme-linked immunosorbent assay. Methylated human serum albumin was used to bind native group A polysaccharide to microtiter plate surfaces. The ...

  17. Is the Use of a Surrogate Urethra an Option in Prostate High-Dose-Rate Brachytherapy?

    International Nuclear Information System (INIS)

    Purpose: To investigate the accuracy and the dosimetric consequences of substituting a surrogate urethra assumed to be at the geometric center of the prostate, in place of the true urethra when using high-dose-rate (HDR) brachytherapy for the treatment of prostate cancer. Methods and Materials: One hundred prostate cancer patients treated with HDR brachytherapy constituted the study group. A pre-plan was made with the urethra visualized. The true urethra was defined, and a surrogate urethra was placed at the geometric center of the prostate. The distance between the two urethras was measured. The deviation was evaluated at the base, middle, and apex. To evaluate the dosimetric consequences for the true urethra when using a surrogate urethra, two different dose plans were made: one based on the true urethra and one based on the surrogate urethra. The dose-volume histograms for the true urethra were analyzed. Results: The deviation between the true urethra and the surrogate urethra was greatest at the base of the prostate. A statistically significant difference was seen between the dosimetric parameters for the true and the surrogate urethra when the dose plan was made using the surrogate urethra. In this situation the dose to the true urethra was increased above our defined maximum tolerance limit. Conclusions: When using dose plans made according to a surrogate urethra the dose to the true urethra might be too high to be acceptable. If the true urethra is not visualized, severe damage could easily develop in a significant number of patients

  18. Optimizing the Measurement of Colostrum Antibody Concentrations for Identifying BVDV Persistently Infected Calves

    Directory of Open Access Journals (Sweden)

    Caitlin J. Jenvey

    2015-03-01

    Full Text Available Colostrum contains substantially higher concentrations of immunoglobulins compared to serum, which may help to improve the utility of diagnostic tests. The aim of this study was to determine the diagnostic value of colostrum antibody concentrations in identifying Bovine Viral Diarrhoea Virus (BVDV PI (persistently infected calf carrying beef heifers following an experimental infection. Colostrum was collected within 12 hours of parturition and tested in undiluted, 1:5, 1:10, 1:100, 1:200, and 1:500 dilutions using an enzyme-linked immunosorbent assay (ELISA for BVDV antibody. Cows were determined to be carrying a PI calf based on positive quantitative Real Time-Polymerase Chain Reaction and antigen ELISA result on pre-colostral serum and ear notch samples collected from their calf. The median ELISA sample-to-positive (S/P ratio for colostrum collected from heifers that carried a PI calf were significantly higher than the median ELISA S/P ratio for colostrum collected from heifers that did not carry a PI calf at dilutions of 1:100, 1:200, and 1:500. This study provides further evidence for increased antigenic stimulation in utero by the BVDV viraemic PI calf, which can also be identified with 100% diagnostic sensitivity when using 1:500 dilution colostrum.

  19. Taylor's dissipation surrogate and its associated anomaly

    CERN Document Server

    McComb, David

    2009-01-01

    It is shown that, for stationary isotropic turbulence, Taylor's well known surrogate for the dissipation can be derived directly from the Karman-Howarth equation and is in fact a surrogate for inertial transfer, which becomes equal to the dissipation rate as the Reynolds number tends to infinity.

  20. The Reparative Motive in Surrogate Mothers.

    Science.gov (United States)

    Kanefield, Linda

    1999-01-01

    Explores the motivations of surrogate mothers, focusing on underlying reparative motive--to compensate for or repair an earlier loss or sense of damage. Provides an overview of the typical surrogate's characteristics and personality, discusses the theoretical underpinnings of the reparative motive, and considers the tension between reparation and…

  1. 34 CFR 303.406 - Surrogate parents.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Surrogate parents. 303.406 Section 303.406 Education... DISABILITIES Procedural Safeguards General § 303.406 Surrogate parents. (a) General. Each lead agency shall ensure that the rights of children eligible under this part are protected if— (1) No parent (as...

  2. 34 CFR 300.519 - Surrogate parents.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Surrogate parents. 300.519 Section 300.519 Education... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents... parent (as defined in § 300.30) can be identified; (2) The public agency, after reasonable...

  3. Use of Surrogate end points in HTA

    Directory of Open Access Journals (Sweden)

    Mangiapane, Sandra

    2009-08-01

    Full Text Available The different actors involved in health system decision-making and regulation have to deal with the question which are valid parameters to assess the health value of health technologies.So called surrogate endpoints represent in the best case preliminary steps in the casual chain leading to the relevant outcome (e. g. mortality, morbidity and are not usually directly perceptible by patients. Surrogate endpoints are not only used in trials of pharmaceuticals but also in studies of other technologies. Their use in the assessment of the benefit of a health technology is however problematic. In this report we intend to answer the following research questions: Which criteria need to be fulfilled for a surrogate parameter to be considered a valid endpoint? Which methods have been described in the literature for the assessment of the validity of surrogate endpoints? Which methodological recommendations concerning the use of surrogate endpoints have been made by international HTA agencies? Which place has been given to surrogate endpoints in international and German HTA reports? For this purpose, we choose three different approaches. Firstly, we conduct a review of the methodological literature dealing with the issue of surrogate endpoints and their validation. Secondly, we analyse current methodological guidelines of HTA agencies members of the International network of agencies for Health Technology Assessment (INAHTA as well as of agencies concerned with assessments for reimbursement purposes. Finally, we analyse the outcome parameter used in a sample of HTA reports available for the public. The analysis of methodological guidelines shows a very cautious position of HTA institutions regarding the use of surrogate endpoints in technology assessment. Surrogate endpoints have not been prominently used in HTA reports. None of the analysed reports based its conclusions solely on the results of surrogate endpoints. The analysis of German HTA reports shows a

  4. A dynamical model of surrogate reactions

    CERN Document Server

    Aritomo, Y; Nishio, K

    2010-01-01

    A new dynamical model is developed to describe the whole process of surrogate reactions; transfer of several nucleons at an initial stage, thermal equilibration of residues leading to washing out of shell effects and decay of populated compound nuclei are treated in a unified framework. Multi-dimensional Langevin equations are employed to describe time-evolution of collective coordinates with a time-dependent potential energy surface corresponding to different stages of surrogate reactions. The new model is capable of calculating spin distributions of the compound nuclei, one of the most important quantity in the surrogate technique. Furthermore, various observables of surrogate reactions can be calculated, e.g., energy and angular distribution of ejectile, and mass distributions of fission fragments. These features are important to assess validity of the proposed model itself, to understand mechanisms of the surrogate reactions and to determine unknown parameters of the model. It is found that spin distribut...

  5. A computational methodology for formulating gasoline surrogate fuels with accurate physical and chemical kinetic properties

    KAUST Repository

    Ahmed, Ahfaz

    2015-03-01

    Gasoline is the most widely used fuel for light duty automobile transportation, but its molecular complexity makes it intractable to experimentally and computationally study the fundamental combustion properties. Therefore, surrogate fuels with a simpler molecular composition that represent real fuel behavior in one or more aspects are needed to enable repeatable experimental and computational combustion investigations. This study presents a novel computational methodology for formulating surrogates for FACE (fuels for advanced combustion engines) gasolines A and C by combining regression modeling with physical and chemical kinetics simulations. The computational methodology integrates simulation tools executed across different software platforms. Initially, the palette of surrogate species and carbon types for the target fuels were determined from a detailed hydrocarbon analysis (DHA). A regression algorithm implemented in MATLAB was linked to REFPROP for simulation of distillation curves and calculation of physical properties of surrogate compositions. The MATLAB code generates a surrogate composition at each iteration, which is then used to automatically generate CHEMKIN input files that are submitted to homogeneous batch reactor simulations for prediction of research octane number (RON). The regression algorithm determines the optimal surrogate composition to match the fuel properties of FACE A and C gasoline, specifically hydrogen/carbon (H/C) ratio, density, distillation characteristics, carbon types, and RON. The optimal surrogate fuel compositions obtained using the present computational approach was compared to the real fuel properties, as well as with surrogate compositions available in the literature. Experiments were conducted within a Cooperative Fuels Research (CFR) engine operating under controlled autoignition (CAI) mode to compare the formulated surrogates against the real fuels. Carbon monoxide measurements indicated that the proposed surrogates

  6. Surrogate Guderley Test Problem Definition

    Energy Technology Data Exchange (ETDEWEB)

    Ramsey, Scott D. [Los Alamos National Laboratory; Shashkov, Mikhail J. [Los Alamos National Laboratory

    2012-07-06

    The surrogate Guderley problem (SGP) is a 'spherical shock tube' (or 'spherical driven implosion') designed to ease the notoriously subtle initialization of the true Guderley problem, while still maintaining a high degree of fidelity. In this problem (similar to the Guderley problem), an infinitely strong shock wave forms and converges in one-dimensional (1D) cylindrical or spherical symmetry through a polytropic gas with arbitrary adiabatic index {gamma}, uniform density {rho}{sub 0}, zero velocity, and negligible pre-shock pressure and specific internal energy (SIE). This shock proceeds to focus on the point or axis of symmetry at r = 0 (resulting in ostensibly infinite pressure, velocity, etc.) and reflect back out into the incoming perturbed gas.

  7. Measurement of DNA repair in Chinese hamster fibroblasts employing flow cytometry and monoclonal antibodies to DNA adducts

    International Nuclear Information System (INIS)

    The authors examined the utility of measuring DNA repair in single cells employing flow cytometric quantitation of fluorescent monoclonal antibodies directed against specific DNA adducts. Two antibodies were employed; the first directed against single strand (ss) bromodeoxyuridine (anti-BrdUrd) and the second against UV light induced ss-thymine dimers (anti-TT). Sensitivity with both monoclonals was highly dependent on DNA denaturation, with the most effective shown to be a 0.5N HCl histone extraction followed by 50% formamide for 30 min at 800C. Unscheduled synthesis following 30 J/m/sup 2/ UV irradiation in Gl/GO plateau phase CHO cells was demonstrated employing the anti-BrdUrd AB method combined with DNA counter-staining with propidium iodide. Data suggest that anti-BrdUrd Ab recognition of newly replicated sequences following UV irradiation may be strongly dependent on chromatin conformation. A linear correlation was observed for mean anti-TT AB fluorescence and UV dose up to a total of 3000 J/m/sup 2/. Also, a rapid reduction in cellular fluorescence, presumably reflecting dimer excision was observed when the cells were returned to 370C before fixation. Finally, data from various repair deficient CHO cells will be compared employing these methods

  8. Rapid alternative to the clonogenic assay for measuring antibody and complement-mediated killing of tumor cells

    International Nuclear Information System (INIS)

    A study of the methods used to quantitate killing of tumor cells by antibody and complement has highlighted a number of problems. Using leukemia as a model, the authors have found that the release of 51Cr from labeled tumor cells treated with antibody and complement can be an equivocal measure of cell viability. Combined with its restricted sensitivity (less than a 2 log range of cell killing) this makes this widely used assay of questionable value for detecting small numbers of viable cells, or for identifying subpopulations of complement-resistant cells. As an alternative a [125I]iododeoxyuridine uptake assay has been developed, that combines the simplicity and rapidity of the 51Cr release technique with the sensitivity of a clonogenic assay. This method eliminates the problem of spontaneous isotope release, inherent in prelabeling assays, and variability from experiment to experiment can be avoided by including a viable cell standard curve within each assay. The sensitivity of the 125IUdR uptake method, which can be completed within a day, is similar to that of a 10 day methylcellulose cloning assay and was capable of detecting the presence of a minor subpopulation of complement-resistant tumor cells

  9. Usefulness of measuring the concentration of thyroglobulin antibodies in serum of dogs for the assessment of thyroid functioning

    Directory of Open Access Journals (Sweden)

    Popiel Jarosław

    2014-06-01

    Full Text Available The aim of the study was to estimate the usefulness of measuring the thyroglobulin antibodies (TgAbs concentration in dogs’ serum in order to assess thyroid functioning. The study was performed on 383 dogs. The animals were divided into two groups: group A (n = 308 consisted of dogs with hypothyroidism and group B (n = 75 consisted of dogs with euthyreosis. TgAbs was determined in both groups. The reaction to the TgAbs in group A was strongly positive in 32% of dogs, weakly positive in 33% of dogs, and negative in 35% of dogs. The TgAbs were observed in 32% of the dogs from group B, in which 8% of the animals had strongly positive reaction (++ and 24% - slightly positive (+. The correlation between the concentration of total and free fraction of the thyroxin and the level of the TgAbs were observed in group A. The tendency to positive reaction to the antibodies (++ in dogs with lower concentrations of total thyroxine and free thyroxine was observed. It was noted that the presence of the TgAbs was common in dogs with hypothyroidism. However, it could be also found in the animals with euthyreosis.

  10. A rapid and quantitative assay for measuring neutralizing antibodies of Coxsackievirus B3.

    Science.gov (United States)

    Chen, Pan; Wu, Xing; Mao, Qunying; Gao, Fan; Hao, Xiaotian; Bian, Lianlian; Zhu, Fengcai; Li, Wenhui; Xu, Miao; Liang, Zhenglun

    2016-06-01

    Coxsackievirus B3 (CVB3) infection has been found to account for an increasing proportion cases of hand, foot and mouth disease (HFMD) in recent epidemiology studies. CVB3 is a single stranded, non-enveloped RNA virus and the infection can cause prominent health threat to pre-school children. Here, by taking approaches of reverse genetics, we established a single-round infection system for CVB3. The pseudovirus was produced by sequential transfection of CVB3 capsid expresser plasmid and CVB3 replicon RNA bearing firefly luciferase as a reporter. The CVB3 pseudovirus system was used for quantifying neutralizing antibody (NtAb) levels of 720 human serum samples and showed superior specificity and sensitivity comparing traditional cytopathic effect (CPE) assay. Furthermore, we compared the seroprevalence of CVB3 NtAbs in pre-school children and healthy adults, and found that only 11.94% of pre-school children were NtAbs positive which suggested that most children were naive to CVB3 infection; while there is much higher positive rate in adults (60%) indicating that most adults have experienced CVB3 infection during childhood. This rapid and quantitative assay greatly facilitates evaluating the level of NtAbs against CVB3 in populations and will help to advance CVB3 vaccine development. PMID:26947399

  11. Monoclonal antibodies and cancer

    International Nuclear Information System (INIS)

    The usefulness of radiolabeled monoclonal antibodies for imaging and treatment of human (ovarian) cancer was investigated. A review of tumor imaging with monoclonal antibodies is presented. Special attention is given to factors that influence the localization of the antibodies in tumors, isotope choice and methods of radiolabeling of the monoclonal antibodies. Two monoclonal antibodies, OC125 and OV-TL3, with high specificity for human epithelial ovarian cancer are characterized. A simple radio-iodination technique was developed for clinical application of the monoclonal antibodies. The behavior of monoclonal antibodies in human tumor xenograft systems and in man are described. Imaging of tumors is complicated because of high background levels of radioactivity in other sites than the tumor, especially in the bloodpool. A technique was developed to improve imaging of human tumor xenographs in nude mice, using subtraction of a specific and a non-specific antibody, radiolabeled with 111In, 67Ga and 131I. To investigate the capability of the two monoclonal antibodies, to specifically localize in human ovarian carcinomas, distribution studies in mice bearing human ovarian carcinoma xenografts were performed. One of the antibodies, OC125, was used for distribution studies in ovarian cancer patients. OC125 was used because of availability and approval to use this antibody in patients. The same antibody was used to investigate the usefulness of radioimmunoimaging in ovarian cancer patients. The interaction of injected radiolabeled antibody OC125 with circulating antigen and an assay to measure the antibody response in ovarian cancer patients after injection of the antibody is described. 265 refs.; 30 figs.; 19 tabs

  12. Improved surrogate data for nonlinearity tests

    CERN Document Server

    Schreiber, T; Schreiber, Thomas; Schmitz, Andreas

    1996-01-01

    Current tests for nonlinearity compare a time series to the null hypothesis of a Gaussian linear stochastic process. For this restricted null assumption, random surrogates can be constructed which are constrained by the linear properties of the data. We propose a more general null hypothesis allowing for nonlinear rescalings of a Gaussian linear process. We show that such rescalings cannot be accounted for by a simple amplitude adjustment of the surrogates which leads to spurious detection of nonlinearity. An iterative algorithm is proposed to make appropriate surrogates which have the same autocorrelations as the data and the same probability distribution.

  13. The long-term experiences of surrogates: relationships and contact with surrogacy families in genetic and gestational surrogacy arrangements.

    Science.gov (United States)

    Imrie, Susan; Jadva, Vasanti

    2014-10-01

    This study examined the contact arrangements and relationships between surrogates and surrogacy families and whether these outcomes differed according to the type of surrogacy undertaken. Surrogates' motivations for carrying out multiple surrogacy arrangements were also examined, and surrogates' psychological health was assessed. Semi-structured interviews were administered to 34 women who had given birth to a child conceived through surrogacy approximately 7 years prior to interview. Some surrogates had carried out multiple surrogacy arrangements, and data were collected on the frequency, type of contact, and surrogate's feelings about the level of contact in each surrogacy arrangement, the surrogate's relationship with each child and parent, and her experience of, and motivation for, each surrogacy. Questionnaire measures of psychological health were administered. Surrogates had completed a total of 102 surrogacy arrangements and remained in contact with the majority of families, and reported positive relationships in most cases. Surrogates were happy with their level of contact in the majority of arrangements and most were viewed as positive experiences. Few differences were found according to surrogacy type. The primary motivation given for multiple surrogacy arrangements was to help couples have a sibling for an existing child. Most surrogates showed no psychological health problems at the time of data collection. PMID:25131555

  14. Evaluation of an in vitro method for the measurement of specific IgE antibody responses: the rat basophilic leukemia (RBL) cell assay

    International Nuclear Information System (INIS)

    The evaluation of allergenic potential is a key parameter in the safety assessment of novel proteins, including those expressed in genetically modified crops and foodstuffs. The majority of allergic reactions to food proteins are immediate type hypersensitivity reactions in which the principal biological effector is IgE antibody; the accurate measurement of specific IgE antibody is therefore a critical factor in experimental systems designed to characterize protein allergenic potential. Due to the presence of much higher concentrations of other immunoglobulin isotypes, the assessment of specific serum IgE antibody poses substantial technical challenges. We have examined the utility of the rat basophilic leukemia (RBL) cell line for the measurement of murine IgE responses. RBL cells were sensitized with mouse monoclonal anti-dinitrophenyl (DNP) IgE antibody and challenged with DNP-albumin conjugates with various hapten substitution ratios (SR). Polyclonal anti-OVA IgE antisera were also assessed for activity in the RBL assay. Results were compared with titers measured in homologous passive cutaneous anaphylaxis (PCA) assay. Marked degranulation of RBL cells was induced by conjugates with SRs of between 16 and 32, whereas conjugates with lower SRs (of 10 or 3) failed to elicit significant serotonin release. All conjugates were able to induce mast cell degranulation in vivo in a PCA assay. Anti-OVA antisera with PCA titers of 1/32 to 1/64 failed to stimulate RBL cell degranulation, whereas high titer antibody (1/2048 to 1/4096 by PCA) induced a positive RBL cell response. Successful stimulation of RBL cell degranulation requires not only appropriate epitope densities but also high affinity antibody. These data indicate that this assay is inappropriate for the routine analysis of specific polyclonal IgE antibody responses such as those that are induced by exposure to complex protein allergens

  15. Development of a method to measure kinetics of radiolabelled monoclonal antibody in human tumour with applications to microdosimetry: positron emission tomography studies of iodine-124 labelled 3F8 monoclonal antibody in glioma

    International Nuclear Information System (INIS)

    We present a method to assess quantitatively the immuhological characteristics of tumours using radiolabelled monoclonal antibody and positron emission tomography (PET) to improve dosimetry for radioimmunotherapy. This method is illustrated with a glioma patient who injected with 96.2 MPq of iodine-124 labelled 3FB, a murine antibody (IgG3) specific against the ganglioside GD2. Serial PET scans and plasma samples were taken over 11 days. A three-compartment model was used to estimate the plasma to tumour transfer constant (K1), the tumour to plasma transfer constant k2, the association and dissociation constants (k3, k4) of antibody binding, and the binding potential. Tumour radioactivity peaked at 18 h at 0.0045% ID/g. The kinetic parameters were estimated to be: K1=0.048 ml h-1 g-1, k2=0.16 h-1, k3=0.03 h-1, k4=0.015 h-1 and BP=2.25. Based on these kinetic parameters, the amount of tumour-bound radiolabelled monoclonal antibody was calculated. This method permits estimates of both macrodosimetry and microdosimetry at the cellular level based on in vivo non-invasive measurement. (orig.)

  16. Surrogate Motherhood II: Reflections after "Baby M."

    Science.gov (United States)

    Schwartz, Lita Linzer

    1988-01-01

    Discusses the "Baby M" surrogate motherhood case which has produced heated debate in popular media, legal publications, and other professional journals. Summarizes arguments offered and reasoning behind actions of judiciary. (Author/ABL)

  17. Simplified modeling strategies for surrogate validation with multivariate failure-time data

    OpenAIRE

    CORTINAS ABRAHANTES, Jose; Burzykowski, Tomasz

    2010-01-01

    The linear mixed effects model has become a standard tool for the analysis of continuous hierarchical data such as, for example, repeated measures or data from meta-analyses. However, in certain situations the model does pose unavoidable computational problems. In the context of surrogate markers, this problem has appeared when using an estimation and prediction-based approach for the evaluation of surrogate endpoints. Convergence problems can occur mainly due to small between-trial variabili...

  18. Theoretical challenges of determining low-energy neutron-capture cross sections via the Surrogate Technique

    International Nuclear Information System (INIS)

    Cross sections for radiative neutron capture on unstable nuclei at low energies are difficult to calculate with high precision, and can be impossible to measure directly. It is therefore important to explore alternative methods. The prospects of one such method, the Surrogate Nuclear Reaction Technique, is currently being investigated at Lawrence Livermore National Laboratory. The purpose of this paper is to outline the strategy for combining the results from a surrogate experiment with theoretical calculations in order to extract the desired cross section

  19. Regression calibration with more surrogates than mismeasured variables

    KAUST Repository

    Kipnis, Victor

    2012-06-29

    In a recent paper (Weller EA, Milton DK, Eisen EA, Spiegelman D. Regression calibration for logistic regression with multiple surrogates for one exposure. Journal of Statistical Planning and Inference 2007; 137: 449-461), the authors discussed fitting logistic regression models when a scalar main explanatory variable is measured with error by several surrogates, that is, a situation with more surrogates than variables measured with error. They compared two methods of adjusting for measurement error using a regression calibration approximate model as if it were exact. One is the standard regression calibration approach consisting of substituting an estimated conditional expectation of the true covariate given observed data in the logistic regression. The other is a novel two-stage approach when the logistic regression is fitted to multiple surrogates, and then a linear combination of estimated slopes is formed as the estimate of interest. Applying estimated asymptotic variances for both methods in a single data set with some sensitivity analysis, the authors asserted superiority of their two-stage approach. We investigate this claim in some detail. A troubling aspect of the proposed two-stage method is that, unlike standard regression calibration and a natural form of maximum likelihood, the resulting estimates are not invariant to reparameterization of nuisance parameters in the model. We show, however, that, under the regression calibration approximation, the two-stage method is asymptotically equivalent to a maximum likelihood formulation, and is therefore in theory superior to standard regression calibration. However, our extensive finite-sample simulations in the practically important parameter space where the regression calibration model provides a good approximation failed to uncover such superiority of the two-stage method. We also discuss extensions to different data structures.

  20. Comparison of radioimmunoassay and enzyme-linked immunosorbent assay in measurement of antibodies to Neisseria meningitidis group A capsular polysaccharide.

    OpenAIRE

    Beuvery, E C; Kayhty, M H; Leussink, A B; Kanhai, V

    1984-01-01

    Antibodies to meningococcal group A polysaccharide were determined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) in serum samples from 16 adults vaccinated with bivalent meningococcal group A and C polysaccharide vaccine. The specific antibody levels in the serum samples were expressed as micrograms of antibody protein per milliliter of serum. For RIA the polysaccharide was radiolabeled extrinsically with 125I. Both native polysaccharide and polysaccharide labeled wi...

  1. Semiparametric inference for surrogate endpoints with bivariate censored data.

    Science.gov (United States)

    Ghosh, Debashis

    2008-03-01

    Considerable attention has been recently paid to the use of surrogate endpoints in clinical research. We deal with the situation where the two endpoints are both right censored. While proportional hazards analyses are typically used for this setting, their use leads to several complications. In this article, we propose the use of the accelerated failure time model for analysis of surrogate endpoints. Based on the model, we then describe estimation and inference procedures for several measures of surrogacy. A complication is that potentially both the independent and dependent variable are subject to censoring. We adapt the Theil-Sen estimator to this problem, develop the associated asymptotic results, and propose a novel resampling-based technique for calculating the variances of the proposed estimators. The finite-sample properties of the estimation methodology are assessed using simulation studies, and the proposed procedures are applied to data from an acute myelogenous leukemia clinical trial. PMID:17651457

  2. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test ... Normally, there are no antibodies against insulin in your blood. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or ...

  3. Anti‐pneumococcal antibody titre measurement: what useful information does it yield?

    OpenAIRE

    Balmer, Paul; Cant, Andrew J.; Borrow, Ray

    2006-01-01

    Measuring and interpretation of the immune response to pneumococcal polysaccharides is a complex field, owing to the diversity of the pneumococcal polysaccharide capsular types, different vaccine formulations including both polysaccharide and conjugate vaccines, diverse pneumococcal serological assays, lack of immunogenicity data for the conjugate in a number of at‐risk groups and complex vaccine schedules. Even the reasons for performing pneumococcal serology can be complex, as assays may be...

  4. Cytokine measurements and possible interference from heterophilic antibodies--problems and solutions experienced with rheumatoid factor

    DEFF Research Database (Denmark)

    Bartels, Else Marie; Ribel-Madsen, Søren

    2013-01-01

    Cytokines are important in the understanding of the immune process in health and disease and are valuable indicators in diagnostics. Measurements of cytokines are based on immunometric methods, and it is important to understand possible pitfalls in these methods to produce reliable cytokine data...... PEG precipitation, but other efficient, but more expensive, methods, such as precipitation using Protein L or commercially available blocking agents, are also available. Interference of RF is at present not tested in all cytokine assays, but degree of interference from RF, human anti-animal and...

  5. Antithyroid microsomal antibody

    Science.gov (United States)

    Thyroid antimicrosomal antibody; Antimicrosomal antibody; Microsomal antibody; Thyroid peroxidase antibody; TPOAb ... Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also been linked to an increased risk ...

  6. Verification of the Surrogate Ratio Method

    CERN Document Server

    Chiba, Satoshi

    2010-01-01

    Effects of difference in the spin and parity distributions for the surrogate and neutron-induced reactions are investigated. It was found that the surrogate ratio method can be employed to determine neutron fission and capture cross sections if 1) weak Weisskopf-Ewing condition (defined in this paper) is satisfied, 2) there exist two surrogate reactions whose spin-parity distributions of the decaying nuclei are almost equivalent, and 3) difference of the representative spin values between the neutron-induced and surrogate reactions is no much larger than 10 $\\hbar$. The last condition may be loosened for the fission channel since the condition 1) seems to be valid for wider regions of spin. Achievable accuracy is estimated to be around 5 and 10 % for fission and capture channels, respectively, for nuclei of the Uranium region. The surrogate absolute method, on the contrary, can be only marginally applicable to determination of fission cross sections, but there will be little hope to apply this method for capt...

  7. Evaluation of surrogate boilers for steam generators

    International Nuclear Information System (INIS)

    Steam generator damage in pressurized water reactors is a continuing problem which results from a combination of factors including mechanical design, thermal hydraulics, materials selection, fabrication techniques, water chemistry, and system design and operation. A wide variety of steam generator damage mechanisms has been identified in operating PWRs including intergranular attack, thinning, stress corrosion cracking, erosion, denting, fatigue cracking, pitting, and fretting. Model boilers operated in parallel to the steam generators, i.e., surrogate boilers, may provide a useful tool in the study of these damage mechanisms, their causative factors, and the effects of corrosion actions. To evaluate the applicability of surrogate boilers to such studies, Steam Generator Owners Group I project S111-2 was established. Evaluation of numerous surrogate boiler design alternates led to identification of several possible acceptable approaches. The appropriate surrogate feedwater was identified as plant feedwater. Capability to operate with a tube-side temperature similar to the hot-leg temperature was considered necessary as was the ability to provide mechanical, thermal, and chemical corrosion acceleration. Practical and economically feasible surrogate boiler designs were developed in response to these design requirements

  8. Modeling of Heating and Evaporation of FACE I Gasoline Fuel and its Surrogates

    KAUST Repository

    Elwardany, Ahmed

    2016-04-05

    The US Department of Energy has formulated different gasoline fuels called \\'\\'Fuels for Advanced Combustion Engines (FACE)\\'\\' to standardize their compositions. FACE I is a low octane number gasoline fuel with research octane number (RON) of approximately 70. The detailed hydrocarbon analysis (DHA) of FACE I shows that it contains 33 components. This large number of components cannot be handled in fuel spray simulation where thousands of droplets are directly injected in combustion chamber. These droplets are to be heated, broken-up, collided and evaporated simultaneously. Heating and evaporation of single droplet FACE I fuel was investigated. The heating and evaporation model accounts for the effects of finite thermal conductivity, finite liquid diffusivity and recirculation inside the droplet, referred to as the effective thermal conductivity/effective diffusivity (ETC/ED) model. The temporal variations of the liquid mass fractions of the droplet components were used to characterize the evaporation process. Components with similar evaporation characteristics were merged together. A representative component was initially chosen based on the highest initial mass fraction. Three 6 components surrogates, Surrogate 1-3, that match evaporation characteristics of FACE I have been formulated without keeping same mass fractions of different hydrocarbon types. Another two surrogates (Surrogate 4 and 5) were considered keeping same hydrocarbon type concentrations. A distillation based surrogate that matches measured distillation profile was proposed. The calculated molar mass, hydrogen-to-carbon (H/C) ratio and RON of Surrogate 4 and distillation based one are close to those of FACE I.

  9. Mechanical Properties of Nuclear Fuel Surrogates using Picosecond Laser Ultrasonics

    Energy Technology Data Exchange (ETDEWEB)

    David Hurley; Marat Khafizov; Farhad Farzbod; Eric Burgett

    2013-05-01

    Detailed understanding between microstructure evolution and mechanical properties is important for designing new high burnup nuclear fuels. In this presentation we discuss the use of picosecond ultrasonics to measure localize changes in mechanical properties of fuel surrogates. We develop measurement techniques that can be applied to investigate heterogeneous elastic properties caused by localize changes in chemistry, grain microstructure caused by recrystallization, and mechanical properties of small samples prepared using focused ion beam sample preparation. Emphasis is placed on understanding the relationship between microstructure and mechanical properties

  10. [Immunological surrogate endpoints to evaluate vaccine efficacy].

    Science.gov (United States)

    Jin, Pengfei; Li, Jingxin; Zhou, Yang; Zhu, Fengcai

    2015-12-01

    An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description. PMID:26887309

  11. Attitudes toward surrogate motherhood in Canada.

    Science.gov (United States)

    Krishnan, V

    1994-01-01

    The issue of surrogate motherhood captured worldwide attention with the Baby M case in the United States. Some medical practitioners now claim that the surrogate arrangement may be the answer for certain women who are unable to conceive children naturally. Feminist activists are highly critical about the issue. In her landmark book The Mother Machine, Corea (1985) called surrogates "breeders," women whose bodies are being used by men. Lawyers and ethicists debate whether surrogacy is baby selling or not, and religious fundamentalists have condemned any form of procreation outside the "normal" or "natural" form of sexual relations within a marriage. But what do Canadian women think about commercial surrogacy? Findings pertaining to this issue from the latest national fertility survey of 5,315 women in the reproductive ages of 18-49 are reported. PMID:8056650

  12. Surrogate mothers: not so novel after all.

    Science.gov (United States)

    Robertson, J A

    1983-10-01

    A law professor examines the legal, psychological, social, and ethical issues that arise in surrogate mothering and the problems that this procedure may create for the biological and adoptive parents, the child, and the state. Robertson considers the central issue of this and other "collaborative reproduction" methods to be the extent and nature of third party involvement rather than the deliberate separation of biologic and social parentage. He believes that the state's power to regulate surrogate arrangements may be limited by a couple's constitutional right to make procreative decisions. An insert on page 31 of Robertson's article summarizes the guidelines on "Ethical Issues in Surrogate Motherhood" issued in May 1983 by the American College of Obstetricians and Gynecologists. PMID:6643034

  13. Legal regulation of surrogate motherhood in Israel.

    Science.gov (United States)

    Frenkel, D A

    2001-01-01

    The Israeli Law on surrogate motherhood demands a preconception agreement to include payments to be made to the surrogate mother. Surrogacy arrangements with family members are forbidden. Commercial surrogacy is allowed and encouraged. The Law causes many problems. Validity of consent given by surrogate mothers is doubtful. Possible future psychological harm are ignored. There is a danger of "commodification" of children. Abusing women of low socio-economic status as breeding machines may be another outcome. No clear responsibility is imposed on the "intended parents" for an impaired child. The law ignores possibility of divorce or death of the "intended parents" before the child's birth. Splitting motherhood is another social problem that has to be dealt with. So far the sperm of the husband from the "intended parents" has to be used, but further steps may follow. It is not certain that a policy of "positive eugenics" will not develop. PMID:11817392

  14. Reduced cost mission design using surrogate models

    Science.gov (United States)

    Feldhacker, Juliana D.; Jones, Brandon A.; Doostan, Alireza; Hampton, Jerrad

    2016-01-01

    This paper uses surrogate models to reduce the computational cost associated with spacecraft mission design in three-body dynamical systems. Sampling-based least squares regression is used to project the system response onto a set of orthogonal bases, providing a representation of the ΔV required for rendezvous as a reduced-order surrogate model. Models are presented for mid-field rendezvous of spacecraft in orbits in the Earth-Moon circular restricted three-body problem, including a halo orbit about the Earth-Moon L2 libration point (EML-2) and a distant retrograde orbit (DRO) about the Moon. In each case, the initial position of the spacecraft, the time of flight, and the separation between the chaser and the target vehicles are all considered as design inputs. The results show that sample sizes on the order of 102 are sufficient to produce accurate surrogates, with RMS errors reaching 0.2 m/s for the halo orbit and falling below 0.01 m/s for the DRO. A single function call to the resulting surrogate is up to two orders of magnitude faster than computing the same solution using full fidelity propagators. The expansion coefficients solved for in the surrogates are then used to conduct a global sensitivity analysis of the ΔV on each of the input parameters, which identifies the separation between the spacecraft as the primary contributor to the ΔV cost. Finally, the models are demonstrated to be useful for cheap evaluation of the cost function in constrained optimization problems seeking to minimize the ΔV required for rendezvous. These surrogate models show significant advantages for mission design in three-body systems, in terms of both computational cost and capabilities, over traditional Monte Carlo methods.

  15. Prediction of transgenic tobacco plant processing properties by ultra scale down and physical property measurement for monoclonal antibody production.

    OpenAIRE

    Hassan, S. Y.

    2008-01-01

    There are numerous potential advantages of producing significant quantities of a monoclonal antibody (MAb) via transgenic tobacco plants over other heterologous production systems, thus paving the way for new prophylactic and therapeutic applications within global human and animal health. However, current information on the key processing factors for large scale production of antibodies from transgenic plants is limited. This thesis presents the issues involved in the production of monoclonal...

  16. Effect of influenza A/equine/H3N8 virus isolate variation on the measurement of equine antibody responses.

    OpenAIRE

    Bogdan, J R; Morley, P S; Townsend, H G; Haines, D M

    1993-01-01

    This study has tested the effect of using homologous or heterologous equine influenza A virus isolates to evaluate serum antibody levels to influenza A virus in vaccinated and naturally-infected horses. In addition, the potential effect of antigenic selection of virus variants in egg versus tissue culture propagation systems was studied. Serum antibody levels in samples from horses recently infected with a local influenza A virus isolate (A/equine 2/Saskatoon/1/90) or recently vaccinated with...

  17. Development and Optimization of High-Throughput Methods To Measure Plasmodium falciparum-Specific Growth Inhibitory Antibodies

    OpenAIRE

    Persson, Kristina E. M.; Lee, Chee T.; Marsh, Kevin; Beeson, James G.

    2006-01-01

    Antibodies that inhibit replication of Plasmodium falciparum in erythrocytes are thought to be important both in acquired immunity to malaria and as mediators of immunity generated by candidate blood-stage vaccines. However, several constraints have limited the study of these functional antibodies in population studies and vaccine trials. We report the development and optimization of high-throughput growth inhibition assays with improved sensitivity that use minimal volumes of test serum. The...

  18. Spin-dependent observables in surrogate reactions

    CERN Document Server

    Chiba, Satoshi; Aritomo, Yoshihiro

    2011-01-01

    Observables emitted from various spin states in compound U nuclei are investigated to validate usefulness of the surrogate reaction method. It was found that energy spectrum of cascading $\\gamma$-rays and their multiplicities, spectrum of evaporated neutrons, and mass-distribution of fission fragments show clear dependence on the spin of decaying nuclei. The present results indicate that they can be used to infer populated spin distributions which significantly affect the decay branching ratio of the compound system produced by the surrogate reactions.

  19. Natural versus Surrogate Keys. Performance and Usability

    Directory of Open Access Journals (Sweden)

    Dragos-Paul POP

    2011-06-01

    Full Text Available Choosing the primary key for a table proves to be one of the most important steps in database design. But what happens when we have to pick between a natural or a surrogate key? Is there any performance issue that we must have in mind? Does the literature have a preferred pick? Is usability a concern? We’ll have a look at the advantages and disadvantages of both natural and surrogate keys and the performance and usability issues they address.

  20. AFM force measurements of the gp120-sCD4 and gp120 or CD4 antigen-antibody interactions

    International Nuclear Information System (INIS)

    Highlights: → The unbinding force of sCD4-gp120 interaction was 25.45 ± 20.46 pN. → The unbinding force of CD4 antigen-antibody interaction was 51.22 ± 34.64 pN. → The unbinding force of gp120 antigen-antibody interaction was 89.87 ± 44.63 pN. → The interaction forces between various HIV inhibitors and the target molecules are significantly different. → Functionalizing on AFM tip or substrate of an interaction pair caused different results. -- Abstract: Soluble CD4 (sCD4), anti-CD4 antibody, and anti-gp120 antibody have long been regarded as entry inhibitors in human immunodeficiency virus (HIV) therapy. However, the interactions between these HIV entry inhibitors and corresponding target molecules are still poorly understood. In this study, atomic force microscopy (AFM) was utilized to investigate the interaction forces among them. We found that the unbinding forces of sCD4-gp120 interaction, CD4 antigen-antibody interaction, and gp120 antigen-antibody interaction were 25.45 ± 20.46, 51.22 ± 34.64, and 89.87 ± 44.63 pN, respectively, which may provide important mechanical information for understanding the effects of viral entry inhibitors on HIV infection. Moreover, we found that the functionalization of an interaction pair on AFM tip or substrate significantly influenced the results, implying that we must perform AFM force measurement and analyze the data with more caution.

  1. Compaction behavior of surrogate degraded emplaced WIPP waste.

    Energy Technology Data Exchange (ETDEWEB)

    Broome, Scott Thomas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bronowski, David R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kuthakun, Souvanny James [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Herrick, Courtney Grant [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Pfeifle, Thomas W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-03-01

    The present study results are focused on laboratory testing of surrogate waste materials. The surrogate wastes correspond to a conservative estimate of degraded Waste Isolation Pilot Plant (WIPP) containers and TRU waste materials at the end of the 10,000 year regulatory period. Testing consists of hydrostatic, triaxial, and uniaxial strain tests performed on surrogate waste recipes that were previously developed by Hansen et al. (1997). These recipes can be divided into materials that simulate 50% and 100% degraded waste by weight. The percent degradation indicates the anticipated amount of iron corrosion, as well as the decomposition of cellulosics, plastics, and rubbers (CPR). Axial, lateral, and volumetric strain and axial, lateral, and pore stress measurements were made. Two unique testing techniques were developed during the course of the experimental program. The first involves the use of dilatometry to measure sample volumetric strain under a hydrostatic condition. Bulk moduli of the samples measured using this technique were consistent with those measured using more conventional methods. The second technique involved performing triaxial tests under lateral strain control. By limiting the lateral strain to zero by controlling the applied confining pressure while loading the specimen axially in compression, one can maintain a right-circular cylindrical geometry even under large deformations. This technique is preferred over standard triaxial testing methods which result in inhomogeneous deformation or (3z(Bbarreling(3y. (BManifestations of the inhomogeneous deformation included non-uniform stress states, as well as unrealistic Poissons ratios (> 0.5) or those that vary significantly along the length of the specimen. Zero lateral strain controlled tests yield a more uniform stress state, and admissible and uniform values of Poissons ratio.

  2. Partitioning of polychlorinated biphenyls into human cells and adipose tissues: evaluation of octanol, triolein, and liposomes as surrogates

    NARCIS (Netherlands)

    Quinn, Cristina L.; Van Der Heijden, Stephan A.; Wania, Frank; Jonker, Michiel T O

    2014-01-01

    Whereas octanol, triacylglycerides, and liposomes have all been proposed as surrogates for measuring the affinity of hydrophobic organic contaminants to human lipids, no comparative evaluation of their suitability exists. Here we conducted batch sorption experiments with polyoxymethylene passive sam

  3. A novel surrogate index for hepatic insulin resistance.

    LENUS (Irish Health Repository)

    Vangipurapu, J

    2011-03-01

    In epidemiological and genetic studies surrogate indices are needed to investigate insulin resistance in different insulin-sensitive tissues. Our objective was to develop a surrogate index for hepatic insulin resistance.

  4. Testing the surrogate zeta-function method

    International Nuclear Information System (INIS)

    Use of the surrogate zeta-function method was crucial in calculating the Casimir energy in non-Abelian Kaluza-Klein theories. We establish the validity of this method for the case that the background metric is (Euclidean space)x(N-sphere). Our techniques do not apply to the case where the background is (Minkowski-space)x(N-sphere)

  5. Testing for Coupling Asymmetry using Surrogate Data

    Czech Academy of Sciences Publication Activity Database

    Paluš, Milan; Mussiza, B.; Stefanovska, A.

    2007-01-01

    Roč. 2, č. 2-3 (2007), s. 327-344. ISSN 1556-3995 EU Projects: European Commission(XE) 517133 - BRACCIA Grant ostatní: Czech and Slovenian MES(XX) KONTAKT 1/2005-6 Institutional research plan: CEZ:AV0Z10300504 Keywords : coupling asymmetry * causality * hypothesis testing * surrogate data Subject RIV: BA - General Mathematics

  6. Surrogate data for non-stationary signals

    CERN Document Server

    Schmitz, A; Schmitz, Andreas; Schreiber, Thomas

    1999-01-01

    Standard tests for nonlinearity reject the null hypothesis of a Gaussian linear process whenever the data is non-stationary. Thus, they are not appropriate to distinguish nonlinearity from non-stationarity. We address the problem of generating proper surrogate data corresponding to the null hypothesis of an ARMA process with slowly varying coefficients.

  7. Nitrate Salt Surrogate Blending Scoping Test Plan

    Energy Technology Data Exchange (ETDEWEB)

    Anast, Kurt Roy [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-11-13

    Test blending equipment identified in the “Engineering Options Assessment Report: Nitrate Salt Waste Stream Processing”. Determine if the equipment will provide adequate mixing of zeolite and surrogate salt/Swheat stream; optimize equipment type and operational sequencing; impact of baffles and inserts on mixing performance; and means of validating mixing performance

  8. The value of surrogate endpoints for predicting real-world survival across five cancer types.

    Science.gov (United States)

    Shafrin, Jason; Brookmeyer, Ron; Peneva, Desi; Park, Jinhee; Zhang, Jie; Figlin, Robert A; Lakdawalla, Darius N

    2016-04-01

    Objective It is unclear how well different outcome measures in randomized controlled trials (RCTs) perform in predicting real-world cancer survival. We assess the ability of RCT overall survival (OS) and surrogate endpoints - progression-free survival (PFS) and time to progression (TTP) - to predict real-world OS across five cancers. Methods We identified 20 treatments and 31 indications for breast, colorectal, lung, ovarian, and pancreatic cancer that had a phase III RCT reporting median OS and median PFS or TTP. Median real-world OS was determined using a Kaplan-Meier estimator applied to patients in the Surveillance and Epidemiology End Results (SEER)-Medicare database (1991-2010). Performance of RCT OS and PFS/TTP in predicting real-world OS was measured using t-tests, median absolute prediction error, and R(2) from linear regressions. Results Among 72,600 SEER-Medicare patients similar to RCT participants, median survival was 5.9 months for trial surrogates, 14.1 months for trial OS, and 13.4 months for real-world OS. For this sample, regression models using clinical trial OS and trial surrogates as independent variables predicted real-world OS significantly better than models using surrogates alone (P = 0.026). Among all real-world patients using sample treatments (N = 309,182), however, adding trial OS did not improve predictive power over predictions based on surrogates alone (P = 0.194). Results were qualitatively similar using median absolute prediction error and R(2) metrics. Conclusions Among the five tumor types investigated, trial OS and surrogates were each independently valuable in predicting real-world OS outcomes for patients similar to trial participants. In broader real-world populations, however, trial OS added little incremental value over surrogates alone. PMID:26743800

  9. Surrogate losses: Understandings of pregnancy loss and assisted reproduction among surrogate mothers.

    Science.gov (United States)

    Berend, Zsuzsa

    2010-06-01

    I explore surrogate mothers' narrative construction of pregnancy loss on surrogacy support websites. Communicating via the Internet, women construct the public online world of surrogacy. Drawing on anthropological and sociological literature I investigate the connections between conceptualizations of loss and understandings of technological practices and the consequences of these understandings for assisted reproduction. Surrogate mothers define loss broadly, ranging from failure to conceive to miscarriage and stillbirth; loss means the failure to give a baby to the intended parents. Assisted reproductive technologies contribute to loss by raising expectations of success, by attempting to maximize results through the transfer of multiple fertilized ova, and by early monitoring and testing. However, surrogates collectively understand technology as a positive force and advocate for reproductive technology. Surrogates' resolve to "give the gift of life" makes them vulnerable to failure and loss, yet also informs repeated efforts to bear children for others with technological assistance. PMID:20550095

  10. Dry deposition of nitrate and sulphate on surrogate surfaces

    International Nuclear Information System (INIS)

    Airborne velocities and deposition fluxes (DF) of NO3-1 and SO4-2 on various surrogate surfaces, specifically petridishes of polypropylene and glass, marble slabs, ceramic tiles, and stainless steel plates, were measured between January and June, 1991. DFs were higher in the summer months, but varied with the surface, decreasing in the order above. In the summer, NO3-1 DFs were higher than corresponding SO4-2 values. In the winter, this trend was reversed. Deposition velocities of both species were of the order of 10-1cm s-1

  11. Surrogate Nuclear Reactions and the origin of the heavy elements

    International Nuclear Information System (INIS)

    An innovative method for indirectly determining reaction cross sections via Surrogate Nuclear Reactions is presented. Exploring indirect approaches for obtaining reaction cross sections is important since a large number of nuclear reactions relevant to astrophysics cannot be measured with currently available techniques. A program is outlined for developing a comprehensive framework for planing and interpreting experiments that can yield the cross sections of interest. The applications will focus on reactions involving unstable nuclei that play a key role in the production of the elements between iron and uranium

  12. A Bayesian approach to estimate the accuracy of "in-house" ELISA assay to measure rabies antibodies from compulsory vaccinated dogs and cattle

    OpenAIRE

    AHC Nogueira; Silva, C.; Gomes, MR; ACG Rosa; MCR Luvizotto; TC Cardoso

    2009-01-01

    Rabies is a vaccine-preventable disease that causes acute encephalitis in mammals, and it is still a significant public health problem in numerous countries. Infected dogs represent the main vectors involved in human rabies. Additionally, cattle rearing close to geographic areas where vampire bats are found presents an important connection with rural epidemiology. We applied two "in-house" enzyme-linked immunosorbent assay (ELISA) methodologies, considered alternatives to measure antibodies f...

