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Sample records for antibodies measuring surrogates

  1. 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.

  2. Hepatology may have problems with putative surrogate outcome measures

    DEFF Research Database (Denmark)

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

    2007-01-01

    hepatitis C, serum bilirubin concentration following ursodeoxycholic acid or immunosuppressants for patients with primary biliary cirrhosis, and nutritional outcomes following artificial nutrition for liver patients may not be valid surrogates for morbidity or mortality. The challenge is to develop reliable...

  3. Measurement of arterial wall thickness as a surrogate marker for atherosclerosis

    NARCIS (Netherlands)

    de Groot, E; Hovingh, GK; Wiegman, A; Duriez, P; Smit, AJ; Fruchart, JC; Kastelein, JJP

    2004-01-01

    Large observational studies and atherosclerosis regression trials of lipid-modifying pharmacotherapy have established that intima-media thickness of the carotid and femoral arteries, as measured noninvasively by B-mode ultrasound, is a valid surrogate marker for the progression of atherosclerotic di

  4. Anti-idiotypic antibodies function as a surrogate surface epitope of Brugia malayi infective larvae.

    Science.gov (United States)

    Carlow, C K; Busto, P; Storey, N; Philipp, M

    1990-07-01

    Anti-idiotypic (AB2) antibodies were generated in rabbits following immunization with a murine IgM monoclonal antibody (AB1) recognizing a surface determinant of Brugia malayi infective stage larvae. AB2 specifically inhibited the binding of AB1 to B. malayi larvae. Furthermore, AB2 had the ability to mimic the original antigen since mice immunized with AB2 possessed serum antibodies (AB3) specific for the B. malayi surface determinant. The presence of anti-surface antibodies (AB3 and AB1) induced either by AB2 immunization or by administration of AB1, did not alter the outcome of an intraperitoneal infection of B. malayi larvae in BABL/c mice when compared to untreated animals. AB3 antibodies like AB1, were IgM, thus indicating an isotype restricted response to the B. malayi epitope. There were no detectable cell mediated responses to the surface determinant in mice immunized with AB2, assessed by lymphocyte blastogenesis or IL3 production in vitro in response to the idiotope as presented by living larvae. The lack of cellular responses and/or the previously demonstrated rapid shedding of the epitope may explain the inability of AB1 or AB2 to protect mice against larval challenge in this study.

  5. Stochastic Surrogates for Measurements and Computer Models of Fluids

    NARCIS (Netherlands)

    De Baar, J.H.S.

    2014-01-01

    Both measurements and computer simulations of fluids introduce a prediction problem. A Particle Image Velocimetry (PIV) measurement of a flow field results in a discrete grid of velocity vectors, from which we aim to predict the velocity field or related quantities. In Computational Fluid Dynamics (

  6. Measuring (n,f) cross sections of plutonium nuclei via the surrogate method

    Science.gov (United States)

    Hughes, R. O.; Beausang, C. W.; Ross, T. J.; Gell, K.; Good, E.; Tarlow, T.; Burke, J. T.; Casperson, R. J.; McCleskey, M.; Saastamoinen, A.; Cooper, N.; Humby, P.

    2012-10-01

    Neutron-induced cross section measurements of exotic nuclei provide a significant experimental challenge due to the need for radioactive targets and high neutron fluxes. Over the past few years the surrogate method has been shown to provide a means of indirectly measuring certain neutron-induced cross sections. Recent results benchmarking (p,t-f) and (p,d-f) reactions as surrogates for (n,f) cross section measurements in uranium nuclei show good agreement with literature data [1]. Building on this work, the use of (p,t-f) and (p,d-f) reactions has very recently been extended to surrogate measurements of the poorly established ^236Pu(n,f) and ^237Pu(n,f) cross sections. The experiment was performed at Texas A&M University using a 30 MeV proton beam from the K150 cyclotron, incident on ^239Pu and ^235U targets. Charged particle-fission and charged particle-γ coincidence data were collected using the combined silicon telescope and γ-ray array: STARLiTe. Preliminary results will be presented. This work was supported by DoE Grant Numbers: DE-FG52-09 NA29454 and DE-FG02-05 ER41379 (UR) and DE-AC52-07 NA27344 (LLNL).[4pt] [1] R.O. Hughes et al., PRC 85, 024613 (2012).

  7. 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.