  13. Bayesian meta-analytical methods to incorporate multiple surrogate endpoints in drug development process.

    Science.gov (United States)

    Bujkiewicz, Sylwia; Thompson, John R; Riley, Richard D; Abrams, Keith R

    2016-03-30

    A number of meta-analytical methods have been proposed that aim to evaluate surrogate endpoints. Bivariate meta-analytical methods can be used to predict the treatment effect for the final outcome from the treatment effect estimate measured on the surrogate endpoint while taking into account the uncertainty around the effect estimate for the surrogate endpoint. In this paper, extensions to multivariate models are developed aiming to include multiple surrogate endpoints with the potential benefit of reducing the uncertainty when making predictions. In this Bayesian multivariate meta-analytic framework, the between-study variability is modelled in a formulation of a product of normal univariate distributions. This formulation is particularly convenient for including multiple surrogate endpoints and flexible for modelling the outcomes which can be surrogate endpoints to the final outcome and potentially to one another. Two models are proposed, first, using an unstructured between-study covariance matrix by assuming the treatment effects on all outcomes are correlated and second, using a structured between-study covariance matrix by assuming treatment effects on some of the outcomes are conditionally independent. While the two models are developed for the summary data on a study level, the individual-level association is taken into account by the use of the Prentice's criteria (obtained from individual patient data) to inform the within study correlations in the models. The modelling techniques are investigated using an example in relapsing remitting multiple sclerosis where the disability worsening is the final outcome, while relapse rate and MRI lesions are potential surrogates to the disability progression. PMID:26530518

  14. Validating (d,pγ) as a surrogate for neutron capture

    International Nuclear Information System (INIS)

    The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the r-process may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,pγ) reaction at low energies was identified as a promising surrogate for the (n,γ) reaction, as both reactions share many characteristics. We report on a program to validate (d,pγ) as a surrogate for (n,γ) using 95Mo as a target. The experimental campaign includes direct measurements of the γ-ray intensities from the decay of excited states populated in the 95Mo(n,γ) and 95Mo(d,pγ) reactions.

  15. Neutron-induced capture cross sections via the surrogate reaction method

    International Nuclear Information System (INIS)

    The surrogate reaction method is an indirect way of determining cross sections for nuclear reactions that proceed through a compound nucleus. This technique enables neutron-induced cross sections to be extracted for nuclear reactions on short-lived unstable nuclei that otherwise can not be measured. This technique has been successfully applied to determine the neutron-induced fission cross sections of several short-lived nuclei. In this work, we investigate whether this powerful technique can also be used to determine of neutron-induced capture cross sections. For this purpose we use the surrogate reaction 174Yb(3He, pγ)176Lu to infer the well known 175Lu(n, γ) cross section and compare the results with the directly measured neutron-induced data. This surrogate experiment has been performed in March 2010. The experimental technique used and the first preliminary results will be presented. (authors)

  16. Neutron-induced cross section of actinides via the surrogate-reaction method

    International Nuclear Information System (INIS)

    The surrogate-reaction method is an indirect way of determining cross sections for reactions that proceed through a compound nucleus. It consists of using a transfer reaction to produce the same decaying nucleus as the one formed in the desired neutron-induced reaction. This technique may enable neutron-induced cross sections to be extracted for short-lived nuclei that otherwise cannot be measured. However, the validity of the surrogate method for extracting capture cross sections has to be investigated. In this work we study the reactions 238U(d,p)239U, 238U(3He,t)238Np, 238U(3He,4He)237U as surrogates for neutron-induced reactions on 238U, 237Np and 236U, respectively, for which good quality data exist. The experimental set-up enabled the measurement of fission and gamma-decay probabilities. First results are presented and discussed. (authors)

  17. Validating (d,pγ) as a surrogate for neutron capture

    Energy Technology Data Exchange (ETDEWEB)

    Ratkiewicz, A. [Rutgers Univ., New Brunswick, NJ (United States); Cizewski, J. A. [Rutgers Univ., New Brunswick, NJ (United States); Pain, S. D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Adekola, A. S. [Rutgers Univ., New Brunswick, NJ (United States); Burke, J. T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Casperson, R. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Fotiadis, Nikolaos [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); McCleskey, M. [Texas A & M Univ., College Station, TX (United States); Burcher, S. [Rutgers Univ., New Brunswick, NJ (United States); Shand, C. M [Rutgers Univ., New Brunswick, NJ (United States); Austin, R. A. E. [Saint Mary' s Univ., Halifax (Canada); Baugher, T. [Rutgers Univ., New Brunswick, NJ (United States); Carpenter, M. P. [Argonne National Lab. (ANL), Argonne, IL (United States); Devlin, Matthew James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Escher, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hardy, S. [Rutgers Univ., New Brunswick, NJ (United States); Hatarik, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Howard, M. E. [Rutgers Univ., New Brunswick, NJ (United States); Hughes, R. O. [Univ. of Richmond, VA (United States); Jones, K. L. [Univ. of Tennessee, Knoxville, TN (United States); Kozub, R. L. [Tennessee Technological Univ., Cookeville, TN (United States); Lister, C. J. [Univ. of Massachusetts, Lowell, MA (United States); Manning, B. [Rutgers Univ., New Brunswick, NJ (United States); O' Donnell, John M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Peters, W. A. [oak ridge associated Univ., TN (United States); Ross, T. J. [Univ. of Richmond, VA (United States); Scielzo, N. D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Seweryniak, D. [Argonne National Lab. (ANL), Argonne, IL (United States); Zhu, S. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-02-13

    The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the r-process may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,pγ) reaction at low energies was identified as a promising surrogate for the (n,γ) reaction, as both reactions share many characteristics. We report on a program to validate (d,pγ) as a surrogate for (n,γ) using 95Mo as a target. The experimental campaign includes direct measurements of the γ-ray intensities from the decay of excited states populated in the 95Mo(n,γ) and 95Mo(d,pγ) reactions.

  18. Neutron-induced cross sections of actinides via the surrogate-reaction method

    Directory of Open Access Journals (Sweden)

    Ducasse Q.

    2013-12-01

    Full Text Available The surrogate-reaction method is an indirect way of determining cross sections for reactions that proceed through a compound nucleus. This technique may enable neutron-induced cross sections to be extracted for short-lived nuclei that otherwise cannot be measured. However, the validity of the surrogate method has to be investigated. In particular, the absence of a compound nucleus formation and the Jπ dependence of the decay probabilities may question the method. In this work we study the reactions 238U(d,p239U, 238U(3He,t238Np, 238U(3He,4He237U as surrogates for neutron-induced reactions on 238U, 237Np and 236U, respectively, for which good quality data exist. The experimental set-up enabled the measurement of fission and gamma-decay probabilities. The first results are hereby presented.

  19. Neutron-induced cross sections of actinides via the surrogate-reaction method

    Directory of Open Access Journals (Sweden)

    Tveten G. M.

    2013-03-01

    Full Text Available The surrogate-reaction method is an indirect way of determining cross sections for reactions that proceed through a compound nucleus. This technique may enable neutron-induced cross sections to be extracted for short-lived nuclei that otherwise cannot be measured. However, the validity of the surrogate method for extracting capture cross sections has to be investigated. In this work we study the reactions 238U(d,p239U, 238U(3He,t238Np, 238U(3He,4He237U as surrogates for neutroninduced reactions on 238U, 237Np and 236U, respectively, for which good quality data exist. The experimental set-up enabled the measurement of fission and gamma-decay probabilities. First results are presented and discussed.

  20. Validating (d,p gamma) as a Surrogate for Neutron Capture

    International Nuclear Information System (INIS)

    The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the r-process may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,pγ) reaction at low energies was identified as a promising surrogate for the (n,γ) reaction, as both reactions share many characteristics. We report on a program to validate (d,pγ) as a surrogate for (n,γ) using 95Mo as a target. The experimental campaign includes direct measurements of the γ-ray intensities from the decay of excited states populated in the 95Mo(n,γ) and 95Mo(d,pγ) reactions

  1. Neutron-induced cross sections of actinides via the surrogate-reaction method

    International Nuclear Information System (INIS)

    The surrogate-reaction method is an indirect way of determining cross sections for reactions that proceed through a compound nucleus. This technique may enable neutron-induced cross sections to be extracted for short-lived nuclei that otherwise cannot be measured. However, the validity of the surrogate method has to be investigated. In particular, the absence of a compound nucleus formation and the Jπ dependence of the decay probabilities may question the method. In this work we study the reactions 238U(d,p) 239U, 238U(3He,t)238Np, 238U(3He,4He)237U as surrogates for neutron-induced reactions on 238U, 237Np and 236U, respectively, for which good quality data exist. The experimental set-up enabled the measurement of fission and gamma-decay probabilities. The first results are hereby presented. (authors)

  2. Diagnostic significance of measurements of specific IgG antibodies to Pseudomonas aeruginosa by three different serological methods

    DEFF Research Database (Denmark)

    Pressler, T.; Karpati, F.; Granstrom, M.;

    2008-01-01

    characterize patients with different infection status. Elevated levels of specific anti-Pseudomonas antibodies showed to be the risk factor for developing chronic Pa infection. Due to the specificity of the tests, antibiotic treatment based on serology might be considered in selected cases. There is a window...

  3. Large Discrepancy in the Results of Sensitive Measurements of Thyroglobulin Antibodies in the Follow-Up on Thyroid Cancer

    DEFF Research Database (Denmark)

    Nygaard, Birte; Faber, Jens Oscar; Bentzen, Jens

    2012-01-01

    During follow-up on patients treated for differentiated thyroid cancer, thyroglobulin (Tg) antibodies can interfere with the Tg assay, making the use of Tg less reliable as a tumor marker. Purpose: To compare Tg and Tg autoantibodies (Tg- Ab) methods used in Denmark, regarding the number of patient...

  4. A Statistical Estimation Approach for Quantitative Concentrations of Compounds Lacking Authentic Standards/Surrogates Based on Linear Correlations between Directly Measured Detector Responses and Carbon Number of Different Functional Groups

    Directory of Open Access Journals (Sweden)

    Yong-Hyun Kim

    2013-01-01

    Full Text Available A statistical approach was investigated to estimate the concentration of compounds lacking authentic standards/surrogates (CLASS. As a means to assess the reliability of this approach, the response factor (RF of CLASS is derived by predictive equations based on a linear regression (LR analysis between the actual RF (by external calibration of 18 reference volatile organic compounds (VOCs consisting of six original functional groups and their physicochemical parameters ((1 carbon number (CN, (2 molecular weight (MW, and (3 boiling point (BP. If the experimental bias is estimated in terms of percent difference (PD between the actual and projected RF, the least bias for 18 VOCs is found from CN (17.9±19.0%. In contrast, the PD values against MW and BP are 40.6% and 81.5%, respectively. Predictive equations were hence derived via an LR analysis between the actual RF and CN for 29 groups: (1 one group consisting of all 18 reference VOCs, (2 three out of six original functional groups, and (3 25 groups formed randomly from the six functional groups. The applicability of this method was tested by fitting these 29 equations into each of the six original functional groups. According to this approach, the mean PD for 18 compounds dropped as low as 5.60±5.63%. This approach can thus be used as a practical tool to assess the quantitative data for CLASS.

  5. Reversible Bending Fatigue Testing on Zry-4 Surrogate Rods

    International Nuclear Information System (INIS)

    Testing high-burnup spent nuclear fuel (SNF) presents many challenges in areas such as specimen preparation, specimen installation, mechanical loading, load control, measurements, data acquisition, and specimen disposal because these tasks are complicated by the radioactivity of the test specimens. Research and comparison studies conducted at Oak Ridge National Laboratory (ORNL) resulted in a new concept in 2010 for a U-frame testing setup on which to perform hot-cell reversible bending fatigue testing. Subsequently, the three-dimensional finite element analysis and the engineering design of components were completed. In 2013 the ORNL team finalized the upgrade of the U-frame testing setup and the integration of the U-frame setup into a Bose dual linear motor test bench to develop a cyclic integrated reversible-bending fatigue tester (CIRFT). A final check was conducted on the CIRFT test system in August 2013, and the CIRFT was installed in the hot cell in September 2013 to evaluate both the static and dynamic mechanical response of SNF rods under simulated loads. The fatigue responses of Zircaloy-4 (Zry-4) cladding and the role of pellet pellet and pellet clad interactions are critical to SNF vibration integrity, but such data are not available due to the unavailability of an effective testing system. While the deployment of the developed CIRFT test system in a hot cell will provide the opportunity to generate the data, the use of a surrogate rod has proven quite effective in identifying the underlying deformation mechanism of an SNF composite rod under an equivalent loading condition. This paper presents the experimental results of using surrogate rods under CIRFT reversible cyclic loading. Specifically, monotonic and cyclic bending tests were conducted on surrogate rods made of a Zry-4 tube and alumina pellet inserts, both with and without an epoxy bond

  6. Reversible Bending Fatigue Testing on Zry-4 Surrogate Rods

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jy-An John [ORNL; Wang, Hong [ORNL; Bevard, Bruce Balkcom [ORNL; Howard, Rob L [ORNL

    2014-01-01

    Testing high-burnup spent nuclear fuel (SNF) presents many challenges in areas such as specimen preparation, specimen installation, mechanical loading, load control, measurements, data acquisition, and specimen disposal because these tasks are complicated by the radioactivity of the test specimens. Research and comparison studies conducted at Oak Ridge National Laboratory (ORNL) resulted in a new concept in 2010 for a U-frame testing setup on which to perform hot-cell reversible bending fatigue testing. Subsequently, the three-dimensional finite element analysis and the engineering design of components were completed. In 2013 the ORNL team finalized the upgrade of the U-frame testing setup and the integration of the U-frame setup into a Bose dual linear motor test bench to develop a cyclic integrated reversible-bending fatigue tester (CIRFT). A final check was conducted on the CIRFT test system in August 2013, and the CIRFT was installed in the hot cell in September 2013 to evaluate both the static and dynamic mechanical response of SNF rods under simulated loads. The fatigue responses of Zircaloy-4 (Zry-4) cladding and the role of pellet pellet and pellet clad interactions are critical to SNF vibration integrity, but such data are not available due to the unavailability of an effective testing system. While the deployment of the developed CIRFT test system in a hot cell will provide the opportunity to generate the data, the use of a surrogate rod has proven quite effective in identifying the underlying deformation mechanism of an SNF composite rod under an equivalent loading condition. This paper presents the experimental results of using surrogate rods under CIRFT reversible cyclic loading. Specifically, monotonic and cyclic bending tests were conducted on surrogate rods made of a Zry-4 tube and alumina pellet inserts, both with and without an epoxy bond.

  7. Adolescents and Young Women's Use of a Microbicide Surrogate Product When Receiving Oral Sex

    Science.gov (United States)

    Auslander, Beth; Catallozzi, Marina; Davis, Gray; Succop, Paul A.; Stanberry, Lawrence R.; Rosenthal, Susan L.

    2015-01-01

    Study Objective Genital herpes, which can be spread through oral sex, is an important target for microbicides. We examined episode-specific predictors of young women's receptive oral sex and of microbicide surrogate use. Design Longitudinal study Setting Participants were recruited to participate in a microbicide acceptability study from adolescent clinics and local colleges and through snowballing. Participants Young women (ages 14 to 21 years) who reported sexual contact on at least one weekly phone interview (n = 181) were included from the larger sample of 208 young women. Main Outcome Measures On weekly diary phone interviews, participants reported whether or not their last sexual contact included receptive oral sex and whether or not their last sexual contact included use of a microbicide surrogate. Results and Conclusions Participants reported a total of 1042 episodes of sexual contact; 311 included receptive oral sex and 354 included microbicide surrogate use. Being older, having sex for the first time with a partner, and having given oral sex were associated with having received oral sex during a sexual episode. Being older, being African American, and having discussed the microbicide surrogate with their partner were associated with having used the microbicide surrogate use during a sexual episode. These results indicate that oral sex should be considered in the design of clinical trials. Future studies need to evaluate ways to promote consistent microbicide use in the context of receiving oral sex as well as those factors (e.g., taste, pleasure) which may serve as a barrier. PMID:24315715

  8. Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success

    Science.gov (United States)

    Pogue, Brian W.; Elliott, Jonathan T.; Kanick, Stephen C.; Davis, Scott C.; Samkoe, Kimberley S.; Maytin, Edward V.; Pereira, Stephen P.; Hasan, Tayyaba

    2016-04-01

    Photodynamic therapy (PDT) can be a highly complex treatment, with many parameters influencing treatment efficacy. The extent to which dosimetry is used to monitor and standardize treatment delivery varies widely, ranging from measurement of a single surrogate marker to comprehensive approaches that aim to measure or estimate as many relevant parameters as possible. Today, most clinical PDT treatments are still administered with little more than application of a prescribed drug dose and timed light delivery, and thus the role of patient-specific dosimetry has not reached widespread clinical adoption. This disconnect is at least partly due to the inherent conflict between the need to measure and understand multiple parameters in vivo in order to optimize treatment, and the need for expedience in the clinic and in the regulatory and commercialization process. Thus, a methodical approach to selecting primary dosimetry metrics is required at each stage of translation of a treatment procedure, moving from complex measurements to understand PDT mechanisms in pre-clinical and early phase I trials, towards the identification and application of essential dose-limiting and/or surrogate measurements in phase II/III trials. If successful, identifying the essential and/or reliable surrogate dosimetry measurements should help facilitate increased adoption of clinical PDT. In this paper, examples of essential dosimetry points and surrogate dosimetry tools that may be implemented in phase II/III trials are discussed. For example, the treatment efficacy as limited by light penetration in interstitial PDT may be predicted by the amount of contrast uptake in CT, and so this could be utilized as a surrogate dosimetry measurement to prescribe light doses based upon pre-treatment contrast. Success of clinical ALA-based skin lesion treatment is predicted almost uniquely by the explicit or implicit measurements of photosensitizer and photobleaching, yet the individualization of treatment

  9. Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success.

    Science.gov (United States)

    Pogue, Brian W; Elliott, Jonathan T; Kanick, Stephen C; Davis, Scott C; Samkoe, Kimberley S; Maytin, Edward V; Pereira, Stephen P; Hasan, Tayyaba

    2016-04-01

    Photodynamic therapy (PDT) can be a highly complex treatment, with many parameters influencing treatment efficacy. The extent to which dosimetry is used to monitor and standardize treatment delivery varies widely, ranging from measurement of a single surrogate marker to comprehensive approaches that aim to measure or estimate as many relevant parameters as possible. Today, most clinical PDT treatments are still administered with little more than application of a prescribed drug dose and timed light delivery, and thus the role of patient-specific dosimetry has not reached widespread clinical adoption. This disconnect is at least partly due to the inherent conflict between the need to measure and understand multiple parameters in vivo in order to optimize treatment, and the need for expedience in the clinic and in the regulatory and commercialization process. Thus, a methodical approach to selecting primary dosimetry metrics is required at each stage of translation of a treatment procedure, moving from complex measurements to understand PDT mechanisms in pre-clinical and early phase I trials, towards the identification and application of essential dose-limiting and/or surrogate measurements in phase II/III trials. If successful, identifying the essential and/or reliable surrogate dosimetry measurements should help facilitate increased adoption of clinical PDT. In this paper, examples of essential dosimetry points and surrogate dosimetry tools that may be implemented in phase II/III trials are discussed. For example, the treatment efficacy as limited by light penetration in interstitial PDT may be predicted by the amount of contrast uptake in CT, and so this could be utilized as a surrogate dosimetry measurement to prescribe light doses based upon pre-treatment contrast. Success of clinical ALA-based skin lesion treatment is predicted almost uniquely by the explicit or implicit measurements of photosensitizer and photobleaching, yet the individualization of treatment

  10. Solubility of actinide surrogates in nuclear glasses

    International Nuclear Information System (INIS)

    This paper discusses the results of a study of actinide surrogates in a nuclear borosilicate glass to understand the effect of processing conditions (temperature and oxidizing versus reducing conditions) on the solubility limits of these elements. The incorporation of cerium oxide, hafnium oxide, and neodymium oxide in this borosilicate glass was investigated. Cerium is a possible surrogate for tetravalent and trivalent actinides, hafnium for tetravalent actinides, and neodymium for trivalent actinides. The material homogeneity was studied by optical, scanning electron microscopy. Cerium LIII XANES spectroscopy showed that the Ce3+/Cetotal ratio increased from about 0.5 to 0.9 as the processing temperature increased from 1100 to 1400 deg. C. Cerium LIII XANES spectroscopy also confirmed that the increased Ce solubility in glasses melted under reducing conditions was due to complete reduction of all the cerium in the glass. The most significant results pointed out in the current study are that the solubility limits of the actinide surrogates increases with the processing temperature and that Ce3+ is shown to be more soluble than Ce4+ in this borosilicate glass

  11. Biomarkers and surrogate endpoints in kidney disease.

    Science.gov (United States)

    Hartung, Erum A

    2016-03-01

    Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. "Hard" endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease. PMID:25980469

  12. Surrogate formulations for thermal treatment of low-level mixed waste. Part 1: Radiological surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Stockdale, J.A.D.; Bostick, W.D.; Hoffmann, D.P. [Martin Marietta Energy Systems, Inc., Oak Ridge, TN (United States); Lee, H.T. [Oak Ridge Associated Universities, TN (United States)

    1994-01-01

    The evaluation and comparison of proposed thermal treatment systems for mixed wastes can be expedited by tests in which the radioactive components of the wastes are replaced by surrogate materials chosen to mimic, as far as is possible, the chemical and physical properties of the radioactive materials of concern. In this work, sponsored by the Mixed Waste Integrated Project of the US Department of Energy, the authors have examined reported experience with such surrogates and suggest a simplified standard list of materials for use in tests of thermal treatment systems. The chief radioactive nuclides of concern in the treatment of mixed wastes are {sup 239}Pu, {sup 238}U, {sup 235}U, {sup 137}Cs, {sup 103}Ru, {sup 99}Tc, and {sup 90}Sr. These nuclides are largely by-products of uranium enrichment, reactor fuel reprocessing, and weapons program activities. Cs, Ru, and Sr all have stable isotopes that can be used as perfect surrogates for the radioactive forms. Technetium exists only in radioactive form, as do plutonium and uranium. If one wishes to preclude radioactive contamination of the thermal treatment system under trial burn, surrogate elements must be chosen for these three. For technetium, the authors suggest the use of natural ruthenium, and for both plutonium and uranium, they recommend cerium. The seven radionuclides listed can therefore be simulated by a surrogate package containing stable isotopes of ruthenium, strontium, cesium, and cerium.

  13. Development of a Specific Monoclonal Antibody-Based ELISA to Measure the Artemether Content of Antimalarial Drugs

    OpenAIRE

    Suqin Guo; Yongliang Cui; Lishan He; Liang Zhang; Zhen Cao; Wei Zhang; Rui Zhang; Guiyu Tan; Baomin Wang; Liwang Cui

    2013-01-01

    Artemether is one of the artemisinin derivatives that are active ingredients in antimalarial drugs. Counterfeit and substandard antimalarial drugs have become a serious problem, which demands reliable analytical tools and implementation of strict regulation of drug quality. Structural similarity among artemisinin analogs is a challenge to develop immunoassays that are specific to artemisinin derivatives. To produce specific antibodies to artemether, we used microbial fermentation of artemethe...

  14. Pseudo-periodic surrogate test to sample time series in stochastic softening Duffing oscillator

    International Nuclear Information System (INIS)

    Identification of typical noise-contaminated sample response is a hard task in a nonlinear system under stochastic background since irregularity of the sample response may come from measure noise, dynamical noise, or nonlinear effect, etc., and conventional dynamical methods are generally not useful. Here, the pseudo-periodic surrogate algorithm by Small is employed to test the sample time series in the softening Duffing oscillator under the Gaussian white noise excitation. The correlation dimensions of the noisy periodic and the noise-induced chaotic time series of the system are compared with those of their corresponding surrogate data respectively, the leading Lyapunov exponents by Rosenstein's algorithm are also presented for comparison

  15. Technological advances in suspended-sediment surrogate monitoring

    Science.gov (United States)

    Gray, John R.; Gartner, Jeffrey W.

    2009-01-01

    Surrogate technologies to continuously monitor suspended sediment show promise toward supplanting traditional data collection methods requiring routine collection and analysis of water samples. Commercially available instruments operating on bulk optic (turbidity), laser optic, pressure difference, and acoustic backscatter principles are evaluated based on cost, reliability, robustness, accuracy, sample volume, susceptibility to biological fouling, and suitable range of mass concentration and particle size distribution. In situ turbidimeters are widely used. They provide reliable data where the point measurements can be reliably correlated to the river's mean cross section concentration value, effects of biological fouling can be minimized, and concentrations remain below the sensor's upper measurement limit. In situ laser diffraction instruments have similar limitations and can cost 6 times the approximate $5000 purchase price of a turbidimeter. However, laser diffraction instruments provide volumetric-concentration data in 32 size classes. Pressure differential instruments measure mass density in a water column, thus integrating substantially more streamflow than a point measurement. They are designed for monitoring medium-to-large concentrations, are generally unaffected by biological fouling, and cost about the same as a turbidimeter. However, their performance has been marginal in field applications. Acoustic Doppler profilers use acoustic backscatter to measure suspended sediment concentrations in orders of magnitude more streamflow than do instruments that rely on point measurements. The technology is relatively robust and generally immune to effects of biological fouling. Cost of a single-frequency device is about double that of a turbidimeter. Multifrequency arrays also provide the potential to resolve concentrations by clay silt versus sand size fractions. Multifrequency hydroacoustics shows the most promise for revolutionizing collection of continuous

  16. A monoclonal antibody against leptin.

    Science.gov (United States)

    Mahmoudian, Jafar; Jeddi-Tehrani, Mahmood; Bayat, Ali Ahmad; Mahmoudi, Ahmad Reza; Vojgani, Yasaman; Tavangar, Banafsheh; Hadavi, Reza; Zarei, Saeed

    2012-10-01

    Leptin is an important protein that regulates energy storage and homeostasis in humans and animals. Leptin deficiency results in various abnormalities such as diabetes, obesity, and infertility. Producing a high affinity monoclonal antibody against human leptin provides an important tool to monitor and trace leptin function in different biological fluids. In this study, recombinant human leptin was conjugated to KLH and injected into mice. After immunization, mouse myeloma SP2/0 cells were fused with murine splenocytes followed by selection of antibody-producing hybridoma cells. After screening of different hybridoma colonies by ELISA, a high affinity antibody was selected and purified by affinity chromatography. The affinity constant of the antibody was measured by ELISA. Western blot, immunocytochemistry, and flow cytometry experiments were used to characterize the antibody. The anti-leptin antibody had a high affinity (around 1.13 × 10(-9) M) for its antigen. The saturation of the antibody with leptin (20 moles leptin per 1 mole antibody) in Western blot analysis proved that the antibody had specific binding to its antigen. Immunocytochemistry and flow cytometry on JEG-3 (human placental choriocarcinoma cell) cells revealed that the anti-leptin antibody recognized intracellular leptin. In conclusion, we report here the production and characterization of a murine anti-leptin antibody with high affinity for human leptin. PMID:23098305

  17. Methodology for Formulating Diesel Surrogate Fuels with Accurate Compositional, Ignition-Quality, and Volatility Characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, C. J.; Cannella, W. J.; Bruno, T. J.; Bunting, B.; Dettman, H. D.; Franz, J. A.; Huber, M. L.; Natarajan, M.; Pitz, W. J.; Ratcliff, M. A.; Wright, K.

    2012-06-21

    In this study, a novel approach was developed to formulate surrogate fuels having characteristics that are representative of diesel fuels produced from real-world refinery streams. Because diesel fuels typically consist of hundreds of compounds, it is difficult to conclusively determine the effects of fuel composition on combustion properties. Surrogate fuels, being simpler representations of these practical fuels, are of interest because they can provide a better understanding of fundamental fuel-composition and property effects on combustion and emissions-formation processes in internal-combustion engines. In addition, the application of surrogate fuels in numerical simulations with accurate vaporization, mixing, and combustion models could revolutionize future engine designs by enabling computational optimization for evolving real fuels. Dependable computational design would not only improve engine function, it would do so at significant cost savings relative to current optimization strategies that rely on physical testing of hardware prototypes. The approach in this study utilized the state-of-the-art techniques of {sup 13}C and {sup 1}H nuclear magnetic resonance spectroscopy and the advanced distillation curve to characterize fuel composition and volatility, respectively. The ignition quality was quantified by the derived cetane number. Two well-characterized, ultra-low-sulfur No.2 diesel reference fuels produced from refinery streams were used as target fuels: a 2007 emissions certification fuel and a Coordinating Research Council (CRC) Fuels for Advanced Combustion Engines (FACE) diesel fuel. A surrogate was created for each target fuel by blending eight pure compounds. The known carbon bond types within the pure compounds, as well as models for the ignition qualities and volatilities of their mixtures, were used in a multiproperty regression algorithm to determine optimal surrogate formulations. The predicted and measured surrogate-fuel properties were

  18. Investigation of the interaction between Tc85-11 protein and antibody anti-T. cruzi by AFM and amperometric measurements

    International Nuclear Information System (INIS)

    This present work reports on development of an amperometric immunosensor for the diagnosis of Chagas' disease using a specific glycoprotein of the trypomastigote surface, which belongs to the Tc85-11 protein family of Trypanosoma cruzi (T. cruzi). An atomically flat gold surface on a silicon substrate and gold screen-printed electrodes were functionalized with cystamine and later activated with glutaraldehyde (GA), which was used to form covalent bonds with the purified recombinant antigen (Tc85-11). The antigen reacts with the antibody from the serum, and the affinity reaction was monitored directly using atomic force microscopy or amperometry through a secondary antibody tagged to peroxidase (HRP). Surface imaging allowed to us to differentiate the modification steps and antigen-antibody interaction allowed to distinguish the affinity reactions. In the amperometric immunosensor, peroxidase catalyses the L2 formation in the presence of hydrogen peroxide and potassium iodide, and the reduction current intensity was measured at a given potential with screen-printed electrodes. The immunosensor was applied to sera of chagasic patients and patients having different systemic diseases

  19. Performance Evaluation of the VIDAS(®) Measles IgG Assay and Its Diagnostic Value for Measuring IgG Antibody Avidity in Measles Virus Infection.

    Science.gov (United States)

    Dina, Julia; Creveuil, Christian; Gouarin, Stephanie; Viron, Florent; Hebert, Amelie; Freymuth, Francois; Vabret, Astrid

    2016-01-01

    The objective of this study is primarily to compare the performance of the VIDAS(®) Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost(®) Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA(®) (Microimmune). The sensitivity and the agreement of the VIDAS(®) Measles IgG assay compared to the Enzygnost(®) Anti-measles Virus/IgG assay and the Measles IgG CAPTURE EIA(®) assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS(®) Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS(®) CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI) AI > 0.6. The VIDAS(®) Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects. PMID:27556477

  20. Performance Evaluation of the VIDAS® Measles IgG Assay and Its Diagnostic Value for Measuring IgG Antibody Avidity in Measles Virus Infection

    Science.gov (United States)

    Dina, Julia; Creveuil, Christian; Gouarin, Stephanie; Viron, Florent; Hebert, Amelie; Freymuth, Francois; Vabret, Astrid

    2016-01-01

    The objective of this study is primarily to compare the performance of the VIDAS® Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost® Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA® (Microimmune). The sensitivity and the agreement of the VIDAS® Measles IgG assay compared to the Enzygnost® Anti-measles Virus/IgG assay and the Measles IgG CAPTURE EIA® assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS® Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS® CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI) AI > 0.6. The VIDAS® Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects. PMID:27556477

  1. Neutron-induced fission cross sections of short-lived actinides via the surrogate reaction method

    International Nuclear Information System (INIS)

    A brief discussion of surrogate reaction methods has been made and some of the recent results on neutron induced fission cross section measurements have been presented. The validation of the EMPIRE-3.1. predictions on neutron induced cross sections corresponding to fission barriers used from Barrier Formula (BF) and RIPL-1 libraries have been discussed

  2. Selecting surrogate endpoints for estimating pesticide effects on avian reproductive success

    Science.gov (United States)

    A Markov chain nest productivity model (MCnest) has been developed for projecting the effects of a specific pesticide-use scenario on the annual reproductive success of avian species of concern. A critical element in MCnest is the use of surrogate endpoints, defined as measured ...

  3. Evidence against the use of surrogates for biomonitoring of Neotropical floodplains

    NARCIS (Netherlands)

    Padial, A.A.; Declerck, S.A.J.; De Meester, L.; Bonecker, C.C.; Lansac-Toha, F.A.; Rodrigues, L.C.; Takeda, A.; Train, S.; Velho, L.F.M.; Bini, L.M.S

    2012-01-01

    1. Community concordance measures the level of association between the compositional patterns shown by two groups of organisms. If strong community concordance occurs, one group could be used as a surrogate for another in conservation planning and biodiversity monitoring. In this study, we evaluated

  4. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE)

    DEFF Research Database (Denmark)

    Vestbo, J; Anderson, W; Coxson, H O;

    2008-01-01

    plethysmography), chest computed tomography, biomarker measurement (in blood, sputum, urine and exhaled breath condensate), health outcomes, body impedance, resting oxygen saturation and 6-min walking distance. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points is the largest study...

  5. Probing hydrogen bonds in the antibody-bound HIV-1 gp120 V3 loop by solid state NMR REDOR measurements

    International Nuclear Information System (INIS)

    We describe solid state NMR measurements on frozen solutions of the complex of the 24-residue HIV-1 gp120 V3 loop peptide RP135 with the Fab fragment of the anti-gp120 antibody 0.5β, using rotational echo double resonance (REDOR). In order to probe possible hydrogen bonding between arginine side chains and glycine backbone carbonyls in the region of the conserved Gly-Pro-Gly-Arg (GPGR) motif of the V3 loop, RP135 samples were prepared with 15N labels at the η nitrogen positions of arginine side chains and 13C labels at glycine carbonyl positions and 13C-detected 13C-15N REDOR measurements were performed on peptide/antibody complexes of these labeled samples. Such hydrogen bonding was previously observed in a crystal structure of the V3 loop peptide/antibody complex RP142/59.1 [Ghiara et al. (1994) Science, 264, 82-85], but is shown by the REDOR measurements to be absent in the RP135/0.5β complex. These results confirm the antibody-dependent conformational differences in the GPGR motif suggested by previously reported solid state NMR measurements of φ and Ψ backbone dihedral angles in the RP135/0.5β complex. In addition, we describe REDOR measurements on the helical synthetic peptide MB(i+4)EK in frozen solution that establish our ability to detect 13C-15N dipole-dipole couplings in the distance range appropriate to these hydrogen bonding studies. We also report the results of molecular modeling calculations on the central portion RP135, using a combination of the solid state NMR restraints of Weliky et al. [Nat. Struct. Biol., 6, 141-145, 1999] and the liquid state NMR restraints of Tugarinov et al. (Nat. Struct. Biol., 6, 331-335, 1999]. The dynamics calculations demonstrate the mutual compatibility of the two sets of experimental structural restraints and reduce ambiguities in the solid state NMR restraints that result from symmetry and signal-to-noise considerations

  6. Identifying experimental surrogates for Bacillus anthracis spores: a review

    Directory of Open Access Journals (Sweden)

    Greenberg David L

    2010-09-01

    Full Text Available Abstract Bacillus anthracis, the causative agent of anthrax, is a proven biological weapon. In order to study this threat, a number of experimental surrogates have been used over the past 70 years. However, not all surrogates are appropriate for B. anthracis, especially when investigating transport, fate and survival. Although B. atrophaeus has been widely used as a B. anthracis surrogate, the two species do not always behave identically in transport and survival models. Therefore, we devised a scheme to identify a more appropriate surrogate for B. anthracis. Our selection criteria included risk of use (pathogenicity, phylogenetic relationship, morphology and comparative survivability when challenged with biocides. Although our knowledge of certain parameters remains incomplete, especially with regards to comparisons of spore longevity under natural conditions, we found that B. thuringiensis provided the best overall fit as a non-pathogenic surrogate for B. anthracis. Thus, we suggest focusing on this surrogate in future experiments of spore fate and transport modelling.

  7. Neutron-induced capture cross sections via the surrogate reaction method

    International Nuclear Information System (INIS)

    The surrogate reaction method is an indirect way of determining cross sections for nuclear reactions that proceed through a compound nucleus. In this method, the compound nucleus is produced via an alternative (surrogate) reaction and its decay (by fission, gamma or neutron emission) is measured in coincidence with the outgoing appropriate charged particle. This technique has enabled neutron-induced cross sections to be extracted for nuclear reactions on short-lived nuclei that otherwise could not be measured. The CENBG collaboration has successfully applied this technique to determine the neutron-induced fission cross sections of several short-lived nuclei such as 233Pa, 242,243Cm and 241Am. These data are very important for the development of the Th/U cycle and for minor actinide transmutation. We currently investigate whether this powerful technique can also be used to determine the neutron-induced capture cross sections. For this purpose we will use the surrogate reaction 174Yb(3He,pγ)176Lu to infer the well known 175Lu(n,γ) cross section and compare the results with the directly measured neutron-induced data. The experimental set-up and the first results will be presented. We will also discuss our future plans to use the surrogate method for extracting actinides (n,γ) cross sections. (authors)

  8. Correlation of lung tumor motion with external surrogate indicators of respiration

    International Nuclear Information System (INIS)

    Purpose: To assess the correlation of respiratory volume and abdominal displacement with tumor motion as seen with X-ray fluoroscopy. Measurements throughout the patient's treatment course allowed an assessment of the interfractional reproducibility of this correlation. Methods and materials: Data were acquired from 11 patients; 5 were studied over multiple days. Measurements of respiratory volume by spirometry and abdominal displacement by a real-time position tracking system were correlated to simultaneously acquired X-ray fluoroscopy measurements of superior-inferior tumor displacement. The linear correlation coefficient was computed for each data acquisition. The phase relationship between the surrogate and tumor signals was estimated through cross-correlation delay analysis. Results: Correlation coefficients ranged from very high to very low (0.99-0.39, p < 0.0001). The correlation between tumor displacement and respiratory volume was higher and more reproducible from day to day than between tumor displacement and abdominal displacement. A nonzero phase relationship was observed in nearly all patients (-0.65 to +0.50 s). This relationship was observed to vary over inter- and intrafractional time scales. Only 1 of 5 patients studied over multiple days had a consistent relationship between tumor motion and either surrogate. Conclusions: Respiratory volume has a more reproducible correlation with tumor motion than does abdominal displacement. If forming a tumor-surrogate prediction model from a limited series of observations, the use of surrogates to guide treatment might result in geographic miss

  9. Surrogate data method applied to nonlinear time series

    OpenAIRE

    Luo, Xiaodong; Nakamura, Tomomichi; Small, Michael

    2006-01-01

    The surrogate data method is widely applied as a data dependent technique to test observed time series against a barrage of hypotheses. However, often the hypotheses one is able to address are not those of greatest interest, particularly for system known to be nonlinear. In the review we focus on techniques which overcome this shortcoming. We summarize a number of recently developed surrogate data methods. While our review of surrogate methods is not exhaustive, we do focus on methods which m...

  10. Surrogate pregnancy: a guide for Canadian prenatal health care providers

    OpenAIRE

    Reilly, Dan R.

    2007-01-01

    Providing health care for a woman with a surrogate pregnancy involves unique challenges. Although the ethical debate surrounding surrogacy continues, Canada has banned commercial, but not altruistic, surrogacy. In the event of a custody dispute between a surrogate mother and the individual(s) intending to parent the child, it is unclear how Canadian courts would rule. The prenatal health care provider must take extra care to protect the autonomy and privacy rights of the surrogate. There is l...

  11. Development of a specific monoclonal antibody-based ELISA to measure the artemether content of antimalarial drugs.

    Directory of Open Access Journals (Sweden)

    Suqin Guo

    Full Text Available Artemether is one of the artemisinin derivatives that are active ingredients in antimalarial drugs. Counterfeit and substandard antimalarial drugs have become a serious problem, which demands reliable analytical tools and implementation of strict regulation of drug quality. Structural similarity among artemisinin analogs is a challenge to develop immunoassays that are specific to artemisinin derivatives. To produce specific antibodies to artemether, we used microbial fermentation of artemether to obtain 9-hydroxyartemether, which was subsequently used to prepare a 9-O-succinylartemether hapten for conjugation with ovalbumin as the immunogen. A monoclonal antibody (mAb, designated as 2G12E1, was produced with high specificity to artemether. 2G12E1 showed low cross reactivities to dihydroartemisinin, artemisinin, artesunate and other major antimalarial drugs. An indirect competitive enzyme linked immunosorbent assay (icELISA developed showed a concentration causing 50% of inhibition for artemether as 3.7 ng mL⁻¹ and a working range of 0.7-19 ng mL⁻¹. The icELISA was applied for determination of artemether content in different commercial drugs and the results were comparable to those determined by high-performance liquid chromatography analysis. In comparison with reported broad cross activity of anti-artemisinin mAbs, the most notable advantage of the 2G12E1-based ELISA is its high specificity to artemether only.

  12. Boosted Surrogate Models in Evolutionary Optimization

    Czech Academy of Sciences Publication Activity Database

    Holeňa, Martin

    Seňa : Pont, 2009 - (Vojtáš, P.), s. 15-22 ISBN 978-80-970179-2-7. [ITAT 2009. Conference on Theory and Practice of Information Theory. Kráľova studňa (SK), 25.09.2009-29.09.2009] R&D Projects: GA ČR GA201/08/1744 Institutional research plan: CEZ:AV0Z10300504 Keywords : evolutionary optimization * genetic algorithms * surrogate modelling * regression models * boosting Subject RIV: IN - Informatics, Computer Science

  13. Bispecific antibodies.

    Science.gov (United States)

    Kontermann, Roland E; Brinkmann, Ulrich

    2015-07-01

    Bispecific antibodies (bsAbs) combine specificities of two antibodies and simultaneously address different antigens or epitopes. BsAbs with 'two-target' functionality can interfere with multiple surface receptors or ligands associated, for example with cancer, proliferation or inflammatory processes. BsAbs can also place targets into close proximity, either to support protein complex formation on one cell, or to trigger contacts between cells. Examples of 'forced-connection' functionalities are bsAbs that support protein complexation in the clotting cascade, or tumor-targeted immune cell recruiters and/or activators. Following years of research and development (R&D), the first bsAb was approved in 2009. Another bsAb entered the market in December 2014 and several more are in clinical trials. Here, we describe the potentials of bsAbs to become the next wave of antibody-based therapies, focusing on molecules in clinical development. PMID:25728220

  14. Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

    International Nuclear Information System (INIS)

    Purpose: To investigate the effect of tumor site, measurement precision, tumor–surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor–surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor–surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3–3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

  15. Effectiveness of external respiratory surrogates for in vivo liver motion estimation

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kai-Hsiang; Ho, Ming-Chih; Yeh, Chi-Chuan; Chen, Yu-Chien; Lian, Feng-Li; Lin, Win-Li; Yen, Jia-Yush; Chen, Yung-Yaw [Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10041, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan (China); Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Institute of Biomedical Engineering, National Taiwan University, Taipei 10041, Taiwan (China); Department of Mechanical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Department of Electrical Engineering and Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan (China)

    2012-08-15

    Purpose: Due to low frame rate of MRI and high radiation damage from fluoroscopy and CT, liver motion estimation using external respiratory surrogate signals seems to be a better approach to track liver motion in real-time for liver tumor treatments in radiotherapy and thermotherapy. This work proposes a liver motion estimation method based on external respiratory surrogate signals. Animal experiments are also conducted to investigate related issues, such as the sensor arrangement, multisensor fusion, and the effective time period. Methods: Liver motion and abdominal motion are both induced by respiration and are proved to be highly correlated. Contrary to the difficult direct measurement of the liver motion, the abdominal motion can be easily accessed. Based on this idea, our study is split into the model-fitting stage and the motion estimation stage. In the first stage, the correlation between the surrogates and the liver motion is studied and established via linear regression method. In the second stage, the liver motion is estimated by the surrogate signals with the correlation model. Animal experiments on cases of single surrogate signal, multisurrogate signals, and long-term surrogate signals are conducted and discussed to verify the practical use of this approach. Results: The results show that the best single sensor location is at the middle of the upper abdomen, while multisurrogate models are generally better than the single ones. The estimation error is reduced from 0.6 mm for the single surrogate models to 0.4 mm for the multisurrogate models. The long-term validity of the estimation models is quite satisfactory within the period of 10 min with the estimation error less than 1.4 mm. Conclusions: External respiratory surrogate signals from the abdomen motion produces good performance for liver motion estimation in real-time. Multisurrogate signals enhance estimation accuracy, and the estimation model can maintain its accuracy for at least 10 min. This

  16. Effectiveness of external respiratory surrogates for in vivo liver motion estimation

    International Nuclear Information System (INIS)

    Purpose: Due to low frame rate of MRI and high radiation damage from fluoroscopy and CT, liver motion estimation using external respiratory surrogate signals seems to be a better approach to track liver motion in real-time for liver tumor treatments in radiotherapy and thermotherapy. This work proposes a liver motion estimation method based on external respiratory surrogate signals. Animal experiments are also conducted to investigate related issues, such as the sensor arrangement, multisensor fusion, and the effective time period. Methods: Liver motion and abdominal motion are both induced by respiration and are proved to be highly correlated. Contrary to the difficult direct measurement of the liver motion, the abdominal motion can be easily accessed. Based on this idea, our study is split into the model-fitting stage and the motion estimation stage. In the first stage, the correlation between the surrogates and the liver motion is studied and established via linear regression method. In the second stage, the liver motion is estimated by the surrogate signals with the correlation model. Animal experiments on cases of single surrogate signal, multisurrogate signals, and long-term surrogate signals are conducted and discussed to verify the practical use of this approach. Results: The results show that the best single sensor location is at the middle of the upper abdomen, while multisurrogate models are generally better than the single ones. The estimation error is reduced from 0.6 mm for the single surrogate models to 0.4 mm for the multisurrogate models. The long-term validity of the estimation models is quite satisfactory within the period of 10 min with the estimation error less than 1.4 mm. Conclusions: External respiratory surrogate signals from the abdomen motion produces good performance for liver motion estimation in real-time. Multisurrogate signals enhance estimation accuracy, and the estimation model can maintain its accuracy for at least 10 min. This

  17. High-resolution computed tomography of the chest in children with cystic fibrosis: support for use as an outcome surrogate

    International Nuclear Information System (INIS)

    Background. Outcome surrogates are indicators that reflect, rather than directly measure, patient benefit. In order to provide useful results, however, outcome surrogates must be carefully chosen and must meet specific criteria. Objective. To support development of high-resolution computed tomography (HRCT) as an outcome surrogate in cystic fibrosis (CF) by demonstrating the ability of HRCT to show short-term improvement in the appearance of the lungs in children with CF. Materials and methods. HRCT was performed at admission and after discharge on 8 children during 15 admissions for acute pulmonary exacerbation of CF. Three radiologists scored each study separately, then compared admission and discharge pairs. Results. HRCT scores improved in 13/15 admissions. Mean score decreased from 25 to 22. The decrease was significant (P = 0.014). Comparison of admission and discharge scans showed improvement in peribronchial thickening (P = 0.007), mucous plugging (P = 0.002), and overall appearance (P = 0.025). Conclusion. HRCT has the potential to be a useful outcome surrogate in CF. A necessary attribute of an outcome surrogate is that it improves rapidly with effective therapy. Despite widespread belief among radiologists and pulmonologists that HRCT meets this criterion, no previous report has demonstrated this ability in children. These findings support further development of HRCT as an outcome surrogate in children with CF. (orig.)

  18. Accuracy preserving surrogate for neutron transport calculations

    International Nuclear Information System (INIS)

    Recent advances in reduced order modeling and exact-to-precision generalized perturbation theory are combined in a novel algorithm that constructs a surrogate model for the Boltzmann equation, commonly used in assembly calculations to functionalize the few-group cross-sections in terms of the various assembly types, depletion characteristics, and thermal-hydraulics conditions. First, the algorithm employs reduced order modeling to determine the dominant input parameters, aggregated in the so-called active subspace, using a random sample of first-order derivatives calculated using an adjoint model. Next, exact-to-precision generalized perturbation theory identifies an active subspace for the state solution (i.e., angular flux) and constructs a surrogate model that is parameterized over the active subspace of the input parameters. This approach is shown to significantly reduce computational time needed for the analysis of a large number of model variations, while meeting the user-defined accuracy requirements. Numerical experiments are employed to demonstrate the mechanics and application of the proposed approach to assembly calculations commonly used in reactor physics analysis. (author)

  19. Estimating Predictability Redundancy and Surrogate Data Method

    CERN Document Server

    Pecen, L

    1995-01-01

    A method for estimating theoretical predictability of time series is presented, based on information-theoretic functionals---redundancies and surrogate data technique. The redundancy, designed for a chosen model and a prediction horizon, evaluates amount of information between a model input (e.g., lagged versions of the series) and a model output (i.e., a series lagged by the prediction horizon from the model input) in number of bits. This value, however, is influenced by a method and precision of redundancy estimation and therefore it is a) normalized by maximum possible redundancy (given by the precision used), and b) compared to the redundancies obtained from two types of the surrogate data in order to obtain reliable classification of a series as either unpredictable or predictable. The type of predictability (linear or nonlinear) and its level can be further evaluated. The method is demonstrated using a numerically generated time series as well as high-frequency foreign exchange data and the theoretical ...

  20. Surrogate Motherhood and Abortion for Fetal Abnormality.

    Science.gov (United States)

    Walker, Ruth; van Zyl, Liezl

    2015-10-01

    A diagnosis of fetal abnormality presents parents with a difficult - even tragic - moral dilemma. Where this diagnosis is made in the context of surrogate motherhood there is an added difficulty, namely that it is not obvious who should be involved in making decisions about abortion, for the person who would normally have the right to decide - the pregnant woman - does not intend to raise the child. This raises the question: To what extent, if at all, should the intended parents be involved in decision-making? In commercial surrogacy it is thought that as part of the contractual agreement the intended parents acquire the right to make this decision. By contrast, in altruistic surrogacy the pregnant woman retains the right to make these decisions, but the intended parents are free to decide not to adopt the child. We argue that both these strategies are morally unsound, and that the problems encountered serve to highlight more fundamental defects within the commercial and altruistic models, as well as in the legal and institutional frameworks that support them. We argue in favour of the professional model, which acknowledges the rights and responsibilities of both parties and provides a legal and institutional framework that supports good decision-making. In particular, the professional model acknowledges the surrogate's right to decide whether to undergo an abortion, and the intended parents' obligation to accept legal custody of the child. While not solving all the problems that arise in surrogacy, the model provides a framework that supports good decision-making. PMID:25688455

  1. Cellular impedance measurement as a new tool for poxvirus titration, antibody neutralization testing and evaluation of antiviral substances

    International Nuclear Information System (INIS)

    Research highlights: → Real-time data acquisition by RT-CES requires low operative effort. → Time to result is reduced by using RT-CES instead of conventional methods. → RT-CES enables quantification of virus titers in unknown samples. → RT-CES is a useful tool for high-throughput characterization of antiviral agents. → An RT-CES-based virus neutralization test was established. -- Abstract: Impedance-based biosensing known as real-time cell electronic sensing (RT-CES) belongs to an emerging technology for analyzing the status of cells in vitro. In the present study protocols were developed for an RT-CES-based system (xCELLigenceTM, Roche Applied Science, ACEA Biosciences Inc.) to supplement conventional techniques in pox virology. First, proliferation of cells susceptible to orthopoxviruses was monitored. For virus titration cells were infected with vaccinia virus and cell status, represented by the dimensionless impedance-based cell index (CI), was monitored. A virus-dose dependent decrease in electrical impedance could be shown. Calculation of calibration curves at a suitable CI covering a dynamic range of 4 log enabled the quantification of virus titers in unknown samples. Similarly, antiviral effects could be determined as shown for anti-poxviral agents ST-246 and Cidofovir. Published values for the in vitro concentration that inhibited virus replication by 50% (IC50) could be confirmed while cytotoxicity in effective concentrations was excluded in long-term incubation experiments. Finally, an RT-CES-based virus neutralization test was established. Various poxvirus-specific antibodies were examined for their neutralizing activity and a calculation mode for the neutralizing antibody titer was introduced. In summary, the presented RT-CES-based methods outmatch end-point assays by observing the cell population throughout the entire experiment while workload and time to result are reduced.

  2. Cellular impedance measurement as a new tool for poxvirus titration, antibody neutralization testing and evaluation of antiviral substances

    Energy Technology Data Exchange (ETDEWEB)

    Witkowski, Peter T. [Robert Koch-Institut, Zentrum fuer Biologische Sicherheit 1, Nordufer 20, 13353 Berlin (Germany); Charite Universitaetsmedizin, CCM, Institut fuer Virologie, Helmut Ruska Haus, Chariteplatz 1, 10117 Berlin (Germany); Schuenadel, Livia, E-mail: SchuenadelL@rki.de [FU-Berlin, Fachbereich Biologie, Chemie, Pharmazie, Takustrasse 3, 14195 Berlin (Germany); Robert Koch-Institut, Zentrum fuer Biologische Sicherheit 1, Nordufer 20, 13353 Berlin (Germany); Wiethaus, Julia; Bourquain, Daniel R.; Kurth, Andreas; Nitsche, Andreas [Robert Koch-Institut, Zentrum fuer Biologische Sicherheit 1, Nordufer 20, 13353 Berlin (Germany)

    2010-10-08

    Research highlights: {yields} Real-time data acquisition by RT-CES requires low operative effort. {yields} Time to result is reduced by using RT-CES instead of conventional methods. {yields} RT-CES enables quantification of virus titers in unknown samples. {yields} RT-CES is a useful tool for high-throughput characterization of antiviral agents. {yields} An RT-CES-based virus neutralization test was established. -- Abstract: Impedance-based biosensing known as real-time cell electronic sensing (RT-CES) belongs to an emerging technology for analyzing the status of cells in vitro. In the present study protocols were developed for an RT-CES-based system (xCELLigence{sup TM}, Roche Applied Science, ACEA Biosciences Inc.) to supplement conventional techniques in pox virology. First, proliferation of cells susceptible to orthopoxviruses was monitored. For virus titration cells were infected with vaccinia virus and cell status, represented by the dimensionless impedance-based cell index (CI), was monitored. A virus-dose dependent decrease in electrical impedance could be shown. Calculation of calibration curves at a suitable CI covering a dynamic range of 4 log enabled the quantification of virus titers in unknown samples. Similarly, antiviral effects could be determined as shown for anti-poxviral agents ST-246 and Cidofovir. Published values for the in vitro concentration that inhibited virus replication by 50% (IC{sub 50}) could be confirmed while cytotoxicity in effective concentrations was excluded in long-term incubation experiments. Finally, an RT-CES-based virus neutralization test was established. Various poxvirus-specific antibodies were examined for their neutralizing activity and a calculation mode for the neutralizing antibody titer was introduced. In summary, the presented RT-CES-based methods outmatch end-point assays by observing the cell population throughout the entire experiment while workload and time to result are reduced.

  3. Temporal surrogates of spatial turbulent statistics the Taylor hypothesis revisted

    CERN Document Server

    Lvov, V S; Procaccia, I; L'vov, Victor S.; Pomyalov, Anna; Procaccia, Itamar

    1999-01-01

    The Taylor hypothesis which allows surrogating spatial measurements requiring many experimental probes by time series from one or two probes is examined on the basis of a simple analytic model of turbulent statistics. The main points are as follows: (i) The Taylor hypothesis introduces systematic errors in the evaluation of scaling exponents. (ii) When the mean wind $\\bar{V}_0$ is not infinitely larger than the root-mean-square longitudinal turbulent fluctuations $v_T$, the effective Taylor advection velocity $V_{ad}$ should take the latter into account. (iii) When two or more probes are employed the application of the Taylor hypothesis and the optimal choice of the effective advecting wind $V_{ad}$ need extra care. We present practical considerations for minimizing the errors incurred in experiments using one or two probes. (iv) Analysis of the Taylor hypothesis when different probes experience different mean winds is offered.

  4. Neutron-induced cross sections of short-lived nuclei via the surrogate reaction method

    International Nuclear Information System (INIS)

    The measurement of neutron-induced cross sections of short-lived nuclei is extremely difficult due to the radioactivity of the samples. The surrogate reaction method is an indirect way of determining cross sections for nuclear reactions that proceed through a compound nucleus. This method presents the advantage that the target material can be stable or less radioactive than the material required for a neutron-induced measurement. In this work, we investigate whether this technique can be used to determine neutron-induced capture cross sections in the rare-earth region. We have performed an experiment to study the validity of the surrogate method for extracting neutron-induced capture cross sections. We have used the well known 175Lu(n,γ) and 172Yb(n,γ) cross sections to study the 174Yb(3He,p)176Lu and 174Yb (3He,4He)173Yb surrogate reactions. Our experimental results indicate that the angular momentum populated in the transfer reactions used is significantly higher than the one populated in neutron-induced reactions. These differences explain the big discrepancies observed between the surrogate capture measurements and the neutron-induced data. At low excitation energy, the compound elastic (n,n) decay channel is predominant and has the particularity to be extremely sensitive to the spin and the parity of the decaying nucleus. Our experimental data clearly reflect that this decay channel is not accessible in the transfer reactions we have considered. This study is extremely important in view of the application of the surrogate method to infer capture cross sections of actinides

  5. INTEC SBW Solid Sludge Surrogate Recipe and Validation

    International Nuclear Information System (INIS)

    A nonhazardous INTEC tank farm sludge surrogate that incorporated metathesis reactions to generate solids from solutions of known elements present in the radioactive INTEC tank farm sodium-bearing waste sludges was formulated. Elemental analyses, physical property analyses, and filtration testing were performed on waste surrogate and tank farm waste samples, and the results were compared. For testing physical systems associated with moving the tank farm solids, the surrogate described in this report is the best currently available choice. No other available surrogate exhibits the noted similarities in behavior to the sludges. The chemical morphology, particle size distribution, and settling and flow characteristics of the surrogate were similar to those exhibited by the waste sludges. Nonetheless, there is a difference in chemical makeup of the surrogate and the tank farm waste. If a chemical treatment process were to be evaluated for final treatment and disposition of the waste sludges, the surrogate synthesis process would likely require modification to yield a surrogate with a closer matching chemical composition

  6. INTEC SBW Solid Sludge Surrogate Recipe and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Maio, Vince; Janikowski, Stuart; Johnson, Jim; Maio, Vince; Pao, Jenn-Hai

    2004-06-01

    A nonhazardous INTEC tank farm sludge surrogate that incorporated metathesis reactions to generate solids from solutions of known elements present in the radioactive INTEC tank farm sodium-bearing waste sludges was formulated. Elemental analyses, physical property analyses, and filtration testing were performed on waste surrogate and tank farm waste samples, and the results were compared. For testing physical systems associated with moving the tank farm solids, the surrogate described in this report is the best currently available choice. No other available surrogate exhibits the noted similarities in behavior to the sludges. The chemical morphology, particle size distribution, and settling and flow characteristics of the surrogate were similar to those exhibited by the waste sludges. Nonetheless, there is a difference in chemical makeup of the surrogate and the tank farm waste. If a chemical treatment process were to be evaluated for final treatment and disposition of the waste sludges, the surrogate synthesis process would likely require modification to yield a surrogate with a closer matching chemical composition.

  7. Surrogate Modeling for Geometry Optimization in Material Design

    DEFF Research Database (Denmark)

    Rojas Larrazabal, Marielba de la Caridad; Abraham, Yonas B.; Holzwarth, Natalie A.W.; Plemmons, Robert J.

    2007-01-01

    We propose a new approach based on surrogate modeling for geometry optimization in material design. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)......We propose a new approach based on surrogate modeling for geometry optimization in material design. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)...

  8. Determining neutron-capture cross sections via the surrogate reaction technique

    CERN Document Server

    Forssén, C; Escher, J; Hoffman, R D; Kelley, K

    2007-01-01

    Indirect methods play an important role in the determination of nuclear reaction cross sections that are hard to measure directly. In this paper we investigate the feasibility of using the so-called surrogate method to extract neutron-capture cross sections for low energy compound-nuclear reactions in spherical and near-spherical nuclei. We present the surrogate method and develop a statistical nuclear-reaction simulation to explore different approaches to utilize surrogate reaction data. We assess the success of each approach by comparing the extracted cross sections with a predetermined benchmark. In particular, we employ regional systematics of nuclear properties in the 34 <= Z <= 46 region to calculate (n,gamma) cross sections for a series of Zr isotopes, and to simulate a surrogate experiment and the extraction of the desired cross section. We identify one particular approach that may provide very useful estimates of the cross section, and we discuss some of the limitations of the method. General r...

  9. A case study on the use of appropriate surrogates for antecedent moisture conditions (AMCs

    Directory of Open Access Journals (Sweden)

    G. A. Ali

    2010-06-01

    Full Text Available While a large number of non-linear hillslope and catchment rainfall-runoff responses have been attributed to the temporal variability in antecedent moisture conditions (AMCs, two problems emerge: 1 the difficulty of measuring AMCs, and 2 the absence of explicit guidelines for the choice of surrogates or proxies for AMCs. This paper aims at determining whether or not multiple surrogates for AMCs should be used in order not to bias our understanding of a system hydrological behaviour. We worked in a small forested catchment, the Hermine, where soil moisture has been measured at 121 different locations at four depths on 16 occasions. Without making any assumption on active processes, we used various linear and nonlinear regression models to evaluate the point-scale temporal relations between actual soil moisture contents and selected meteorological-based surrogates for AMCs. We then mapped the nature of the "best fit" model to identify 1 spatial clusters of soil moisture monitoring sites whose hydrological behaviour was similar, and 2 potential topographic influences on these behaviours. Two conclusions stood out. Firstly, it was shown that the sole reference to AMCs indices traditionally used in catchment hydrology, namely antecedent rainfall amounts summed over periods of seven or ten days, would have led to an incomplete understanding of the Hermine catchment dynamics. Secondly, the relationships between point-scale soil moisture content and surrogates for AMCs were not spatially homogeneous, thus revealing a mosaic of linear and nonlinear catchment "active" and "contributing" sources whose location was often controlled by surface terrain attributes or the topography of a soil-confining layer interface. These results represent a step forward in developing a hydrological conceptual model for the Hermine catchment as they indicate depth-specific processes and spatially-variable triggering conditions. Further investigations are, however, necessary

  10. Development of an RF-EMF Exposure Surrogate for Epidemiologic Research

    OpenAIRE

    Katharina Roser; Anna Schoeni; Alfred Bürgi; Martin Röösli

    2015-01-01

    Exposure assessment is a crucial part in studying potential effects of RF-EMF. Using data from the HERMES study on adolescents, we developed an integrative exposure surrogate combining near-field and far-field RF-EMF exposure in a single brain and whole-body exposure measure. Contributions from far-field sources were modelled by propagation modelling and multivariable regression modelling using personal measurements. Contributions from near-field sources were assessed from both, questionnaire...

  11. Evaluation of the double antibody - solid phase radioimmunoassay technique in plasma LH and FSH and urinary LH measurements

    International Nuclear Information System (INIS)

    Double antibody phase (DASP) radioimmunoassay methods for plasma LH and FSH and urinary LH were developed and carefully evaluated as to their reliability and practicability. The peptide hormones were iodinated enzymatically with immobilized lactoperoxidase which resulted in pure and stable products of unchanged immunoreactivity. The sensitivities of these assay methods are 0.02, 0.17 and 0.20 mlU/tube for plasma LH (MRC 68/40) and FSH (MRC 68/39) and urinary LH (IRP-HMG, urinary), respectively. Interassay coefficients of variation obtained over a 6-18 month period were 14.2, 14.7 and 12.8%, respectively. The latter values for plasma LH and FSH assays were obtained from one level pool samples, and the value for urinary LH is the mean of those obtained from two pools of different levels. Plasma reference values for LH and FSH obtained using these methods are about 1.8-2.9 times higher than those cited for other types of radioimmunoassay. However, the values obtained for LH in urine are similar to those reported in the literature. It is suggested that the DASP technique is less influenced by interference from plasma proteins and because of this gives plasma values closer to the true ones. It is concluded that the methods are well suited for use as routine clinical assays in laboratories with a high work load. (Auth.)

  12. Development of a simple method for the immobilization of anti-thyroxine antibody on polystyrene tubes for use in the measurement of total thyroxine in serum

    International Nuclear Information System (INIS)

    We describe a simple method for the immobilisation of anti-thyroxine antibody on to the surface of polystyrene tubes and a simple assay format for the quantitative estimation of total thyroxine in serum. The immobilisation of anti-thyroxine antibody was achieved through passive adsorption of normal rabbit gamma globulin and anti-rabbit antibody raised in goat, as immune bridges. This procedure ensured minimum utilisation of primary and secondary antibody as neat sera without precipitation or affinity purification. The developed assay system using these antibody coated tubes covers a range of 0-240 ng/mL of thyroxine with intra and inter assay variations of less than 10 %. (author)

  13. A simple nonradioactive method for the determination of the binding affinities of antibodies induced by hapten bioconjugates for drugs of abuse.

    Science.gov (United States)

    Torres, Oscar B; Antoline, Joshua F G; Li, Fuying; Jalah, Rashmi; Jacobson, Arthur E; Rice, Kenner C; Alving, Carl R; Matyas, Gary R

    2016-02-01

    The accurate analytical measurement of binding affinities of polyclonal antibody in sera to heroin, 6-acetylmorphine (6-AM), and morphine has been a challenging task. A simple nonradioactive method that uses deuterium-labeled drug tracers and equilibrium dialysis (ED) combined with ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) to measure the apparent dissociation constant (K d) of antibodies to 6-AM and morphine is described. The method can readily detect antibodies with K d in the low nanomolar range. Since heroin is rapidly degraded in sera, esterase inhibitors were included in the assay, greatly reducing heroin hydrolysis. MS/MS detection directly measured the heroin in the assay after overnight ED, thereby allowing the quantitation of % bound heroin in lieu of K d as an alternative measurement to assess heroin binding to polyclonal antibody sera. This is the first report that utilizes a solution-based assay to quantify heroin-antibody binding without being confounded by the presence of 6-AM and morphine and to measure K d of polyclonal antibody to 6-AM. Hapten surrogates 6-AcMorHap, 6-PrOxyHap, MorHap, DiAmHap, and DiPrOxyHap coupled to tetanus toxoid (TT) were used to generate high affinity antibodies to heroin, 6-AM, and morphine. In comparison to competition ED-UPLC/MS/MS which gave K d values in the nanomolar range, the commonly used competition enzyme-linked immunosorbent assay (ELISA) measured the 50% inhibition concentration (IC50) values in the micromolar range. Despite the differences in K d and IC50 values, similar trends in affinities of hapten antibodies to heroin, 6-AM, and morphine were observed by both methods. Competition ED-UPLC/MS/MS revealed that among the five TT-hapten bioconjugates, TT-6-AcMorHap and TT-6-PrOxyHap induced antibodies that bound heroin, 6-AM, and morphine. In contrast, TT-MorHap induced antibodies that poorly bound heroin, while TT-DiAmHap and TT-DiPrOxyHap induced antibodies either did not

  14. Likelihood smoothing using gravitational wave surrogate models

    CERN Document Server

    Cole, Robert H

    2014-01-01

    Likelihood surfaces in the parameter space of gravitational wave signals can contain many secondary maxima, which can prevent search algorithms from finding the global peak and correctly mapping the distribution. Traditional schemes to mitigate this problem maintain the number of secondary maxima and thus retain the possibility that the global maximum will remain undiscovered. By contrast, the recently proposed technique of likelihood transform can modify the structure of the likelihood surface to reduce its complexity. We present a practical method to carry out a likelihood transform using a Gaussian smoothing kernel, utilising gravitational wave surrogate models to perform the smoothing operation analytically. We demonstrate the approach with Newtonian and post-Newtonian waveform models for an inspiralling circular compact binary.

  15. Surrogate Motherhood: A Trust-Based Approach.

    Science.gov (United States)

    Beier, Katharina

    2015-12-01

    Because it is often argued that surrogacy should not be treated as contractual, the question arises in which terms this practice might then be couched. In this article, I argue that a phenomenology of surrogacy centering on the notion of trust provides a description that is illuminating from the moral point of view. My thesis is that surrogacy establishes a complex and extended reproductive unit--the "surrogacy triad" consisting of the surrogate mother, the child, and the intending parents--whose constituents are bound together by mutual trustful commitments. Even though a trust-based approach does not provide an ultimate answer to whether surrogacy should be sanctioned or prohibited, it allows for at least some practical suggestions. In particular, I will argue that, under certain conditions, surrogacy is tenable within familial or other significant relationships, and I will stress the necessity of acknowledging the new relationships and moral commitments that result from this practice. PMID:26449234

  16. Tractable Experiment Design via Mathematical Surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Brian J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-29

    This presentation summarizes the development and implementation of quantitative design criteria motivated by targeted inference objectives for identifying new, potentially expensive computational or physical experiments. The first application is concerned with estimating features of quantities of interest arising from complex computational models, such as quantiles or failure probabilities. A sequential strategy is proposed for iterative refinement of the importance distributions used to efficiently sample the uncertain inputs to the computational model. In the second application, effective use of mathematical surrogates is investigated to help alleviate the analytical and numerical intractability often associated with Bayesian experiment design. This approach allows for the incorporation of prior information into the design process without the need for gross simplification of the design criterion. Illustrative examples of both design problems will be presented as an argument for the relevance of these research problems.

  17. Multi-Surrogate Modeling for Computational Cost Reduction

    International Nuclear Information System (INIS)

    To utilize high-fidelity simulation for computationally intensive engineering applications such as sensitivity analysis and uncertainty quantification, the surrogate modeling techniques have become an indispensable tool and have been widely used. However, for reactor physics problems that can be characterized as very large number of input parameters (i.e. reaction cross sections), the required computational cost to build a surrogate model itself would be impractical with the sole conventional surrogate modeling techniques. We have been exploring the efficient way of reducing the computational cost in surrogate modeling and contributed the surrogate approach incorporated with reduced order modeling techniques. Basic approach summarized in Ref. is to transform the input parameters into low dimension by hybridizing two prominent methods - variational methods and sampling methods. As a preprocessing for the surrogate modeling, the influential subspace of the input parameters with respect to response change is extracted by range finding algorithm and the input parameters are projected onto that subspace. Because the number of subspace basis vectors are much smaller than the number of input parameters, reduced order form of the surrogate model can be constructed, which means that the number of unknowns to be determined in the surrogate modeling is reduced and, opposed to the curse of dimensionality, one can save significant computational cost to generate the training sample set. This study is the extension of the previous method for further cost reduction. In Ref., the input parameter transformation and the surrogate modeling are conducted independently. By doing that, one can estimate the error due to input parameter transformation and the surrogate modeling, separately and theoretically one can eliminate the error due to input parameter transformation within the machine precision. However, in practice, the input parameter variations, which may be considered significant

  18. An evaluation of culture results during treatment for tuberculosis as surrogate endpoints for treatment failure and relapse.

    Directory of Open Access Journals (Sweden)

    Patrick P J Phillips

    Full Text Available It is widely acknowledged that new regimens are urgently needed for the treatment of tuberculosis. The primary endpoint in the Phase III trials is a composite outcome of failure at the end of treatment or relapse after stopping treatment. Such trials are usually both long and expensive. Valid surrogate endpoints measured during or at the end of treatment could dramatically reduce both the time and cost of assessing the effectiveness of new regimens. The objective of this study was to evaluate sputum culture results on solid media during treatment as surrogate endpoints for poor outcome. Data were obtained from twelve randomised controlled trials conducted by the British Medical Research Council in the 1970s and 80s in East Africa and East Asia, consisting of 6974 participants and 49 different treatment regimens. The month two culture result was shown to be a poor surrogate in East Africa but a good surrogate in Hong Kong. In contrast, the month three culture was a good surrogate in trials conducted in East Africa but not in Hong Kong. As well as differences in location, ethnicity and probable strain of Mycobacteria tuberculosis, Hong Kong trials more often evaluated regimens with rifampicin throughout and intermittent regimens, and patients in East African trials more often presented with extensive cavitation and were slower to convert to culture negative during treatment. An endpoint that is a summary measure of the longitudinal profile of culture results over time or that is able to detect the presence of M. tuberculosis later in treatment is more likely to be a better endpoint for a phase II trial than a culture result at a single time point and may prove to be an acceptable surrogate. More data are needed before any endpoint can be used as a surrogate in a confirmatory phase III trial.

  19. Determination of the 241Pu(n,f) reaction cross sections by surrogate ratio method

    International Nuclear Information System (INIS)

    In a recent work, direct measurement of neutron induced fission cross section of 241Pu(T1/2 = 14.1 yrs), has been carried out using neutron time of flight. Differences between the reported experimental measurement and evaluation by standard libraries exceeds by 30%, thus it is suggested to carry out further confirmatory measurements on 241Pu(n,f) cross sections. In this paper, we report the use of 238U(6Li,d)242Pu and 232Th(6Li,d)236U transfer reactions as surrogate of 241Pu(n,f) and 235U(n,f) compound nuclear reactions respectively. By employing the surrogate ratio method (SRM) and taking 235U(n,f) as reference, the 241Pu(n,f) cross sections have been determined in the equivalent neutron energy range of 11.0 MeV-16.0 MeV

  20. Measurement of Levels of Ebstein-Barr Virus Antibodies in Patients with Hodgkins Lymphoma and Comparison with Normal Population

    Directory of Open Access Journals (Sweden)

    M Mortazavi-zadeh

    2004-07-01

    Full Text Available Introduction: Hodgkins lymphoma is a unique malignancy with unknown etiology .Curability and prognosis of Hodgkin,s disease (HD depends on quickly early diagnosis .One of hypothesis proposed for the cause of this disease is Epstein- Barr virus infection and its activity in HD patients . Material and Methods:This case- control study was performed to determine the type and titers of antibodies against EBV capsid Antigens (Anti VCA IgM & IgG in HD patients as compared to the general population and its relation to age , sex , and subtype of Hodgkin. Thus, a fifty- person group of Hodgkin disease patients as the case group and a fifty – person group from the general population with the same age and sex characteristics as the control group were studied. Result: There was no significant difference for mean titer of IgM between two age ranges in each group of case and control. Also, there was statistically no significant difference between case and control groups ( P.Value=0.558 .Most of the patients as well as non affected persons had negative IgM titers. Regarding IgG, there was statistically no significant difference between case and control groups for being either negative or positive, and most persons (92% of each group and were positive for IgG, but mean titer of IgG was 2.87 mmol/lit in case group and 1.50 mmol/lit in control group , and this difference between two groups was statistically significant (Pvalue = 0.0001 . Conclusion: High titer of Anti-VCA IgG in Hodgkin disease patients compared to general population as seen in this study can explain over activity of EBV in Hodgkin's disease patients and the probable role of EBV in establishment and/or activity of the disease.

  1. Analytical QbD: development of a native gel electrophoresis method for measurement of monoclonal antibody aggregates.

    Science.gov (United States)

    Pathak, Mili; Dutta, Debayon; Rathore, Anurag

    2014-08-01

    This paper presents a quality by design (QbD) based development of a novel native PAGE (N-PAGE) method as a low-cost analytical tool for analysis of aggregates of monoclonal antibodies. Comparability to the present gold standard of SEC has been established. The motivation is the fact that SEC requires relatively expensive equipment and consumables, thus making N-PAGE relevant to those academicians and other small companies involved in early-stage development of biotherapeutics that do not have access to SEC, especially in developing countries. Furthermore, SEC suffers from certain disadvantages including the possibility of secondary interactions between the stationary phase and analyte resulting in higher elution time and therefore underestimation of the analyte size. The proposed N-PAGE method can also serve as an orthogonal analytical method for aggregate analysis. A QbD-based approach has been used for development and optimization of the protocol. First, initial screening studies were carried out with parameters including the running buffer pH, running buffer molarity, gel buffer pH, loading dye, sample concentration, and running voltage. Next, optimization of operating parameters was performed using principles of design of experiments. The final optimized protocol was compared to the traditional SEC method and the results were found to be comparable. While N-PAGE has been in use for protein analysis for several decades, use of N-PAGE for analysis of mAb aggregates with data comparable to SEC such as the case presented here is novel. PMID:24643784

  2. A double antibody radioimmunoassay for measurement of IgG, IgA and IgM synthesized by human lymphocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Asano,Taro

    1981-11-01

    Full Text Available To investigate cellular interactions between human T and B lymphocytes in various diseases, we established a technique to prove terminal differentiation of B lymphocytes into immunoglobulin synthesizing and secreting cells. We also established a double antibody radioimmunoassay to measure the amount of IgG, IgA and IgM synthesized and secreted in culture supernatants. Purified immunoglobulins were obtained from sera of patients with myeloma or macroglobulinemia. The peripheral blood lymphocytes from 25 normal individuals had the geometric mean synthetic rates of 1886 ng for IgG, 1607 ng for IgA and 1173 ng for IgM per 1 X 10(6 cells when cultured for nine days in the presence of pokeweed mitogen. The method is simple and sensitive, and is thought to be useful for examining human lymphocyte function in vitro.

  3. A Bayesian approach to estimate the accuracy of "in-house" ELISA assay to measure rabies antibodies from compulsory vaccinated dogs and cattle

    Directory of Open Access Journals (Sweden)

    AHC Nogueira

    2009-01-01

    Full Text Available Rabies is a vaccine-preventable disease that causes acute encephalitis in mammals, and it is still a significant public health problem in numerous countries. Infected dogs represent the main vectors involved in human rabies. Additionally, cattle rearing close to geographic areas where vampire bats are found presents an important connection with rural epidemiology. We applied two "in-house" enzyme-linked immunosorbent assay (ELISA methodologies, considered alternatives to measure antibodies from vaccinated dogs and cattle, without employing the gold standard approach. The ELISA assays were performed on individual serum samples taken from domestic adult dogs and cows compulsory vaccinated against rabies (147 urban dogs and 64 cows; n = 211. The sandwich and liquid-phase competitive ELISA (scELISA and lpcELISA, considered "in-house" assays, were performed according to previous works. The only statistical methodology that allows this study is the Bayesian approach, developed to replace the conventional Hui-Walter paradigm. For conditional independent Bayesian model (one population, two tests and no gold standard the prior information for sensitivity and specificity of each test, mode, prevalence and transformed (á, â were submitted to Bayesian inference. The "in-house" lpcELISA revealed 16 - out of 261 serum samples - negative results, whereas in scELISA all results were positive. The Bayesian approach showed that prior information was specified for all parameters; posterior medians were Se scELISA 89%, Sp scELISA 88%, Sp lpcELISA 95% Se lpcELISA 98%, and prevalence (pi of 99%, without the use of gold standard analysis to measure specific anti-rabies antibodies.

  4. Results from Oritavancin Resistance Surveillance Programs (2011 to 2014): Clarification for Using Vancomycin as a Surrogate To Infer Oritavancin Susceptibility.

    Science.gov (United States)

    Jones, Ronald N; Moeck, Greg; Arhin, Francis F; Dudley, Michael N; Rhomberg, Paul R; Mendes, Rodrigo E

    2016-05-01

    Measurement of vancomycin susceptibility has been shown to be highly predictive as a surrogate measure of oritavancin susceptibility among clinically indicated Gram-positive species. Results of studying over 30,000 pathogens (from 2011 to 2014) by cross-susceptibility analysis and determining the poor reproducibility of oritavancin-nonsusceptible results showed nearly perfect surrogate testing accuracy (99.86 to 99.94%). Any isolate of an indicated organism species with locally reproducible oritavancin-nonsusceptible results (extremely rare) should be referred to a reference laboratory for confirmation of the results and determination of the resistance mechanism. PMID:26926647

  5. Effect of pH on the Electrophoretic Mobility of Spores of Bacillus anthracis and Its Surrogates in Aqueous Solutions

    Science.gov (United States)

    Electrophoretic mobility (EPM) of endospores of Bacillus anthracis and surrogates were measured in aqueous solution across a broad pH range and several ionic strengths. EPM values trended around phylogenetic clustering based on the 16S rRNA gene. Measurements reported here prov...

  6. Intermediate markers as surrogate endpoints in cancer research.

    Science.gov (United States)

    Schatzkin, A

    2000-08-01

    Because studies with surrogate cancer endpoints can be smaller, faster, and substantially less expensive than those with frank cancer outcomes, the use of surrogate endpoints is undeniably attractive. This attractiveness is likely to grow in coming years as the rapidly advancing discoveries in cell and molecular biology generate new therapies requiring testing and new markers that could plausibly serve as surrogates for cancer. Surrogate endpoint studies can certainly be suggestive. They continue to play a legitimate role in phase II studies, and they may give the right answers about intervention effects on or exposure associations with cancer. The problem is the uncertainty attached to most potential surrogates. Except for those few surrogates that are both necessary for and developmentally relatively close to cancer, the existence of plausible alternative pathways makes inferences about cancer from many surrogates problematic. Merely being on the causal pathway to cancer does not in itself constitute surrogate validity. It is the totality of causal connections that is critical. There is, unfortunately, a fairly extensive history of quite plausible surrogate markers giving the wrong answer about various chronic disease therapies. There is no reason to believe that cancer surrogacy is immune to such inferential difficulties. This article is, in part, an invitation, even a plea, for researchers to carry out the investigations necessary to evaluate potential surrogates, particularly surrogate-cancer studies and intervention or exposure-surrogate-cancer mediation analyses. Such studies are needed to generalize from surrogate endpoint findings to cancer. There is, however, an implicit and perhaps unavoidable irony here: the large, long, expensive studies required to evaluate potential surrogates fully are precisely the studies that surrogates were designed to replace. The exposure dependence alluded to earlier complicates matters further: establishing validity for a

  7. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-06-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

  8. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-01-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

  9. 89 Zr(n, γ) from a surrogate reaction approach

    Science.gov (United States)

    Ota, Shuya; Burke, J. T.; Casperson, R. J.; Escher, J. E.; Hughes, R. O.; Ressler, J. J.; Scielzo, N. D.; Thompson, I.; Austin, R. A. E.; McCleskey, E.; McCleskey, M.; Saastamoinen, A.; Benstead, J.; Ross, T.

    2014-09-01

    While recent studies have demonstrated the validity of the surrogate reaction approach for studying fission cross sections of short-lived actinides, its applicability for (n, γ) is still under investigation. We studied the γ-decay of 90Zr produced by 91Zr(p,d) in order to infer the 89Zr(n, γ) cross sections. The experiments were carried out at the K150 Cyclotron facility at Texas A&M University with a 28.5-MeV proton beam. The reaction deuterons were measured at forward angles of 30-60° with the STARS (Silicon Telescope Array for Reaction Studies) array of three segmented Micron S2 silicon detectors. Compound nuclei with energies up to a few MeV above the neutron separation thresholds were populated. The coincident γ-rays were measured with the LiTeR (Livermore Texas Richmond) array of five Compton-suppressed HPGe clovers. We will present results of γ-emission probabilities of 89Zr(n, γ) and some theoretical discussions. While recent studies have demonstrated the validity of the surrogate reaction approach for studying fission cross sections of short-lived actinides, its applicability for (n, γ) is still under investigation. We studied the γ-decay of 90Zr produced by 91Zr(p,d) in order to infer the 89Zr(n, γ) cross sections. The experiments were carried out at the K150 Cyclotron facility at Texas A&M University with a 28.5-MeV proton beam. The reaction deuterons were measured at forward angles of 30-60° with the STARS (Silicon Telescope Array for Reaction Studies) array of three segmented Micron S2 silicon detectors. Compound nuclei with energies up to a few MeV above the neutron separation thresholds were populated. The coincident γ-rays were measured with the LiTeR (Livermore Texas Richmond) array of five Compton-suppressed HPGe clovers. We will present results of γ-emission probabilities of 89Zr(n, γ) and some theoretical discussions. This work was performed under the auspices of the US Department of Energy by Lawrence Livermore National Laboratory

  10. Validation of (n,gamma) surrogate methods and the 95Mo(n,gamma) reaction

    Science.gov (United States)

    Cizewski, J. A.; Adekola, A. S.; Howard, M. E.; Manning, B.; Ratkiewicz, A.; Couture, A. J.; Devlin, M.; Fotiades, N.; Nelson, R. O.; O'Donnell, J. M.; Peters, W. A.; Burke, J. T.; Escher, J. E.; Hatarik, R.; Scielzo, N. D.

    2012-10-01

    Neutron capture on unstable isotopes is important for the synthesis of heavy elements through both the r and s processes and so for nuclear energy and stockpile stewardship science. However, it is difficult to measure these cross sections directly with neutrons on targets that live less than about 100 days. Therefore, there has been a concerted effort by many groups [J.E. Escher RMP 84, 353 (2012) and references therein] to develop a validated surrogate reaction for neutron capture, a reaction that predominantly occurs at relatively low neutron energies where the angular momentum dependence needs to be taken into account. Many of the surrogate approaches use partial cross sections of discrete low-lying gamma-ray transitions to deduce the decay of the compound nucleus. Yet there have been very few measurements of the intensity of these discrete transitions in (n,g) as a function of neutron energy up to 200 keV. As part of the program to validate (d,pg) as a surrogate for neutron capture, we have recently measured the intensity of yrast transitions in 96Mo populated by the 95Mo(n,g) reaction with a small array of HPGe detectors on FP12 at the Lujan Center of LANSCE. Preliminary results of these measurements and the status of the (d,pg) validation program with 95Mo targets will be presented.

  11. Experimental approaches to studying the fission process using the surrogate reaction technique

    International Nuclear Information System (INIS)

    Over the past several years, Lawrence Livermore National Laboratory has been developing the surrogate technique to study the properties of fission and perform precision cross section measurements. The surrogate technique allows nuclear physicists to measure previously unattainable compound-nuclear cross sections of nuclei currently one to two nucleons away from a stable or long lived (∼ 10,000 y) nucleus. The goal of the surrogate technique is to create the same excited compound nucleus as is produced in a specific desired direct neutron reaction, study the decay channels and extract the cross section of choice; (n,γ), (n,2n) or (n,f). This may be accomplished via an inelastic scattering reaction (e.g. (p,p'), (d,d'), (3He,3He')), a neutron transfer reaction (e.g. (d,p), (18O,16O)), or a pick-up reaction such as (3He,4He). To measure the decay channels (gamma-ray or fission) we have constructed the Silicon Telescope Array for Reactions Studies (STARS), the Livermore Berkeley Array for Collaborative Experiments (LIBERACE) and the HYDRA array for precision fission studies. Preliminary results from a recent 238Pu(n,f) measurement are presented. (authors)

  12. A response-modeling alternative to surrogate models for support in computational analyses

    International Nuclear Information System (INIS)

    Often, the objectives in a computational analysis involve characterization of system performance based on some function of the computed response. In general, this characterization includes (at least) an estimate or prediction for some performance measure and an estimate of the associated uncertainty. Surrogate models can be used to approximate the response in regions where simulations were not performed. For most surrogate modeling approaches, however (1) estimates are based on smoothing of available data and (2) uncertainty in the response is specified in a point-wise (in the input space) fashion. These aspects of the surrogate model construction might limit their capabilities. One alternative is to construct a probability measure, G(r), for the computer response, r, based on available data. This 'response-modeling' approach will permit probability estimation for an arbitrary event, E(r), based on the computer response. In this general setting, event probabilities can be computed: prob(E)=∫r I(E(r))dG(r) where I is the indicator function. Furthermore, one can use G(r) to calculate an induced distribution on a performance measure, pm. For prediction problems where the performance measure is a scalar, its distribution F pm is determined by: F pm(z)=∫r I(pm(r)≤z)dG(r). We introduce response models for scalar computer output and then generalize the approach to more complicated responses that utilize multiple response models

  13. Determination of the 234Pa(n, f) reaction cross section by hybrid surrogate ratio method

    International Nuclear Information System (INIS)

    In an earlier work, we employed a new hybrid surrogate ratio approach to determine the 233Pa(n, f) cross sections for the first time in the equivalent neutron energy range of 11.5 MeV to 16.5 MeV using 6Li + 232Th transfer-fission correlation measurements. The 234Pa isotope produced in thorium-uranium fuel cycle is having half-life of 6.8 hrs. There is no neutron induced fission cross section data available in the literature for this system. We report first time results on 243Pa(n, f) cross sections in the equivalent neutron energy range of 10.5 MeV to 15.5 MeV using 7Li + 232Th transfer-fission correlation measurements with in the framework of hybrid surrogate method

  14. Surrogate reactions: the Weisskopf-Ewing approximation and its limitations

    International Nuclear Information System (INIS)

    A brief description of the Surrogate reaction method, an indirect approach for determining compound-nuclear reaction cross sections, is presented. The Weisskopf-Ewing limit, an approximation scheme that is typically employed in the analysis of Surrogate experiments, is considered and its validity and limitations are discussed. Particularly the assumption in the surrogate-reaction process that the result of the initial direct reaction is a fully-equilibrated compound nucleus is not obviously correct and needs to be checked by appropriate calculations

  15. Surrogate markers of long-term outcome in primary total hip arthroplasty

    Science.gov (United States)

    Malak, T. T.; Broomfield, J. A. J.; Palmer, A. J. R.; Hopewell, S.; Carr, A.; Brown, C.; Prieto-Alhambra, D.

    2016-01-01

    Objectives High failure rates of metal-on-metal hip arthroplasty implants have highlighted the need for more careful introduction and monitoring of new implants and for the evaluation of the safety of medical devices. The National Joint Registry and other regulatory services are unable to detect failing implants at an early enough stage. We aimed to identify validated surrogate markers of long-term outcome in patients undergoing primary total hip arthroplasty (THA). Methods We conducted a systematic review of studies evaluating surrogate markers for predicting long-term outcome in primary THA. Long-term outcome was defined as revision rate of an implant at ten years according to National Institute of Health and Care Excellence guidelines. We conducted a search of Medline and Embase (OVID) databases. Separate search strategies were devised for the Cochrane database and Google Scholar. Each search was performed to include articles from the date of their inception to June 8, 2015. Results Our search strategy identified 1082 studies of which 115 studies were included for full article review. Following review, 17 articles were found that investigated surrogate markers of long-term outcome. These included one systematic review, one randomised control trial (RCT), one case control study and 13 case series. Validated surrogate markers included Radiostereometric Analysis (RSA) and Einzel-Bild-Röntgen-Analyse (EBRA), each measuring implant migration and wear. We identified five RSA studies (one systematic review and four case series) and four EBRA studies (one RCT and three case series). Patient Reported Outcome Measures (PROMs) at six months have been investigated but have not been validated against long-term outcomes. Conclusions This systematic review identified two validated surrogate markers of long-term primary THA outcome: RSA and EBRA, each measuring implant migration and wear. We recommend the consideration of RSA in the pre-market testing of new implants. EBRA can

  16. Monoclonal anti-acid-labile subunit oligopeptide antibodies and their use in a two-site immunoassay for ALS measurement in humans.

    Science.gov (United States)

    Stadler, S; Wu, Z; Dressendörfer, R A; Morrison, K M; Khare, A; Lee, P D; Strasburger, C J

    2001-06-01

    Quantification of the acid-labile subunit (ALS) has to date been restricted to immunoassays utilizing polyclonal antibodies. By immunization with N-terminal and C-terminal specific ALS oligopeptides, we generated monoclonal antibodies (mAbs) that target ALS-specific sequences outside the nonspecific leucine-rich repeats in the ALS molecule. For mAb selection, a special screening method was developed. Monoclonal antibody 5C9, which targets the N-terminus of ALS, is immobilized and the anti-ALS mAb 7H3, directed against the C-terminus, is biotinylated and used as tracer Ab. Due to the extreme pH-lability of ALS, changes in immunorecognition of ALS were investigated after acidification for protein unfolding in different pH ranges and in a time-dependent manner. It was determined that acidification of the serum samples to pH 2.7 for 30 min, followed by neutralization and dilution to 1:100 was the optimal acid-neutralization method. For standardization purposes, a serum pool derived from healthy volunteers was assigned the value 1 U/ml ALS. The sandwich assay has a working range with a linear dose-response curve in a log/log system between 0.005 and 10 U/ml. ALS levels in seven acromegalic patients ranged from 2.0 to 4.2 U/ml, and in 12 untreated growth hormone deficient patients from 0.036 to 0.986 U/ml (mean=0.45 U/ml). After 12 months of growth hormone therapy, ALS levels increased significantly to 1.18+/-0.45 U/ml (mean+/-SD; p<0.0006). The increase ranged from 0.48 to 1.4 U/ml. The change in ALS with growth hormone (GH) therapy correlated closer with the change in IGF-I (r=0.798, p=0.0057; Spearman rank correlation) than with the change in insulin-like growth factor binding protein (IGFBP3; r=0.549, p=0.057). This specific sandwich assay for the measurement of ALS provides a potentially valuable indicator of growth hormone secretory status. With this mAb-based immunofluorometric assay, the nonspecific detection of other proteins containing leucine-rich repeat

  17. Validation of pulse rate variability as a surrogate for heart rate variability in chronically instrumented rabbits

    OpenAIRE

    Pellegrino, Peter R.; Schiller, Alicia M.; Zucker, Irving H.