  8. Surrogate Measurements of Actinide (n,2n) Cross Sections with NeutronSTARS

    Energy Technology Data Exchange (ETDEWEB)

    Casperson, R. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Burke, J. T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hughes, R. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Akindele, O. A. [Univ. of California, Berkeley, CA (United States); Koglin, J. D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Wang, B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Tamashiro, A. [Oregon State Univ., Corvallis, OR (United States)

    2016-09-27

    Directly measuring (n,2n) cross sections on short-lived actinides presents a number of experimental challenges. The surrogate reaction technique is an experimental method for measuring cross sections on short-­lived isotopes, and it provides a unique solution for measuring (n,2n) cross sections. This technique involves measuring a charged-­particle reaction cross section, where the reaction populates the same compound nucleus as the reaction of interest. To perform these surrogate (n,2n) cross section measurements, a silicon telescope array has been placed along a beam line at the Texas A&M University Cyclotron Institute, which is surrounded by a large tank of gadolinium-doped liquid scintillator, which acts as a neutron detector. The combination of the charge-particle and neutron-detector arrays is referred to as NeutronSTARS. In the analysis procedure for calculating the (n,2n) cross section, the neutron detection efficiency and time structure plays an important role. Due to the lack of availability of isotropic, mono-energetic neutron sources, modeling is an important component in establishing this efficiency and time structure. This report describes the NeutronSTARS array, which was designed and commissioned during this project. It also describes the surrogate reaction technique, specifically referencing a 235U(n,2n) commissioning measurement that was fielded during the past year. Advanced multiplicity analysis techniques have been developed for this work, which should allow for efficient analysis of 241Pu(n,2n) and 239Pu(n,2n) cross section measurements

  9. Laminar Flame Speeds of Gasoline Surrogates Measured with the Flat Flame Method

    KAUST Repository

    Liao, Y.-H.

    2016-01-27

    © 2016 American Chemical Society. The adiabatic, laminar flame speeds of gasoline surrogates at atmospheric pressure over a range of equivalence ratios of = 0.8-1.3 and unburned gas temperatures of 298-400 K are measured with the flat flame method, which produces a one-dimensional flat flame free of stretch. Surrogates used in the current work are the primary reference fuels (PRFs, mixtures of n-heptane and isooctane), the toluene reference fuels (TRFs, mixtures of toluene and PRFs), and the ethanol reference fuels (ERFs, mixtures of ethanol and PRFs). In general, there is good agreement between the present work and the literature data for single-component fuel and PRF mixtures. Surrogates of TRF mixtures are found to exhibit comparable flame speeds to a real gasoline, while there is discrepancy observed between isooctane and gasoline. Moreover, the laminar flame speeds of TRF mixtures with similar fractions of n-heptane are found to be insensitive to the quantity of toluene in the mixture. Mixtures of ERFs exhibit comparable flame speeds to those of TRFs with similar mole fractions of n-heptane and isooctane.

  10. Synthetic aperture acoustic measurements of stationary suspended cinderblock and surrogate substitutes

    Science.gov (United States)

    Bishop, Steven; Woods, Teresa; Vignola, Joe; Judge, John; Soumekh, Mehrdad

    2009-05-01

    A synthetic aperture acoustic approach is used as a standoff method to assess material properties of a typical cinder block, referred to as a concrete masonry unit (CMU), and a variety of CMU surrogates. The objective is to identify anomalies in CMU wall surfaces. The acoustic specular return and phase change across the blocks are the fundamental measurements of interest. The CMU surrogates are created from commercially available closed cell expanding foam. Results from three test articles are presented that show potentially exploitable differences in terms of acoustic magnitude and acoustic phase response between the surrogates and typical CMUs. The test articles are; a typical CMU, a foam block, and a foam block with an embedded steel object. All test articles are similar in size and shape, and both foam blocks are covered in grout so that surface appearance closely matches that of a CMU. The results show that each of the test articles has characteristics that may be used for discrimination and anomaly detection.

  11. Surrogate Measures of Insulin Resistance in Middle-aged Non-diabetic Subjects

    Directory of Open Access Journals (Sweden)