    2014-01-01

    Heart rate variability (HRV) is a function of cardiac autonomic tone that is widely used in both clinical and animal studies. In preclinical studies, HRV measures are frequently derived using the arterial pulse waveform from an implanted pressure telemetry device, termed pulse rate variability (PRV), instead of the electrocardiogram signal in accordance with clinical guidelines. The acceptability of PRV as a surrogate for HRV in instrumented animals is unknown. Using rabbits implanted with in...

  18. Soleus Muscle as a Surrogate for Health Status in Human Heart Failure.

    Science.gov (United States)

    Green, Daniel J; Panizzolo, Fausto A; Lloyd, David G; Rubenson, Jonas; Maiorana, Andrew J

    2016-01-01

    We propose the hypothesis that soleus muscle function may provide a surrogate measure of functional capacity in patients with heart failure. We summarize literature pertaining to skeletal muscle as a locus of fatigue and present our recent findings, using in vivo imaging in combination with biomechanical experimentation and modeling, to reveal novel structure-function relationships in chronic heart failure skeletal muscle and gait. PMID:26509482

  19. Is House-Dust Nicotine a Good Surrogate for Household Smoking?

    OpenAIRE

    WHITEHEAD, TODD; Metayer, Catherine; Ward, Mary H; Nishioka, Marcia G.; Gunier, Robert; Colt, Joanne S.; Reynolds, Peggy; Selvin, Steve; Buffler, Patricia; Rappaport, Stephen M.

    2009-01-01

    The literature is inconsistent regarding associations between parental smoking and childhood leukemia, possibly because previous studies used self-reported smoking habits as surrogates for children's true exposures to cigarette smoke. Here, the authors investigated the use of nicotine concentrations in house dust as measures of children's exposure to cigarette smoke in 469 households from the Northern California Childhood Leukemia Study (1999–2007). House dust was collected by using high-volu...

  20. Cell diameter measurements obtained with a handheld cell counter could be used as a surrogate marker of G2/M arrest and apoptosis in colon cancer cell lines exposed to SN-38

    Energy Technology Data Exchange (ETDEWEB)

    Tahara, Makiko [Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Utsunomiya, Tochigi (Japan); Department of Gastrointestinal Surgery, Jichi Medical University, Shimotsuke, Tochigi (Japan); Inoue, Takeshi [Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Utsunomiya, Tochigi (Japan); Miyakura, Yasuyuki; Horie, Hisanaga; Yasuda, Yoshikazu [Department of Gastrointestinal Surgery, Jichi Medical University, Shimotsuke, Tochigi (Japan); Fujii, Hirofumi [Division of Clinical Oncology, Jichi Medical University, Shimotsuke, Tochigi (Japan); Kotake, Kenjiro [Department of Surgery, Tochigi Cancer Center, Utsunomiya, Tochigi (Japan); Sugano, Kokichi, E-mail: ksugano@tcc.pref.tochigi.lg.jp [Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Utsunomiya, Tochigi (Japan)

    2013-05-17

    Highlights: •Chemo-sensitivity to SN-38 was assayed by the automated cell counter. •Colon cancer cell line, HCT116 cells were more sensitive to SN-38 than HT29 cells. •Increase of cell size reflects G2/M arrest. •Appearance of small particles indicates cell apoptosis. -- Abstract: In vitro assessment of chemosensitivity are important for experiments evaluating cancer therapies. The Scepter 2.0 cell counter, an automated handheld device based on the Coulter principle of impedance-based particle detection, enables the accurate discrimination of cell populations according to cell size and volume. In this study, the effects of SN-38, the active metabolite of irinotecan, on the colon cancer cell lines HCT116 and HT29 were evaluated using this device. The cell count data obtained with the Scepter counter were compared with those obtained with the {sup 3}H-thymidine uptake assay, which has been used to measure cell proliferation in many previous studies. In addition, we examined whether the changes in the size distributions of these cells reflected alterations in the frequency of cell cycle arrest and/or apoptosis induced by SN-38 treatment. In our experiments using the Scepter 2.0 cell counter, the cell counts were demonstrated to be accurate and reproducible measure and alterations of cell diameter reflected G2/M cell cycle arrest and apoptosis. Our data show that easy-to-use cell counting tools can be utilized to evaluate the cell-killing effects of novel treatments on cancer cells in vitro.

  1. Cell diameter measurements obtained with a handheld cell counter could be used as a surrogate marker of G2/M arrest and apoptosis in colon cancer cell lines exposed to SN-38

    International Nuclear Information System (INIS)

    Highlights: •Chemo-sensitivity to SN-38 was assayed by the automated cell counter. •Colon cancer cell line, HCT116 cells were more sensitive to SN-38 than HT29 cells. •Increase of cell size reflects G2/M arrest. •Appearance of small particles indicates cell apoptosis. -- Abstract: In vitro assessment of chemosensitivity are important for experiments evaluating cancer therapies. The Scepter 2.0 cell counter, an automated handheld device based on the Coulter principle of impedance-based particle detection, enables the accurate discrimination of cell populations according to cell size and volume. In this study, the effects of SN-38, the active metabolite of irinotecan, on the colon cancer cell lines HCT116 and HT29 were evaluated using this device. The cell count data obtained with the Scepter counter were compared with those obtained with the 3H-thymidine uptake assay, which has been used to measure cell proliferation in many previous studies. In addition, we examined whether the changes in the size distributions of these cells reflected alterations in the frequency of cell cycle arrest and/or apoptosis induced by SN-38 treatment. In our experiments using the Scepter 2.0 cell counter, the cell counts were demonstrated to be accurate and reproducible measure and alterations of cell diameter reflected G2/M cell cycle arrest and apoptosis. Our data show that easy-to-use cell counting tools can be utilized to evaluate the cell-killing effects of novel treatments on cancer cells in vitro

  2. Monoclonal antibodies

    International Nuclear Information System (INIS)

    Monoclonal antibodies (MAbs) are antibodies having single specificity for a given antigen site (epitope). The development of hybridoma technology and the relative ease by which MAbs can be prepared has revolutionized many aspects of serological applications in diagnosis and differentiation of disease producing agents. The property of monospecificity offers advantages in diagnostic applications over polyclonal sera in that tests can be defined exactly with regard to the antigen detected and the affinity of reaction between the given antigenic site and the monoclonal reagent. In addition, MAbs offer better possibilities for test standardization, because the same reagent can be used in different laboratories. Such an MAb can be supplied by a central laboratory or 'grown' from hybridoma cells, ensuring that the resultant product is identical from laboratory to laboratory and that the part of the test involving the MAb reaction is the same. The methodologies for inoculation regimes, mice, cloning methods, selection of fusion partners, etc., have been validated extensively in developed country laboratories. The decision to establish a MAb production facility must be examined on a strict cost-benefit basis, since it is still expensive to produce a product. There are many MAbs available that should be sought to allow exploitation in developing tests. If a production facility is envisaged, it should produce reagents for national needs, i.e. there should be a clear problem oriented approach whereby exact needs are defined. In the field of veterinary applications, MAbs are the central reagent in many immunoassays based on the enzyme linked immunosorbent assay (ELISA). The development of specific tests for diagnosing diseases is dominated by MAbs and has been fuelled by a strong research base, mainly in developed countries allied to developing countries through the study of related diseases. Thus, there are very many assays dependent on MAbs, some of which form the basis of

  3. SURROGATE MOTHER DALAM PERSPEKTIF HUKUM PIDANA INDONESIA

    Directory of Open Access Journals (Sweden)

    Mr. Muntaha

    2013-04-01

    Full Text Available The development of science and technology, in particular in the field of health, has already recently brought a huge advantage and problem in human life. An example of technological marvel that not only requires deep legal thoughts but also at the same time solution is the bio-medical technology advancement of surrogacy. Surrogacy deals with human’s inclination towards reproductive activity. However, it opens up legal complication, in particular with regards to the potential commission of a criminal action as well as to the notion of doctor’s liability. Perkembangan ilmu dan teknologi di bidang kesehatan yang semakin maju dan pesat telah membawa berbagai manfaat dan masalah dalam kehidupan manusia dewasa ini. Salah satu perkembangan yang tidak hanya membutuhkan pemikiran di bidang hukum, tetapi juga sekaligus solusinya adalah mengenai kecanggihan teknologi bio-medis surrogate mother. Surrogacy menyentuh sisi kemanusiaan seorang insan terhadap reproduksi. Akan tetapi, lembaga surrogacy juga membawa komplikasi hukum terutama terkait dengan potensi tindak pidana dan dengan persoalan tanggung jawab dokter.

  4. Benchmarking the x-ray phase contrast imaging for ICF DT ice characterization using roughened surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Dewald, E; Kozioziemski, B; Moody, J; Koch, J; Mapoles, E; Montesanti, R; Youngblood, K; Letts, S; Nikroo, A; Sater, J; Atherton, J

    2008-06-26

    We use x-ray phase contrast imaging to characterize the inner surface roughness of DT ice layers in capsules planned for future ignition experiments. It is therefore important to quantify how well the x-ray data correlates with the actual ice roughness. We benchmarked the accuracy of our system using surrogates with fabricated roughness characterized with high precision standard techniques. Cylindrical artifacts with azimuthally uniform sinusoidal perturbations with 100 um period and 1 um amplitude demonstrated 0.02 um accuracy limited by the resolution of the imager and the source size of our phase contrast system. Spherical surrogates with random roughness close to that required for the DT ice for a successful ignition experiment were used to correlate the actual surface roughness to that obtained from the x-ray measurements. When comparing average power spectra of individual measurements, the accuracy mode number limits of the x-ray phase contrast system benchmarked against surface characterization performed by Atomic Force Microscopy are 60 and 90 for surrogates smoother and rougher than the required roughness for the ice. These agreement mode number limits are >100 when comparing matching individual measurements. We will discuss the implications for interpreting DT ice roughness data derived from phase-contrast x-ray imaging.

  5. Methodology for Formulating Diesel Surrogate Fuels with Accurate Compositional, Ignition-Quality, and Volatility Characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Charles J.; Cannella, William J.; Bruno, Thomas J.; Bunting, Bruce G.; Dettman, Heather; Franz, James A.; Huber, Marcia L.; Natarajan, Mani; Pitz, William J.; Ratcliff, Matthew A.; Wright, Ken

    2012-07-26

    In this study, a novel approach was developed to formulate surrogate fuels having characteristics that are representative of diesel fuels produced from real-world refinery streams. Because diesel fuels typically consist of hundreds of compounds, it is difficult to conclusively determine the effects of fuel composition on combustion properties. Surrogate fuels, being simpler representations of these practical fuels, are of interest because they can provide a better understanding of fundamental fuel-composition and property effects on combustion and emissions-formation processes in internal-combustion engines. In addition, the application of surrogate fuels in numerical simulations with accurate vaporization, mixing, and combustion models could revolutionize future engine designs by enabling computational optimization for evolving real fuels. Dependable computational design would not only improve engine function, it would do so at significant cost savings relative to current optimization strategies that rely on physical testing of hardware prototypes. The approach in this study utilized the stateof- the-art techniques of 13C and 1H nuclear magnetic resonance spectroscopy and the advanced distillation curve to characterize fuel composition and volatility, respectively. The ignition quality was quantified by the derived cetane number. Two wellcharacterized, ultra-low-sulfur #2 diesel reference fuels produced from refinery streams were used as target fuels: a 2007 emissions certification fuel and a Coordinating Research Council (CRC) Fuels for Advanced Combustion Engines (FACE) diesel fuel. A surrogate was created for each target fuel by blending eight pure compounds. The known carbon bond types within the pure compounds, as well as models for the ignition qualities and volatilities of their mixtures, were used in a multiproperty regression algorithm to determine optimal surrogate formulations. The predicted and measured surrogate-fuel properties were quantitatively

  6. SURROGATE SPECIES IN ASSESSING CONTAMINANT RISK FOR ENDANGERED FISHES

    Science.gov (United States)

    Rainbow trout, fathead minnows, and sheepshead minnows were tested as surrogate species to assess contaminant risk for 17 endangered fishes and one toad species. Acute toxicity tests were conducted with carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin in accord...

  7. Optimization using surrogate models - by the space mapping technique

    DEFF Research Database (Denmark)

    Søndergaard, Jacob

    2003-01-01

    conditions are satisfied. So hybrid methods, combining the space mapping technique with classical optimization methods, should be used if convergence to high accuracy is wanted. Approximation abilities of the space mapping surrogate are compared with those of a Taylor model of the expensive model. The space...... mapping surrogate has a lower approximation error for long steps. For short steps, however, the Taylor model of the expensive model is best, due to exact interpolation at the model origin. Five algorithms for space mapping optimization are presented and the numerical performance is evaluated. Three......Surrogate modelling and optimization techniques are intended for engineering design in the case where an expensive physical model is involved. This thesis provides a literature overview of the field of surrogate modelling and optimization. The space mapping technique is one such method...

  8. A new surrogate data method for nonstationary time series

    CERN Document Server

    Guarin, Diego; Delgado, Edilson

    2010-01-01

    Hypothesis testing based on surrogate data has emerged as a popular way to test the null hypothesis that a signal is a realization of a linear stochastic process. Typically, this is done by generating surrogates which are made to conform to autocorrelation (power spectra) and amplitude distribution of the data (this is not necessary if data are Gaussian). Recently, a new algorithm was proposed, the null hypothesis addressed by this algorithm is that data are a realization of a non stationary linear stochastic process, surrogates generated by this algorithm preserve the autocorrelation and local mean and variance of data. Unfortunately, the assumption of Gaussian amplitude distribution is not always valid. Here we propose a new algorithm; the hypothesis addressed by our algorithm is that data are a realization of a nonlinear static transformation of a non stationary linear stochastic process. Surrogates generated by our algorithm preserve the autocorrelation, amplitude distribution and local mean and variance ...

  9. Anticardiolipin antibodies in leptospirosis.

    OpenAIRE

    Rugman, F P; Pinn, G.; Palmer, M. F.; Waite, M.; Hay, C. R.

    1991-01-01

    The clinical course and serology of 16 cases of leptospirosis in an area with an unusually high endemic infection rate were studied to gain further insight into the pathology of the secondary immune phase that is typical of the disease. IgG anticardiolipin antibody concentrations were measured by immunoassay and found to be increased in eight serologically confirmed cases with severe complicated disease, compared with eight patients with relatively uncomplicated leptospirosis who had IgG anti...

  10. Mean Polyp per Patient Is an Accurate and Readily Obtainable Surrogate for Adenoma Detection Rate: Results from an Opportunistic Screening Colonoscopy Program

    OpenAIRE

    Delavari, Alireza; Salimzadeh, Hamideh; Bishehsari, Faraz; Sobh Rakhshankhah, Elham; Delavari, Farnaz; Moossavi, Shirin; Khosravi, Pejman; Nasseri-Moghaddam, Siavosh; Merat, Shahin; Ansari, Reza; Vahedi, Homayoon; Shahbazkhani, Bijan; Saberifiroozi, Mehdi; Sotoudeh, Masoud; Malekzadeh, Reza

    2015-01-01

    BACKGROUND The incidence of colorectal cancer is rising in several developing countries. In the absence of integrated endoscopy and pathology databases, adenoma detection rate (ADR), as a validated quality indicator of screening colonoscopy, is generally difficult to obtain in practice. We aimed to measure the correlation of polyp-related indicators with ADR in order to identify the most accurate surrogate(s) of ADR in routine practice. METHODS We retrospectively reviewed the endoscopic and h...

  11. Neutron-induced fission cross sections of short-lived actinides with the surrogate reaction method

    International Nuclear Information System (INIS)

    We present a review of the fission cross section measurements made by the CENBG collaboration over the last years using the surrogate reaction method. For example the neutron-induced fission cross sections of 233Pa (T1/2=27 d), 242Cm (T1/2=162.8 d) and 243Cm (T1/2=29.1 y) have been obtained by our group with this technique. The advantages and the difficulties of the surrogate method are discussed. Special attention is paid to the comparison between cross sections measured with the surrogate method and those obtained directly with neutrons at low energies. This comparison provides information on possible differences between the spin-parity distributions achieved in the two methods. We measured for the first time the fission cross section of 233Pa. Our results for 231Pa(n,f) revealed that the existing neutron-induced data overestimated the fission cross section above 1.5 MeV. The deduced 241Am(n,f) and 242Cm(n,f) cross sections agree with the available data obtained via neutron-induced reactions. The good agreement observed at the lowest neutron energies between the present results and the neutron-induced data for 242Cm(n,f) and 243Cm(n,f) indicates that the population of excited states generated by the transfer reactions used in this work is similar to the distribution fed in neutron induced reactions. This agreement illustrates the potential of the surrogate reaction method to provide neutron-induced fission cross sections for short-lived nuclei

  12. Human surrogate models of histaminergic and non-histaminergic itch

    DEFF Research Database (Denmark)

    Andersen, Hjalte Holm; Elberling, Jesper; Arendt-Nielsen, Lars

    2015-01-01

    Within the last decade understanding of the mechanistic basis of itch has improved significantly, resulting in the development of several human surrogate models of itch and related dysesthetic states. Well-characterized somatosensory models are useful in basic studies in healthy volunteers, in...... of chronic pruritus, and reliable human surrogate models are a valuable tool in achieving them, both for basic researchers and for clinicians....

  13. Surrogate Head Forms for the Evaluation of Head Injury Risk

    OpenAIRE

    MacAlister, Anna

    2013-01-01

    This paper summarizes the use of surrogate head forms in biomechanical research pertaining to head injury and, more specifically, mild traumatic brain injury. Because cadavers are limited and controlled studies of brain injury using live human subjects would be unethical, surrogate head forms are used to study the response of the human head to impact. Different head forms have been developed and optimized for different purposes. The Hybrid III 50th percentile male crash test dummy was develop...

  14. Emotional experiences in surrogate mothers: A qualitative study

    OpenAIRE

    Hoda Ahmari Tehran; Shohreh Tashi; Nahid Mehran; Narges Eskandari; Tahmineh Dadkhah Tehrani

    2014-01-01

    Background: Surrogacy is one of the new techniques of assisted reproduction technology in which a woman carries and bears a child for another woman. In Iran, many Shia clerics and jurists considered it permissible so there is no religious prohibition for it. In addition to the risk of physical complications for complete surrogate mothers, the possibility of psychological complications resulted from emotional attachment to a living creature in the surrogate mother as another injury requires co...

  15. Families in the making: gestational surrogate mothers in California

    OpenAIRE

    Bjørn, Henriette Hårseide

    2014-01-01

    This thesis is based on a field work I conducted in California from January to June 2012, where I explore how gestational surrogate mothers experience the process of surrogacy and how California law has dealt with ART-cases. Through exploring surrogacy from different view point, and in particular from the view of surrogate mothers, this has given an insightful view into surrogacy in California. I have identified two court cases which are important for the establishment of parental rights in s...

  16. PLAN-TA9-2443(U), Rev. B Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure

    International Nuclear Information System (INIS)

    This document identifies scope and some general procedural steps for performing Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing. This Test Plan describes the requirements, responsibilities, and process for preparing and testing a range of chemical surrogates intended to mimic the energetic response of waste created during processing of legacy nitrate salts. The surrogates developed are expected to bound1 the thermal and mechanical sensitivity of such waste, allowing for the development of process parameters required to minimize the risk to worker and public when processing this waste. Such parameters will be based on the worst-case kinetic parameters as derived from APTAC measurements as well as the development of controls to mitigate sensitivities that may exist due to friction, impact, and spark. This Test Plan will define the scope and technical approach for activities that implement Quality Assurance requirements relevant to formulation and testing.

  17. Monte Carlo simulation of transfer reactions using extended R-matrix theory picturing surrogate-type WFCF features

    Science.gov (United States)

    Bouland, Olivier H.

    2016-03-01

    This article supplies an overview of issues related to the interpretation of surrogate measurement results for neutron-incident cross section predictions; difficulties that are somehow masked by the historical conversion route based on Weisskopf-Ewing approximation. Our proposal is to handle the various difficulties by using a more rigorous approach relying on Monte Carlo simulation of transfer reactions with extended R-matrix theory. The multiple deficiencies of the historical surrogate treatment are recalled but only one is examined in some details here; meaning the calculation of in-out-going channel Width Fluctuation Correction Factors (WFCF) which behavior witness partly the failure of Niels Bohr's compound nucleus theoretical landmark. Relevant WFCF calculations according to neutron-induced surrogate- and cross section-types as a function of neutron-induced fluctuating energy range [0 - 2.1 MeV] are presented and commented in the case of the 240Pu* and 241Pu* compound nucleus isotopes.

  18. PLAN-TA9-2443(U), Rev. B Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Geoffrey Wayne [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-03-16

    This document identifies scope and some general procedural steps for performing Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing. This Test Plan describes the requirements, responsibilities, and process for preparing and testing a range of chemical surrogates intended to mimic the energetic response of waste created during processing of legacy nitrate salts. The surrogates developed are expected to bound1 the thermal and mechanical sensitivity of such waste, allowing for the development of process parameters required to minimize the risk to worker and public when processing this waste. Such parameters will be based on the worst-case kinetic parameters as derived from APTAC measurements as well as the development of controls to mitigate sensitivities that may exist due to friction, impact, and spark. This Test Plan will define the scope and technical approach for activities that implement Quality Assurance requirements relevant to formulation and testing.

  19. Bench-scale Analysis of Surrogates for Anaerobic Digestion Processes.

    Science.gov (United States)

    Carroll, Zachary S; Long, Sharon C

    2016-05-01

    Frequent monitoring of anaerobic digestion processes for pathogen destruction is both cost and time prohibitive. The use of surrogates to supplement regulatory monitoring may be one solution. To evaluate surrogates, a semi-batch bench-scale anaerobic digester design was tested. Bench-scale reactors were operated under mesophilic (36 °C) and thermophilic (53-55 °C) conditions, with a 15 day solids retention time. Biosolids from different facilities and during different seasons were examined. USEPA regulated pathogens and surrogate organisms were enumerated at different times throughout each experiment. The surrogate organisms included fecal coliforms, E. coli, enterococci, male-specific and somatic coliphages, Clostridium perfringens, and bacterial spores. Male-specific coliphages tested well as a potential surrogate organism for virus inactivation. None of the tested surrogate organisms correlated well with helminth inactivation under the conditions studied. There were statistically significant differences in the inactivation rates between the facilities in this study, but not between seasons. PMID:27131309

  20. Monoclonal antibodies.

    Science.gov (United States)

    2009-01-01

    The ability to produce and exploit monoclonal antibodies (mAbs) has revolutionized many areas of biological sciences. The unique property of an mAb is that it is a single species of immunoglobulin (IG) molecule. This means that the specificity of the interaction of the paratopes on the IG, with the epitopes on an antigenic target, is the same on every molecule. This property can be used to great benefit in immunoassays to provide tests of defined specificity and sensitivity, which improve the possibilities of standardization. The performance of assays can often be determined relating the actual weight of antibody (hence the number of molecules) to the activity. Often the production of an mAb against a specific epitope is the only way that biological entities can be differentiated. This chapter outlines the areas involving the development of assays based on mAbs. The problems involved address include the physical aspects of mAbs and how they may affect assay design and also the implications of results based on monospecific reagents. Often these are not fully understood, leading to assays that are less than satisfactory, which does not justify the relatively high cost of preparing and screening of mAbs. There are many textbooks and reviews dealing with the preparation of mAbs, the principles involved, and various purification and manipulative methods for the preparation of fragments and conjugation. There has been little general information attempting to summarize the best approaches to assay design using mAbs. Much time can be wasted through bad planning, and this is particularly relevant to mAbs. A proper understanding of some basic principles is essential. It is beyond the scope of this chapter to discuss all aspects, but major areas are highlighted. PMID:19219589

  1. Traffic signals analysis using qSDiff and qHDiff with surrogate data

    Science.gov (United States)

    Xu, Mengjia; Shang, Pengjian; Xia, Jianan

    2015-11-01

    Complexity in time series is an intriguing feature of living dynamical systems such as traffic systems, with potential use for identification of system state. Here, we introduce a method for complex system analysis, called generalized sample entropy and surrogate data analysis, to measure the complexity in traffic signals. The behavior of the weekday series is quite different from that of the weekend series. In addition, we propose and discuss a new method of multifractality based on multifractal detrended fluctuation analysis (MF-DFA) and surrogate data. MF-DFA is the most popular method to detect multifractal characteristics of nonstationary time series. This new method is further applied to binomial multifractal series and traffic signals of Beijing, China. Results show that multifractal characteristics of the artificial data are regular and distinguishing the traffic signals of different patterns is significant. Besides, we find that there is a connection of multifractal characteristics between binomial multifractal series and traffic signals.

  2. Neutron capture surrogate reaction on 75As in inverse kinematics using (d,pγ)

    International Nuclear Information System (INIS)

    The 75As(d,pγ) reaction in inverse kinematics as a surrogate for neutron capture was performed at Oak Ridge National Laboratory using a deuterated plastic target. The intensity of the 165 keV γ-ray from 76As in coincidence with ejected protons, from exciting 76As above the neutron separation energy populating a compound state, was measured. A tight geometry of four segmented germanium clover γ-ray detectors together with eight ORRUBA-type silicon-strip charged-particle detectors was used to optimize geometric acceptance. The preliminary analysis of the 75As experiment, and the efficacy and future plans of the (d,pγ) surrogate campaign in inverse kinematics, are discussed. (authors)

  3. Neutron capture surrogate reaction on 75As in inverse kinematics using (d,pγ

    Directory of Open Access Journals (Sweden)

    Smith M.S.

    2010-03-01

    Full Text Available The 75As(d,pγ reaction in inverse kinematics as a surrogate for neutron capture was performed at Oak Ridge National Laboratory using a deuterated plastic target. The intensity of the 165 keV γ-ray from 76As in coincidence with ejected protons, from exciting 76As above the neutron separation energy populating a compound state, was measured. A tight geometry of four segmented germanium clover γ-ray detectors together with eight ORRUBA-type silicon-strip charged-particle detectors was used to optimize geometric acceptance. The preliminary analysis of the 75As experiment, and the eïňČcacy and future plans of the (d,pγ surrogate campaign in inverse kinematics, are discussed.

  4. Ignition of alkane-rich FACE gasoline fuels and their surrogate mixtures

    KAUST Repository

    Sarathy, Mani

    2015-01-01

    Petroleum derived gasoline is the most used transportation fuel for light-duty vehicles. In order to better understand gasoline combustion, this study investigated the ignition propensity of two alkane-rich FACE (Fuels for Advanced Combustion Engines) gasoline test fuels and their corresponding PRF (primary reference fuel) blend in fundamental combustion experiments. Shock tube ignition delay times were measured in two separate facilities at pressures of 10, 20, and 40 bar, temperatures from 715 to 1500 K, and two equivalence ratios. Rapid compression machine ignition delay times were measured for fuel/air mixtures at pressures of 20 and 40 bar, temperatures from 632 to 745 K, and two equivalence ratios. Detailed hydrocarbon analysis was also performed on the FACE gasoline fuels, and the results were used to formulate multi-component gasoline surrogate mixtures. Detailed chemical kinetic modeling results are presented herein to provide insights into the relevance of utilizing PRF and multi-component surrogate mixtures to reproduce the ignition behavior of the alkane-rich FACE gasoline fuels. The two FACE gasoline fuels and their corresponding PRF mixture displayed similar ignition behavior at intermediate and high temperatures, but differences were observed at low temperatures. These trends were mimicked by corresponding surrogate mixture models, except for the amount of heat release in the first stage of a two-stage ignition events, when observed. © 2014 The Combustion Institute.

  5. Surrogate ratio methodology for the indirect determination of neutron capture cross sections

    International Nuclear Information System (INIS)

    The relative γ-decay probabilities of the 162Dy to 161Dy and 162Dy to 164Dy residual nuclei, produced using light-ion-induced direct reactions, were measured as a function of excitation energy using the CACTUS array at the Oslo Cyclotron Laboratory. The external surrogate ratio method (SRM) was used to convert these relative γ-decay probabilities into the 161Dy(n,γ) cross section in an equivalent neutron energy range of 130-560 keV. The directly measured 161Dy(n,γ) cross section, obtained from the Evaluated Nuclear Data Files (ENDF/B-VII.0), was compared to the experimentally determined surrogate 161Dy(n,γ) cross section obtained using compound-nucleus pairs with both similar (162Dy to 164Dy) and dissimilar (162Dy to 161Dy) nuclear structures. A γ-ray energy threshold was identified, based upon pairing gap parameters, that provides a first-order correction to the statistical γ-ray tagging approach and improves the agreement between the surrogate cross-section data and the evaluated result.

  6. Surrogate/spent fuel sabotage : aerosol ratio test program and Phase 2 test results.

    Energy Technology Data Exchange (ETDEWEB)

    Borek, Theodore Thaddeus III; Thompson, N. Slater (U.S. Department of Energy); Sorenson, Ken Bryce; Hibbs, R.S. (U.S. Department of Energy); Nolte, Oliver (Fraunhofer Institut fur Toxikologie und Experimentelle Medizin, Germany); Molecke, Martin Alan; Autrusson, Bruno (Institut de Radioprotection et de Surete Nucleaire, France); Young, F. I. (U.S. Nuclear Regulatory Commission); Koch, Wolfgang (Fraunhofer Institut fur Toxikologie und Experimentelle Medizin, Germany); Brochard, Didier (Institut de Radioprotection et de Surete Nucleaire, France); Pretzsch, Gunter Guido (Gesellschaft fur Anlagen- und Reaktorsicherheit, Germany); Lange, Florentin (Gesellschaft fur Anlagen- und Reaktorsicherheit, Germany)

    2004-05-01

    A multinational test program is in progress to quantify the aerosol particulates produced when a high energy density device, HEDD, impacts surrogate material and actual spent fuel test rodlets. This program provides needed data that are relevant to some sabotage scenarios in relation to spent fuel transport and storage casks, and associated risk assessments; the program also provides significant political benefits in international cooperation. We are quantifying the spent fuel ratio, SFR, the ratio of the aerosol particles released from HEDD-impacted actual spent fuel to the aerosol particles produced from surrogate materials, measured under closely matched test conditions. In addition, we are measuring the amounts, nuclide content, size distribution of the released aerosol materials, and enhanced sorption of volatile fission product nuclides onto specific aerosol particle size fractions. These data are crucial for predicting radiological impacts. This document includes a thorough description of the test program, including the current, detailed test plan, concept and design, plus a description of all test components, and requirements for future components and related nuclear facility needs. It also serves as a program status report as of the end of FY 2003. All available test results, observations, and analyses - primarily for surrogate material Phase 2 tests using cerium oxide sintered ceramic pellets are included. This spent fuel sabotage - aerosol test program is coordinated with the international Working Group for Sabotage Concerns of Transport and Storage Casks, WGSTSC, and supported by both the U.S. Department of Energy and Nuclear Regulatory Commission.

  7. Cost-effectiveness of routine measuring of serum drug concentrations and anti-drug antibodies in treatment of rheumatoid arthritis patients with TNF-α blockers

    Directory of Open Access Journals (Sweden)

    Laine J

    2016-04-01

    Full Text Available Juha Laine,1 T Sakari Jokiranta,2,3 Kari K Eklund,4,5 Merja Väkeväinen,1 Kari Puolakka6 1Pfizer Oy, Helsinki, 2United Medix Laboratories Ltd, Espoo, 3Research Programs Unit, Immunobiology, 4Department of Rheumatology, University of Helsinki, 5Helsinki University Central Hospital, Helsinki, 6Department of Medicine, South Karelia, Finland Abstract: Monitoring of anti-drug antibodies (ADAbs or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis. Data on DLs and ADAbs concentrations were obtained in Finland from clinically requested monitoring analyses of 486 and 1,137 samples from patients on adalimumab and infliximab, respectively. DL was within the target range in 42% of samples from adalimumab- and 50.4% of infliximab-treated patients. ADAbs were detected in approximately 20% and 13.5% of samples from adalimumab- and infliximab-treated patients, respectively. ADAbs were found in 52.3% and 41.3% of those with low adalimumab or infliximab DLs, respectively. The monitoring data were incorporated into probabilities for making the optimal treatment decision. Economic impact of clinical decision-making was modeled in a short-term (3–6 months scenario with 100 hypothetical patients. In the model, the combined measurement of DLs and ADAbs was cost-saving compared to the nontesting scenario when the monitoring results affected the treatment decision in at least 2–5 of 100 patients, a proportion which is easily

  8. Neutron-induced capture cross sections of short-lived actinides with the surrogate reaction method

    Directory of Open Access Journals (Sweden)

    Gunsing F.

    2010-03-01

    Full Text Available Determination of neutron-capture cross sections of short-lived nuclei is opening the way to understand and clarify the properties of many nuclei of interest for nuclear structure physics, nuclear astrophysics and particularly for transmutation of nuclear wastes. The surrogate approach is well-recognized as a potentially very useful method to extract neutron cross sections for low-energy compound-nuclear reactions and to overcome the difficulties related to the target radioactivity. In this work we will assess where we stand on these neutron-capture cross section measurements and how we can achieve the short-lived Minor Actinides nuclei involved in the nuclear fuel cycle. The CENBG collaboration applied the surrogate method to determine the neutron-capture cross section of 233Pa (T1/2 = 27 d. The 233Pa (n,γ cross section is then deduced from the measured gamma decay probability of 234Pa compound nucleus formed via the surrogate 232Th(3He,p reaction channel. The obtained cross section data, covering the neutron energy range 0.1 to 1 MeV, have been compared with the predictions of the Hauser-Feshbach statistical model. The importance of establishing benchmarks is stressed for the minor actinides region. However, the lack of desired targets led us to propose recently the 174Yb (3He,pγ reaction as a surrogate reaction for the (n,γ predetermined benchmark cross section of 175Lu. An overview of the experimental setup combining gamma ray detectors such as Ge and C6D6 in coincidence with light charged particles ΔE-E Telescopes will be presented and preliminary results will be discussed.

  9. Real-time surrogate analysis for potential oil and gas contamination of drinking water resources

    Science.gov (United States)

    Son, Ji-Hee; Carlson, Kenneth H.

    2015-09-01

    Public concerns related to the fast-growing shale oil and gas industry have increased during recent years. The major concern regarding shale gas production is the potential of fracturing fluids being injected into the well or produced fluids flowing out of the well to contaminate drinking water resources such as surface water and groundwater. Fracturing fluids contain high total dissolved solids (TDS); thus, changes in TDS concentrations in groundwater might indicate influences of fracturing fluids. An increase of methane concentrations in groundwater could also potentially be due to hydraulic fracturing activities. To understand the possible contamination of groundwater by fracturing activities, real-time groundwater monitoring is being implemented in the Denver-Julesburg basin of northeast Colorado. A strategy of monitoring of surrogate parameters was chosen instead of measuring potential contaminants directly, an approach that is not cost effective or operationally practical. Contaminant surrogates of TDS and dissolved methane were proposed in this study, and were tested for correlation and data distribution with laboratory experiments. Correlations between TDS and electrical conductivity (EC), and between methane contamination and oxidation-reduction potential (ORP) were strong at low concentrations of contaminants (1 mg/L TDS and 0.3 mg/L CH4). Dissolved oxygen (DO) was only an effective surrogate at higher methane concentrations (≥2.5 mg/L). The results indicated that EC and ORP are effective surrogates for detecting concentration changes of TDS and methane, respectively, and that a strategy of monitoring for easy to measure parameters can be effective detecting real-time, anomalous behavior relative to a predetermined baseline.

  10. Neutron-induced capture cross sections of short-lived actinides with the surrogate reaction method

    International Nuclear Information System (INIS)

    The determination of neutron-capture cross sections of short-lived nuclei is opening the way to understand and clarify the properties of many nuclei of interest for nuclear structure physics, nuclear astrophysics and particularly for transmutation of nuclear wastes. The surrogate approach is well-recognized as a potentially very useful method to extract neutron cross sections for low-energy compound-nuclear reactions and to overcome the difficulties related to the target radioactivity. In this work we will assess where we stand on these neutron-capture cross section measurements and how we can achieve the short-lived Minor Actinides nuclei involved in the nuclear fuel cycle. The CENBG collaboration applied the surrogate method to determine the neutron-capture cross section of 233Pa (T1/2=27 d). The 233Pa(n,γ) cross section is then deduced from the measured gamma decay probability of 234Pa compound nucleus formed via the surrogate 232Th(3He,p) reaction channel. The obtained cross section data, covering the neutron energy range 0.1 to 1 MeV, have been compared with the predictions of the Hauser-Feshbach statistical model. The importance of establishing benchmarks is stressed for the minor actinides region. However, the lack of desired targets led us to propose recently the 174Yb (3He,pγ) reaction as a surrogate reaction for the (n,γ) predetermined benchmark cross section of 175Lu. An overview of the experimental setup combining gamma ray detectors such as Ge and C6D6 in coincidence with light charged particles ΔE-E Telescopes will be presented and preliminary results will be discussed. (authors)

  11. Percent recovery of low influent concentrations of microorganism surrogates in small sand columns

    Science.gov (United States)

    Stevenson, M. E.; Blaschke, A. P.

    2012-04-01

    In order to develop a dependable method to calculate the setback distance of a drinking water well from a potential point of microbiological contamination, surrogates are used to perform field tests to avoid using pathogenic micro-organisms. One such surrogate used to model the potential travel time of microbial contamination is synthetic microspheres. The goal of this study is to examine the effect of differing influent colloid concentrations on the percent recovery of microbial surrogates after passing through a soil column. Similar studies have been done to investigate blocking of ideal attachment sites using concentrations between 106 and 1010 particles ml-1. These high concentrations were necessary due to the detection limit of the measuring technique used; however, our measuring technique allows us to test input concentrations ranging from 101 to 106 particles ml-1. These low concentrations are more similar to the concentrations of pathogenic microorganisms present in nature. We have tested the enumeration of 0.5 μm microspheres using a solid-phase cytometer and evaluated their transport in small sand columns. Fluorescent microspheres were purchased for this study with carboxylated surfaces. The soil columns consist of Plexiglas tubes, 30 cm long and 7 cm in diameter, both filled with the same coarse sand. Bromide was used as a conservative tracer, to estimate pore-water velocity and dispersivity, and bromide concentrations were analysed using ion chromatography and bromide probes. Numerical modelling was done using CXTFIT and HYDRUS-1D software programs. The 0.5 μm beads were enumerated in different environmental waters using solid-phase cytometry and compared to counts in sterile water in order to confirm the accuracy of the method. The solid-phase cytometer was able to differentiate the 0.5 μm beads from naturally present autofluorescent particles and bacteria, and therefore, is an appropriate method to enumerate this surrogate.

  12. Immunoglobulins M and G to varicella-zoster virus measured by solid-phase radioimmunoassay: antibody responses to varicella and herpes zoster infections.

    OpenAIRE

    Arvin, A M; Koropchak, C M

    1980-01-01

    Both immunoglobulin M (IgM) and IgG antibodies to varicella-zoster virus (VZV) were detectable in a solid-phase radioimmunoassay with 125I-labeled goat antisera to human immunoglobulins. Primary infection with VZV was associated with early production of IgM and IgG antibodies and rapid development of lymphocyte transformation to VZV antigen. Among eight subjects with varicella tested 1 to 4 days after onset, seven patients had IgG and six patients had IgM antibodies; all patients had both IgG...

  13. TSH receptor antibody titers measured with a third-generation assay did not reflect the activity of Graves' ophthalmopathy in untreated Japanese Graves' disease patients.

    Science.gov (United States)

    Mukasa, Koji; Yoshimura Noh, Jaeduk; Kouzaki, Ai; Ohye, Hidemi; Kunii, Yo; Watanabe, Natsuko; Yoshihara, Ai; Matsumoto, Masako; Suzuki, Miho; Ito, Koichi

    2016-02-29

    TSH receptor antibody (TRAb) titer has been reported to be correlated with Graves' ophthalmopathy (GO). However, the correlation between GO activity and TRAb titer assessed with a third-generation assay has not been reported. We enrolled 238 untreated Graves' disease patients who came to the outpatient clinic of Ito Hospital and 28 patients who were euthyroid. All of the patients were assessed for GO by an ophthalmologist within 3 months of their initial visit to Ito Hospital. Clinical activity score (CAS), short inversion time inversion recovery (STIR), and sum of the maximum external orbital muscle areas (SEOMA) on a frontal sectional magnetic resonance imaging (MRI). The TRAb titer was significantly higher in patients with inactive ophthalmopathy (the inactive-GO group) than in patients with active ophthalmopathy (the active-GO group) (17.7 ± 13.5 IU/L vs 13.0 ± 13.1 IU/L, p=0.0082). The SEOMA values were not correlated with TRAb titer. The prevalence of active-GO was higher in euthyroid patients than in hyperthyroid patients although the difference was not significant. In conclusion, TRAb titer measured with a third-generation assay dose not correlate with GO activity based on MRI findings in untreated Graves' disease patients, and the prevalence of active-GO is higher in euthyroid patients with lower TRAb titers than in hyperthyroid patients. PMID:26581710

  14. Kriging-based generation of optimal databases as forward and inverse surrogate models

    International Nuclear Information System (INIS)

    Numerical methods are used to simulate mathematical models for a wide range of engineering problems. The precision provided by such simulators is usually fine, but at the price of computational cost. In some applications this cost might be crucial. This leads us to consider cheap surrogate models in order to reduce the computation time still meeting the precision requirements. Among all available surrogate models, we deal herein with the generation of an 'optimal' database of pre-calculated results combined with a simple interpolator. A database generation approach is investigated which is intended to achieve an optimal sampling. Such databases can be used for the approximate solution of both forward and inverse problems. Their structure carries some meta-information about the involved physical problem. In the case of the inverse problem, an approach for predicting the uncertainty of the solution (due to the applied surrogate model and/or the uncertainty of the measured data) is presented. All methods are based on kriging—a stochastic tool for function approximation. Illustrative examples are drawn from eddy current non-destructive evaluation

  15. Experimental verification of ion stopping power prediction from dual energy CT data in tissue surrogates

    International Nuclear Information System (INIS)

    We present an experimental verification of stopping-power-ratio (SPR) prediction from dual energy CT (DECT) with potential use for dose planning in proton and ion therapy. The approach is based on DECT images converted to electron density relative to water ϱe/ϱe, w and effective atomic number Zeff. To establish a parameterization of the I-value by Zeff, 71 tabulated tissue compositions were used. For the experimental assessment of the method we scanned 20 materials (tissue surrogates, polymers, aluminum, titanium) at 80/140Sn kVp and 100/140Sn kVp (Sn: additional tin filtration) and computed the ϱe/ϱe, w and Zeff with a purely image based algorithm. Thereby, we found that ϱe/ϱe, w (Zeff) could be determined with an accuracy of 0.4% (1.7%) for the tissue surrogates with known elemental compositions. SPRs were predicted from DECT images for all 20 materials using the presented approach and were compared to measured water-equivalent path lengths (closely related to SPR). For the tissue surrogates the presented DECT approach was found to predict the experimental values within 0.6%, for aluminum and titanium within an accuracy of 1.7% and 9.4% (from 16-bit reconstructed DECT images). (paper)

  16. Laboratory stabilization/solidification of surrogate and actual mixed-waste sludge in glass and grout

    International Nuclear Information System (INIS)

    Grout and glass formulations were developed for the stabilization of highly radioactive tank sludges. These formulations were tested in the laboratory with a surrogate and with a sample of an actual mixed waste tank sludge. The grout formulation was tested at wet-sludge loadings of 50--60 wt%, giving a volume increase of about 40--50 vol%. Dried sludge was vitrified into glass at waste oxide loadings of 40--50 wt%, giving a volume decrease of about 50--60 vol%. The Resource Conservation and Recovery Act (RCRA) metals included in surrogate testing were Ag, Ba, Cd, Cr, Ni, Pb, Se, Tl and Hg. Since vitrification would volatilize, not stabilize mercury, it was not included in the surrogates vitrified. The actual sludge sample was only characteristically hazardous for mercury by the toxic characteristic leaching procedure (TCLP) but exceeded the Universal Treatment Standard (UTS) limit for chromium. The grout and glass formulations stabilized these RCRA metals within UTS limits. In addition, a group leachability index of about 9--10 was measured for both 85Sr and 137Cs, meeting the recommended requirement of >6. The glass leachability index was estimated to be > 18 for cold cesium and strontium

  17. Solubility of actinides and surrogates in nuclear glasses

    International Nuclear Information System (INIS)

    The nuclear wastes are currently incorporated in borosilicate glass matrices. The resulting glass must be perfectly homogeneous. The work discussed here is a study of actinide (thorium and plutonium) solubility in borosilicate glass, undertaken to assess the extent of actinide solubility in the glass and to understand the mechanisms controlling actinide solubilization. Glass specimens containing; actinide surrogates were used to prepare and optimize the fabrication of radioactive glass samples. These preliminary studies revealed that actinide Surrogates solubility in the glass was enhanced by controlling the processing temperature, the dissolution kinetic of the surrogate precursors, the glass composition and the oxidizing versus reducing conditions. The actinide solubility was investigated in the borosilicate glass. The evolution of thorium solubility in borosilicate glass was determined for temperatures ranging from 1200 deg C to 1400 deg C.Borosilicate glass specimens containing plutonium were fabricated. The experimental result showed that the plutonium solubility limit ranged from 1 to 2.5 wt% PuO2 at 1200 deg C. A structural approach based on the determination of the local structure around actinides and their surrogates by EXAFS spectroscopy was used to determine their structural role in the glass and the nature of their bonding with the vitreous network. This approach revealed a correlation between the length of these bonds and the solubility of the actinides and their surrogates. (author)

  18. Uncertainty quantification for accident management using ACE surrogates

    International Nuclear Information System (INIS)

    The alternating conditional expectation (ACE) regression method is used to generate RELAP5 surrogates which are then used to determine the distribution of the peak clad temperature (PCT) during the loss of feedwater accident coupled with a subsequent initiation of the feed and bleed (F and B) operation in the Zion-1 nuclear power plant. The construction of the surrogates assumes conditional independence relations among key reactor parameters. The choice of parameters to model is based on the macroscopic balance statements governing the behavior of the reactor. The peak clad temperature is calculated based on the independent variables that are known to be important in determining the success of the F and B operation. The relationship between these independent variables and the plant parameters such as coolant pressure and temperature is represented by surrogates that are constructed based on 45 RELAP5 cases. The time-dependent PCT for different values of F and B parameters is calculated by sampling the independent variables from their probability distributions and propagating the information through two layers of surrogates. The results of our analysis show that the ACE surrogates are able to satisfactorily reproduce the behavior of the plant parameters even though a quasi-static assumption is primarily used in their construction. The PCT is found to be lower in cases where the F and B operation is initiated, compared to the case without F and B, regardless of the F and B parameters used. (authors)

  19. Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Purpose: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. Methods and Materials: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. Results: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p 0.1). Cox multivariate analyses also showed the same results. Conclusion: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC

  20. Technical Note: Development of a tidal volume surrogate that replaces spirometry for physiological breathing monitoring in 4D CT

    OpenAIRE

    Werner, René; White, Benjamin; Handels, Heinz; Lu, Wei; Low, Daniel A.

    2010-01-01

    Purpose: Spirometry exhibits baseline drift and frequent measurement errors so it cannot be used by itself to provide tidal volume-based image sorting or breathing motion modeling. Other breathing surrogates, in this study an abdominal bellows system, are drift free but do not measure tidal volume. Simultaneously using spirometry and the bellows system allows the user to convert the recorded bellows signal to tidal volume but still relies on spirometry measurements. The authors therefore prop...

  1. Carotid intimal-media thickness as a surrogate for cardiovascular disease events in trials of HMG-CoA reductase inhibitors

    Directory of Open Access Journals (Sweden)

    Morgan Timothy

    2005-03-01

    Full Text Available Abstract Background Surrogate measures for cardiovascular disease events have the potential to increase greatly the efficiency of clinical trials. A leading candidate for such a surrogate is the progression of intima-media thickness (IMT of the carotid artery; much experience has been gained with this endpoint in trials of HMG-CoA reductase inhibitors (statins. Methods and Results We examine two separate systems of criteria that have been proposed to define surrogate endpoints, based on clinical and statistical arguments. We use published results and a formal meta-analysis to evaluate whether progression of carotid IMT meets these criteria for HMG-CoA reductase inhibitors (statins. IMT meets clinical-based criteria to serve as a surrogate endpoint for cardiovascular events in statin trials, based on relative efficiency, linkage to endpoints, and congruency of effects. Results from a meta-analysis and post-trial follow-up from a single published study suggest that IMT meets established statistical criteria by accounting for intervention effects in regression models. Conclusion Carotid IMT progression meets accepted definitions of a surrogate for cardiovascular disease endpoints in statin trials. This does not, however, establish that it may serve universally as a surrogate marker in trials of other agents.

  2. Isolation of Potent CGRP Neutralizing Antibodies Using Four Simple Assays.

    Science.gov (United States)

    Neal, Frances; Arnold, Joanne; Rossant, Christine J; Podichetty, Sadhana; Lowne, David; Dobson, Claire; Wilkinson, Trevor; Colley, Caroline; Howes, Rob; Vaughan, Tristan J

    2016-01-01

    Calcitonin gene-related peptide (CGRP) is a small neuropeptide and a potent vasodilator that is widely associated with chronic pain and migraine. An antibody that inhibits CGRP function would be a potential therapeutic for treatment of these disorders. Here we describe the isolation of highly potent antibodies to CGRP from phage and ribosome display libraries and characterization of their epitope, species cross-reactivity, kinetics, and functional activity. Homogenous time-resolved fluorescence (HTRF) binding assays identified antibodies with the desired species cross-reactivity from naïve libraries, and HTRF epitope competition assays were used to characterize and group scFv by epitope. The functional inhibition of CGRP and species cross-reactivity of purified scFv and antibodies were subsequently confirmed using cAMP assays. We show that epitope competition assays could be used as a surrogate for functional cell-based assays during affinity maturation, in combination with scFv off-rate ranking by biolayer interferometry (BLI). This is the first time it has been shown that off-rate ranking can be predictive of functional activity for anti-CGRP antibodies. Here we demonstrate how, by using just four simple assays, diverse panels of antibodies to CGRP can be identified. These assay formats have potential utility in the identification of antibodies to other therapeutic targets. PMID:26450103

  3. Successful induced non-puerperal lactation in surrogate mothers.

    Science.gov (United States)

    Banapurmath, C R; Banapurmath, S; Kesaree, N

    1993-01-01

    Ten surrogate mothers seen between 1986-91 were encouraged to breast-feed their babies varying in age between 8 days to 5 months. All the 10 surrogate mothers had experienced pregnancy and child birth in the past. The lactational gap varied from 1 year to 16 years. Presence of milk was noted on 3rd to 8th day after attempting induced lactation in 5 mothers. No milk was seen on manual expression of the nipple even after 2 weeks in the other 5 surrogate mothers. Two mothers achieved complete breast-feeding and they fed their babies for 2 years. Three mothers could achieve partial lactation and these mothers fed for 1 year or more. All these 5 babies registered satisfactory growth. PMID:8157333

  4. Mother-daughter in vitro fertilization triplet surrogate pregnancy.

    Science.gov (United States)

    Michelow, M C; Bernstein, J; Jacobson, M J; McLoughlin, J L; Rubenstein, D; Hacking, A I; Preddy, S; Van der Wat, I J

    1988-02-01

    A successful triplet pregnancy has been established in a surrogate gestational mother following the transfer of five embryos fertilized in vitro. The oocytes were donated by her biological daughter, and the sperm obtained from the daughter's husband. The daughter's infertility followed a total abdominal hysterectomy performed for a postpartum hemorrhage as a result of a placenta accreta. Synchronization of both their menstrual cycles was obtained using oral contraceptive suppression for 2 months, followed by stimulation of both the surrogate gestational mother and her daughter such that embryo transfer would occur at least 48 hr after the surrogate gestational mother's own ovulation. This case raises a number of medical, social, psychological, and ethical issues. PMID:3367072

  5. Surrogate Model for Recirculation Phase LBLOCA and DET Application

    International Nuclear Information System (INIS)

    In the nuclear safety field, response surfaces were used in the first demonstration of the code scaling, applicability, and uncertainty (CSAU) methodology to quantify the uncertainty of the peak clad temperature (PCT) during a large-break loss-of-coolant accident (LBLOCA). Surrogates could have applications in other nuclear safety areas such as dynamic probabilistic safety assessment (PSA). Dynamic PSA attempts to couple the probabilistic nature of failure events, component transitions, and human reliability to deterministic calculations of time-dependent nuclear power plant (NPP) responses usually through the use of thermal-hydraulic (TH) system codes. The overall mathematical complexity of the dynamic PSA architectures with many embedded computational expensive TH code calculations with large input/output data streams have limited realistic studies of NPPs. This paper presents a time-dependent surrogate model for the recirculation phase of a hot leg LBLOCA in the OPR-1000. The surrogate model is developed through the ACE algorithm, a powerful nonparametric regression technique, trained on RELAP5 simulations of the LBLOCA. Benchmarking of the surrogate is presented and an application to a simplified dynamic event tree (DET). A time-dependent surrogate model to predict core subcooling during the recirculation phase of a hot leg LBLOCA in the OPR-1000 has been developed. The surrogate assumed the structure of a general discrete time dynamic model and learned the nonlinear functional form by performing nonparametric regression on RELAP5 simulations with the ACE algorithm. The surrogate model input parameters represent mass and energy flux terms to the RCS that appeared as user supplied or code calculated boundary conditions in the RELAP5 model. The surrogate accurately predicted the TH behavior of the core for a variety of HPSI system performance and containment conditions when compared with RELAP5 simulations. The surrogate was applied in a DET application replacing

  6. Surrogate Model for Recirculation Phase LBLOCA and DET Application

    Energy Technology Data Exchange (ETDEWEB)

    Fynan, Douglas A; Ahn, Kwang-Il [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Lee, John C. [Univ. of Michigan, Michigan (United States)

    2014-10-15

    In the nuclear safety field, response surfaces were used in the first demonstration of the code scaling, applicability, and uncertainty (CSAU) methodology to quantify the uncertainty of the peak clad temperature (PCT) during a large-break loss-of-coolant accident (LBLOCA). Surrogates could have applications in other nuclear safety areas such as dynamic probabilistic safety assessment (PSA). Dynamic PSA attempts to couple the probabilistic nature of failure events, component transitions, and human reliability to deterministic calculations of time-dependent nuclear power plant (NPP) responses usually through the use of thermal-hydraulic (TH) system codes. The overall mathematical complexity of the dynamic PSA architectures with many embedded computational expensive TH code calculations with large input/output data streams have limited realistic studies of NPPs. This paper presents a time-dependent surrogate model for the recirculation phase of a hot leg LBLOCA in the OPR-1000. The surrogate model is developed through the ACE algorithm, a powerful nonparametric regression technique, trained on RELAP5 simulations of the LBLOCA. Benchmarking of the surrogate is presented and an application to a simplified dynamic event tree (DET). A time-dependent surrogate model to predict core subcooling during the recirculation phase of a hot leg LBLOCA in the OPR-1000 has been developed. The surrogate assumed the structure of a general discrete time dynamic model and learned the nonlinear functional form by performing nonparametric regression on RELAP5 simulations with the ACE algorithm. The surrogate model input parameters represent mass and energy flux terms to the RCS that appeared as user supplied or code calculated boundary conditions in the RELAP5 model. The surrogate accurately predicted the TH behavior of the core for a variety of HPSI system performance and containment conditions when compared with RELAP5 simulations. The surrogate was applied in a DET application replacing

  7. Surrogate pregnancy: a guide for Canadian prenatal health care providers.

    Science.gov (United States)

    Reilly, Dan R

    2007-02-13

    Providing health care for a woman with a surrogate pregnancy involves unique challenges. Although the ethical debate surrounding surrogacy continues, Canada has banned commercial, but not altruistic, surrogacy. In the event of a custody dispute between a surrogate mother and the individual(s) intending to parent the child, it is unclear how Canadian courts would rule. The prenatal health care provider must take extra care to protect the autonomy and privacy rights of the surrogate. There is limited evidence about the medical and psychological risks of surrogacy. Whether theoretical concerns about these risks are clinically relevant remains unknown. In the face of these uncertainties, the prenatal health care provider should have a low threshold for seeking obstetrical, social work, ethical and legal support. PMID:17296962

  8. Measurement of anti-DFS70 antibodies in patients with ANA-associated autoimmune rheumatic diseases suspicion is cost-effective.

    Science.gov (United States)

    Gundín, Simón; Irure-Ventura, Juan; Asensio, Esther; Ramos, David; Mahler, Michael; Martínez-Taboada, Victor; López-Hoyos, Marcos

    2016-12-01

    The presence of antinuclear antibodies (ANA) is associated with a wide range of ANA-associated autoimmune rheumatic diseases (AARD). The most commonly method used for the detection of ANA is indirect immunofluorescence (IIF) on HEp-2 cells. This method is very sensitive but unspecific. As a consequence, ANA testing on HEp-2 substrates outside a proper clinical specialist framework may lead to inappropriate referrals to tertiary care specialists and, worst case inappropriate and potentially toxic therapy for the patient. Among ANA, isolated anti-DFS70 antibodies represent a potentially important biomarker that can be clinically used to discriminate AARD from non-AARD patients in ANA IIF positive individuals. Therefore, their presence may avoid unnecessary follow-up testing and referrals. In our study, we investigated if the implementation of a new ANA workup algorithm allowing for the identification of anti-DFS70 antibodies is cost-effective through the reduction of both unnecessary follow-up testing and outpatient clinic visits generated by the clinical suspicion of a potential AARD. None of the 181 patients included with a positive monospecific anti-DFS70 antibody result developed SARD during the follow-up period of 10 years. The reduction in number of tests after ANA and anti-DFS70 positive results was significant for anti-ENA (230 vs. 114 tests; p < 0.001) and anti-dsDNA antibodies (448 vs. 114 tests; p < 0.001). In addition, the outpatient clinic visits decreased by 70 % (p < 0.001). In total, the adoption of the new algorithm including anti-DFS70 antibody testing resulted in a cost saving of 60869.53 € for this pilot study. In conclusion, the use of anti-DFS70 antibodies was clearly cost-efficient in our setting. PMID:27473142

  9. Longitudinal volume analysis from computed tomography: reproducibility using adrenal glands as surrogate tumors

    International Nuclear Information System (INIS)

    This study aims to determine the precision (reproducibility) of volume assessment in routine clinical computed tomography (CT) using adrenal glands as surrogate tumors. Seven patients at our institution were identified retrospectively as having received numerous abdominal CT scans (average 13.1, range 5 to 20). The adrenal glands were used as surrogate tumors, assuming no actual volume change. Left and right adrenal gland volumes were assessed by hand segmentation for each patient scan. Over 1240 regions of interest were outlined in total. The reproducibility, expressed as the coefficient of variation (COV), was used to characterize measurement precision. The average volumes were 5.9 and 4.5 cm3 for the left and right adrenal gland, respectively, with COVs of 17.8% and 18.9%, respectively. Using one patient's data (20 scans) as an example surrogate for a spherical tumor, it was calculated that a 13% change in volume (4.2% change in diameter) could be determined with statistical significance at P = 0.05. For this case, cursor positioning error in linear measurement of object size, by even 1 pixel on the CT image, corresponded to a significant change in volume (P=0.05). The precision of volume determination was dependent on total volume. Precision improved with increasing object size (r2=0.367). Given the small dimensions of the adrenal glands, the ∼ 18% COV is likely to be a high estimate compared to larger tumors. Modern CT scanners working with thinner sections (i.e. <1 mm) are likely to produce better measurement precision. The use of volume measurement to quantify changing tumor size is supported as a more precise metric than linear measurement. (author)

  10. Magnetic Resonance Imaging–Guided versus Surrogate-Based Motion Tracking in Liver Radiation Therapy: A Prospective Comparative Study

    Energy Technology Data Exchange (ETDEWEB)

    Paganelli, Chiara, E-mail: chiara.paganelli@polimi.it [Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano (Italy); Seregni, Matteo; Fattori, Giovanni [Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano (Italy); Summers, Paul [Division of Radiology, Istituto Europeo di Oncologia, Milano (Italy); Bellomi, Massimo [Division of Radiology, Istituto Europeo di Oncologia, Milano (Italy); Department of Health Sciences, Università degli Studi di Milano, Milano (Italy); Baroni, Guido; Riboldi, Marco [Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano (Italy); Bioengineering Unit, CNAO Foundation, Pavia (Italy)

    2015-03-15

    Purpose: This study applied automatic feature detection on cine–magnetic resonance imaging (MRI) liver images in order to provide a prospective comparison between MRI-guided and surrogate-based tracking methods for motion-compensated liver radiation therapy. Methods and Materials: In a population of 30 subjects (5 volunteers plus 25 patients), 2 oblique sagittal slices were acquired across the liver at high temporal resolution. An algorithm based on scale invariant feature transform (SIFT) was used to extract and track multiple features throughout the image sequence. The position of abdominal markers was also measured directly from the image series, and the internal motion of each feature was quantified through multiparametric analysis. Surrogate-based tumor tracking with a state-of-the-art external/internal correlation model was simulated. The geometrical tracking error was measured, and its correlation with external motion parameters was also investigated. Finally, the potential gain in tracking accuracy relying on MRI guidance was quantified as a function of the maximum allowed tracking error. Results: An average of 45 features was extracted for each subject across the whole liver. The multi-parametric motion analysis reported relevant inter- and intrasubject variability, highlighting the value of patient-specific and spatially-distributed measurements. Surrogate-based tracking errors (relative to the motion amplitude) were were in the range 7% to 23% (1.02-3.57mm) and were significantly influenced by external motion parameters. The gain of MRI guidance compared to surrogate-based motion tracking was larger than 30% in 50% of the subjects when considering a 1.5-mm tracking error tolerance. Conclusions: Automatic feature detection applied to cine-MRI allows detailed liver motion description to be obtained. Such information was used to quantify the performance of surrogate-based tracking methods and to provide a prospective comparison with respect to MRI

  11. Magnetic Resonance Imaging–Guided versus Surrogate-Based Motion Tracking in Liver Radiation Therapy: A Prospective Comparative Study

    International Nuclear Information System (INIS)

    Purpose: This study applied automatic feature detection on cine–magnetic resonance imaging (MRI) liver images in order to provide a prospective comparison between MRI-guided and surrogate-based tracking methods for motion-compensated liver radiation therapy. Methods and Materials: In a population of 30 subjects (5 volunteers plus 25 patients), 2 oblique sagittal slices were acquired across the liver at high temporal resolution. An algorithm based on scale invariant feature transform (SIFT) was used to extract and track multiple features throughout the image sequence. The position of abdominal markers was also measured directly from the image series, and the internal motion of each feature was quantified through multiparametric analysis. Surrogate-based tumor tracking with a state-of-the-art external/internal correlation model was simulated. The geometrical tracking error was measured, and its correlation with external motion parameters was also investigated. Finally, the potential gain in tracking accuracy relying on MRI guidance was quantified as a function of the maximum allowed tracking error. Results: An average of 45 features was extracted for each subject across the whole liver. The multi-parametric motion analysis reported relevant inter- and intrasubject variability, highlighting the value of patient-specific and spatially-distributed measurements. Surrogate-based tracking errors (relative to the motion amplitude) were were in the range 7% to 23% (1.02-3.57mm) and were significantly influenced by external motion parameters. The gain of MRI guidance compared to surrogate-based motion tracking was larger than 30% in 50% of the subjects when considering a 1.5-mm tracking error tolerance. Conclusions: Automatic feature detection applied to cine-MRI allows detailed liver motion description to be obtained. Such information was used to quantify the performance of surrogate-based tracking methods and to provide a prospective comparison with respect to MRI

  12. Replacing FEA for sheet metal forming by surrogate modeling

    Directory of Open Access Journals (Sweden)

    Simon Wessing

    2014-12-01

    Full Text Available This paper presents an innovative approach for employing surrogate modeling in computer-aided design of sheet metal work pieces. The surrogate models replace expensive finite element analysis and thus shorten development time in the early design stages considerably. We experimentally compare neural networks and Kriging models for the task of predicting the sheet metal thickness after cold forming of B-pillars in automotive engineering. We also discuss some aspects of handling large data-sets and exploiting certain structures in the data.

  13. Surrogate spike train generation through dithering in operational time

    Directory of Open Access Journals (Sweden)

    george L Gerstein

    2010-09-01

    Full Text Available Detecting the excess of spike synchrony and testing its significance can not be done analytically in many types of spike trains and relies on adequate surrogate methods. The main challenge for these methods is to conserve certain features of the spike trains, the two most important being the firing rate and the inter-spike interval statistics. In this study we make use of operational time to introduce generalizations to spike dithering and propose two novel surrogate methods which conserve both features with high accuracy. Compared to earlier approaches, the methods show an improved robustness in detecting excess synchrony between spike trains.

  14. Space Mapping Optimization of Microwave Circuits Exploiting Surrogate Models

    DEFF Research Database (Denmark)

    Bakr, M. H.; Bandler, J. W.; Madsen, Kaj;

    2000-01-01

    A powerful new space-mapping (SM) optimization algorithm is presented in this paper. It draws upon recent developments in both surrogate model-based optimization and modeling of microwave devices, SM optimization is formulated as a general optimization problem of a surrogate model. This model is a...... significant response shift exists. The algorithm is illustrated through the design of a capacitively loaded 10:1 impedance transformer and a double-folded stub filter. A high-temperature superconducting filter is also designed using decoupled frequency and SMs....

  15. Development of a secondary antibody thio-functionalized microcantilever immunosensor and an ELISA for measuring ginsenoside Re content in the herb ginseng.

    Science.gov (United States)

    Nan, Tiegui; Wu, Shangquan; Zhao, Hongwei; Tan, Weiming; Li, Zhaohu; Zhang, Qingchuan; Wang, Baomin

    2012-05-15

    Ginsenoside Re (GRe) is a major active component of the Chinese medicinal herb ginseng, Panax ginseng . A sensitive and specific monoclonal antibody (mAb), designated as mAb3D6, was generated with a GRe-bovine serum albumin conjugate as an immunogen. Microcantilever immunosensors (MCS), one modified with thiolated anti-GRe antibody and one modified with thiolated goat antimouse immunoglobulin G (IgG), were developed to detect the content of ginsenoside. The MCS immobilized with thiolated goat antimouse IgG had a better sensitivity than the MCS modified with thiolated anti-GRe antibody. The advantage of a secondary antibody thio-functionalized MCS was verified with the anti-paclitaxel mAb. An indirect competitive enzyme-linked immunosorbent assay (icELISA) was also established with mAb3D6. The concentration of analyte producing 50% inhibition and the working range of icELISA were 1.20 and 0.15-16.1 ng/mL, respectively. The icELISA had a cross-reactivity of 89% with ginsenoside Rg1 and less than 3% with other ginsenosides. The icELISA and MCS with thiolated secondary antibody were applied for the determination of GRe in ginseng samples, and the results agreed well with those determined by high-performance liquid chromatography. PMID:22494059

  16. Antibodies and Selection of Monoclonal Antibodies.

    Science.gov (United States)

    Hanack, Katja; Messerschmidt, Katrin; Listek, Martin

    2016-01-01

    Monoclonal antibodies are universal binding molecules with a high specificity for their target and are indispensable tools in research, diagnostics and therapy. The biotechnological generation of monoclonal antibodies was enabled by the hybridoma technology published in 1975 by Köhler and Milstein. Today monoclonal antibodies are used in a variety of applications as flow cytometry, magnetic cell sorting, immunoassays or therapeutic approaches. First step of the generation process is the immunization of the organism with appropriate antigen. After a positive immune response the spleen cells are isolated and fused with myeloma cells in order to generate stable, long-living antibody-producing cell lines - hybridoma cells. In the subsequent identification step the culture supernatants of all hybridoma cells are screened weekly for the production of the antibody of interest. Hybridoma cells producing the antibody of interest are cloned by limited dilution till a monoclonal hybridoma is found. This is a very time-consuming and laborious process and therefore different selection strategies were developed since 1975 in order to facilitate the generation of monoclonal antibodies. Apart from common automation of pipetting processes and ELISA testing there are some promising approaches to select the right monoclonal antibody very early in the process to reduce time and effort of the generation. In this chapter different selection strategies for antibody-producing hybridoma cells are presented and analysed regarding to their benefits compared to conventional limited dilution technology. PMID:27236550

  17. Transport behavior of surrogate biological warfare agents in a simulated landfill: Effect of leachate recirculation and water infiltration

    KAUST Repository

    Saikaly, Pascal

    2010-11-15

    An understanding of the transport behavior of biological warfare (BW) agents in landfills is required to evaluate the suitability of landfills for the disposal of building decontamination residue (BDR) following a bioterrorist attack on a building. Surrogate BW agents, Bacillus atrophaeus spores and Serratia marcescens, were spiked into simulated landfill reactors that were filled with synthetic building debris (SBD) and operated for 4 months with leachate recirculation or water infiltration. Quantitative polymerase chain reaction (Q-PCR) was used to monitor surrogate transport. In the leachate recirculation reactors, <10% of spiked surrogates were eluted in leachate over 4 months. In contrast, 45% and 31% of spiked S. marcescens and B. atrophaeus spores were eluted in leachate in the water infiltration reactors. At the termination of the experiment, the number of retained cells and spores in SBD was measured over the depth of the reactor. Less than 3% of the total spiked S. marcescens cells and no B. atrophaeus spores were detected in SBD. These results suggest that significant fractions of the spiked surrogates were strongly attached to SBD. © 2010 American Chemical Society.

  18. Chikungunya virus RNA and antibody testing at a National Reference Laboratory since the emergence of Chikungunya virus in the Americas.

    Science.gov (United States)

    Prince, Harry E; Seaton, Brent L; Matud, Jose L; Batterman, Hollis J

    2015-03-01

    Since first reported in the Americas in December 2013, chikungunya virus (CHIKV) infections have been documented in travelers returning from the Caribbean, with many cases identified by CHIKV antibody and/or RNA testing at our laboratory. We used our large data set to characterize the relationship between antibody titers and RNA detection and to estimate IgM persistence. CHIKV RNA was measured by nucleic acid amplification and CHIKV IgG/IgM by indirect immunofluorescence. Of the 1,306 samples submitted for RNA testing in January through September 2014, 393 (30%) were positive; for 166 RNA-positive samples, CHIKV antibody testing was also ordered, and 84% were antibody negative. Of the 6,971 sera submitted for antibody testing in January through September 2014, 1,811 (26%) were IgM positive; 1,461 IgM positives (81%) were also IgG positive. The relationship between the CHIKV antibody titers and RNA detection was evaluated using 376 IgM-positive samples (138 with RNA testing ordered and 238 deidentified and tested for RNA). RNA detection showed no significant association with the IgM titer but was inversely related to the IgG titer; 63% of the IgG negative sera were RNA positive, compared to 36% of sera with low IgG titers (1:10 to 1:80) and 16% with IgG titers of ≥1:160. Using second-sample results from 62 seroconverters, we estimated that CHIKV IgM persists for 110 days (95% confidence interval, 78 to 150 days) after the initial antibody-negative sample. These findings indicate that (i) RNA detection is more sensitive than antibody detection early in CHIKV infection, (ii) in the absence of RNA results, the IgG titer of the IgM-positive samples may be a useful surrogate for viremia, and (iii) CHIKV IgM persists for approximately 4 months after symptom onset. PMID:25540275

  19. Sister-sister in vitro fertilization surrogate pregnancy with donor sperm: the case for surrogate gestational pregnancy.

    Science.gov (United States)

    Leeton, J; King, C; Harman, J

    1988-10-01

    A case of surrogate pregnancy is described in the sister of a 40-year-old hysterectomized woman where two oocytes of the latter were fertilized in vitro with known donor sperm and transferred into the surrogate. A normal singleton pregnancy developed which was complicated after 24 weeks of gestation with recurrent antepartum hemorrhages due to grade 3 placenta praevia. A healthy female baby was delivered by elective cesarean section at 36 weeks of gestation. The legal, social, psychological, and ethical issues of surrogacy remain unsettled and are discussed in this case report. PMID:3230346

  20. Establishing a theory for deuteron-induced surrogate reactions

    Science.gov (United States)

    Potel, G.; Nunes, F. M.; Thompson, I. J.

    2015-09-01

    Background: Deuteron-induced reactions serve as surrogates for neutron capture into compound states. Although these reactions are of great applicability, no theoretical efforts have been invested in this direction over the last decade. Purpose: The goal of this work is to establish on firm grounds a theory for deuteron-induced neutron-capture reactions. This includes formulating elastic and inelastic breakup in a consistent manner. Method: We describe this process both in post- and prior-form distorted wave Born approximation following previous works and discuss the differences in the formulation. While the convergence issues arising in the post formulation can be overcome in the prior formulation, in this case one still needs to take into account additional terms due to nonorthogonality. Results: We apply our method to the 93Nb(d ,p )X at Ed=15 and 25 MeV and are able to obtain a good description of the data. We look at the various partial wave contributions, as well as elastic versus inelastic contributions. We also connect our formulation with transfer to neutron bound states. Conclusions: Our calculations demonstrate that the nonorthogonality term arising in the prior formulation is significant and is at the heart of the long-standing controversy between the post and the prior formulations of the theory. We also show that the cross sections for these reactions are angular-momentum dependent and therefore the commonly used Weisskopf limit is inadequate. Finally, we make important predictions for the relative contributions of elastic breakup and nonelastic breakup and call for elastic-breakup measurements to further constrain our model.

  1. Summary of Remediated Nitrate Salt Surrogate Formulation and Testing

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Geoffrey Wayne [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Leonard, Philip [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hartline, Ernest Leon [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tian, Hongzhao [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-05

    High Explosives Science and Technology (M-7) completed all required formulation and testing of Remediated Nitrate Salt (RNS) surrogates on April 27, 2016 as specified in PLAN-TA9-2443 Rev B, "Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure", released February 16, 2016. This report summarizes the results of the work and also includes additional documentation required in that test plan. All formulation and testing was carried out according to PLAN-TA9-2443 Rev B. The work was carried out in three rounds, with the full matrix of samples formulated and tested in each round. Results from the first round of formulation and testing were documented in memorandum M7-J6-6042, " Results from First Round of Remediated Nitrate Salt Surrogate Formulation and Testing." Results from the second round of formulation and testing were documented in M7-16-6053 , "Results from the Second Round of Remediated Nitrate Salt Surrogate Formulation and Testing." Initial results from the third round were documented in M7-16-6057, "Initial Results from the Third Round of Remediated Nitrate Salt Formulation and Testing."

  2. Inferring Causality: Coupling Assymetry Tested using Surrogate Data

    Czech Academy of Sciences Publication Activity Database

    Paluš, Milan

    Berlin : European Physical Society, 2005 - (Schöll, E.; Lüdge, K.). s. 132-133 ISBN 2-914771-26-6. [Dynamics Days Europe 2005 /25./. 25.07.2005-28.07.2005, Berlin] Institutional research plan: CEZ:AV0Z10300504 Keywords : inference * causality * surrogate data Subject RIV: BA - General Mathematics

  3. Salmonella surrogate reduction using industrial peanut dry roasting parameters

    Science.gov (United States)

    Studies were conducted to evaluate the effectiveness of industrial peanut dry roasting parameters in Salmonella reduction using a Salmonella surrogate, Enterococcus faecium, which is slightly more heat tolerant than Salmonella. Runner-type peanuts were inoculated with E. faecium and roasted in a lab...

  4. A surrogate-based uncertainty quantification with quantifiable errors

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Y.; Abdel-Khalik, H. S. [North Carolina State Univ., Raleigh, NC 27695 (United States)

    2012-07-01

    Surrogate models are often employed to reduce the computational cost required to complete uncertainty quantification, where one is interested in propagating input parameters uncertainties throughout a complex engineering model to estimate responses uncertainties. An improved surrogate construction approach is introduced here which places a premium on reducing the associated computational cost. Unlike existing methods where the surrogate is constructed first, then employed to propagate uncertainties, the new approach combines both sensitivity and uncertainty information to render further reduction in the computational cost. Mathematically, the reduction is described by a range finding algorithm that identifies a subspace in the parameters space, whereby parameters uncertainties orthogonal to the subspace contribute negligible amount to the propagated uncertainties. Moreover, the error resulting from the reduction can be upper-bounded. The new approach is demonstrated using a realistic nuclear assembly model and compared to existing methods in terms of computational cost and accuracy of uncertainties. Although we believe the algorithm is general, it will be applied here for linear-based surrogates and Gaussian parameters uncertainties. The generalization to nonlinear models will be detailed in a separate article. (authors)

  5. A surrogate-based uncertainty quantification with quantifiable errors

    International Nuclear Information System (INIS)

    Surrogate models are often employed to reduce the computational cost required to complete uncertainty quantification, where one is interested in propagating input parameters uncertainties throughout a complex engineering model to estimate responses uncertainties. An improved surrogate construction approach is introduced here which places a premium on reducing the associated computational cost. Unlike existing methods where the surrogate is constructed first, then employed to propagate uncertainties, the new approach combines both sensitivity and uncertainty information to render further reduction in the computational cost. Mathematically, the reduction is described by a range finding algorithm that identifies a subspace in the parameters space, whereby parameters uncertainties orthogonal to the subspace contribute negligible amount to the propagated uncertainties. Moreover, the error resulting from the reduction can be upper-bounded. The new approach is demonstrated using a realistic nuclear assembly model and compared to existing methods in terms of computational cost and accuracy of uncertainties. Although we believe the algorithm is general, it will be applied here for linear-based surrogates and Gaussian parameters uncertainties. The generalization to nonlinear models will be detailed in a separate article. (authors)

  6. Strength Reliability Analysis of Turbine Blade Using Surrogate Models

    Directory of Open Access Journals (Sweden)

    Wei Duan

    2014-05-01

    Full Text Available There are many stochastic parameters that have an effect on the reliability of steam turbine blades performance in practical operation. In order to improve the reliability of blade design, it is necessary to take these stochastic parameters into account. In this study, a variable cross-section twisted blade is investigated and geometrical parameters, material parameters and load parameters are considered as random variables. A reliability analysis method as a combination of a Finite Element Method (FEM, a surrogate model and Monte Carlo Simulation (MCS, is applied to solve the blade reliability analysis. Based on the blade finite element parametrical model and the experimental design, two kinds of surrogate models, Polynomial Response Surface (PRS and Artificial Neural Network (ANN, are applied to construct the approximation analytical expressions between the blade responses (including maximum stress and deflection and random input variables, which act as a surrogate of finite element solver to drastically reduce the number of simulations required. Then the surrogate is used for most of the samples needed in the Monte Carlo method and the statistical parameters and cumulative distribution functions of the maximum stress and deflection are obtained by Monte Carlo simulation. Finally, the probabilistic sensitivities analysis, which combines the magnitude of the gradient and the width of the scatter range of the random input variables, is applied to evaluate how much the maximum stress and deflection of the blade are influenced by the random nature of input parameters.

  7. Real-time tumor motion estimation using respiratory surrogate via memory-based learning

    International Nuclear Information System (INIS)

    Respiratory tumor motion is a major challenge in radiation therapy for thoracic and abdominal cancers. Effective motion management requires an accurate knowledge of the real-time tumor motion. External respiration monitoring devices (optical, etc) provide a noninvasive, non-ionizing, low-cost and practical approach to obtain the respiratory signal. Due to the highly complex and nonlinear relations between tumor and surrogate motion, its ultimate success hinges on the ability to accurately infer the tumor motion from respiratory surrogates. Given their widespread use in the clinic, such a method is critically needed. We propose to use a powerful memory-based learning method to find the complex relations between tumor motion and respiratory surrogates. The method first stores the training data in memory and then finds relevant data to answer a particular query. Nearby data points are assigned high relevance (or weights) and conversely distant data are assigned low relevance. By fitting relatively simple models to local patches instead of fitting one single global model, it is able to capture highly nonlinear and complex relations between the internal tumor motion and external surrogates accurately. Due to the local nature of weighting functions, the method is inherently robust to outliers in the training data. Moreover, both training and adapting to new data are performed almost instantaneously with memory-based learning, making it suitable for dynamically following variable internal/external relations. We evaluated the method using respiratory motion data from 11 patients. The data set consists of simultaneous measurement of 3D tumor motion and 1D abdominal surface (used as the surrogate signal in this study). There are a total of 171 respiratory traces, with an average peak-to-peak amplitude of ∼15 mm and average duration of ∼115 s per trace. Given only 5 s (roughly one breath) pretreatment training data, the method achieved an average 3D error of 1.5 mm and 95

  8. Recent Progress in the Development of Diesel Surrogate Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, W J

    2009-09-04

    There has been much recent progress in the area of surrogate fuels for diesel. In the last few years, experiments and modeling have been performed on higher molecular weight components of relevance to diesel fuel such as n-hexadecane (n-cetane) and 2,2,4,4,6,8,8-heptamethylnonane (iso-cetane). Chemical kinetic models have been developed for all the n-alkanes up to 16 carbon atoms. Also, there has been much experimental and modeling work on lower molecular weight surrogate components such as n-decane and do-decane which are most relevant to jet fuel surrogates, but are also relevant to diesel surrogates where simulation of the full boiling point range is desired. For the cycloalkanes, experimental work on decalin and tetralin recently has been published. For multi-component surrogate fuel mixtures, recent work on modeling of these mixtures and comparisons to real diesel fuel is reviewed. Detailed chemical kinetic models for surrogate fuels are very large in size. Significant progress also has been made in improving the mechanism reduction tools that are needed to make these large models practicable in multidimensional reacting flow simulations of diesel combustion. Nevertheless, major research gaps remain. In the case of iso-alkanes, there are experiments and modeling work on only one of relevance to diesel: iso-cetane. Also, the iso-alkanes in diesel are lightly branched and no detailed chemical kinetic models or experimental investigations are available for such compounds. More components are needed to fill out the iso-alkane boiling point range. For the aromatic class of compounds, there has been no new work for compounds in the boiling point range of diesel. Most of the new work has been on alkyl aromatics that are of the range C7 to C8, below the C10 to C20 range that is needed. For the chemical class of cycloalkanes, experiments and modeling on higher molecular weight components are warranted. Finally for multi-component surrogates needed to treat real diesel

  9. Recent Progress in the Development of Diesel Surrogate Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, W J; Mueller, C J

    2009-12-09

    There has been much recent progress in the area of surrogate fuels for diesel. In the last few years, experiments and modeling have been performed on higher molecular weight components of relevance to diesel fuel such as n-hexadecane (n-cetane) and 2,2,4,4,6,8,8-heptamethylnonane (iso-cetane). Chemical kinetic models have been developed for all the n-alkanes up to 16 carbon atoms. Also, there has been much experimental and modeling work on lower molecular weight surrogate components such as n-decane and n-dodecane that are most relevant to jet fuel surrogates, but are also relevant to diesel surrogates where simulation of the full boiling point range is desired. For two-ring compounds, experimental work on decalin and tetralin recently has been published. For multi-component surrogate fuel mixtures, recent work on modeling of these mixtures and comparisons to real diesel fuel is reviewed. Detailed chemical kinetic models for surrogate fuels are very large in size. Significant progress also has been made in improving the mechanism reduction tools that are needed to make these large models practicable in multi-dimensional reacting flow simulations of diesel combustion. Nevertheless, major research gaps remain. In the case of iso-alkanes, there are experiments and modeling work on only one of relevance to diesel: iso-cetane. Also, the iso-alkanes in diesel are lightly branched and no detailed chemical kinetic models or experimental investigations are available for such compounds. More components are needed to fill out the iso-alkane boiling point range. For the aromatic class of compounds, there has been no new work for compounds in the boiling point range of diesel. Most of the new work has been on alkyl aromatics that are of the range C7 to C8, below the C10 to C20 range that is needed. For the chemical class of cycloalkanes, experiments and modeling on higher molecular weight components are warranted. Finally for multi-component surrogates needed to treat real

  10. Modified generalized sample entropy and surrogate data analysis for stock markets

    Science.gov (United States)

    Xu, Mengjia; Shang, Pengjian; Huang, Jingjing

    2016-06-01

    In this paper a modified method of generalized sample entropy and surrogate data analysis is proposed as a new measure to assess the complexity of a complex dynamical system such as stock market. The method based on Hausdorff distance presents a different way of time series patterns match showing distinct behaviors of complexity. Simulations are conducted over synthetic and real-world data for providing the comparative study. Results show that the modified method is more sensitive to the change of dynamics and has richer information. In addition, exponential functions can be used to successfully fit the curves obtained from the modified method and quantify the changes of complexity for stock market data.

  11. Frequency of hepatitis B surface antibody (anti-HBs) in various Canadian populations as measured by modified solid-phase radioimmunoassay

    International Nuclear Information System (INIS)

    A short incubation solid-phase radioimmunoassay test was developed and used for the detection of hepatitis B surface antibody (anti-HBs) in the sera collected from patients recovering from hepatitis B infection, health care personnel, staff and residents of an intstitution for the mentally retarded and in pregnant and non-pregnant women in Ontario. (author)

  12. Comparing human norovirus surrogates: murine norovirus and Tulane virus.

    Science.gov (United States)

    Hirneisen, Kirsten A; Kniel, Kalmia E

    2013-01-01

    Viral surrogates are widely used by researchers to predict human norovirus behavior. Murine norovirus (MNV) is currently accepted as the best surrogate and is assumed to mimic the survival and inactivation of human noroviruses. Recently, a new calicivirus, the Tulane virus (TV), was discovered, and its potential as a human norovirus surrogate is being explored. This study aimed to compare the behavior of the two potential surrogates under varying treatments of pH (2.0 to 10.0), chlorine (0.2 to 2,000 ppm), heat (50 to 75°C), and survival in tap water at room (20°C) and refrigeration (4°C) temperatures for up to 30 days. Viral infectivity was determined by the plaque assay for both MNV and TV. There was no significant difference between the inactivation of MNV and TV in all heat treatments, and for both MNV and TV survival in tap water at 20°C over 30 days. At 4°C, MNV remained infectious over 30 days at a titer of approximately 5 log PFU/ml, whereas TV titers decreased significantly by 5 days. MNV was more pH stable, as TV titers were reduced significantly at pH 2.0, 9.0, and 10.0, as compared with pH 7.0, whereas MNV titers were only significantly reduced at pH 10.0. After chlorine treatment, there was no significant difference in virus with the exception of at 2 ppm, where TV decreased significantly compared with MNV. Compared with TV, MNV is likely a better surrogate for human noroviruses, as MNV persisted over a wider range of pH values, at 2 ppm of chlorine, and without a loss of titer at 4°C. PMID:23317870

  13. Deconstructing the surrogate species concept: a life history approach to the protection of ecosystem services

    Science.gov (United States)

    The use of the surrogate species concept is widespread in environmental risk assessment and in particular the protection of species that provide ecosystem services, yet there are no standard protocols in place for the choice of surrogates. Surrogates are often chosen on the basis of convenience or ...

  14. Antiphospholipid Antibody Syndrome

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Antiphospholipid Antibody Syndrome? Antiphospholipid (AN-te-fos-fo-LIP-id) antibody ... weeks or months. This condition is called catastrophic antiphospholipid syndrome (CAPS). People who have APS also are at ...

  15. Antibody Response to Pneumocystis jirovecii

    OpenAIRE

    Daly, Kieran R.; Huang, Laurence; Morris, Alison; Koch, Judy; Crothers, Kristina; Levin, Linda; Eiser, Shary; Satwah, Supriya; Zucchi, Patrizia; Walzer, Peter D.

    2006-01-01

    We conducted a prospective pilot study of the serologic responses to overlapping recombinant fragments of the Pneumocystis jirovecii major surface glycoprotein (Msg) in HIV-infected patients with pneumonia due to P. jirovecii and other causes. Similar baseline geometric mean antibody levels to the fragments measured by an ELISA were found in both groups. Serum antibodies to MsgC in P. jirovecii patients rose to a peak level 3–4 weeks (p50 cells/μL and first episode of pneumocystosis were the ...

  16. The antibody mining toolbox

    OpenAIRE

    D'Angelo, Sara; Glanville, Jacob; Ferrara, Fortunato; Naranjo, Leslie; Gleasner, Cheryl D.; Shen, Xiaohong; Bradbury, Andrew RM; Kiss, Csaba

    2013-01-01

    In vitro selection has been an essential tool in the development of recombinant antibodies against various antigen targets. Deep sequencing has recently been gaining ground as an alternative and valuable method to analyze such antibody selections. The analysis provides a novel and extremely detailed view of selected antibody populations, and allows the identification of specific antibodies using only sequencing data, potentially eliminating the need for expensive and laborious low-throughput ...

  17. Heavy chain only antibodies

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein; Rahbarizadeh, Fatemeh; Ahmadvand, Davoud;

    2013-01-01

    Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen...

  18. Hepatitis A virus antibody

    International Nuclear Information System (INIS)

    A description is presented of a radioimmunoassay designed to prove the presence of the antibody against the hepatitis A virus (HA Ab, anti-Ha) using an Abbott HAVAB set. This proof as well as the proof of the antibody against the nucleus of the hepatitis B virus is based on competition between a normal antibody against hepatitis A virus and a 125I-labelled antibody for the binding sites of a specific antigen spread all over the surface of a tiny ball; this is then indirect proof of the antibody under investigation. The method is described of reading the results from the number of impulses per 60 seconds: the higher the titre of the antibody against the hepatitis A virus in the serum examined, the lower the activity of the specimen concerned. The rate is reported of incidence of the antibody against the hepatitis A virus in a total of 68 convalescents after hepatitis A; the antibody was found in 94.1%. The immunoglobulin made from the convalescents' plasma showed the presence of antibodies in dilutions as high as 1:250 000 while the comparable ratio for normal immunoglobulin Norga was only 1:2500. Differences are discussed in the time incidence of the antibodies against the hepatitis A virus, the antibodies against the surface antigen of hepatitis B, and the antibody against the nucleus of the hepatitis V virus. (author)

  19. Efflux of rhodamine from CD56+ cells as a surrogate marker for reversal of P-glycoprotein-mediated drug efflux by PSC 833

    DEFF Research Database (Denmark)

    Robey, R; Bakke, S; Stein, W;

    1999-01-01

    The expression of high levels of P-glycoprotein (Pgp) in circulating mononuclear cells allowed us to use an ex vivo assay as a surrogate measure of Pgp antagonism. Efflux of rhodamine from CD56(+) cells was measured before the start of PSC 833 and at varying times thereafter. Patients receiving P...

  20. Molecular-specific urokinase antibodies

    Science.gov (United States)

    Atassi, M. Zouhair (Inventor); Morrison, Dennis R. (Inventor)

    2009-01-01

    Antibodies have been developed against the different molecular forms of urokinase using synthetic peptides as immunogens. The peptides were synthesized specifically to represent those regions of the urokinase molecules which are exposed in the three-dimensional configuration of the molecule and are uniquely homologous to urokinase. Antibodies are directed against the lysine 158-isoleucine 159 peptide bond which is cleaved during activation from the single-chain (ScuPA) form to the bioactive double chain (54 KDa and 33 KDa) forms of urokinase and against the lysine 135 lysine 136 bond that is cleaved in the process of removing the alpha-chain from the 54 KDa form to produce the 33 KDa form of urokinase. These antibodies enable the direct measurement of the different molecular forms of urokinase from small samples of conditioned medium harvested from cell cultures.

  1. Quantitative Assessment of Antibody Internalization with Novel Monoclonal Antibodies against Alexa Fluorophores

    OpenAIRE

    Liao-Chan, Sindy; Daine-Matsuoka, Barbara; Heald, Nathan; Wong, Tiffany; Lin, Tracey; Cai, Allen G.; Lai, Michelle; D’Alessio, Joseph A.; Theunissen, Jan-Willem

    2015-01-01

    Antibodies against cell surface antigens may be internalized through their specific interactions with these proteins and in some cases may induce or perturb antigen internalization. The anti-cancer efficacy of antibody-drug conjugates is thought to rely on their uptake by cancer cells expressing the surface antigen. Numerous techniques, including microscopy and flow cytometry, have been used to identify antibodies with desired cellular uptake rates. To enable quantitative measurements of inte...

  2. Measurement of immunoglobulin M, immunoglobulin G, and immunoglobulin A antibodies against Yersinia enterocolitica by enzyme-linked immunosorbent assay: comparison of lipopolysaccharide and whole bacterium as antigen.

    OpenAIRE

    Granfors, K; Viljanen, M K; Toivanen, A

    1981-01-01

    An enzyme-linked immunosorbent assay (ELISA) for the detection and quantitation of human immunoglobulin M (IgM), IgG, and IgA antibodies against Yersinia enterocolitica by using lipopolysaccharides as antigens is described. The results obtained with the lipopolysaccharide ELISA were compared with the results of the whole bacterium ELISA. The correlations observed were good for each immunoglobulin class. Cross-reactions between Y. enterocolitica serotypes O:3 and O:9, Yersinia pseudotuberculos...