    Katalin Csép

    2013-12-01

    Full Text Available Objective: Insulin resistance has been shown to be a risk factor for type 2 diabetes and cardiovascular disease. The assessment of insulin sensitivity in the clinical practice, however, faces several difficulties. The study proposes to analyze surrogate measures of insulin resistance based on fasting insulin levels in central Romania, and check whether the diagnosis of the metabolic syndrome is an adequate strategy to identify middle-aged persons with reduced insulin sensitivity. Methods: Anthropometric measurements, metabolic profile, and surrogates measures of insulin sensitivity (GIR, HOMA, QUICKI, FIRI, Belfiore, Bennett, Raynaud, McAuley index based on fasting insulin levels were assessed in 233 non-diabetic middle aged subjects. Results: Cutoff values, determined as the lowest quartile of insulin sensitivity for fasting insulin, HOMA, IRI (1/QUICKI, FIRI and Belfiore's, Bennett's, Raynaud's and McAuley's insulin sensitivity indices were 10.49 mU/L, 2.1, 3.01, 2.32, and 0.03, 1.34, 3.81, 6.29, 5.82. Components of the metabolic syndrome showed moderate but significant correlations with the surrogate measures of insulin resistance (r = 0.22-0.56, p <0.05. HOMA-IR and McAuley indices were the best predictors of clustered cardiometabolic risk factors (AUC - 0.83, 0.81 and 0.82. The metabolic syndrome diagnosis performed well in identifying patients with reduced insulin sensitivity (McAuley 2: sensitivity - 0.78, specificity - 0.84. Conclusion: Fasting insulin derived insulin sensitivity indices may help the recognittion of insulin resistant states predicting cardiometabolic disorders. Actively looking for insulin resistance by these simple indices, or by diagnosing the metabolic syndrome, those at increased risk can be recognized

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Church, J A; Ahle, L; Bernstein, L A; Cooper, J; Dietrich, F S; Escher, J; Forssen, C; Ai, H; Amro, H; Babilon, M; Beausang, C; Caggiano, J; Heinz, A; Hughes, R; McCutchan, E; Meyer, D; Plettner, C; Ressler, J; Zamfir, V

    2004-07-14

    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 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,{gamma}/n/2n) cross sections. As a benchmark, the reaction {sup 92}Zr({alpha},{alpha}'), surrogate, for n+{sup 91}Zr, 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 {gamma}-ray energies measured with germanium clover detectors from the YRAST (Yale Rochester Array for SpecTroscopy) ball. The experiment and preliminary observations will be discussed.

  14. Non-invasive measurement of X-ray beam heating on a surrogate crystal sample.

    Science.gov (United States)

    Snell, Edward H; Bellamy, Henry D; Rosenbaum, Gerd; van der Woerd, Mark J

    2007-01-01

    Cryocooling is a technique routinely used to mitigate the effects of secondary radiation damage on macromolecules during X-ray data collection. Energy from the X-ray beam absorbed by the sample raises the temperature of the sample. How large is the temperature increase and does this reduce the effectiveness of cryocooling? Sample heating by the X-ray beam has been measured non-invasively for the first time by means of thermal imaging. Specifically, the temperature rise of 1 mm and 2 mm glass spheres (sample surrogates) exposed to an intense synchrotron X-ray beam and cooled in a laminar flow of nitrogen gas is experimentally measured. For the typical sample sizes, photon energies, fluxes, flux densities and exposure times used for macromolecular crystallographic data collection at third-generation synchrotron radiation sources and with the sample accurately centered in the cryostream, the heating by the X-ray beam is only a few degrees. This is not sufficient to raise the sample above the amorphous-ice/crystalline-ice transition temperature and, if the cryostream cools the sample to 100 K, not even enough to significantly enhance radiation damage from secondary effects.

  15. Report on 240Am(n,x) surrogate cross section test measurement

    Energy Technology Data Exchange (ETDEWEB)

    Ressler, J J; Burke, J T; Gostic, J; Bleuel, D; Escher, J E; Henderson, R A; Koglin, J; Reed, T; Scielzo, N D; Stoyer, M A

    2012-02-01

    The main goal of the test measurement was to determine the feasibility of the {sup 243}Am(p,t) reaction as a surrogate for {sup 240}Am(n,f). No data cross section data exists for neutron induced reactions on {sup 240}Am; the half-life of this isotope is only 2.1 days making direct measurements difficult, if not impossible. The 48-hour experiment was conducted using the STARS/LIBERACE experimental facility located at the 88 Inch Cyclotron at Lawrence Berkeley National Laboratory in August 2011. A description of the experiment and results is given. The beam energy was initially chosen to be 39 MeV in order to measure an equivalent neutron energy range from 0 to 20 MeV. However, the proton beam was not stopped in the farady cup and the beam was deposited in the surrounding shielding material. The shielding material was not conductive, and a beam current, needed for proper tuning of the beam as well as experimental monitoring, could not be read. If the {sup 240}Am(n,f) surrogate experiment is to be run at LBNL, simple modifications to the beam collection site will need to be made. The beam energy was reduced to 29 MeV, which was within an energy regime of prior experiments and tuning conditions at STARS/LIBERACE. At this energy, the beam current was successfully tuned and measured. At 29 MeV, data was collected with both the {sup 243}Am and {sup 238}U targets. An example particle identification plot is shown in Fig. 1. The triton-fission coincidence rate for the {sup 243}Am target and {sup 238}U target were measured. Coincidence rates of 0.0233(1) cps and 0.150(6) cps were observed for the {sup 243}Am and {sup 238}U targets, respectively. The difference in count rate is largely attributed to the available target material - the {sup 238}U target contains approximately 7 times more atoms than the {sup 243}Am. A proton beam current of {approx}0.7 nA was used for measurements on both targets. Assuming a full experimental run under similar conditions, an estimate for the