  3. Is blood pressure reduction a valid surrogate endpoint for stroke prevention? an analysis incorporating a systematic review of randomised controlled trials, a by-trial weighted errors-in-variables regression, the surrogate threshold effect (STE and the biomarker-surrogacy (BioSurrogate evaluation schema (BSES

    Directory of Open Access Journals (Sweden)

    Lassere Marissa N

    2012-03-01

    Full Text Available Abstract Background Blood pressure is considered to be a leading example of a valid surrogate endpoint. The aims of this study were to (i formally evaluate systolic and diastolic blood pressure reduction as a surrogate endpoint for stroke prevention and (ii determine what blood pressure reduction would predict a stroke benefit. Methods We identified randomised trials of at least six months duration comparing any pharmacologic anti-hypertensive treatment to placebo or no treatment, and reporting baseline blood pressure, on-trial blood pressure, and fatal and non-fatal stroke. Trials with fewer than five strokes in at least one arm were excluded. Errors-in-variables weighted least squares regression modelled the reduction in stroke as a function of systolic blood pressure reduction and diastolic blood pressure reduction respectively. The lower 95% prediction band was used to determine the minimum systolic blood pressure and diastolic blood pressure difference, the surrogate threshold effect (STE, below which there would be no predicted stroke benefit. The STE was used to generate the surrogate threshold effect proportion (STEP, a surrogacy metric, which with the R-squared trial-level association was used to evaluate blood pressure as a surrogate endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3. Results In 18 qualifying trials representing all pharmacologic drug classes of antihypertensives, assuming a reliability coefficient of 0.9, the surrogate threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41 and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure respectively. The STE and STEP were more robust to measurement error in the independent variable than R-squared trial-level associations. Using the BSES3, assuming a reliability coefficient of 0.9, systolic blood pressure was a B + grade and

  4. 21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antimitochondrial antibody immunological test... Systems § 866.5090 Antimitochondrial antibody immunological test system. (a) Identification. An antimitochondrial antibody immunological test system is a device that consists of the reagents used to measure...

  5. Serum Antibody Response to Clostridium botulinum Toxin in Infant Botulism

    OpenAIRE

    Rubin, Lorry G.; Dezfulian, Manuchehr; Yolken, Robert H.

    1982-01-01

    A serum antibody response has not been previously demonstrated after infection with Clostridium botulinum. We developed an enzyme immunoassay for measuring serum antibody to C. botulinum toxins A, B, and E. This assay system detected a specific immunoglobulin G and immunoglobulin M antibody response to C. botulinum toxin in two patients with infant botulism.

  6. Evidence from Biomarkers and Surrogate Endpoints

    OpenAIRE

    Feigin, Andrew

    2004-01-01

    Summary: The use of physiological, anatomical, and other biological tests is commonplace in the practice of medicine. In neurology, objectively measured tests termed biomarkers (BMs) are playing an increasing role in diagnosis and management of disease, both in clinical practice and in experimental therapeutics. This article will discuss the various applications of BMs to the assessment of therapies for neurological diseases and will use examples from neurological diseases to elucidate the st...

  7. Laminar burning velocities at elevated pressures for gasoline and gasoline surrogates associated with RON

    KAUST Repository

    Mannaa, Ossama

    2015-06-01

    The development and validation of a new gasoline surrogate using laminar flame speed as a target parameter is presented. Laminar burning velocities were measured using a constant-volume spherical vessel with ignition at the center of the vessel. Tested fuels included iso-octane, n-heptane, toluene, various mixtures of primary reference fuels (PRFs) and toluene reference fuels (TRFs) and three gasoline fuels of 70, 85 and 95 RON (FACE J, C and F) at the initial temperature of 358K and pressures up to 0.6MPa in the equivalence ratio ranging from 0.8 to 1.6. Normalized laminar burning velocity data were mapped into a tri-component mixture space at different experimental conditions to allocate different gasoline surrogates for different gasoline fuels, having RON of 70, 85 and 95. The surrogates of TRF-70-4 (17.94% iso-C8H18 +42.06% n-C7H16 +40% C7H8), TRF-85-1 (77.4% iso-C8H18 +17.6% n-C7H16 +5% C7H8), and TRF-95-1 (88.47% iso-C8H18 +6.53% n-C7H16 +5% C7H8) of RON 70, 85 and 95, respectively, are shown to successfully emulate the burning rate characteristics of the gasoline fuels associated with these RONs under the various experimental conditions investigated. An empirical correlation was derived to obtain laminar burning velocities at pressures that are experimentally unattainable as high as 3.0MPa. Laminar burning velocities were comparable to the simulated values for lean and stoichiometric flames but they were relatively higher than the simulated values for rich flames. A flame instability assessment was conducted by determining Markstein length, critical Pecklet number, and critical Karlovitz number at the onset of flame instability.

  8. Enhanced genome editing in mammalian cells with a modified dual-fluorescent surrogate system.

    Science.gov (United States)

    Zhou, Yan; Liu, Yong; Hussmann, Dianna; Brøgger, Peter; Al-Saaidi, Rasha Abdelkadhem; Tan, Shuang; Lin, Lin; Petersen, Trine Skov; Zhou, Guang Qian; Bross, Peter; Aagaard, Lars; Klein, Tino; Rønn, Sif Groth; Pedersen, Henrik Duelund; Bolund, Lars; Nielsen, Anders Lade; Sørensen, Charlotte Brandt; Luo, Yonglun

    2016-07-01

    Programmable DNA nucleases such as TALENs and CRISPR/Cas9 are emerging as powerful tools for genome editing. Dual-fluorescent surrogate systems have been demonstrated by several studies to recapitulate DNA nuclease activity and enrich for genetically edited cells. In this study, we created a single-strand annealing-directed, dual-fluorescent surrogate reporter system, referred to as C-Check. We opted for the Golden Gate Cloning strategy to simplify C-Check construction. To demonstrate the utility of the C-Check system, we used the C-Check in combination with TALENs or CRISPR/Cas9 in different scenarios of gene editing experiments. First, we disrupted the endogenous pIAPP gene (3.0 % efficiency) by C-Check-validated TALENs in primary porcine fibroblasts (PPFs). Next, we achieved gene-editing efficiencies of 9.0-20.3 and 4.9 % when performing single- and double-gene targeting (MAPT and SORL1), respectively, in PPFs using C-Check-validated CRISPR/Cas9 vectors. Third, fluorescent tagging of endogenous genes (MYH6 and COL2A1, up to 10.0 % frequency) was achieved in human fibroblasts with C-Check-validated CRISPR/Cas9 vectors. We further demonstrated that the C-Check system could be applied to enrich for IGF1R null HEK293T cells and CBX5 null MCF-7 cells with frequencies of nearly 100.0 and 86.9 %, respectively. Most importantly, we further showed that the C-Check system is compatible with multiplexing and for studying CRISPR/Cas9 sgRNA specificity. The C-Check system may serve as an alternative dual-fluorescent surrogate tool for measuring DNA nuclease activity and enrichment of gene-edited cells, and may thereby aid in streamlining programmable DNA nuclease-mediated genome editing and biological research. PMID:26755436

  9. Using a surrogate contact pair to evaluate polyethylene wear in prosthetic knee joints.

    Science.gov (United States)

    Sanders, Anthony P; Lockard, Carly A; Weisenburger, Joel N; Haider, Hani; Raeymaekers, Bart

    2016-01-01

    With recent improvements to the properties of ultra-high molecular weight polyethylene (UHMWPE) used in joint replacements, prosthetic knee and hip longevity may extend beyond two decades. However, it is difficult and costly to replicate such a long in vivo lifetime using clinically relevant in vitro wear testing approaches such as walking gait joint simulators. We advance a wear test intermediate in complexity between pin-on-disk and knee joint simulator tests. The test uses a surrogate contact pair, consisting of a surrogate femoral and tibial specimen that replicate the contact mechanics of any full-scale knee condyle contact pair. The method is implemented in a standard multi-directional pin-on-disk wear test machine, and we demonstrate its application via a two-million-cycle wear test of three different UHMWPE formulations. Further, we demonstrate the use of digital photography and image processing to accurately quantify fatigue damage based on the reduced transmission of light through a damage area in a UHMWPE specimen. The surrogate contact pairs replicate the knee condyle contact areas within -3% to +12%. The gravimetric wear test results reflect the dose of crosslinking radiation applied to the UHMWPE: 35 kGy yielded a wear rate of 7.4 mg/Mcycles, 55 kGy yielded 1.0 mg/Mcycles, and 75 kGy (applied to a 0.1% vitamin E stabilized UHMWPE) yielded 1.5 mg/Mcycles. A precursor to spalling fatigue is observed and precisely measured in the radiation-sterilized (35 kGy) and aged UHMWPE specimen. The presented techniques can be used to evaluate the high-cycle fatigue performance of arbitrary knee condyle contact pairs under design-specific contact stresses, using existing wear test machines. This makes the techniques more economical and well-suited to standardized comparative testing. PMID:25677393

  10. Validity of sealant retention as surrogate for caries prevention--a systematic review.

    Directory of Open Access Journals (Sweden)

    Steffen Mickenautsch

    Full Text Available INTRODUCTION/AIM: To appraise the clinical literature in determining whether loss of complete sealant retention as surrogate endpoint is directly associated with caries occurrence on sealed teeth as its clinical endpoint and to apply the appraised evidence in testing the null-hypothesis that the retention/caries ratio between different types of sealant materials (resin and glass-ionomer cement is not statistically significant (= Prentice criterion for surrogate endpoint validity. METHODS: Databases searched PubMed/Medline, Directory of Open Access Journals; IndMed, Scielo. Systematic reviews were checked for suitable trials. The search terms: "fiss* AND seal*" and "fissure AND sealant" were used. Article selection criteria were: clinical trial reporting on the retention and caries occurrence of resin and/or glass-ionomer cement (GIC fissure sealed permanent molar teeth; minimum 24-month follow-up period; systematic review or meta-analysis. Datasets and information were extracted from accepted trials. The principle outcome measure was the ratio of Risk of loss of complete retention to the Risk of caries occurrence per sealant type (RCR. Risk of bias was assessed in trials and sensitivity analysis with regard to potential confounding factors conducted. The null-hypothesis was tested by graphical and statistical methods. RESULTS: The risk of loss of complete retention of sealant materials was associated with the risk of caries occurrence for resin but not for GIC based sealants. The difference between RCR values of the two sealant types was statistically significant (p<0.05. The null-hypothesis was rejected. CONCLUSIONS: The current clinical evidence suggests that complete retention of pit and fissure sealants may not be a valid surrogate endpoint for caries prevention as its clinical endpoint. Further research is required to corroborate the current results.

  11. Development of a surrogate model for elemental analysis using a natural gamma ray spectroscopy tool

    International Nuclear Information System (INIS)

    A systematic computational method for obtaining accurate elemental standards efficiently for varying borehole conditions was developed based on Monte Carlo simulations, surrogate modeling, and data assimilation. Elemental standards are essential for spectral unfolding in formation evaluation applications commonly used for nuclear well logging tools. Typically, elemental standards are obtained by standardized measurements, but these experiments are expensive and lack the flexibility to address different logging conditions. In contrast, computer-based Monte Carlo simulations provide an accurate and more flexible approach to obtaining elemental standards for formation evaluation. The presented computational method recognizes that in contrast to typical neutron–photon simulations, where the source is typically artificial and well characterized (Galford, 2009), an accurate knowledge of the source is essential for matching the obtained Monte Carlo elemental standards with their experimental counterparts. Therefore, source distributions are adjusted to minimize the L2 difference of the Monte Carlo computed and experimental standards. Subsequently, an accurate surrogate model is developed accounting for different casing and cement thicknesses, and tool positions within the borehole. The adjusted source distributions are then utilized to generate and validate spectra for varying borehole conditions: tool position, casing and cement thickness. The effect of these conditions on the spectra are investigated and discussed in this work. Given that Monte Carlo modeling provides much lower cost and more flexibility, employing Monte Carlo could enhance the processing of nuclear tool logging data computed standards. - Highlights: • A novel computational model for efficiently computing elemental standards for varying borehole conditions has been developed. • A model of an experimental test pit was implemented in the Monte Carlo code GEANT4 for computing elemental standards.

  12. Antiviral Effect of Korean Red Ginseng Extract and Ginsenosides on Murine Norovirus and Feline Calicivirus as Surrogates for Human Norovirus

    OpenAIRE

    Lee, Min Hwa; Lee, Bog-Hieu; Jung, Ji-Youn; Cheon, Doo-Sung; Kim, Kyung-Tack; Choi, Changsun

    2011-01-01

    Korean red ginseng has been studied various biological activities such as immune, anti-oxidative, anti-microbial, and anticancer activities but antiviral mechanism needs further studies. In this study, we aimed to examine the antiviral effects of Korea red ginseng extract and ginsenosides on norovirus surrogate, including murine norovirus (MNV) and feline calicivirus (FCV). We evaluated the pre-, co-, and post-treatment effects of Korean red ginseng (KRG), ginsenosides Rb1 and Rg1. To measure...

  13. To What Extent is Blood a Reasonable Surrogate for Brain in Gene Expression Studies: Estimation from Mouse Hippocampus and Spleen

    OpenAIRE

    Davies, Matthew N; Lawn, Sarah; Whatley, Steven; Fernandes, Cathy; Robert W Williams; Schalkwyk, Leonard C

    2009-01-01

    Microarrays are designed to measure genome-wide differences in gene expression. In cases where a tissue is not accessible for analysis (e.g. human brain), it is of interest to determine whether a second, accessible tissue could be used as a surrogate for transcription profiling. Surrogacy has applications in the study of behavioural and neurodegenerative disorders. Comparison between hippocampus and spleen mRNA obtained from a mouse recombinant inbred panel indicates a high degree of correlat...

  14. Resident physician interactions with surrogate decision-makers: the resident experience.

    Science.gov (United States)

    Reckrey, Jennifer M; McKee, M Diane; Sanders, Justin J; Lipman, Hannah I

    2011-12-01

    This study explored interactions between medical residents and patient surrogates in order to clarify resident understanding of roles and relationships, resident emotional experience, and resident learning processes. Qualitative analysis of in-depth interviews were used involving three family medicine residency programs serving culturally diverse, urban, underserved patient populations. Eighteen second- and third-year trainees described a memorable interaction with a surrogate and then were prompted to discuss their learning experience and their role in the interaction. Interviews were transcribed verbatim and analyzed through an iterative process. Residents experienced significant emotional burden during interactions yet continued to value their relationships with surrogates. Despite their reservations about giving recommendations, residents adopted a variety of roles with surrogates as they gave support, information, and advice. Although residents reported little formal education about surrogate decision-making, they relied on passive role modeling and their own previous experiences to help surrogates make decisions. Residents have complex and emotionally significant interactions with surrogates despite minimal formal education about surrogate decision-making. Educational efforts should seek to help residents understand their own emotions and the ethical beliefs that underlie the roles they adopt with surrogates. This will help residents to facilitate value-based conversations with surrogates and better support surrogates in the decision-making process. PMID:22092192

  15. Bos taurus genome sequence reveals the assortment of immunoglobulin and surrogate light chain genes in domestic cattle

    Directory of Open Access Journals (Sweden)

    Liljavirta Jenni

    2009-04-01

    Full Text Available Abstract Background The assortment of cattle immunoglobulin and surrogate light chain genes has been extracted from the version 3.1 of Bos taurus genome sequence as a part of an international effort to sequence and annotate the bovine genome. Results 63 variable lambda chain and 22 variable kappa chain genes were identified and phylogenetically assigned to 8 and 4 subgroups, respectively. The specified phylogenetic relationships are compatible with the established ruminant light chain variable gene families or subgroups. Because of gaps and uncertainties in the assembled genome sequence, the number of genes might change in the future versions of the genome sequence. In addition, three bovine surrogate light chain genes were identified. The corresponding cDNAs were cloned and the expression of the surrogate light chain genes was demonstrated from fetal material. Conclusion The bovine kappa gene locus is compact and simple which may reflect the preferential use of the lambda chain in cattle. The relative orientation of variable and joining genes in both loci are consistent with a deletion mechanism in VJ joining. The orientation of some variable genes cannot be determined from the data available. The number of functional variable genes is moderate when compared to man or mouse. Thus, post-recombinatorial mechanisms might contribute to the generation of the bovine pre-immune antibody repertoire. The heavy chains probably contribute more to recombinational immunoglobulin repertoire diversity than the light chains but the heavy chain locus could not be annotated from the version 3.1 of Bos taurus genome.

  16. Test your surrogate data before you test for nonlinearity

    CERN Document Server

    Kugiumtzis, D

    1999-01-01

    The schemes for the generation of surrogate data in order to test the null hypothesis of linear stochastic process undergoing nonlinear static transform are investigated as to their consistency in representing the null hypothesis. In particular, we pinpoint some important caveats of the prominent algorithm of amplitude adjusted Fourier transform surrogates (AAFT) and compare it to the iterated AAFT (IAAFT), which is more consistent in representing the null hypothesis. It turns out that in many applications with real data the inferences of nonlinearity after marginal rejection of the null hypothesis were premature and have to be re-investigated taken into account the inaccuracies in the AAFT algorithm, mainly concerning the mismatching of the linear correlations. In order to deal with such inaccuracies we propose the use of linear together with nonlinear polynomials as discriminating statistics. The application of this setup to some well-known real data sets cautions against the use of the AAFT algorithm.

  17. Very Short Literature Survey From Supervised Learning To Surrogate Modeling

    CERN Document Server

    Brusan, Altay

    2012-01-01

    The past century was era of linear systems. Either systems (especially industrial ones) were simple (quasi)linear or linear approximations were accurate enough. In addition, just at the ending decades of the century profusion of computing devices were available, before then due to lack of computational resources it was not easy to evaluate available nonlinear system studies. At the moment both these two conditions changed, systems are highly complex and also pervasive amount of computation strength is cheap and easy to achieve. For recent era, a new branch of supervised learning well known as surrogate modeling (meta-modeling, surface modeling) has been devised which aimed at answering new needs of modeling realm. This short literature survey is on to introduce surrogate modeling to whom is familiar with the concepts of supervised learning. Necessity, challenges and visions of the topic are considered.

  18. Environmental persistence of Tulane virus - a surrogate for human norovirus.

    Science.gov (United States)

    Arthur, Sabastine Eugene; Gibson, Kristen Elizabeth

    2016-05-01

    Human noroviruses (HuNoVs) are the leading cause of acute viral gastroenteritis worldwide. The persistence of HuNoV in the environment contributes significantly to its transmission to humans. Surrogate viruses are used to study HuNoV owing to the lack of a cell culture system for this virus. Here, the persistence of Tulane virus (TV) - a novel HuNoV surrogate - in surface water (SW) and groundwater (GW) as well as on acrylic-based solid (ABS) and stainless steel (SS) surfaces was investigated. After 28 days, TV remained stable in SW (ABS, with corresponding D values of 18.5 ± 0.34 and 13.1 ± 0.36 days, respectively. This is the first study to demonstrate the persistence of TV in environmental waters and on fomite surfaces. PMID:26825139

  19. A Parallel and Distributed Surrogate Model Implementation for Computational Steering

    KAUST Repository

    Butnaru, Daniel

    2012-06-01

    Understanding the influence of multiple parameters in a complex simulation setting is a difficult task. In the ideal case, the scientist can freely steer such a simulation and is immediately presented with the results for a certain configuration of the input parameters. Such an exploration process is however not possible if the simulation is computationally too expensive. For these cases we present in this paper a scalable computational steering approach utilizing a fast surrogate model as substitute for the time-consuming simulation. The surrogate model we propose is based on the sparse grid technique, and we identify the main computational tasks associated with its evaluation and its extension. We further show how distributed data management combined with the specific use of accelerators allows us to approximate and deliver simulation results to a high-resolution visualization system in real-time. This significantly enhances the steering workflow and facilitates the interactive exploration of large datasets. © 2012 IEEE.

  20. Gaseous pollutants in particulate matter epidemiology: confounders or surrogates?

    OpenAIRE

    Sarnat, J A; Schwartz, J.; Catalano, P J; Suh, H H

    2001-01-01

    Air pollution epidemiologic studies use ambient pollutant concentrations as surrogates of personal exposure. Strong correlations among numerous ambient pollutant concentrations, however, have made it difficult to determine the relative contribution of each pollutant to a given health outcome and have led to criticism that health effect estimates for particulate matter may be biased due to confounding. In the current study we used data collected from a multipollutant exposure study conducted i...

  1. ASM-MOMA: Multiobjective Memetic Algorithm with Aggregate Surrogate Model

    Czech Academy of Sciences Publication Activity Database

    Pilát, M.; Neruda, Roman

    Piscataway : IEEE, 2011, s. 1202-1208. ISBN 978-1-4244-7834-7. [CEC 2011. Congress on Evolutionary Computation. New Orleans (US), 05.06.2011-08.06.2011] R&D Projects: GA ČR GAP202/11/1368 Institutional research plan: CEZ:AV0Z10300504 Keywords : multiobjective optimization * evolutionary algorithms * surrogate models * meta-model Subject RIV: IN - Informatics, Computer Science

  2. Current issues on a standard for surrogate pregnancy procedures

    OpenAIRE

    Ha, Jung-Ok

    2012-01-01

    While Korea does not have any legal statement on surrogacy, treatments are carried out in practice. As a result, every Institutional Review Board (IRB) of each fertility clinic faces an ethical predicament in reviewing each case. There is a need to arrange the institutions' own standards of surrogate pregnancy procedures before the establishment of national or professional regulation. This article examines the legal, social, and medical issues of surrogacy to help IRBs to judge their cases.

  3. Current issues on a standard for surrogate pregnancy procedures.

    Science.gov (United States)

    Ha, Jung-Ok

    2012-12-01

    While Korea does not have any legal statement on surrogacy, treatments are carried out in practice. As a result, every Institutional Review Board (IRB) of each fertility clinic faces an ethical predicament in reviewing each case. There is a need to arrange the institutions' own standards of surrogate pregnancy procedures before the establishment of national or professional regulation. This article examines the legal, social, and medical issues of surrogacy to help IRBs to judge their cases. PMID:23346523

  4. Hypervolume-Based Surrogate Model for MO-CMA-ES

    Czech Academy of Sciences Publication Activity Database

    Pilát, M.; Neruda, Roman

    Piscataway: IEEE Computer Society, 2015, s. 604-611. ISBN 978-1-5090-0163-7. ISSN 1082-3409. [ICTAI 2015. IEEE International Conference on Tools with Artificial Intelligence /27./. Vietri sul Mare (IT), 09.11.2015-11.11.2015] R&D Projects: GA ČR GA15-19877S Institutional support: RVO:67985807 Keywords : MO-CMA-ES * hypervolume * surrogate modelling * multi-objective optimization Subject RIV: IN - Informatics, Computer Science

  5. Toward a psychology of surrogate decision-making

    OpenAIRE

    Richard J Tunney; Ziegler, Fenja V.

    2015-01-01

    Many of the decisions that we make in everyday life are made for the benefit of other people. However, research suggests that people often make decisions on behalf of other people that are different from those that the other person would choose for himself or herself. This raises practical problems in the case of legally designated surrogate decision-makers who may not meet the legal normative benchmark — the substituted judgment standard. We review evidence from our own ...

  6. Accuracy of surrogate solutions of integral equations by feedforward networks

    Czech Academy of Sciences Publication Activity Database

    Kůrková, Věra

    Cham : Springer, 2014 - (Kóczy, L.; Pozna, C.; Kacprzyk, J.), s. 91-102 ISBN 978-3-319-03205-4. - (Studies in Computational Intelligence . 530) R&D Projects: GA ČR GAP202/11/1368; GA MŠk(CZ) LD13002 Institutional support: RVO:67985807 Keywords : surrogate modeling by neural networks * approximate solutions of integral equations * feedforward neural networks * model complexity * rates of approximation Subject RIV: IN - Informatics, Computer Science

  7. Commercial agencies and surrogate motherhood: a transaction cost approach.

    Science.gov (United States)

    Galbraith, Mhairi; McLachlan, Hugh V; Swales, J Kim

    2005-03-01

    In this paper we investigate the legal arrangements involved in UK surrogate motherhood from a transaction-cost perspective. We outline the specific forms the transaction costs take and critically comment on the way in which the UK institutional and organisational arrangements at present adversely influence transaction costs. We then focus specifically on the potential role of surrogacy agencies and look at UK and US evidence on commercial and voluntary agencies. Policy implications follow. PMID:15889679

  8. The diaphragm as an anatomic surrogate for lung tumor motion

    Science.gov (United States)

    Cerviño, Laura I.; Chao, Alvin K. Y.; Sandhu, Ajay; Jiang, Steve B.

    2009-06-01

    Lung tumor motion due to respiration poses a challenge in the application of modern three-dimensional conformal radiotherapy. Direct tracking of the lung tumor during radiation therapy is very difficult without implanted fiducial markers. Indirect tracking relies on the correlation of the tumor's motion and the surrogate's motion. The present paper presents an analysis of the correlation between tumor motion and diaphragm motion in order to evaluate the potential use of diaphragm as a surrogate for tumor motion. We have analyzed the correlation between diaphragm motion and superior-inferior lung tumor motion in 32 fluoroscopic image sequences from ten lung cancer patients. A simple linear model and a more complex linear model that accounts for phase delays between the two motions have been used. Results show that the diaphragm is a good surrogate for tumor motion prediction for most patients, resulting in an average correlation factor of 0.94 and 0.98 with each model respectively. The model that accounts for delays leads to an average localization prediction error of 0.8 mm and an error at the 95% confidence level of 2.1 mm. However, for one patient studied, the correlation is much weaker compared to other patients. This indicates that, before using diaphragm for lung tumor prediction, the correlation should be examined on a patient-by-patient basis.

  9. Progress in Chemical Kinetic Modeling for Surrogate Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, W J; Westbrook, C K; Herbinet, O; Silke, E J

    2008-06-06

    Gasoline, diesel, and other alternative transportation fuels contain hundreds to thousands of compounds. It is currently not possible to represent all these compounds in detailed chemical kinetic models. Instead, these fuels are represented by surrogate fuel models which contain a limited number of representative compounds. We have been extending the list of compounds for detailed chemical models that are available for use in fuel surrogate models. Detailed models for components with larger and more complicated fuel molecular structures are now available. These advancements are allowing a more accurate representation of practical and alternative fuels. We have developed detailed chemical kinetic models for fuels with higher molecular weight fuel molecules such as n-hexadecane (C16). Also, we can consider more complicated fuel molecular structures like cyclic alkanes and aromatics that are found in practical fuels. For alternative fuels, the capability to model large biodiesel fuels that have ester structures is becoming available. These newly addressed cyclic and ester structures in fuels profoundly affect the reaction rate of the fuel predicted by the model. Finally, these surrogate fuel models contain large numbers of species and reactions and must be reduced for use in multi-dimensional models for spark-ignition, HCCI and diesel engines.

  10. Diaphragm as an anatomic surrogate for lung tumor motion

    CERN Document Server

    Cervino, Laura I; Sandhu, Ajay; Jiang, Steve B

    2009-01-01

    Lung tumor motion due to respiration poses a challenge in the application of modern three-dimensional conformal radiotherapy. Direct tracking of the lung tumor during radiation therapy is very difficult without implanted fiducial markers. Indirect tracking relies on the correlation of the tumor's motion and the surrogate's motion. The present paper presents an analysis of the correlation between the tumor motion and the diaphragm motion in order to evaluate the potential use of diaphragm as a surrogate for tumor motion. We have analyzed the correlation between diaphragm motion and superior-inferior lung tumor motion in 32 fluoroscopic image sequences from 10 lung cancer patients. A simple linear model and a more complex linear model that accounts for phase delays between the two motions have been used. Results show that the diaphragm is a good surrogate for tumor motion prediction for most patients, resulting in an average correlation factor of 0.94 and 0.98 with each model respectively. The model that accoun...

  11. Surrogate Assisted Design Optimization of an Air Turbine

    Directory of Open Access Journals (Sweden)

    Rameez Badhurshah

    2014-01-01

    Full Text Available Surrogates are cheaper to evaluate and assist in designing systems with lesser time. On the other hand, the surrogates are problem dependent and they need evaluation for each problem to find a suitable surrogate. The Kriging variants such as ordinary, universal, and blind along with commonly used response surface approximation (RSA model were used in the present problem, to optimize the performance of an air impulse turbine used for ocean wave energy harvesting by CFD analysis. A three-level full factorial design was employed to find sample points in the design space for two design variables. A Reynolds-averaged Navier Stokes solver was used to evaluate the objective function responses, and these responses along with the design variables were used to construct the Kriging variants and RSA functions. A hybrid genetic algorithm was used to find the optimal point in the design space. It was found that the best optimal design was produced by the universal Kriging while the blind Kriging produced the worst. The present approach is suggested for renewable energy application.

  12. The Confucian bioethics of surrogate decision making: its communitarian roots.

    Science.gov (United States)

    Fan, Ruiping

    2011-10-01

    The family is the exemplar community of Chinese society. This essay explores how Chinese communitarian norms, expressed in thick commitments to the authority and autonomy of the family, are central to contemporary Chinese bioethics. In particular, it focuses on the issue of surrogate decision making to illustrate the Confucian family-grounded communitarian bioethics. The essay first describes the way in which the family, in Chinese bioethics, functions as a whole to provide consent for significant medical and surgical interventions when a patient has lost decision-making capacity. It is argued that the practice of not having an established order for surrogate decision makers (e.g., spouse, children, and then parents), as it is done in the United States, reflects the acknowledgment that the family as a social reality cannot be reduced to a stereotype of the appropriate order of default decision makers. This description of the family as being in authority to make surrogate decisions for an incompetent family member is enriched by an elaboration of the differences among the concepts of patient autonomy, family autonomy, and moral autonomy. The Chinese model, as well as the Confucian communitarian life of families, engages a family autonomy that is supported by a Confucian understanding of moral autonomy, rather than individual autonomy. Finally, the issue of possible conflicts between patient and family interests in relation to a patient's past wishes in the Chinese model is addressed in light of the role of the physician. PMID:21858670

  13. Evaluation of bone surrogates for indirect and direct ballistic fractures.

    Science.gov (United States)

    Bir, Cynthia; Andrecovich, Chris; DeMaio, Marlene; Dougherty, Paul J

    2016-04-01

    The mechanism of injury for fractures to long bones has been studied for both direct ballistic loading as well as indirect. However, the majority of these studies have been conducted on both post-mortem human subjects (PMHS) and animal surrogates which have constraints in terms of storage, preparation and testing. The identification of a validated bone surrogate for use in forensic, medical and engineering testing would provide the ability to investigate ballistic loading without these constraints. Two specific bone surrogates, Sawbones and Synbone, were evaluated in comparison to PMHS for both direct and indirect ballistic loading. For the direct loading, the mean velocity to produce fracture was 121 ± 19 m/s for the PMHS, which was statistically different from the Sawbones (140 ± 7 m/s) and Synbone (146 ± 3 m/s). The average distance to fracture in the indirect loading was .70 cm for the PMHS. The Synbone had a statistically similar average distance to fracture (.61 cm, p=0.54) however the Sawbones average distance to fracture was statistically different (.41 cm, pballistic testing was not identified and future work is warranted. PMID:26867672

  14. A Neutralizing Antibody Assay Based on a Reporter of Antibody-Dependent Cell-Mediated Cytotoxicity.

    Science.gov (United States)

    Wu, Yuling; Li, Jia J; Kim, Hyun Jun; Liu, Xu; Liu, Weiyi; Akhgar, Ahmad; Bowen, Michael A; Spitz, Susan; Jiang, Xu-Rong; Roskos, Lorin K; White, Wendy I

    2015-11-01

    Benralizumab is a humanized anti-IL5 receptor α (IL5Rα) monoclonal antibody (mAb) with enhanced (afucosylation) antibody-dependent cell-mediated cytotoxicity (ADCC) function. An ADCC reporter cell-based neutralizing antibody (NAb) assay was developed and characterized to detect NAb against benralizumab in human serum to support the clinical development of benralizumab. The optimal ratio of target cells to effector cells was 3:1. Neither parental benralizumab (fucosylated) nor benralizumab Fab resulted in ADCC activity, confirming the requirement for ADCC activity in the NAb assay. The serum tolerance of the cells was determined to be 2.5%. The cut point derived from normal and asthma serum samples was comparable. The effective range of benralizumab was determined, and 35 ng/mL [80% maximal effective concentration (EC80)] was chosen as the standard concentration to run in the assessment of NAb. An affinity purified goat anti-benralizumab polyclonal idiotype antibody preparation was shown to have NAb since it inhibited ADCC activity in a dose-dependent fashion. The low endogenous concentrations of IL5 and soluble IL5 receptor (sIL5R) did not demonstrate to interfere with the assay. The estimated assay sensitivities at the cut point were 1.02 and 1.10 μg/mL as determined by the surrogate neutralizing goat polyclonal and mouse monoclonal anti-drug antibody (ADA) controls, respectively. The assay can detect NAb (at 2.5 μg/mL) in the presence of 0.78 μg/mL benralizumab. The assay was not susceptible to non-specific matrix effects. This study provides an approach and feasibility of developing an ADCC cell-based NAb assay to support biopharmaceuticals with an ADCC function. PMID:26205082

  15. Statistical Surrogate Models for Estimating Probability of High-Consequence Climate Change

    Science.gov (United States)

    Field, R.; Constantine, P.; Boslough, M.

    2011-12-01

    We have posed the climate change problem in a framework similar to that used in safety engineering, by acknowledging that probabilistic risk assessments focused on low-probability, high-consequence climate events are perhaps more appropriate than studies focused simply on best estimates. To properly explore the tails of the distribution requires extensive sampling, which is not possible with existing coupled atmospheric models due to the high computational cost of each simulation. We have developed specialized statistical surrogate models (SSMs) that can be used to make predictions about the tails of the associated probability distributions. A SSM is different than a deterministic surrogate model in that it represents each climate variable of interest as a space/time random field, that is, a random variable for every fixed location in the atmosphere at all times. The SSM can be calibrated to available spatial and temporal data from existing climate databases, or to a collection of outputs from general circulation models. Because of its reduced size and complexity, the realization of a large number of independent model outputs from a SSM becomes computationally straightforward, so that quantifying the risk associated with low-probability, high-consequence climate events becomes feasible. A Bayesian framework was also developed to provide quantitative measures of confidence, via Bayesian credible intervals, to assess these risks. To illustrate the use of the SSM, we considered two collections of NCAR CCSM 3.0 output data. The first collection corresponds to average December surface temperature for years 1990-1999 based on a collection of 8 different model runs obtained from the Program for Climate Model Diagnosis and Intercomparison (PCMDI). We calibrated the surrogate model to the available model data and make various point predictions. We also analyzed average precipitation rate in June, July, and August over a 54-year period assuming a cyclic Y2K ocean model. We

  16. Surrogate Markers of Visceral Adiposity in Young Adults: Waist Circumference and Body Mass Index Are More Accurate than Waist Hip Ratio, Model of Adipose Distribution and Visceral Adiposity Index

    OpenAIRE

    Susana Borruel; Moltó, José F.; Macarena Alpañés; Elena Fernández-Durán; Francisco Álvarez-Blasco; Manuel Luque-Ramírez; Héctor F Escobar-Morreale

    2014-01-01

    Surrogate indexes of visceral adiposity, a major risk factor for metabolic and cardiovascular disorders, are routinely used in clinical practice because objective measurements of visceral adiposity are expensive, may involve exposure to radiation, and their availability is limited. We compared several surrogate indexes of visceral adiposity with ultrasound assessment of subcutaneous and visceral adipose tissue depots in 99 young Caucasian adults, including 20 women without androgen excess, 53...

  17. Use of surrogate technologies to estimate suspended sediment in the Clearwater River, Idaho, and Snake River, Washington, 2008-10

    Science.gov (United States)

    Wood, Molly S.; Teasdale, Gregg N.

    2013-01-01

    Elevated levels of fluvial sediment can reduce the biological productivity of aquatic systems, impair freshwater quality, decrease reservoir storage capacity, and decrease the capacity of hydraulic structures. The need to measure fluvial sediment has led to the development of sediment surrogate technologies, particularly in locations where streamflow alone is not a good estimator of sediment load because of regulated flow, load hysteresis, episodic sediment sources, and non-equilibrium sediment transport. An effective surrogate technology is low maintenance and sturdy over a range of hydrologic conditions, and measured variables can be modeled to estimate suspended-sediment concentration (SSC), load, and duration of elevated levels on a real-time basis. Among the most promising techniques is the measurement of acoustic backscatter strength using acoustic Doppler velocity meters (ADVMs) deployed in rivers. The U.S. Geological Survey, in cooperation with the U.S. Army Corps of Engineers, Walla Walla District, evaluated the use of acoustic backscatter, turbidity, laser diffraction, and streamflow as surrogates for estimating real-time SSC and loads in the Clearwater and Snake Rivers, which adjoin in Lewiston, Idaho, and flow into Lower Granite Reservoir. The study was conducted from May 2008 to September 2010 and is part of the U.S. Army Corps of Engineers Lower Snake River Programmatic Sediment Management Plan to identify and manage sediment sources in basins draining into lower Snake River reservoirs. Commercially available acoustic instruments have shown great promise in sediment surrogate studies because they require little maintenance and measure profiles of the surrogate parameter across a sampling volume rather than at a single point. The strength of acoustic backscatter theoretically increases as more particles are suspended in the water to reflect the acoustic pulse emitted by the ADVM. ADVMs of different frequencies (0.5, 1.5, and 3 Megahertz) were tested to

  18. Radioimmunological proof of thyroglobulin antibodies in humans by the use of a double antibody method

    International Nuclear Information System (INIS)

    Thyroid antibodies, especially thyroglobulin antibodies, allow themselves to be proven with the double antibody method, in competitive radio binding assays and with the solid phase technique. These methods offer advantages relative to sensitivity and quantifiability. In this work a sensitive radioimmunoassay as a double antibody method was worked out whereby a 125 I-thyroglobulin/thyroglobulin antibody immune complex was precipitated out using anti-human immunoglobulin. The measured results from the radioimmunoassay show a good correlation with the results of the immune histological findings. A high to very high Tg antibody level occurs with autoimmune thyroiditis (80%), primary hypothyroidism (74%) and hyperthyroidism (70%). The control values with healthy people came to less than 5% specific binding. In correlation with the results of other authors this method is advantageous relative to test start and evaluation procedures. (orig.)

  19. Chromium leaching from a silicone foam-encapsulated mixed waste surrogate

    International Nuclear Information System (INIS)

    This study assessed chromium leaching from silicone foam-encapsulated salt waste, using a surrogate formulated after Department of Energy complex mixed waste. Two commercial formulations of silicone foam (Wacker ELEKTROGUARD 2100 and General Electric RTV-664) were evaluated as a function of waste load (28--48 wt%). Chromium leaching was formulation specific and increased with increasing waste load as measured by the Toxicity Characteristic Leaching Procedure (TCLP). Chromium release followed transport controlled dissolution at all waste loads under TCLP (cut samples) and Accelerated Leach Test (ALT) (molded samples) conditions. Aqueous and surface complexation modeling was also used to describe reduced chromium effective diffusivity due to iron oxide addition. Comparison of modeling and measured diffusivities as a function of waste load demonstrated that the total available iron surface site concentration increased with increasing waste load, consistent with pore differences measured by image analysis. These results provide a basis for further work on modeling and engineering waste encapsulation using silicone foam

  20. Cross Sections for Neutron-induced Reactions on Actinide Targets Extracted from Surrogate Experiments: A Status Report

    Energy Technology Data Exchange (ETDEWEB)

    Escher, J E; Burke, J T; Dietrich, F S; Lesher, S R; Scielzo, N D; Thompson, I J; Younes, W

    2009-10-01

    The Surrogate nuclear reactions method, an indirect approach for determining cross sections for compound-nuclear reactions involving difficult-to-measure targets, is reviewed. Focusing on cross sections for neutron-induced reactions on actinides, we review the successes of past and present applications of the method and assess its uncertainties and limitations. The approximations used in the analyses of most experiments work reasonably well for (n,f) cross sections for neutron energies above 1-2 MeV, but lead to discrepancies for low-energy (n,f) reactions, as well as for (n,{gamma}) applications. Correcting for some of the effects neglected in the approximate analyses leads to improved (n,f) results. We outline steps that will further improve the accuracy and reliability of the Surrogate method and extend its applicability to reactions that cannot be approached with the present implementation of the method.

  1. (Mis)use of (133)Ba as a calibration surrogate for (131)I in clinical activity calibrators.

    Science.gov (United States)

    Zimmerman, B E; Bergeron, D E

    2016-03-01

    Using NIST-calibrated solutions of (131)Ba and (131)I in the 5mL NIST ampoule geometry, measurements were made in three NIST-maintained Capintec activity calibrators and the NIST Vinten 671 ionization chamber to evaluate the suitability of using (133)Ba as a calibration surrogate for (131)I. For the Capintec calibrators, the (133)Ba response was a factor of about 300% higher than that of the same amount of (131)I. For the Vinten 671, the Ba-133 response was about 7% higher than that of (131)I. These results demonstrate that (133)Ba is a poor surrogate for (131)I. New calibration factors for these radionuclides in the ampoule geometry for the Vinten 671 and Capintec activity calibrators were also determined. PMID:26653213

  2. Reliable diagnosis of murine type 1 diabetes using a panel of autoantigens and "antigen surrogates" mounted onto a liquid array.

    Science.gov (United States)

    Doran, Todd M; Morimoto, Jumpei; Simanski, Scott; McEnaney, Patrick J; Kodadek, Thomas

    2015-11-01

    Autoantibodies raised against β cell antigens are the most reliable preclinical biomarkers for predicting the imminent onset of type 1 diabetes mellitus (T1DM). The most current detection platforms are technically challenging or are run on clinically esoteric equipment. Here, we present a straightforward approach to detect autoantibody biomarkers that employs highly PEGylated microspheres onto which are mounted various capture agents that include affinity-tagged antigens or small molecule "antigen surrogates." After incubation with small quantities of serum, the bound autoantibodies can be measured using a standard flow cytometer. By multiplexing this assay, we show that a panel of antigen and antigen surrogates reliably predicts hyperglycemia in a mouse model of diabetes without false positives. PMID:26390856

  3. To what extent is blood a reasonable surrogate for brain in gene expression studies: estimation from mouse hippocampus and spleen

    Directory of Open Access Journals (Sweden)

    MatthewNDavies

    2009-10-01

    Full Text Available Microarrays are designed to measure genome-wide differences in gene expression. In cases where a tissue is not accessible for analysis (e.g. human brain, it is of interest to determine whether a second, accessible tissue could be used as a surrogate for transcription profiling. Surrogacy has applications in the study of behavioural and neurodegenerative disorders. Comparison between hippocampus and spleen mRNA obtained from a mouse recombinant inbred panel indicates a high degree of correlation between the tissues for genes that display a high heritability of expression level. This correlation is not limited to apparent expression differences caused by sequence polymorphisms in the target sequences and includes both cis and trans genetic effects. A tissue such as blood could therefore give surrogate information on expression in brain for a subset of genes, in particular those co-expressed between the two tissues, which have heritably varying expression.

  4. Validation of pulse rate variability as a surrogate for heart rate variability in chronically instrumented rabbits.

    Science.gov (United States)

    Pellegrino, Peter R; Schiller, Alicia M; Zucker, Irving H

    2014-07-01

    Heart rate variability (HRV) is a function of cardiac autonomic tone that is widely used in both clinical and animal studies. In preclinical studies, HRV measures are frequently derived using the arterial pulse waveform from an implanted pressure telemetry device, termed pulse rate variability (PRV), instead of the electrocardiogram signal in accordance with clinical guidelines. The acceptability of PRV as a surrogate for HRV in instrumented animals is unknown. Using rabbits implanted with intracardiac leads and chronically implanted pressure transducers, we investigated the correlation and agreement of time-domain, frequency-domain, and nonlinear indexes of HRV and PRV at baseline. We also investigated the effects of ventricular pacing and autonomic blockade on both measures. At baseline, HRV and PRV time- and frequency-domain parameters showed robust correlations and moderate to high agreement, whereas nonlinear parameters showed slightly weaker correlations and varied agreement. Ventricular pacing almost completely eliminated HRV, and spectral analysis of the PRV signal revealed a HRV-independent rhythm. After cardiac autonomic blockade with atropine or metoprolol, the changes in time- and non-normalized frequency-domain measures of PRV continued to show strong correlations and moderate to high agreement with corresponding changes in HRV measures. Blockade-induced changes in nonlinear PRV indexes correlated poorly with HRV changes and showed weak agreement. These results suggest that time- and frequency-domain measures of PRV are acceptable surrogates for HRV even in the context of changing cardiac autonomic tone, but caution should be used when nonlinear measures are a primary end point or when HRV is very low as HRV-independent rhythms may predominate. PMID:24791786

  5. Engineering antibody therapeutics.

    Science.gov (United States)

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  6. Spin differences in the 90Zr compound nucleus induced by (p ,p') , (p ,d ) , and (p ,t ) surrogate reactions

    Science.gov (United States)

    Ota, S.; Burke, J. T.; Casperson, R. J.; Escher, J. E.; Hughes, R. O.; Ressler, J. J.; Scielzo, N. D.; Thompson, I. J.; Austin, R. A. E.; Abromeit, B.; Foley, N. J.; McCleskey, E.; McCleskey, M.; Park, H. I.; Saastamoinen, A.; Ross, T. J.

    2015-11-01

    The effect of the production mechanism on the decay of a compound nucleus is investigated. The nucleus 90Zr was produced by three different reactions, namely 90Zr(p ,p') 90Zr , 91Zr(p ,d ) 90Zr , and 92Zr(p ,t ) 90Zr , which served as surrogate reactions for 89Zr(n ,γ ) . The spin-parity (Jπ) distributions of the states populated by these reactions were studied to investigate the surrogate reaction approach, which aims at indirectly determining cross sections for compound-nuclear reactions involving unstable targets such as 89Zr . Discrete γ rays, associated with transitions in 90Zr and 89Zr , were measured in coincidence with light ions for scattering angles of 25∘-60∘ and 90Zr excitation energies extending above the neutron separation energy. The measured transition systematics were used to gain insights into the Jπ distributions of 90Zr . The 90Zr(p ,p') reaction was found to produce fewer γ rays associated with transitions involving high spin states (J =6 -8 ℏ ) than the other two reactions, suggesting that inelastic scattering preferentially populates states in 90Zr that have lower spins than those populated in the transfer reactions investigated. The γ -ray production was also observed to vary by factors of 2-3 with the angle at which the outgoing particle was detected. These findings are relevant to the application of the surrogate reaction approach.

  7. Maximum inspiratory pressure, a surrogate parameter for the assessment of ICU-acquired weakness

    Directory of Open Access Journals (Sweden)

    Gerovasili Vasiliki

    2011-06-01

    Full Text Available Abstract Background Physical examination has been advocated as a primary determinant of ICU-acquired weakness (ICU-AW. The purpose of the study is to investigate ICU-AW development by using Maximum Inspiratory Pressure (MIP as a surrogate parameter of the standardized method to evaluate patients' peripheral muscle strength. Methods Seventy-four patients were recruited in the study and prospectively evaluated in a multidisciplinary university ICU towards the appearance of ICU-AW. APACHE II admission score was 16 ± 6 and ICU stay 26 ± 18 days. ICU-AW was diagnosed with the Medical Research Council (MRC scale for the clinical evaluation of muscle strength. MIP was measured using the unidirectional valve method, independently of the patients' ability to cooperate. Results A significant correlation was found between MIP and MRC (r = 0.68, p 2O for MIP was defined by ROC curve analysis for ICU-AW diagnosis (88% sensitivity,76% specificity. Patients with MIP below the cut-off point of 36 cmH2O had a significant greater weaning period (10 ± 14 versus 3 ± 3 days, p = 0.004 also shown by Kaplan-Meier analysis (log-rank:8.2;p = 0.004. Conclusions MIP estimated using the unidirectional valve method may be a potential surrogate parameter for the assessment of muscle strength compromise, useful for the early detection of ICU-AW.

  8. Statistical surrogate models for prediction of high-consequence climate change.

    Energy Technology Data Exchange (ETDEWEB)

    Constantine, Paul; Field, Richard V., Jr.; Boslough, Mark Bruce Elrick

    2011-09-01

    In safety engineering, performance metrics are defined using probabilistic risk assessments focused on the low-probability, high-consequence tail of the distribution of possible events, as opposed to best estimates based on central tendencies. We frame the climate change problem and its associated risks in a similar manner. To properly explore the tails of the distribution requires extensive sampling, which is not possible with existing coupled atmospheric models due to the high computational cost of each simulation. We therefore propose the use of specialized statistical surrogate models (SSMs) for the purpose of exploring the probability law of various climate variables of interest. A SSM is different than a deterministic surrogate model in that it represents each climate variable of interest as a space/time random field. The SSM can be calibrated to available spatial and temporal data from existing climate databases, e.g., the Program for Climate Model Diagnosis and Intercomparison (PCMDI), or to a collection of outputs from a General Circulation Model (GCM), e.g., the Community Earth System Model (CESM) and its predecessors. Because of its reduced size and complexity, the realization of a large number of independent model outputs from a SSM becomes computationally straightforward, so that quantifying the risk associated with low-probability, high-consequence climate events becomes feasible. A Bayesian framework is developed to provide quantitative measures of confidence, via Bayesian credible intervals, in the use of the proposed approach to assess these risks.

  9. Development of a surrogate model for elemental analysis using a natural gamma ray spectroscopy tool.

    Science.gov (United States)

    Zhang, Qiong

    2015-10-01

    A systematic computational method for obtaining accurate elemental standards efficiently for varying borehole conditions was developed based on Monte Carlo simulations, surrogate modeling, and data assimilation. Elemental standards are essential for spectral unfolding in formation evaluation applications commonly used for nuclear well logging tools. Typically, elemental standards are obtained by standardized measurements, but these experiments are expensive and lack the flexibility to address different logging conditions. In contrast, computer-based Monte Carlo simulations provide an accurate and more flexible approach to obtaining elemental standards for formation evaluation. The presented computational method recognizes that in contrast to typical neutron-photon simulations, where the source is typically artificial and well characterized (Galford, 2009), an accurate knowledge of the source is essential for matching the obtained Monte Carlo elemental standards with their experimental counterparts. Therefore, source distributions are adjusted to minimize the L2 difference of the Monte Carlo computed and experimental standards. Subsequently, an accurate surrogate model is developed accounting for different casing and cement thicknesses, and tool positions within the borehole. The adjusted source distributions are then utilized to generate and validate spectra for varying borehole conditions: tool position, casing and cement thickness. The effect of these conditions on the spectra are investigated and discussed in this work. Given that Monte Carlo modeling provides much lower cost and more flexibility, employing Monte Carlo could enhance the processing of nuclear tool logging data computed standards. PMID:26123106

  10. SOX9 is a novel cancer stem cell marker surrogated by osteopontin in human hepatocellular carcinoma

    Science.gov (United States)

    Kawai, Takayuki; Yasuchika, Kentaro; Ishii, Takamichi; Miyauchi, Yuya; Kojima, Hidenobu; Yamaoka, Ryoya; Katayama, Hokahiro; Yoshitoshi, Elena Yukie; Ogiso, Satoshi; Kita, Sadahiko; Yasuda, Katsutaro; Fukumitsu, Ken; Komori, Junji; Hatano, Etsuro; Kawaguchi, Yoshiya; Uemoto, Shinji

    2016-01-01

    The current lack of cancer stem cell (CSC) markers that are easily evaluated by blood samples prevents the establishment of new therapeutic strategies in hepatocellular carcinoma (HCC). Herein, we examined whether sex determining region Y-box 9 (SOX9) represents a new CSC marker, and whether osteopontin (OPN) can be used as a surrogate marker of SOX9 in HCC. In HCC cell lines transfected with a SOX9 promoter-driven enhanced green fluorescence protein gene, FACS-isolated SOX9+ cells were capable of self-renewal and differentiation into SOX9− cells, and displayed high proliferation capacity in vitro. Xenotransplantation experiments revealed that SOX9+ cells reproduced, differentiated into SOX9− cells, and generated tumors at a high frequency in vivo. Moreover, SOX9+ cells were found to be involved in epithelial-mesenchymal transition (EMT) and activation of TGFb/Smad signaling. Gain/loss of function experiments showed that SOX9 regulates Wnt/beta-catenin signaling, including cyclin D1 and OPN. Immunohistochemistry of 166 HCC surgical specimens and serum OPN measurements showed that compared to SOX9− patients, SOX9+ patients had significantly poorer recurrence-free survival, stronger venous invasion, and higher serum OPN levels. In conclusion, SOX9 is a novel HCC-CSC marker regulating the Wnt/beta-catenin pathway and its downstream target, OPN. OPN is a useful surrogate marker of SOX9 in HCC. PMID:27457505

  11. Modeling of NO sensitization of IC engines surrogate fuels auto-ignition and combustion

    CERN Document Server

    Anderlohr, Jörg; Bounaceur, Roda; Battin-Leclerc, Frédérique

    2009-01-01

    This paper presents a new chemical kinetic model developed for the simulation of auto-ignition and combustion of engine surrogate fuel mixtures sensitized by the presence of NOx. The chemical mechanism is based on the PRF auto-ignition model (n-heptane/iso-octane) of Buda et al. [1] and the NO/n-butane/n-pentane model of Glaude et al. [2]. The later mechanism has been taken as a reference for the reactions of NOx with larger alcanes (n-heptane, iso-octane). A coherent two components engine fuel surrogate mechanism has been generated which accounts for the influence of NOx on auto-ignition. The mechanism has been validated for temperatures between 700 K and 1100 K and pressures between 1 and 10 atm covering the temperature and pressure ranges characteristic of engine post-oxidation thermodynamic conditions. Experiments used for validation include jet stirred reactor conditions for species evolution as a function of temperature, as well as diesel HCCI engine experiments for auto-ignition delay time measurements...

  12. Evaluating two sparse grid surrogates and two adaptation criteria for groundwater Bayesian uncertainty quantification

    Science.gov (United States)

    Zeng, Xiankui; Ye, Ming; Burkardt, John; Wu, Jichun; Wang, Dong; Zhu, Xiaobin

    2016-04-01

    Sparse grid (SG) stochastic collocation methods have been recently used to build accurate but cheap-to-run surrogates for groundwater models to reduce the computational burden of Bayesian uncertainty analysis. The surrogates can be built for either a log-likelihood function or state variables such as hydraulic head and solute concentration. Using a synthetic groundwater flow model, this study evaluates the log-likelihood and head surrogates in terms of the computational cost of building them, the accuracy of the surrogates, and the accuracy of the distributions of model parameters and predictions obtained using the surrogates. The head surrogates outperform the log-likelihood surrogates for the following four reasons: (1) the shape of the head response surface is smoother than that of the log-likelihood response surface in parameter space, (2) the head variation is smaller than the log-likelihood variation in parameter space, (3) the interpolation error of the head surrogates does not accumulate to be larger than the interpolation error of the log-likelihood surrogates, and (4) the model simulations needed for building one head surrogate can be recycled for building others. For both log-likelihood and head surrogates, adaptive sparse grids are built using two indicators: absolute error and relative error. The adaptive head surrogates are insensitive to the error indicators, because the ratio between the two indicators is hydraulic head, which has small variation in the parameter space. The adaptive log-likelihood surrogates based on the relative error indicators outperform those based on the absolute error indicators, because adaptation based on the relative error indicator puts more sparse-grid nodes in the areas in the parameter space where the log-likelihood is high. While our numerical study suggests building state-variable surrogates and using the relative error indicator for building log-likelihood surrogates, selecting appropriate type of surrogates and

  13. Entropy of the EEG in transition to burst suppression in deep anesthesia: Surrogate analysis.

    Science.gov (United States)

    Anier, Andres; Lipping, Tarmo; Jantti, Ville; Puumala, Pasi; Huotari, Ari-Matti

    2010-01-01

    In this paper 5 methods for the assessment of signal entropy are compared in their capability to follow the changes in the EEG signal during transition from continuous EEG to burst suppression in deep anesthesia. To study the sensitivity of the measures to phase information in the signal, phase randomization as well as amplitude adjusted surrogates are also analyzed. We show that the selection of algorithm parameters and the use of normalization are important issues in interpretation and comparison of the results. We also show that permutation entropy is the most sensitive to phase information among the studied measures and that the EEG signal during high amplitude delta activity in deep anesthesia is of highly nonlinear nature. PMID:21095969

  14. ANTI DEOXYRIBONUCLEIC ACID AND ANTINUCLEAR ANTIGEN ANTIBODIES IN GRAVES’ DISEASE

    Directory of Open Access Journals (Sweden)

    H. Mostafavi

    2005-05-01

    Full Text Available Graves’ disease is an autoimmune disorder characterized by presence of antibodies directed against thyroid stimulating hormone (TSH receptor or nearby region. Other serological abnormalities like antibodies to double stranded DNA (ds–DNA and antinuclear antibodies (ANA have also been observed. We studied antibodies to ds-DNA and ANA in our patients with Graves’ disease and compared them with control group. Sera of 84 patients (29 males, 55 females with diagnosis of Graves’ disease were prepared and level of antibodies to ds-DNA and ANA were measured and compared with 41 healthy persons (15 males, 26 females. The level of antibodies to ds-DNA and ANA in patients and control group did not show any significant difference. Our results were different from other studies in other countries. The difference may be explained by difference in our method of antibody measurement or genetic background which needs to be confirmed by HLA studies of our population.

  15. Self-Adaptive Surrogate-Assisted Covariance Matrix Adaptation Evolution Strategy

    CERN Document Server

    Loshchilov, Ilya; Sebag, Michèle

    2012-01-01

    This paper presents a novel mechanism to adapt surrogate-assisted population-based algorithms. This mechanism is applied to ACM-ES, a recently proposed surrogate-assisted variant of CMA-ES. The resulting algorithm, saACM-ES, adjusts online the lifelength of the current surrogate model (the number of CMA-ES generations before learning a new surrogate) and the surrogate hyper-parameters. Both heuristics significantly improve the quality of the surrogate model, yielding a significant speed-up of saACM-ES compared to the ACM-ES and CMA-ES baselines. The empirical validation of saACM-ES on the BBOB-2012 noiseless testbed demonstrates the efficiency and the scalability w.r.t the problem dimension and the population size of the proposed approach, that reaches new best results on some of the benchmark problems.

  16. One mum too few: maternal status in host surrogate motherhood arrangements.

    Science.gov (United States)

    Oultram, Stuart

    2015-06-01

    In a host surrogate motherhood arrangement, the surrogate agrees to be implanted with, and carry to term, an embryo created from the commissioning couple's gametes. When the surrogate child is born, it is the surrogate mother who, according to UK law, holds the legal status of mother. By contrast, the commissioning mother possesses no maternal status and she can only attain it once the surrogate agrees to the completion of the arrangement. One consequence of this is that, in the event that a host arrangement fails, the commissioning mother is left without maternal status. In this paper, I argue that this denial of maternal status misrepresents the commissioning mother's role in the host arrangement and her relationship with the surrogate child. Consequently, I suggest that commissioning mothers participating in host surrogacy arrangements ought to be granted the status of mother in the event that the arrangement fails. PMID:25139932

  17. Fast and accurate prediction of numerical relativity waveforms from binary black hole mergers using surrogate models

    CERN Document Server

    Blackman, Jonathan; Galley, Chad R; Szilagyi, Bela; Scheel, Mark A; Tiglio, Manuel; Hemberger, Daniel A

    2015-01-01

    Simulating a binary black hole coalescence by solving Einstein's equations is computationally expensive, requiring days to months of supercomputing time. In this paper, we construct an accurate and fast-to-evaluate surrogate model for numerical relativity (NR) waveforms from non-spinning binary black hole coalescences with mass ratios from $1$ to $10$ and durations corresponding to about $15$ orbits before merger. Our surrogate, which is built using reduced order modeling techniques, is distinct from traditional modeling efforts. We find that the full multi-mode surrogate model agrees with waveforms generated by NR to within the numerical error of the NR code. In particular, we show that our modeling strategy produces surrogates which can correctly predict NR waveforms that were {\\em not} used for the surrogate's training. For all practical purposes, then, the surrogate waveform model is equivalent to the high-accuracy, large-scale simulation waveform but can be evaluated in a millisecond to a second dependin...

  18. Evaluation of a quantitative fluorescence immunoassay (FIAX) for detection of serum antibody to Borrelia burgdorferi.

    OpenAIRE

    Pennell, D R; Wand, P J; Schell, R F

    1987-01-01

    A quantitative, indirect, fluorescence immunoassay (FIAX; Whittaker Bioproducts, Inc.) was compared with the conventional indirect fluorescent-antibody test for detection of serum antibody to Borrelia burgdorferi. FIAX correlated well with the indirect fluorescent-antibody test (r = 0.72). FIAX is a convenient and dependable means of measuring serum antibody to B. burgdorferi.

  19. Affinity purification of antibodies

    Science.gov (United States)

    Antibodies are provided in a variety of formats that includes antiserum, hybridoma culture supernatant or ascites. They can all be used successfully in crude form for the detection of target antigens by immunoassay. However, it is advantageous to use purified antibody in defined quantity to facil...

  20. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  1. Production Of Human Antibodies

    Science.gov (United States)

    Sammons, David W.; Neil, Garry A.

    1993-01-01

    Process for making human monoclonal antibodies based on combination of techniques. Antibodies made active against specific antigen. Process involves in vivo immunization of human B lymphocyte cells in mice. B cells of interest enriched in vitro before fusion. Method potentially applicable to any antigen. Does not rely on use of Epstein-Barr virus at any step. Human lymphocytes taken from any source.

  2. RBC Antibody Screen

    Science.gov (United States)

    ... the baby is Rh-positive and the mother's antibody status is negative for anti-D, the mother is given additional RhIG. This test also may be used to help diagnose autoimmune-related hemolytic anemia ... when a person produces antibodies against his or her own RBC antigens. This ...

  3. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    Yeast surface display is an effective tool for antibody affinity maturation because yeast can be used as an all-in-one workhorse to assemble, display and screen diversified antibody libraries. By employing the natural ability of yeast Saccharomyces cerevisiae to efficiently recombine multiple DNA...

  4. Cerium as a surrogate in the plutonium immobilization waste form

    Science.gov (United States)

    Marra, James Christopher

    In the aftermath of the Cold War, approximately 50 tonnes (MT) of weapons useable plutonium (Pu) has been identified as excess. The U.S. Department of Energy (DOE) has decided that at least a portion of this material will be immobilized in a titanate-based ceramic for final disposal in a geologic repository. The baseline formulation was designed to produce a ceramic consisting primarily of a highly substituted pyrochlore with minor amounts of brannerite and hafnia-substituted rutile. Since development studies with actual actinide materials is difficult, surrogates have been used to facilitate testing. Cerium has routinely been used as an actinide surrogate in actinide chemistry and processing studies. Although cerium appeared as an adequate physical surrogate for powder handling and general processing studies, cerium was found to act significantly different from a chemical perspective in the Pu ceramic form. The reduction of cerium at elevated temperatures caused different reaction paths toward densification of the respective forms resulting in different phase assemblages and microstructural features. Single-phase fabrication studies and cerium oxidation state analyses were performed to further quantify these behavioral differences. These studies indicated that the major phases in the final phase assemblages contained point defects likely leading to their stability. Additionally, thermochemical arguments predicted that the predominant pyrochlore phase in the ceramic was metastable. The apparent metastabilty associated with primary phase in the Pu ceramic form indicated that additional studies must be performed to evaluate the thermodynamic properties of these compounds. Moreover, the metastability of this predominant phase must be considered in assessment of long-term behavior (e.g. radiation stability) of this ceramic.

  5. Uncertainty quantification of squeal instability via surrogate modelling

    Science.gov (United States)

    Nobari, Amir; Ouyang, Huajiang; Bannister, Paul

    2015-08-01

    One of the major issues that car manufacturers are facing is the noise and vibration of brake systems. Of the different sorts of noise and vibration, which a brake system may generate, squeal as an irritating high-frequency noise costs the manufacturers significantly. Despite considerable research that has been conducted on brake squeal, the root cause of squeal is still not fully understood. The most common assumption, however, is mode-coupling. Complex eigenvalue analysis is the most widely used approach to the analysis of brake squeal problems. One of the major drawbacks of this technique, nevertheless, is that the effects of variability and uncertainty are not included in the results. Apparently, uncertainty and variability are two inseparable parts of any brake system. Uncertainty is mainly caused by friction, contact, wear and thermal effects while variability mostly stems from the manufacturing process, material properties and component geometries. Evaluating the effects of uncertainty and variability in the complex eigenvalue analysis improves the predictability of noise propensity and helps produce a more robust design. The biggest hurdle in the uncertainty analysis of brake systems is the computational cost and time. Most uncertainty analysis techniques rely on the results of many deterministic analyses. A full finite element model of a brake system typically consists of millions of degrees-of-freedom and many load cases. Running time of such models is so long that automotive industry is reluctant to do many deterministic analyses. This paper, instead, proposes an efficient method of uncertainty propagation via surrogate modelling. A surrogate model of a brake system is constructed in order to reproduce the outputs of the large-scale finite element model and overcome the issue of computational workloads. The probability distribution of the real part of an unstable mode can then be obtained by using the surrogate model with a massive saving of

  6. Monte Carlo simulation of transfer reactions using extended R-matrix theory picturing surrogate-type WFCF features

    Directory of Open Access Journals (Sweden)

    Bouland Olivier H.

    2016-01-01

    Full Text Available This article supplies an overview of issues related to the interpretation of surrogate measurement results for neutron-incident cross section predictions; difficulties that are somehow masked by the historical conversion route based on Weisskopf-Ewing approximation. Our proposal is to handle the various difficulties by using a more rigorous approach relying on Monte Carlo simulation of transfer reactions with extended R-matrix theory. The multiple deficiencies of the historical surrogate treatment are recalled but only one is examined in some details here; meaning the calculation of in-out-going channel Width Fluctuation Correction Factors (WFCF which behavior witness partly the failure of Niels Bohr’s compound nucleus theoretical landmark. Relevant WFCF calculations according to neutron-induced surrogate- and cross section-types as a function of neutron-induced fluctuating energy range [0 - 2.1 MeV] are presented and commented in the case of the 240Pu* and 241Pu* compound nucleus isotopes.

  7. Lipoprotein ratios as surrogate markers for insulin resistance in South indians with normoglycemic nondiabetic acute coronary syndrome.

    Science.gov (United States)

    Rajappa, Medha; Sridhar, M G; Balachander, J; Sethuraman, K R; Rajendiran, Kalai Selvi

    2014-01-01

    Background. Insulin resistance has been associated with dyslipidemia and cardiovascular disease. Even though homeostasis model assessment of insulin resistance (HOMA-IR) is a well-known insulin resistance predictor, estimation of serum lipoprotein ratios has been recently suggested as a surrogate marker for insulin resistance. Here, we evaluated the relationship between lipoprotein ratios and insulin resistance in normoglycemic nondiabetic south Indians with acute coronary syndrome. Methods. 100 normoglycemic nondiabetic ACS patients and 140 controls were enrolled in the study. Levels of fasting glucose, fasting insulin, and lipid profile [total cholesterol (TC), triglycerides (TG), and high density lipoprotein cholesterol (HDL-C)], lipoprotein(a) [Lp(a)] levels were measured and lipoprotein ratios were computed. HOMA-IR was used to calculate the insulin resistance. Receiver operating characteristic curves (ROC) analysis was used to compare the power of these lipoprotein ratios to predict insulin resistance. Results. Lipoprotein ratios were significantly higher in normoglycemic nondiabetic ACS patients, as compared to healthy controls, and were significantly correlated with HOMA-IR by Spearman's rank correlation analysis. ROC curve showed that Lp(a)/HDL-C and TG/HDL-C ratios were the best surrogate predictors of insulin resistance in normoglycemic nondiabetic ACS. Conclusion. This study demonstrates that serum lipoprotein ratios significantly correlate with insulin resistance in normoglycemic nondiabetic ACS. Lp(a)/HDL-C and TG/HDL-C ratios could be used as surrogate markers of insulin resistance in atherosclerosis-prone south Indians with normoglycemic nondiabetic ACS. PMID:24959351

  8. Diesel Surrogate Fuels for Engine Testing and Chemical-Kinetic Modeling: Compositions and Properties

    OpenAIRE

    Mueller, Charles J.; Cannella, William J.; Bays, J. Timothy; Bruno, Thomas J.; DeFabio, Kathy; Dettman, Heather D.; Gieleciak, Rafal M.; Huber, Marcia L.; Kweon, Chol-Bum; McConnell, Steven S.; Pitz, William J.; Ratcliff, Matthew A.

    2016-01-01

    The primary objectives of this work were to formulate, blend, and characterize a set of four ultralow-sulfur diesel surrogate fuels in quantities sufficient to enable their study in single-cylinder-engine and combustion-vessel experiments. The surrogate fuels feature increasing levels of compositional accuracy (i.e., increasing exactness in matching hydrocarbon structural characteristics) relative to the single target diesel fuel upon which the surrogate fuels are based. This approach was tak...

  9. A two-layer surrogate-assisted particle swarm optimization algorithm

    OpenAIRE

    Sun, C.; Jin, Y.; Zeng, J; Yu, Y

    2014-01-01

    Like most evolutionary algorithms, particle swarm optimization (PSO) usually requires a large number of fitness evaluations to obtain a sufficiently good solution. This poses an obstacle for applying PSO to computationally expensive problems. This paper proposes a two-layer surrogate-assisted PSO (TLSAPSO) algorithm, in which a global and a number of local surrogate models are employed for fitness approximation. The global surrogate model aims to smooth out the local optima of the original mu...

  10. Synthesis and in vitro and in vivo inhibition potencies of highly relevant nerve agent surrogates.

    Science.gov (United States)

    Meek, Edward C; Chambers, Howard W; Coban, Alper; Funck, Kristen E; Pringle, Ronald B; Ross, Matthew K; Chambers, Janice E

    2012-04-01

    Four nonvolatile nerve agent surrogates, 4-nitrophenyl ethyl dimethylphosphoramidate (NEDPA, a tabun surrogate), 4-nitrophenyl ethyl methylphosphonate (NEMP, a VX surrogate), and two sarin surrogates, phthalimidyl isopropyl methylphosphonate (PIMP) and 4-nitrophenyl isopropyl methylphosphonate (NIMP), were synthesized and tested as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. These surrogates were designed to phosphorylate cholinesterases with the same moiety as their respective nerve agents, making them highly relevant for the study of cholinesterase reactivators. Surrogates were characterized by liquid chromatography-mass spectrometry and nuclear magnetic resonance. NEMP, PIMP, and NIMP were potent inhibitors of rat brain, skeletal muscle, diaphragm, and serum AChE as well as human erythrocyte AChE and serum BuChE in vitro. PIMP was determined to degrade quickly in aqueous solution, making it useful for in vitro assays only, and NEDPA was not a potent inhibitor of AChE or BuChE in vitro; therefore, these two surrogates were not tested in subsequent in vivo studies. Sublethal dosages (yielding about 80% brain AChE inhibition) were determined for both the stable sarin surrogate, NIMP (0.325 mg/kg ip), and the VX surrogate, NEMP (0.4 mg/kg ip), in adult male rats. Time course studies indicated the time to peak brain AChE inhibition for both NIMP and NEMP to be 1 h postexposure. Both surrogates yielded severe cholinergic signs. These dosages did not require the addition of atropine to prevent lethality, and the rate of AChE aging was slow, making these surrogates useful for reactivation studies both in vitro and in vivo. The surrogates synthesized in this study are potent yet safer to test than nerve agents and are useful tools for initial screening of nerve agent oxime therapeutics. PMID:22247004

  11. Identifying experimental surrogates for Bacillus anthracis spores: a review

    OpenAIRE

    Greenberg David L; Busch Joseph D; Keim Paul; Wagner David M

    2010-01-01

    Abstract Bacillus anthracis, the causative agent of anthrax, is a proven biological weapon. In order to study this threat, a number of experimental surrogates have been used over the past 70 years. However, not all surrogates are appropriate for B. anthracis, especially when investigating transport, fate and survival. Although B. atrophaeus has been widely used as a B. anthracis surrogate, the two species do not always behave identically in transport and survival models. Therefore, we devised...

  12. Quantitative prediction of respiratory tidal volume based on the external torso volume change: a potential volumetric surrogate

    Science.gov (United States)

    Li, Guang; Arora, Naveen C.; Xie, Huchen; Ning, Holly; Lu, Wei; Low, Daniel; Citrin, Deborah; Kaushal, Aradhana; Zach, Leor; Camphausen, Kevin; Miller, Robert W.

    2009-04-01

    An external respiratory surrogate that not only highly correlates with but also quantitatively predicts internal tidal volume should be useful in guiding four-dimensional computed tomography (4DCT), as well as 4D radiation therapy (4DRT). A volumetric surrogate should have advantages over external fiducial point(s) for monitoring respiration-induced motion of the torso, which deforms in synchronization with a patient-specific breathing pattern. This study establishes a linear relationship between the external torso volume change (TVC) and lung air volume change (AVC) by validating a proposed volume conservation hypothesis (TVC = AVC) throughout the respiratory cycle using 4DCT and spirometry. Fourteen patients' torso 4DCT images and corresponding spirometric tidal volumes were acquired to examine this hypothesis. The 4DCT images were acquired using dual surrogates in ciné mode and amplitude-based binning in 12 respiratory stages, minimizing residual motion artifacts. Torso and lung volumes were calculated using threshold-based segmentation algorithms and volume changes were calculated relative to the full-exhalation stage. The TVC and AVC, as functions of respiratory stages, were compared, showing a high correlation (r = 0.992 ± 0.005, p tidal volumes, showing a similar linearity (slope = 1.030 ± 0.092, R2 = 0.947). In contrast, the thoracic and abdominal heights measured from 4DCT showed relatively low correlation (0.28 ± 0.44 and 0.82 ± 0.30, respectively) and location-dependent phase shifts. This novel approach establishes the foundation for developing an external volumetric respiratory surrogate.

  13. Quantitative prediction of respiratory tidal volume based on the external torso volume change: a potential volumetric surrogate

    International Nuclear Information System (INIS)

    An external respiratory surrogate that not only highly correlates with but also quantitatively predicts internal tidal volume should be useful in guiding four-dimensional computed tomography (4DCT), as well as 4D radiation therapy (4DRT). A volumetric surrogate should have advantages over external fiducial point(s) for monitoring respiration-induced motion of the torso, which deforms in synchronization with a patient-specific breathing pattern. This study establishes a linear relationship between the external torso volume change (TVC) and lung air volume change (AVC) by validating a proposed volume conservation hypothesis (TVC = AVC) throughout the respiratory cycle using 4DCT and spirometry. Fourteen patients' torso 4DCT images and corresponding spirometric tidal volumes were acquired to examine this hypothesis. The 4DCT images were acquired using dual surrogates in cine mode and amplitude-based binning in 12 respiratory stages, minimizing residual motion artifacts. Torso and lung volumes were calculated using threshold-based segmentation algorithms and volume changes were calculated relative to the full-exhalation stage. The TVC and AVC, as functions of respiratory stages, were compared, showing a high correlation (r = 0.992 ± 0.005, p 2 = 0.980) without phase shift. The AVC was also compared to the spirometric tidal volumes, showing a similar linearity (slope = 1.030 ± 0.092, R2 = 0.947). In contrast, the thoracic and abdominal heights measured from 4DCT showed relatively low correlation (0.28 ± 0.44 and 0.82 ± 0.30, respectively) and location-dependent phase shifts. This novel approach establishes the foundation for developing an external volumetric respiratory surrogate.

  14. Quantitative prediction of respiratory tidal volume based on the external torso volume change: a potential volumetric surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Li Guang; Arora, Naveen C; Xie Huchen; Ning, Holly; Citrin, Deborah; Kaushal, Aradhana; Zach, Leor; Camphausen, Kevin; Miller, Robert W [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Lu Wei; Low, Daniel [Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO 63110 (United States)], E-mail: ligeorge@mail.nih.gov

    2009-04-07

    An external respiratory surrogate that not only highly correlates with but also quantitatively predicts internal tidal volume should be useful in guiding four-dimensional computed tomography (4DCT), as well as 4D radiation therapy (4DRT). A volumetric surrogate should have advantages over external fiducial point(s) for monitoring respiration-induced motion of the torso, which deforms in synchronization with a patient-specific breathing pattern. This study establishes a linear relationship between the external torso volume change (TVC) and lung air volume change (AVC) by validating a proposed volume conservation hypothesis (TVC = AVC) throughout the respiratory cycle using 4DCT and spirometry. Fourteen patients' torso 4DCT images and corresponding spirometric tidal volumes were acquired to examine this hypothesis. The 4DCT images were acquired using dual surrogates in cine mode and amplitude-based binning in 12 respiratory stages, minimizing residual motion artifacts. Torso and lung volumes were calculated using threshold-based segmentation algorithms and volume changes were calculated relative to the full-exhalation stage. The TVC and AVC, as functions of respiratory stages, were compared, showing a high correlation (r = 0.992 {+-} 0.005, p < 0.0001) as well as a linear relationship (slope = 1.027 {+-} 0.061, R{sup 2} = 0.980) without phase shift. The AVC was also compared to the spirometric tidal volumes, showing a similar linearity (slope = 1.030 {+-} 0.092, R{sup 2} = 0.947). In contrast, the thoracic and abdominal heights measured from 4DCT showed relatively low correlation (0.28 {+-} 0.44 and 0.82 {+-} 0.30, respectively) and location-dependent phase shifts. This novel approach establishes the foundation for developing an external volumetric respiratory surrogate.

  15. Antibodies Against Three Forms of Urokinase

    Science.gov (United States)

    Morrison, Dennis R.; Atassi, M. Zouhair

    2007-01-01

    Antibodies that bind to preselected regions of the urokinase molecule have been developed. These antibodies can be used to measure small quantities of each of three molecular forms of urokinase that could be contained in microsamples or conditioned media harvested from cultures of mammalian cells. Previously available antibodies and assay techniques do not yield both clear distinctions among, and measurements of, all three forms. Urokinase is a zymogen that is synthesized in a single-chain form, called ScuPA, which is composed of 411 amino acid residues (see figure). ScuPA has very little enzyme activity, but it can be activated in two ways: (1) by cleavage of the peptide bond lysine 158/isoleucine 159 and the loss of lysine 158 to obtain the high molecular-weight (HMW) form of the enzyme or (2) by cleavage of the bond lysine 135/lysine 136 to obtain the low-molecular-weight (LMW) form of the enzyme. The antibodies in question were produced in mice and rabbits by use of peptides as immunogens. The peptides were selected to obtain antibodies that bind to regions of ScuPA that include the lysine 158/isoleucine 159 and the lysine 135/lysine 136 bonds. The antibodies include monoclonal and polyclonal ones that yield indications as to whether either of these bonds is intact. The polyclonal antibodies include ones that preferentially bind to the HMW or LMW forms of the urokinase molecule. The monoclonal antibodies include ones that discriminate between the ScuPA and the HMW form. A combination of these molecular-specific antibodies will enable simultaneous assays of the ScuPA, HMW, and LMW forms in the same specimen of culture medium.

  16. RBF-based surrogate model for evolutionary optimization

    Czech Academy of Sciences Publication Activity Database

    Bajer, Lukáš; Holeňa, Martin

    Seňa: PONT s.r.o., 2012 - (Horváth, T.), s. 3-8 ISBN 978-80-971144-0-4. [ITAT 2012. Conference on Theory and Practice of Information Technologies. Ždiar (SK), 17.09.2012-21.09.2012] R&D Projects: GA ČR GA201/08/0802 Grant ostatní: GA UK(CZ) 278511/2011 Institutional support: RVO:67985807 Keywords : surrogate models * mixed-variable optimization * rbf networks * evolutionary optimization Subject RIV: IN - Informatics, Computer Science

  17. On Surrogate Data Testing for Linearity based on the Periodogram

    CERN Document Server

    Timmer, J

    1995-01-01

    The method of surrogate data is a tool to test whether data were generated by some class of model. Tests based on the periodogram have been proposed to decide if linear systems driven by Gaussian noise could have generated a sample time series. We show that this procedure based on the periodogram, in general, misspecifies the test statistic. Based on the theory of linear systems we suggest an alternative procedure to obtain the correct distribution of the test statistic and discuss problems of this approach.

  18. Surrogate solutions of Fredholm equations by feedforward networks

    Czech Academy of Sciences Publication Activity Database

    Kůrková, Věra

    Seňa : PONT s.r.o., 2012 - (Horváth, T.), s. 49-54 ISBN 978-80-971144-0-4. [ITAT 2012. Conference on Theory and Practice of Information Technologies. Ždiar (SK), 17.09.2012-21.09.2012] R&D Projects: GA MŠk OC10047 Institutional support: RVO:67985807 Keywords : surrogate modeling by neural networks * Fredholm integral equations * rates of approximation * model complexity Subject RIV: IN - Informatics, Computer Science http://ceur-ws.org/Vol-990/paper8.pdf

  19. Structure of correlations with partially surrogated price fluctuations

    Science.gov (United States)

    Lim, Gyuchang; Kim, Sooyong; Chang, Ki-Ho; Kim, Kyungsik

    2009-03-01

    The well-known facts of financial markets support that the price fluctuation contains information about the complexity of interactions among market participants. In this work, we present a new surrogate method to find the dependency of higher- order correlations on the magnitude of price fluctuations. By sorting returns into several groups with respect to the level of fluctuations, we show that the large fluctuations characterize the structure of temporal correlations of a financial time series. In particular, by investigating the positive and negative parts separately, we confirm that risk-averse behavior of traders is explicitly observed in financial markets.

  20. ACOG committee opinion number 397, February 2008: surrogate motherhood.

    Science.gov (United States)

    2008-02-01

    Ethical responsibilities are described for obstetrician-gynecologists who choose to participate in surrogacy arrangements by 1) advising couples who are considering surrogacy, 2) counseling potential surrogate mothers, 3) providing obstetric services for pregnant women participating in surrogacy, or 4) offering assisted reproductive technologies related to surrogacy. Although the obligations of physicians will vary depending on the type and level of their involvement, in all cases physicians should carefully examine all relevant issues related to surrogacy, including medical, ethical, legal, and psychologic aspects. PMID:18238989

  1. Using Surrogate Modeling to Improve Evolutionary Optimization in Catalysis

    Czech Academy of Sciences Publication Activity Database

    Hartman, David; Holeňa, Martin

    Praha : Matfyzpress, 2009 - (Obdržálek, J.; Plátek, M.), s. 3-19 ISBN 978-80-7378-095-1. [ MIS 2009. Malý informatický seminář /26./. Josefův důl (CZ), 17.01.2009-24.01.2009] R&D Projects: GA ČR GA201/08/0802 Institutional research plan: CEZ:AV0Z10300504 Keywords : chemoinformatics * evolutionry optimization * genetic algorithms * surrogate modelling * artificial neural networks Subject RIV: IN - Informatics, Computer Science

  2. Surrogate Modeling in the Evolutionary Optimization of Catalytic Materials

    Czech Academy of Sciences Publication Activity Database

    Holeňa, Martin; Linke, D.; Bajer, Lukáš

    New York: ACM, 2012 - (Soule, T.), s. 1095-1102 ISBN 978-1-4503-1177-9. [GECCO 2012. Genetic and Evolutionary Computation Conference. Conference on Genetic Algorithms /21./ and Annual Genetic Programming Conference /17./. Philadelphia (US), 07.07.2012-11.07.2012] R&D Projects: GA ČR GA201/08/0802; GA ČR GAP202/11/1368 Grant ostatní: GA UK(CZ) 278511/2011 Institutional support: RVO:67985807 Keywords : evolutionary optimization * mixed optimization * surrogate modeling * model suitability * applications in chemistry Subject RIV: IN - Informatics, Computer Science

  3. Assessing the Suitability of Surrogate Models in Evolutionary Optimization

    Czech Academy of Sciences Publication Activity Database

    Holeňa, Martin; Demut, R.

    Seňa: PONT s.r.o., 2011 - (Lopatková, M.), s. 31-38 ISBN 978-80-89557-02-8. [ITAT 2011. Conference on Theory and Practice of Information Technologies. Ždiar (SK), 17.09.2011-21.09.2011] R&D Projects: GA ČR GAP202/11/1368 Institutional research plan: CEZ:AV0Z10300504 Keywords : evolutionary optimization * blackbox optimization * surrogate modelling * model suitability * reliability of prediction Subject RIV: IN - Informatics, Computer Science

  4. Surrogate Modelling of Solutions of Integral Equations by Neural Networks

    Czech Academy of Sciences Publication Activity Database

    Kůrková, Věra

    Heidelberg: Springer, 2012 - (Iliadis, L.; Maglogiannis, I.; Papadopoulos, H.), s. 88-96. (IFIP Advances in Information and Communication Technology. 381). ISBN 978-3-642-33408-5. ISSN 1868-4238. [AIAI 2012. IFIP WG 12.5 International Conference /8./. Halkidiki (GR), 27.09.2012-30.09.2012] R&D Projects: GA MŠk OC10047 Institutional support: RVO:67985807 Keywords : surrogate modelling by neural networks * Fredholm integral equations * rates of approximation * model complexity Subject RIV: IN - Informatics, Computer Science

  5. Ppb detection of Sarin surrogate in liquid solutions

    Science.gov (United States)

    Hamel, Matthieu; Hamoniaux, Jennifer; Rocha, Licinio; Normand, Stéphane

    2013-05-01

    Sarin, a well-known chemical warfare agent, is toxic for concentrations as low as 0.03 ppm in the air (Immediately Dangerous to Life or Health value). A technology providing "on the field" detection could be fluorescence spectroscopy. This presentation shows a sensitive method for the detection of Diethyl Chlorophosphate (DCP), a Sarin surrogate, which provides in a few seconds a turn-off fluorescence response of the sensor for ppb levels of DCP. For instance, a I/I0 = 0.68 (fluorescence quenching) was obtained when the sensor was exposed to 16 ppb of DCP.

  6. Biopolicies and biotechnologies: reflections on surrogate maternity in India

    Directory of Open Access Journals (Sweden)

    Mónica Amador

    2010-07-01

    Full Text Available This article explores the impact of biotechnology, particularly on assisted reproductive technologies such as surrogate motherhood. The study is based on interviews and field work conducted in the city of Hyderabad in India within the frame of the seminar on “Research Methodology” given by Dr. Rohan D´Souza at the Centre for Studies in Science Policy at the Jawaharlal Nehru University in India. The theoretical framework of this analysis focuses on exploring concepts such as cyborg (Haraway,1991 and subaltern subject (Spivak, 1998 in the context of biotechnological production in India

  7. Influenza-Specific Antibody-Dependent Phagocytosis

    OpenAIRE

    Ana-Sosa-Batiz, Fernanda; Vanderven, Hillary; Jegaskanda, Sinthujan; Johnston, Angus; Rockman, Steven; Laurie, Karen; Barr, Ian; Reading, Patrick; Lichtfuss, Marit; Stephen J Kent

    2016-01-01

    Background Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized. Methods We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, ...

  8. Identification of surrogates of protection against yersiniosis in immersion vaccinated Atlantic salmon.

    Directory of Open Access Journals (Sweden)

    Andrew R Bridle

    Full Text Available Simple cost-effective bacterins are the earliest and most successfully used commercial vaccines in fish. In particular, those prepared from Yersinia ruckeri have proven effective at controlling Enteric Red Mouth Disease (ERM and yersiniosis in rainbow trout and Atlantic salmon, respectively. However, the emergence of outbreaks of ERM caused by atypical biotypes of Y. ruckeri and reports of vaccine failure resulting in mass mortality of hatchery Atlantic salmon has reinvigorated interest in vaccines against fish bacterial diseases. Therefore the objective of this study was to identify surrogates of protection against yersiniosis using cDNA microarray to characterise the response of host genes in the gills of unvaccinated and vaccinated Atlantic salmon challenged with Y. ruckeri. Differentially expressed genes were identified using two-way ANOVA and restricted to those with >2.5-fold change at P<0.05. Using cDNA microarray we identified the expression of 6 genes in response to infection and 4 genes associated with the protective host response to yersiniosis. Analysis by real-time PCR confirmed that three immunologically relevant genes, namely a cathelicidin (47-fold and a C-type lectin (19-fold increased in response to yersiniosis. Including collagenase (17-fold increase, an important tissue remodelling and repair enzyme, these genes represent 3 of 6 non-protective and/or pathological responses to yersiniosis. Genes associated with the protective host response included an immunoglobulin gene and a selenoprotein that showed significant fold changes (15-fold increases each, highlighting the importance of antibody-mediated protection against yersiniosis. These findings provide much needed knowledge of the host-pathogen interaction in response to bacterial infection and immunisation in fish. Significantly, we identified a transcriptional biosignature consisting of predominantly immune-relevant genes (14 up and 3 down-regulated in the gills of Atlantic

  9. Selection of Recombinant Human Antibodies.

    Science.gov (United States)

    Tomszak, Florian; Weber, Susanne; Zantow, Jonas; Schirrmann, Thomas; Hust, Michael; Frenzel, André

    2016-01-01

    Since the development of therapeutic antibodies the demand of recombinant human antibodies is steadily increasing. Traditionally, therapeutic antibodies were generated by immunization of rat or mice, the generation of hybridoma clones, cloning of the antibody genes and subsequent humanization and engineering of the lead candidates. In the last few years, techniques were developed that use transgenic animals with a human antibody gene repertoire. Here, modern recombinant DNA technologies can be combined with well established immunization and hybridoma technologies to generate already affinity maturated human antibodies. An alternative are in vitro technologies which enabled the generation of fully human antibodies from antibody gene libraries that even exceed the human antibody repertoire. Specific antibodies can be isolated from these libraries in a very short time and therefore reduce the development time of an antibody drug at a very early stage.In this review, we describe different technologies that are currently used for the in vitro and in vivo generation of human antibodies. PMID:27236551

  10. The proposed model surrogate parenthood act: a legislative response to the challenges of reproductive technology.

    Science.gov (United States)

    Manus, M L

    1996-01-01

    In this Article, Manus proposes a Model Surrogate Parenthood Act. He examines the medical and scientific history of surrogacy and reviews the jurisprudence in the area, specifically the constitutional relationship between procreation rights and surrogacy. The author asserts that surrogate motherhood cannot be, and indeed, should not be, eradicated through legislation criminalizing it. The proposed Model Act, presented here in its entirety, attempts to reduce the problems inherent in the concept of surrogate parenthood by putting the process under strict court supervision and by zealously protecting the rights of the surrogate mother and the child to be conceived. PMID:12071207

  11. Oral priming with replicating adenovirus serotype 4 followed by subunit H5N1 vaccine boost promotes antibody affinity maturation and expands H5N1 cross-clade neutralization.

    Science.gov (United States)

    Khurana, Surender; Coyle, Elizabeth M; Manischewitz, Jody; King, Lisa R; Ishioka, Glenn; Alexander, Jeff; Smith, Jon; Gurwith, Marc; Golding, Hana

    2015-01-01

    A Phase I trial conducted in 2009-2010 demonstrated that oral vaccination with a replication competent Ad4-H5 (A/Vietnam) vector with dosages ranging from 107-1011 viral particles was well tolerated. HA-specific T-cell responses were efficiently induced, but very limited hemagglutination-inhibiting (HI) humoral responses were measured. However, a single boost of Ad4-H5-Vtn vaccinated individuals with a unadjuvanted licensed H5N1 (A/Vietnam) subunit vaccine resulted in superior HI titers compared with unprimed subjects. In the current study, the impact of Ad4-H5 priming on the quality of the polyclonal humoral immune response was evaluated using a real-time kinetics assay by surface plasmon resonance (SPR). Total binding of serum polyclonal antibodies from the Ad4-H5-Vtn primed groups against both homologous H5N1-A/Vietnam/1194/2004 (clade 1) and heterologous A/Indonesia-5/2005 (clade 2.1) HA1 head domain was significantly higher compared with sera from individuals that received subunit H5N1 vaccination alone. SPR measurements also demonstrated that the antigen-antibody complex dissociation rates (a surrogate for antibody affinity) of serum antibodies against the HA1 of H5N1-A/Vietnam were significantly higher in the Ad4-H5 primed groups compared with those from the unprimed group. Furthermore, strong correlations were observed between the antibody affinities for HA1 (but not HA2) and the virus neutralization titers against the homologous strain and a panel of heterologous clade 2 H5N1 strains. These findings support the concept of oral prime-boost vaccine approaches against pandemic influenza to elicit long-term memory B cells with high affinity capable of rapid response to variant pandemic viruses likely to emerge and adapt to human transmissions. PMID:25629161

  12. Gasoline surrogate modeling of gasoline ignition in a rapid compression machine and comparison to experiments

    Energy Technology Data Exchange (ETDEWEB)

    Mehl, M; Kukkadapu, G; Kumar, K; Sarathy, S M; Pitz, W J; Sung, S J

    2011-09-15

    The use of gasoline in homogeneous charge compression ignition engines (HCCI) and in duel fuel diesel - gasoline engines, has increased the need to understand its compression ignition processes under engine-like conditions. These processes need to be studied under well-controlled conditions in order to quantify low temperature heat release and to provide fundamental validation data for chemical kinetic models. With this in mind, an experimental campaign has been undertaken in a rapid compression machine (RCM) to measure the ignition of gasoline mixtures over a wide range of compression temperatures and for different compression pressures. By measuring the pressure history during ignition, information on the first stage ignition (when observed) and second stage ignition are captured along with information on the phasing of the heat release. Heat release processes during ignition are important because gasoline is known to exhibit low temperature heat release, intermediate temperature heat release and high temperature heat release. In an HCCI engine, the occurrence of low-temperature and intermediate-temperature heat release can be exploited to obtain higher load operation and has become a topic of much interest for engine researchers. Consequently, it is important to understand these processes under well-controlled conditions. A four-component gasoline surrogate model (including n-heptane, iso-octane, toluene, and 2-pentene) has been developed to simulate real gasolines. An appropriate surrogate mixture of the four components has been developed to simulate the specific gasoline used in the RCM experiments. This chemical kinetic surrogate model was then used to simulate the RCM experimental results for real gasoline. The experimental and modeling results covered ultra-lean to stoichiometric mixtures, compressed temperatures of 640-950 K, and compression pressures of 20 and 40 bar. The agreement between the experiments and model is encouraging in terms of first

  13. Antibody discovery: sourcing of monoclonal antibody variable domains.

    Science.gov (United States)

    Strohl, William R

    2014-03-01

    Historically, antibody variable domains for therapeutic antibodies have been sourced primarily from the mouse IgG repertoire, and typically either chimerized or humanized. More recently, human antibodies from transgenic mice producing human IgG, phage display libraries, and directly from human B lymphocytes have been used more broadly as sources of antibody variable domains for therapeutic antibodies. Of the total 36 antibodies approved by major maket regulatory agencies, the variable domain sequences of 26 originate from the mouse. Of these, four are marketed as murine antibodies (of which one is a mouse-rat hybrid IgG antibody), six are mouse-human chimeric antibodies, and 16 are humanized. Ten marketed antibodies have originated from human antibody genes, three isolated from phage libraries of human antibody genes and seven from transgenic mice producing human antibodies. Five antibodies currently in clinical trials have been sourced from camelids, as well as two from non-human primates, one from rat, and one from rabbit. Additional sources of antibody variable domains that may soon find their way into the clinic are potential antibodies from sharks and chickens. Finally, the various methods for retrieval of antibodies from humans, mouse and other sources, including various display technologies and amplification directly from B cells, are described. PMID:24168292

  14. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Herbinet, O; Pitz, W J; Westbrook, C K

    2007-09-17

    A detailed chemical kinetic mechanism has been developed and used to study the oxidation of methyl decanoate, a surrogate for biodiesel fuels. This model has been built by following the rules established by Curran et al. for the oxidation of n-heptane and it includes all the reactions known to be pertinent to both low and high temperatures. Computed results have been compared with methyl decanoate experiments in an engine and oxidation of rapeseed oil methyl esters in a jet stirred reactor. An important feature of this mechanism is its ability to reproduce the early formation of carbon dioxide that is unique to biofuels and due to the presence of the ester group in the reactant. The model also predicts ignition delay times and OH profiles very close to observed values in shock tube experiments fueled by n-decane. These model capabilities indicate that large n-alkanes can be good surrogates for large methyl esters and biodiesel fuels to predict overall reactivity, but some kinetic details, including early CO2 production from biodiesel fuels, can be predicted only by a detailed kinetic mechanism for a true methyl ester fuel. The present methyl decanoate mechanism provides a realistic kinetic tool for simulation of biodiesel fuels.

  15. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Herbinet, O; Pitz, W J; Westbrook, C K

    2007-09-20

    A detailed chemical kinetic mechanism has been developed and used to study the oxidation of methyl decanoate, a surrogate for biodiesel fuels. This model has been built by following the rules established by Curran et al. for the oxidation of n-heptane and it includes all the reactions known to be pertinent to both low and high temperatures. Computed results have been compared with methyl decanoate experiments in an engine and oxidation of rapeseed oil methyl esters in a jet stirred reactor. An important feature of this mechanism is its ability to reproduce the early formation of carbon dioxide that is unique to biofuels and due to the presence of the ester group in the reactant. The model also predicts ignition delay times and OH profiles very close to observed values in shock tube experiments fueled by n-decane. These model capabilities indicate that large n-alkanes can be good surrogates for large methyl esters and biodiesel fuels to predict overall reactivity, but some kinetic details, including early CO{sub 2} production from biodiesel fuels, can be predicted only by a detailed kinetic mechanism for a true methyl ester fuel. The present methyl decanoate mechanism provides a realistic kinetic tool for simulation of biodiesel fuels.

  16. Bayesian calibration of the Community Land Model using surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Ray, Jaideep [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hou, Zhangshuan [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Huang, Maoyi [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Swiler, Laura Painton [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-02-01

    We present results from the Bayesian calibration of hydrological parameters of the Community Land Model (CLM), which is often used in climate simulations and Earth system models. A statistical inverse problem is formulated for three hydrological parameters, conditional on observations of latent heat surface fluxes over 48 months. Our calibration method uses polynomial and Gaussian process surrogates of the CLM, and solves the parameter estimation problem using a Markov chain Monte Carlo sampler. Posterior probability densities for the parameters are developed for two sites with different soil and vegetation covers. Our method also allows us to examine the structural error in CLM under two error models. We find that surrogate models can be created for CLM in most cases. The posterior distributions are more predictive than the default parameter values in CLM. Climatologically averaging the observations does not modify the parameters' distributions significantly. The structural error model reveals a correlation time-scale which can be used to identify the physical process that could be contributing to it. While the calibrated CLM has a higher predictive skill, the calibration is under-dispersive.

  17. Cerium as a Surrogate in the Plutonium Immobilized Form

    International Nuclear Information System (INIS)

    The Department of Energy (DOE) plans to immobilize a portion of the excess weapons useable plutonium in a ceramic form for final geologic disposal. The proposed immobilization form is a titanate based ceramic consisting primarily of a pyrochlore phase with lesser amounts of brannerite, rutile, zirconolite, vitreous phases and/or other minor phases depending on the impurities present in the feed. The ceramic formulation is cold-pressed and then densified via a reactive sintering process. Cerium has been used as a surrogate for plutonium to facilitate formulation development and process testing. The use of cerium vs. plutonium results in differences in behavior during sintering of the ceramic form. The phase development progression and final phase assemblage is different when cerium is substituted for the actinides in the form. However, the physical behavior of cerium oxide powder and the formation of a pyrochlore-rich ceramic of similar density to the actinide-bearing material make cerium an adequate surrogate for formulation and process development studies

  18. Behavior of radioactive metal surrogates under various waste combustion conditions

    International Nuclear Information System (INIS)

    A laboratory investigation of the behavior of radioactive metals under the various waste combustion atmospheres was conducted to predict the parameters that influence their partitioning behavior during waste incineration. Neodymium, samarium, cerium, gadolinium, cesium and cobalt were used as non-radioactive surrogate metals that are representative of uranium, plutonium, americium, curium, radioactive cesium, and radioactive cobalt, respectively. Except for cesium, all of the investigated surrogate metal compounds converted into each of their stable oxides at medium temperatures from 400 to 900 .deg. C, under oxygen-deficient and oxygen-sufficient atmospheres (0.001-atm and 0.21-atm O2). At high temperatures above 1,400 .deg. C, cerium, neodymium and samarium in the form of their oxides started to vaporize but the vaporization rates were very slow up to 1500 .deg. C. Inorganic chlorine (NaCl) as well as organic chlorine (PVC) did not impact the volatility of investigated Nd2O3, CoO and Cs2O. The results of laboratory investigations suggested that the combustion chamber operating parameters affecting the entrainment of particulate and filtration equipment operating parameters affecting particle collection efficiency be the governing parameters of alpha radionuclides partitioning during waste incineration

  19. Physical and mechanical properties of degraded waste surrogate material

    International Nuclear Information System (INIS)

    This paper discusses rock mechanics testing of surrogate materials to provide failure criteria for compacted, degraded nuclear waste. This daunting proposition was approached by first assembling all known parameters such as the initial waste inventory and rock mechanics response of the underground setting after the waste is stored. Conservative assumptions allowing for extensive degradation processes helped quantify the lowest possible strength conditions of the future state of the waste. In the larger conceptual setting, computations involve degraded waste behavior in transient pressure gradients as gas exits the waste horizon into a wellbore. Therefore, a defensible evaluation of tensile strength is paramount for successful analyses and intentionally provided maximal failed volumes. The very conservative approach assumes rampant degradation to define waste surrogate composition. Specimens prepared from derivative degradation product were consolidated into simple geometries for rock mechanics testing. Tensile strength thus derived helped convince a skeptical peer review panel that drilling into the Waste Isolation Pilot Plant (WIPP) would not likely expel appreciable solids via the drill string

  20. An extensive library of surrogate peptides for all human proteins.

    Science.gov (United States)

    Mohammed, Yassene; Borchers, Christoph H

    2015-11-01

    Selecting the most appropriate surrogate peptides to represent a target protein is a major component of experimental design in Multiple Reaction Monitoring (MRM). Our software PeptidePicker with its v-score remains distinctive in its approach of integrating information about the proteins, their tryptic peptides, and the suitability of these peptides for MRM that is available online in UniProtKB, NCBI's dbSNP, ExPASy, PeptideAtlas, PRIDE, and GPMDB. The scoring algorithm reflects our "best knowledge" for selecting candidate peptides for MRM, based on the uniqueness of the peptide in the targeted proteome, its physiochemical properties, and whether it has previously been observed. Here we present an updated approach where we have already compiled a list of all possible surrogate peptides of the human proteome. Using our stringent selection criteria, the list includes 165k suitable MRM peptides covering 17k proteins of the human reviewed proteins in UniProtKB. Compared to average of 2-4min per protein for retrieving and integrating the information, the precompiled list includes all peptides available instantly. This allows a more cohesive and faster design of a multiplexed MRM experiment and provides insights into evidence for a protein's existence. We will keep this list up-to-date as proteomics data repositories continue to grow. This article is part of a Special Issue entitled: Computational Proteomics. PMID:26232110

  1. The development of radioactive sample surrogates for training and exercises

    Energy Technology Data Exchange (ETDEWEB)

    Martha Finck; Bevin Brush; Dick Jansen; David Chamberlain; Don Dry; George Brooks; Margaret Goldberg

    2012-03-01

    The development of radioactive sample surrogates for training and exercises Source term information is required for to reconstruct a device used in a dispersed radiological dispersal device. Simulating a radioactive environment to train and exercise sampling and sample characterization methods with suitable sample materials is a continued challenge. The Idaho National Laboratory has developed and permitted a Radioactive Response Training Range (RRTR), an 800 acre test range that is approved for open air dispersal of activated KBr, for training first responders in the entry and exit from radioactively contaminated areas, and testing protocols for environmental sampling and field characterization. Members from the Department of Defense, Law Enforcement, and the Department of Energy participated in the first contamination exercise that was conducted at the RRTR in the July 2011. The range was contaminated using a short lived radioactive Br-82 isotope (activated KBr). Soil samples contaminated with KBr (dispersed as a solution) and glass particles containing activated potassium bromide that emulated dispersed radioactive materials (such as ceramic-based sealed source materials) were collected to assess environmental sampling and characterization techniques. This presentation summarizes the performance of a radioactive materials surrogate for use as a training aide for nuclear forensics.

  2. Simultaneous Thermal Analysis of Remediated Nitrate Salt Surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Wayne, David Matthew [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-13

    The actinide engineering and science group (MET-1) have completed simultaneous thermal analysis and offgas analysis by mass spectrometry (STA-MS) of remediated nitrate salt (RNS) surrogates formulated by the high explosives science and technology group (M-7). The 1.0 to 1.5g surrogate samples were first analyzed as received, then a new set was analyzed with 100-200mL 10M HNO3 +0.3 MHF added, and a third set was analyzed after 200 mL of a concentrated Pu-AM spike (in 10M HNO3 +0.3 MHF) was added. The acid and spike solutions were formulated by the actinide analytical chemistry group (C-AAC) using reagent-grade HNO3 and HF, which was also used to dissolve a small quantity of mixed, high-fired PuO2/ AmO2 oxide.

  3. Imaging biomarkers as surrogate endpoints for drug development

    International Nuclear Information System (INIS)

    The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

  4. Defining useful surrogates for user participation in online medical learning.

    LENUS (Irish Health Repository)

    Beddy, Peter

    2012-02-01

    "School for Surgeons" is a web-based distance learning program which provides online clinical-based tutorials to surgical trainees. Our aim was to determine surrogates of active participation and to assess the efficacy of methods to improve usage. Server logs of the 82 participants in the "School for Surgeons" were assessed for the two terms of the first year of the program. Data collected included total time online, mean session time, page requests, numbers of sessions online and the total number of assignments. An intervention regarding comparative peer usage patterns was delivered to the cohort between terms one and two. Of the 82 trainees enrolled, 83% (85% second term) logged into the program. Of all participants 88% (97% second term) submitted at least one assignment. Median submissions were four (eight second term) per trainee. Assignment submission closely correlated with number of sessions, total time online, downloads and page requests. Peer-based comparative feedback resulted in a significant increase in the number of assignments submitted (p < 0.01). Despite its recent introduction, "School for Surgeons" has a good participation rate. Assignment submission is a valid surrogate for usage. Students can be encouraged to move from passive observation to active participation in a virtual learning environment by providing structured comparative feedback ranking their performance.

  5. Eight years' experience with an IVF surrogate gestational pregnancy programme.

    Science.gov (United States)

    Raziel, Arieh; Schachter, Morey; Strassburger, Deborah; Komarovsky, Dafna; Ron-El, Raphael; Friedler, Shevach

    2005-08-01

    The aim of this study was to retrospectively audit eight years' experience of an IVF surrogate gestational programme and to compare the outcome of surrogacy due to absence of the uterus with surrogacy indicated for repeated IVF failure and recurrent abortions. A total of 60 cycles of IVF surrogate pregnancy were initiated in 19 treated couples. Absence of the uterus was the indication for surrogacy in 10 cases: Rokitansky syndrome (eight cases) and post-hysterectomy (two cases) designated as group A. The indications in the remaining nine patients (group B) were: IVF implantation failure (three cases), habitual abortions (four cases) and deteriorating maternal diseases (two cases). IVF performance and subsequent pregnancy outcome of groups A and B were compared. There was no difference in ovarian stimulation parameters and in IVF performance between the groups A and B. The overall pregnancy rate per transfer was 10/60 (17%). The pregnancy rates per patient and per transfer were 7/10 (70%) and 7/35 (20%) in group A compared with 3/9 (33%) and 3/25 (12%) in group B. A median number of three treatment cycles were needed to achieve pregnancy. In conclusion, the existence or absence of the uterus in the commissioning mothers is irrelevant for their IVF performance and conception rates. In patients who conceived after more than three IVF cycles, an additional 'oocyte factor' might be present. PMID:16168227

  6. Nano-clustering of ligands on surrogate antigen presenting cells modulates T cell membrane adhesion and organization.

    Science.gov (United States)

    Dillard, Pierre; Pi, Fuwei; Lellouch, Annemarie C; Limozin, Laurent; Sengupta, Kheya

    2016-03-14

    We investigate the adhesion and molecular organization of the plasma membrane of T lymphocytes interacting with a surrogate antigen presenting cell comprising glass supported ordered arrays of antibody (α-CD3) nano-dots dispersed in a non-adhesive matrix of polyethylene glycol (PEG). The local membrane adhesion and topography, as well as the distribution of the T cell receptors (TCRs) and the kinase ZAP-70, are influenced by dot-geometry, whereas the cell spreading area is determined by the overall average density of the ligands rather than specific characteristics of the dots. TCR clusters are recruited preferentially to the nano-dots and the TCR cluster size distribution has a weak dot-size dependence. On the patterns, the clusters are larger, more numerous, and more enriched in TCRs, as compared to the homogeneously distributed ligands at comparable concentrations. These observations support the idea that non-ligated TCRs residing in the non-adhered parts of the proximal membrane are able to diffuse and enrich the existing clusters at the ligand dots. However, long distance transport is impaired and cluster centralization in the form of a central supramolecular cluster (cSMAC) is not observed. Time-lapse imaging of early cell-surface contacts indicates that the ZAP-70 microclusters are directly recruited to the site of the antibody dots and this process is concomitant with membrane adhesion. These results together point to a complex interplay of adhesion, molecular organization and activation in response to spatially modulated stimulation. PMID:26887857

  7. A surrogate for networks -- How scale-free is my scale-free network?

    CERN Document Server

    Small, Michael; Stemler, Thomas

    2013-01-01

    Complex networks are now being studied in a wide range of disciplines across science and technology. In this paper we propose a method by which one can probe the properties of experimentally obtained network data. Rather than just measuring properties of a network inferred from data, we aim to ask how typical is that network? What properties of the observed network are typical of all such scale free networks, and which are peculiar? To do this we propose a series of methods that can be used to generate statistically likely complex networks which are both similar to the observed data and also consistent with an underlying null-hypothesis -- for example a particular degree distribution. There is a direct analogy between the approach we propose here and the surrogate data methods applied to nonlinear time series data.

  8. Characterization of Pu colloidal and aqueous species in Yucca Mountain groundwater surrogate

    International Nuclear Information System (INIS)

    The speciation and formation of Pu intrinsic colloids from an initial solution of Pu(V) were studied at pH 1, pH 3, pH 6, pIH 8, and pH 11. The medium was a surrogate Yucca Mountain groundwater from well J-l 3 under air atmosphere. The solutions were monitored for several months. Samples were analyzed using liquid scintillation counting, ultra filtration, solvent extraction: photon correlation spectroscopy, and laser-induced photo-acoustic breakdown and emission spectroscopy. Redox potentials were measured periodically. The time dependencies of soluble and colloidal Pu concentrations are reported. The size and concentration of Pu colloid particles were estimated

  9. Characterization of Pu colloidal and aqueous species in Yucca Mountain groundwater surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Bourcier, W L; Brachmann, A; Jardine, L J; Palmer, C E; Romanovski, V V; Shaw, H F

    1999-08-11

    The speciation and formation of Pu intrinsic colloids from an initial solution of Pu(V) were studied at pH 1, pH 3, pH 6, pIH 8, and pH 11. The medium was a surrogate Yucca Mountain groundwater from well J-l 3 under air atmosphere. The solutions were monitored for several months. Samples were analyzed using liquid scintillation counting, ultra filtration, solvent extraction: photon correlation spectroscopy, and laser-induced photo-acoustic breakdown and emission spectroscopy. Redox potentials were measured periodically. The time dependencies of soluble and colloidal Pu concentrations are reported. The size and concentration of Pu colloid particles were estimated.

  10. Dry bag isostatic pressing for improved green strength of surrogate nuclear fuel pellets

    International Nuclear Information System (INIS)

    Dry bag isostatic pressing is proposed for mass production of nuclear fuel pellets. Dry bag isostatically pressed rods of a fuel surrogate (95% CeO2-5% HfO2) 200 mm long by 8 mm diameter were cut into pellets using a wire saw. Four different binders and CeO2 powder obtained from two different sources were investigated. The strength of the isostatically pressed pellets for all binder systems measured by diametral compression was about 50% higher than pellets produced by uniaxial dry pressing at the same pressure. It was proposed that the less uniform density of uniaxially pressed pellets accounted for the lower strength. The strength of pellets containing CeO2 powder with significantly higher moisture content was five times higher than pellets containing CeO2 powder with a low moisture content even though they were 25% less dense. Capillary pressure of the moisture was thought to supply the added binding strength.

  11. Monoclonal Antibodies Attached to Carbon Nanotube Transistors for Paclitaxel Detection

    Science.gov (United States)

    Lee, Wonbae; Lau, Calvin; Richardson, Mark; Rajapakse, Arith; Weiss, Gregory; Collins, Philip; UCI, Molecular Biology; Biochemistry Collaboration; UCI, Departments of Physics; Astronomy Collaboration

    Paclitaxel is a naturally-occurring pharmaceutical used in numerous cancer treatments, despite its toxic side effects. Partial inhibition of this toxicity has been demonstrated using weakly interacting monoclonal antibodies (3C6 and 8A10), but accurate monitoring of antibody and paclitaxel concentrations remains challenging. Here, single-molecule studies of the kinetics of antibody-paclitaxel interactions have been performed using single-walled carbon nanotube field-effect transistors. The devices were sensitized with single antibody attachments to record the single-molecule binding dynamics of paclitaxel. This label-free technique recorded a range of dynamic interactions between the antibody and paclitaxel, and it provided sensitive paclitaxel detection for pM to nM concentrations. Measurements with two different antibodies suggest ways of extending this working range and uncovering the mechanistic differences among different antibodies.

  12. Radiolabelled antibodies in imaging

    International Nuclear Information System (INIS)

    Recent technological advances make it possible to produce pure (monoclonal) antibodies in unlimited quantities without the need for continuous immunization of animals and to label these antibodies with a variety of radionuclides which can be traced by single-photon computed tomography. An outline review of the state of the art is presented, with particular reference to the imaging of myocardial infarcts and to tumour imaging studies using labelled monoclonal antibodies (sup(99m)Tc and 125I). Lengthy bibliography. (U.K.)

  13. Use of surrogate outcomes in US FDA drug approvals, 2003–2012: a survey

    Science.gov (United States)

    Yu, Tsung; Hsu, Yea-Jen; Fain, Kevin M; Boyd, Cynthia M; Holbrook, Janet T; Puhan, Milo A

    2015-01-01

    Objective To evaluate, across a spectrum of diseases, how often surrogate outcomes are used as a basis for drug approvals by the US Food and Drug Administration (FDA), and whether and how the rationale for using treatment effects on surrogates as predictors of treatment effects on patient-centred outcomes is discussed. Study design and setting We used the Drugs@FDA website to identify drug approvals produced from 2003 to 2012 by the FDA. We focused on four diseases (chronic obstructive pulmonary disease (COPD), type 1 or 2 diabetes, glaucoma and osteoporosis) for which surrogates are commonly used in trials. We reviewed the drug labels and medical reviews to provide empirical evidence on how surrogate outcomes are handled by the FDA. Results Of 1043 approvals screened, 58 (6%) were for the four diseases of interest. Most drugs for COPD (7/9, 78%), diabetes (26/26, 100%) and glaucoma (9/9, 100%) were approved based on surrogates while for osteoporosis, most drugs (10/14, 71%) were also approved for patient-centred outcomes (fractures). The rationale for using surrogates was discussed in 11 of the 43 (26%) drug approvals based on surrogates. In these drug approvals, we found drug approvals for diabetes are more likely than the other examined conditions to contain a discussion of trial evidence demonstrating that treatment effects on surrogate outcomes predict treatment effects on patient-centred outcomes. Conclusions Our results suggest that the FDA did not use a consistent approach to address surrogates in assessing the benefits and harms of drugs for COPD, type 1 or 2 diabetes, glaucoma and osteoporosis. For evaluating new drugs, patient-centred outcomes should be chosen whenever possible. If the use of surrogate outcomes is necessary, then a consistent approach is important to review the evidence for surrogacy and consider surrogate's usage in the treatment and population under study. PMID:26614616

  14. Extraction of monoclonal antibodies (IgG1) using anionic and anionic/nonionic reverse micelles.

    Science.gov (United States)

    George, Daliya A; Stuckey, David C

    2010-01-01

    Purification schemes for antibody production based on affinity chromatography are trying to keep pace with increases in cell culture expression levels and many current research initiatives are focused on finding alternatives to chromatography for the purification of Monoclonal antibodies (MAbs). In this article, we have investigated an alternative separation technique based on liquid-liquid extraction called the reverse micellar extraction. We extracted MAb (IgG1) using reverse micelles of an anionic surfactant, sodium bis 2-ethyl-hexyl sulfosuccinate (AOT) and a combination of anionic (AOT) and nonionic surfactants (Brij-30, Tween-85, Span-85) using isooctane as the solvent system. The extraction efficiency of IgG1 was studied by varying parameters, such as pH of the aqueous phase, cation concentration, and type and surfactant concentration. Using the AOT/Isooctane reverse micellar system, we could achieve good overall extraction of IgG1 (between 80 and 90%), but only 30% of the bioactivity of IgG1 could be recovered at the end of the extraction by using its binding to affinity chromatography columns as a surrogate measure of activity. As anionic surfactants were suspected as being one of the reasons for the reduced activity, we decided to combine a nonionic surfactant with an anionic surfactant and then study its effect on the extraction efficiency and bioactivity. The best results were obtained using an AOT/Brij-30/Isooctane reverse micellar system, which gave an overall extraction above 90 and 59% overall activity recovery. An AOT/Tween-85/Isooctane reverse micellar system gave an overall extraction of between 75 and 80% and overall activity recovery of around 40-45%. The results showed that the activity recovery of IgG1 can be significantly enhanced using different surfactant combination systems, and if the recovery of IgG1 can be further enhanced, the technique shows considerable promise for the downstream purification of MAbs. PMID:20665658

  15. A Surrogate-based Adaptive Sampling Approach for History Matching and Uncertainty Quantification

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weixuan; Zhang, Dongxiao; Lin, Guang

    2015-02-25

    A critical procedure in reservoir simulations is history matching (or data assimilation in a broader sense), which calibrates model parameters such that the simulation results are consistent with field measurements, and hence improves the credibility of the predictions given by the simulations. Often there exist non-unique combinations of parameter values that all yield the simulation results matching the measurements. For such ill-posed history matching problems, Bayesian theorem provides a theoretical foundation to represent different solutions and to quantify the uncertainty with the posterior PDF. Lacking an analytical solution in most situations, the posterior PDF may be characterized with a sample of realizations, each representing a possible scenario. A novel sampling algorithm is presented here for the Bayesian solutions to history matching problems. We aim to deal with two commonly encountered issues: 1) as a result of the nonlinear input-output relationship in a reservoir model, the posterior distribution could be in a complex form, such as multimodal, which violates the Gaussian assumption required by most of the commonly used data assimilation approaches; 2) a typical sampling method requires intensive model evaluations and hence may cause unaffordable computational cost. In the developed algorithm, we use a Gaussian mixture model as the proposal distribution in the sampling process, which is simple but also flexible to approximate non-Gaussian distributions and is particularly efficient when the posterior is multimodal. Also, a Gaussian process is utilized as a surrogate model to speed up the sampling process. Furthermore, an iterative scheme of adaptive surrogate refinement and re-sampling ensures sampling accuracy while keeping the computational cost at a minimum level. The developed approach is demonstrated with an illustrative example and shows its capability in handling the above-mentioned issues. Multimodal posterior of the history matching

  16. Decay of maternal antibodies in broiler chickens.

    Science.gov (United States)

    Gharaibeh, Saad; Mahmoud, Kamel

    2013-09-01

    The objective of this study was to determine the decay rate of maternal antibodies against major broiler chicken pathogens. A total of 30 one-day-old broiler chicks were obtained from a commercial hatchery and reared in isolation. These chicks were retrieved from a parent flock that received a routine vaccination program. Chicks were bled at hatch and sequentially thereafter every 5 d through 30 d of age. Maternal antibody titers were measured by ELISA for avian encephalomyelitis (AEV), avian influenza virus (AIV), chicken anemia virus (CAV), infectious bursal disease virus (IBDV), infectious bronchitis virus (IBV), infectious laryngotracheitis virus (ILTV), Mycoplasma gallisepticum (MG), Mycoplasma synoviae (MS), and reovirus (Reo). Maternal antibody titers for Newcastle disease virus (NDV) were measured using a hemagglutination inhibition test. Half-life estimates of maternal antibody titers were 5.3, 4.2, 7, 5.1, 3.9, 3.8, 4.9, 4.1, 6.3, and 4.7 d for AEV, AIV, CAV, IBDV, IBV, ILTV, MG, MS, NDV, and Reo, respectively. The statistical analysis revealed significant differences among half-lives of maternal antibody titers against certain pathogens. Furthermore, all maternal antibody titers were depleted by 10 d of age except for IBDV. PMID:23960115

  17. Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3.

    Directory of Open Access Journals (Sweden)

    Christian Roussilhon

    2007-11-01

    Full Text Available BACKGROUND: Surrogate markers of protective immunity to malaria in humans are needed to rationalize malaria vaccine discovery and development. In an effort to identify such markers, and thereby provide a clue to the complex equation malaria vaccine development is facing, we investigated the relationship between protection acquired through exposure in the field with naturally occurring immune responses (i.e., induced by the parasite to molecules that are considered as valuable vaccine candidates. METHODS AND FINDINGS: We analyzed, under comparative conditions, the antibody responses of each of six isotypes to five leading malaria vaccine candidates in relation to protection acquired by exposure to natural challenges in 217 of the 247 inhabitants of the African village of Dielmo, Senegal (96 children and 121 older adolescents and adults. The status of susceptibility or resistance to malaria was determined by active case detection performed daily by medical doctors over 6 y from a unique follow-up study of this village. Of the 30 immune responses measured, only one, antibodies of the IgG3 isotype directed to merozoite surface protein 3 (MSP3, was strongly associated with clinical protection against malaria in all age groups, i.e., independently of age. This immunological parameter had a higher statistical significance than the sickle cell trait, the strongest factor of protection known against Plasmodium falciparum. A single determination of antibody was significantly associated with the clinical outcome over six consecutive years in children submitted to massive natural parasite challenges by mosquitoes (over three parasite inoculations per week. Finally, the target epitopes of these antibodies were found to be fully conserved. CONCLUSIONS: Since anti-MSP3 IgG3 antibodies can naturally develop along with protection against P. falciparum infection in young children, our results provide the encouraging indication that these antibodies should be

  18. The haemolytic antibody isotope release (HAIR) assay; an efficient alternative technique to conventional plaque assays

    International Nuclear Information System (INIS)

    The haemolytic antibody isotope release (HAIR) assay quantitates antibody production by splenic antibody-producing cells by lysis of chromium-51-labelled sheep red blood cells. The amount of antibody quantitated by the HAIR assay directly correlates with the number of antibody-producing cells measured by a conventional plaque assay. The HAIR assay is an easy, sensitive, and reproducible technique that is especially useful when large numbers of animals are required for testing. (author)

  19. On the vicissitudes of early primary surrogate mothering II: loss of the surrogate mother and arrest of mourning.

    Science.gov (United States)

    Hardin, H T; Hardin, D H

    2000-01-01

    Among the catastrophic events experienced by infants and young children, one of the most frequent is the loss of an early primary surrogate mother (EPSM). Usually permanent, the loss is often followed by the advent of a new, "replacement" caregiver. One aspect of the emotional environment is unique to this kind of caregiving situation: that parents are often unable to validate the true nature of their child's relationship with the EPSM or, ultimately, the trauma experienced by the child when the EPSM leaves. The marked discrepancy between the parent's and the infant or child's experience of the surrogate mothering leads to an arrest of the child's mourning process, with the potential for serious developmental consequences. Issues related to EPSM loss and its aftermath are examined in the light of two examples. Further exploration of the environment of this kind of caregiving directs attention to the critical need to nurture and protect the attachments of both the infant or child and the parent to the ESPM. PMID:11212189

  20. Modeling Pancreatic Tumor Motion Using 4-Dimensional Computed Tomography and Surrogate Markers

    Energy Technology Data Exchange (ETDEWEB)

    Huguet, Florence [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Department of Radiation Oncology, Hôpitaux Universitaires Paris Est, Hôpital Tenon, University Paris VI, Paris (France); Yorke, Ellen D.; Davidson, Margaret [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Jackson, Andrew; Mageras, Gig S. [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Wu, Abraham J. [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Goodman, Karyn A., E-mail: GoodmanK@mskcc.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

    2015-03-01

    Purpose: To assess intrafractional positional variations of pancreatic tumors using 4-dimensional computed tomography (4D-CT), their impact on gross tumor volume (GTV) coverage, the reliability of biliary stent, fiducial seeds, and the real-time position management (RPM) external marker as tumor surrogates for setup of respiratory gated treatment, and to build a correlative model of tumor motion. Methods and Materials: We analyzed the respiration-correlated 4D-CT images acquired during simulation of 36 patients with either a biliary stent (n=16) or implanted fiducials (n=20) who were treated with RPM respiratory gated intensity modulated radiation therapy for locally advanced pancreatic cancer. Respiratory displacement relative to end-exhalation was measured for the GTV, the biliary stent, or fiducial seeds, and the RPM marker. The results were compared between the full respiratory cycle and the gating interval. Linear mixed model was used to assess the correlation of GTV motion with the potential surrogate markers. Results: The average ± SD GTV excursions were 0.3 ± 0.2 cm in the left-right direction, 0.6 ± 0.3 cm in the anterior-posterior direction, and 1.3 ± 0.7 cm in the superior-inferior direction. Gating around end-exhalation reduced GTV motion by 46% to 60%. D95% was at least the prescribed 56 Gy in 76% of patients. GTV displacement was associated with the RPM marker, the biliary stent, and the fiducial seeds. The correlation was better with fiducial seeds and with biliary stent. Conclusions: Respiratory gating reduced the margin necessary for radiation therapy for pancreatic tumors. GTV motion was well correlated with biliary stent or fiducial seed displacements, validating their use as surrogates for daily assessment of GTV position during treatment. A patient-specific internal target volume based on 4D-CT is recommended both for gated and not-gated treatment; otherwise, our model can be used to predict the degree of GTV motion.

  1. Modeling Pancreatic Tumor Motion Using 4-Dimensional Computed Tomography and Surrogate Markers

    International Nuclear Information System (INIS)

    Purpose: To assess intrafractional positional variations of pancreatic tumors using 4-dimensional computed tomography (4D-CT), their impact on gross tumor volume (GTV) coverage, the reliability of biliary stent, fiducial seeds, and the real-time position management (RPM) external marker as tumor surrogates for setup of respiratory gated treatment, and to build a correlative model of tumor motion. Methods and Materials: We analyzed the respiration-correlated 4D-CT images acquired during simulation of 36 patients with either a biliary stent (n=16) or implanted fiducials (n=20) who were treated with RPM respiratory gated intensity modulated radiation therapy for locally advanced pancreatic cancer. Respiratory displacement relative to end-exhalation was measured for the GTV, the biliary stent, or fiducial seeds, and the RPM marker. The results were compared between the full respiratory cycle and the gating interval. Linear mixed model was used to assess the correlation of GTV motion with the potential surrogate markers. Results: The average ± SD GTV excursions were 0.3 ± 0.2 cm in the left-right direction, 0.6 ± 0.3 cm in the anterior-posterior direction, and 1.3 ± 0.7 cm in the superior-inferior direction. Gating around end-exhalation reduced GTV motion by 46% to 60%. D95% was at least the prescribed 56 Gy in 76% of patients. GTV displacement was associated with the RPM marker, the biliary stent, and the fiducial seeds. The correlation was better with fiducial seeds and with biliary stent. Conclusions: Respiratory gating reduced the margin necessary for radiation therapy for pancreatic tumors. GTV motion was well correlated with biliary stent or fiducial seed displacements, validating their use as surrogates for daily assessment of GTV position during treatment. A patient-specific internal target volume based on 4D-CT is recommended both for gated and not-gated treatment; otherwise, our model can be used to predict the degree of GTV motion

  2. Anti-sulfotyrosine antibodies

    Science.gov (United States)

    Bertozzi, Carolyn R.; Kehoe, John; Bradbury, Andrew M.

    2009-09-15

    The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

  3. HIV Antibody Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? HIV Antibody and HIV Antigen (p24) Share this page: Was this page helpful? Also known as: HIV Screening Tests; AIDS Test; AIDS Screen; HIV Serology; ...

  4. Antinuclear antibody panel

    Science.gov (United States)

    ... blood may be due to: Chronic liver disease Collagen vascular disease Drug-induced lupus erythematosus Myositis (inflammatory muscle disease) ... Saunders; 2011:chap 51. Read More Antibody Arthritis Collagen vascular disease Drug-induced lupus erythematosus Liver disease Scleroderma Systemic ...

  5. PRODUCTION OF MONOCLONAL ANTIBODIES

    Directory of Open Access Journals (Sweden)

    TOLKOVA E.S.

    2015-01-01

    Full Text Available The article considers the use of monoclonal antibodies in immunotherapy and immunodiagnostics of oncological diseases and their production using hybridoma technolody with flow diagram and technological scheme of manufacturing process

  6. PRODUCTION OF MONOCLONAL ANTIBODIES

    OpenAIRE

    TOLKOVA E.S.

    2015-01-01

    The article considers the use of monoclonal antibodies in immunotherapy and immunodiagnostics of oncological diseases and their production using hybridoma technolody with flow diagram and technological scheme of manufacturing process

  7. Method for detecting pathogens attached to specific antibodies

    Science.gov (United States)

    Miles, Robin R.; Venkateswaran, Kodumudi S.; Fuller, Christopher K.

    2005-01-25

    The use of impedance measurements to detect the presence of pathogens attached to antibody-coated beads. In a fluidic device antibodies are immobilized on a surface of a patterned interdigitated electrode. Pathogens in a sample fluid streaming past the electrode attach to the immobilized antibodies, which produces a change in impedance between two adjacent electrodes, which impedance change is measured and used to detect the presence of a pathogen. To amplify the signal, beads coated with antibodies are introduced and the beads would stick to the pathogen causing a greater change in impedance between the two adjacent electrodes.

  8. Expression of Recombinant Antibodies

    OpenAIRE

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transg...

  9. Myth and reality: practical test system for the measurement of anti-DNA antibodies in the diagnosis of systemic lupus erythematosus (SLE).

    Science.gov (United States)

    McCloskey, Laura J; Christner, Paul; Jacobs-Kosmin, Dana; Jaskowski, Troy D; Hill, Harry R; Lakos, Gabriella; Teodorescu, Marius

    2010-01-01

    The myth persists that only the labor intensive Farr radioimmunoassay and Crithidia luciliae immunofluorescence (CL-IFA) are systemic lupus erythematosus (SLE)-specific tests. We compared them to ELISA with bacteriophage lambda DNA (EL-dsDNA) and denatured calf thymus DNA (EL-ssDNA). By percentile ranking, the specificity cut-off level was set both out of clinical context (SOCC) on 100 blood bank donors, and in clinical context (SICC) on 100 patients with either rheumatoid arthritis or scleroderma (50/50). Clinical sensitivity was calculated on 100 random SLE patients. At 95% SICC, the sensitivity of Farr, CL-IFA, EL-dsDNA, and EL-ssDNA was similar (95%CI): 76% (66-84), 76% (66-84), 63% (53-72), and 75% (65-83), respectively; 87% of the patients were positive by at least one method and 55%by all methods. At 99% SICC, the sensitivity was also similar (95% CI): 57% (47-67), 47% (37-57), 58% (47-67), and 43% (33-53), respectively. The areas under ROC curve were similar (95% CI) when patients were used as controls for specificity. At 99% SOCC, EL-ssDNA identified 89% positive, 2 negative but positive by another method at 95% SICC, and 9 negative (i.e. 89/2/9), followed by CL-IFA (80/6/14), Farr (76/12/12), and EL-dsDNA (64/23/13). Thus, at relatively low cost and easy automation, under the same conditions of specificity, the two ELISA tests combined were at least as good, if not superior, to CL-IFA or Farr: they showed similar clinical sensitivity and also identified more patients with anti-DNA antibodies. PMID:20333761

  10. Adaptive spectral tensor-strain decomposition for the construction of surrogate models

    DEFF Research Database (Denmark)

    Bigoni, Daniele; Engsig-Karup, Allan Peter; Marzouk, Youssef M.

    The construction of surrogate models is important as a mean of acceleration in computational methods for uncertainty quantification (UQ). When the forward model is particularly expensive, surrogate models can be used for the forward propagation of uncertainty [4] and the solution of inference pro...

  11. Comparison of surrogate models with different methods in groundwater remediation process

    Indian Academy of Sciences (India)

    Jiannan Luo; Wenxi Lu

    2014-10-01

    Surrogate modelling is an effective tool for reducing computational burden of simulation optimization. In this article, polynomial regression (PR), radial basis function artificial neural network (RBFANN), and kriging methods were compared for building surrogate models of a multiphase flow simulation model in a simplified nitrobenzene contaminated aquifer remediation problem. In the model accuracy analysis process, a 10-fold cross validation method was adopted to evaluate the approximation accuracy of the three surrogate models. The results demonstrated that: RBFANN surrogate model and kriging surrogate model had acceptable approximation accuracy, and further that kriging model’s approximation accuracy was slightly higher than RBFANN model. However, the PR model demonstrated unacceptably poor approximation accuracy. Therefore, the RBFANN and kriging surrogates were selected and used in the optimization process to identify the most cost-effective remediation strategy at a nitrobenzene-contaminated site. The optimal remediation costs obtained with the two surrogate-based optimization models were similar, and had similar computational burden. These two surrogate-based optimization models are efficient tools for optimal groundwater remediation strategy identification.

  12. Surrogate Parents and Children with Disabilities: State-Level Approaches. inForum

    Science.gov (United States)

    Muller, Eve

    2009-01-01

    Based on a survey of states, this document summarizes state-level approaches to using surrogate parents in order to meet the needs of children with disabilities. Most respondents noted that their states had issued policy or formal guidance pertaining to surrogate parents and children with disabilities, and most also described efforts to ensure…

  13. Feasibility of using anatomical surrogates for predicting the position of lung tumours

    International Nuclear Information System (INIS)

    We studied the use of internal anatomical surrogates (carina and diaphragm) for the purpose of predicting the 3D position of lung tumours in 41 patients, in whom repeat 4DCT scans were available. Despite using two surrogates, significant prediction errors were observed, which varied depending on tumour position, baseline tumour motion and respiratory phase.

  14. Role of the direct mechanisms in the deuteron-induced surrogate reactions

    CERN Document Server

    Avrigeanu, M

    2015-01-01

    An extended analysis of the key role of direct interactions, i.e., breakup, stripping and pick-up processes, for the deuteron–induced surrogate reactions is presented. Particular comments concern the deuteron breakup which is dominant in the case of the ( d; p g ) surrogate reactions on actinides target nuclei, around the Coulomb barrier.

  15. THE QUESTION OF INHERITANCE RIGHTS OF SURROGATE CHILDREN IN THE LEGISLATION OF THE RUSSIAN FEDERATION

    Directory of Open Access Journals (Sweden)

    Leskova J. G.

    2015-09-01

    Full Text Available Norms of the active Russian legislation enshrining the inheritance rights and defining the status of surrogate children, surrogate mother and the genetic parents connecting to the question of the obtaining and realization of the inheritance rights of these children are subjected to a detail analyze in the article. The authors described uncertainties and double-meanings of some occasions of appearing of surrogate children’s inheritance rights, what arise in practice, for example, when surrogate mother in childbirth could not give her agreement for registration people, who had given their genetic material, as parents of surrogate child. The authors found out imperfection of active legislation of Russian Federation in the context of question of surrogate children’s inheritance rights in case of genetic parents’ death before childbirth. Other important question, that the authors tried to resolve in the article, is connected with child’s inheritance rights, who was conceived after death of his genetic parents. Also the attention is focused on the absence legal mechanisms of action on genetic parents, who refuse surrogate children, in the Family Code of Russian Federation and in Civil Code of Russian Federation. Authors reached a conclusion that surrogate children’s inheritance rights should be legal regulated in detail. Some suggestions on these issues are offered in the article

  16. Use of surrogate travel to lower training costs and reduce person-rems

    International Nuclear Information System (INIS)

    In the commercial nuclear power industry where access on site may be prohibited by regulations, procedures, or the potential of extremely high radiation levels, a surrogate travel system has potential for the reduction of both exposure and personnel training time. A prototype surrogate travel system using a microcomputer-assisted laser optical video disc has been developed by Southern California Edison and Combustion Engineering

  17. Inconsistent reporting of surrogate outcomes in randomised clinical trials: cohort study

    DEFF Research Database (Denmark)

    La Cour, Jeppe Lerche; Brok, Jesper; Gøtzsche, Peter C

    2010-01-01

    To assess if authors of randomised clinical trials convey the fact that they have used surrogate outcomes and discussed their validity.......To assess if authors of randomised clinical trials convey the fact that they have used surrogate outcomes and discussed their validity....

  18. Critical review of norovirus surrogates in food safety research: rationale for considering volunteer studies

    Science.gov (United States)

    The inability to propagate human norovirus (NoV) or to clearly differentiate infectious from noninfectious virus particles have led to the use of surrogate viruses, like feline calicivirus (FCV) and murine norovirus-1 (MNV), which are propagatable in cell culture. The use of surrogates is predicate...

  19. DNA Stains as Surrogate Nucleobases in Fluorogenic Hybridization Probes.

    Science.gov (United States)

    Hövelmann, Felix; Seitz, Oliver

    2016-04-19

    The increasing importance assigned to RNA dynamics in cells and tissues calls for probe molecules that enable fluorescence microscopy imaging in live cells. To achieve this goal, fluorescence dyes are conjugated with oligonucleotides so as to provide strong emission upon hybridization with the target molecule. The impressive 10(3)-fold fluorescence intensification observed when DNA stains such as thiazole orange (TO) interact with double-stranded DNA is intriguing and prompted the exploration of oligonucleotide conjugates. However, nonspecific interactions of DNA stains with polynucleotides tend to increase background, which would affect the contrast achievable in live-cell imaging. This Account describes the development of DNA-stain-labeled hybridization probes that provide high signal-to-background. We focus on our contributions in context with related advances from other laboratories. The emphasis will be on the requirements of RNA imaging in live cells. To reduce background, intercalator dyes such as TO were appended to peptide nucleic acid (PNA), which is less avidly recognized by DNA stains than DNA/RNA. Constraining the TO dye as a nucleobase surrogate in "forced intercalation (FIT) probes" improved the target specificity, presumably by helping to prevent unspecific interactions. The enforcement of TO intercalation between predetermined base pairs upon formation of the probe-target duplex provided for high brightness and enabled match/mismatch selectivity beyond stringency of hybridization. We show examples that highlight the use of PNA FIT probes in the imaging of mRNA, miRNA, and lncRNA in living cells. The "FIT approach" was recently extended to DNA probes. Signal brightness can become limiting when low-abundance targets ought to be visualized over cellular autofluorescence. We discuss strategies that further the brightness of signaling by FIT probes. Multilabeling with identical dyes does not solve the brightness issue. To avoid self-quenching, we

  20. Physiological correlates of maternal separation in surrogate-reared infants: a study in altered attachment bonds.

    Science.gov (United States)

    Reite, M; Short, R; Seiler, C

    1978-09-01

    Three pigtail infant monkeys (Macaca nemestrina) were separated from their mothers shortly after birth and raised in social isolation on cloth surrogates. At about 24 weeks of age they were surgically implanted with multichannel biotelemetry systems. Following the collection of baseline behavioral and physiological data, the cloth surrogates were removed for 4 days, then returned. The behavioral and physiological (heart rate, body temperature, sleep patterns) reaction to separation from the surrogate was much less intense than is the case in group-living pigtail infants that are separated from their mothers, suggesting that the attachment bond to a cloth surrogate may be different than the bond to a living mother in a social group. Heart rate mean values and variability were similar in surrogate-reared and mother-reared infants, suggesting a degree of environmental independence in heart rate regulation. PMID:99340