  16. Evaluating outer segment length as a surrogate measure of peak foveal cone density.

    Science.gov (United States)

    Wilk, Melissa A; Wilk, Brandon M; Langlo, Christopher S; Cooper, Robert F; Carroll, Joseph

    2017-01-01

    Adaptive optics (AO) imaging tools enable direct visualization of the cone photoreceptor mosaic, which facilitates quantitative measurements such as cone density. However, in many individuals, low image quality or excessive eye movements precludes making such measures. As foveal cone specialization is associated with both increased density and outer segment (OS) elongation, we sought to examine whether OS length could be used as a surrogate measure of foveal cone density. The retinas of 43 subjects (23 normal and 20 albinism; aged 6-67years) were examined. Peak foveal cone density was measured using confocal adaptive optics scanning light ophthalmoscopy (AOSLO), and OS length was measured using optical coherence tomography (OCT) and longitudinal reflectivity profile-based approach. Peak cone density ranged from 29,200 to 214,000cones/mm(2) (111,700±46,300cones/mm(2)); OS length ranged from 26.3 to 54.5μm (40.5±7.7μm). Density was significantly correlated with OS length in albinism (pdensity as a function of OS length was created based on histology and optimized to fit the albinism data. The model includes triangular cone packing, a cylindrical OS with a fixed volume of 136.6μm(3), and a ratio of OS to inner segment width that increased linearly with increasing OS length (R(2)=0.72). Normal subjects showed no apparent relationship between cone density and OS length. In the absence of adequate AOSLO imagery, OS length may be used to estimate cone density in patients with albinism. Whether this relationship exists in other patient populations with foveal hypoplasia (e.g., premature birth, aniridia, isolated foveal hypoplasia) remains to be seen.

  17. Surrogate light chain is required for central and peripheral B-cell tolerance and inhibits anti-DNA antibody production by marginal zone B cells.

    Science.gov (United States)

    Ren, Weicheng; Grimsholm, Ola; Bernardi, Angelina I; Höök, Nina; Stern, Anna; Cavallini, Nicola; Mårtensson, Inga-Lill

    2015-04-01

    Selection of the primary antibody repertoire takes place in pro-/pre-B cells, and subsequently in immature and transitional B cells. At the first checkpoint, μ heavy (μH) chains assemble with surrogate light (SL) chain into a precursor B-cell receptor. In mice lacking SL chain, μH chain selection is impaired, and serum autoantibody levels are elevated. However, whether the development of autoantibody-producing cells is due to an inability of the resultant B-cell receptors to induce central and/or peripheral B-cell tolerance or other factors is unknown. Here, we show that receptor editing is defective, and that a higher proportion of BM immature B cells are prone to undergoing apoptosis. Furthermore, transitional B cells are also more prone to undergoing apoptosis, with a stronger selection pressure to enter the follicular B-cell pool. Those that enter the marginal zone (MZ) B-cell pool escape selection and survive, possibly due to the B-lymphopenia and elevated levels of B-cell activating factor. Moreover, the MZ B cells are responsible for the elevated IgM anti-dsDNA antibody levels detected in these mice. Thus, the SL chain is required for central and peripheral B-cell tolerance and inhibits anti-DNA antibody production by MZ B cells.

  18. Thermal inactivation of human norovirus surrogates in spinach and measurement of its uncertainty.

    Science.gov (United States)

    Bozkurt, Hayriye; D'souza, Doris H; Davidson, P Michael

    2014-02-01

    Leafy greens, including spinach, have potential for human norovirus transmission through improper handling and/or contact with contaminated water. Inactivation of norovirus prior to consumption is essential to protect public health. Because of the inability to propagate human noroviruses in vitro, murine norovirus (MNV-1) and feline calicivirus (FCV-F9) have been used as surrogates to model human norovirus behavior under laboratory conditions. The objectives of this study were to determine thermal inactivation kinetics of MNV-1 and FCV-F9 in spinach, compare first-order and Weibull models, and measure the uncertainty associated with the process. D-values were determined for viruses at 50, 56, 60, 65, and 72 °C in 2-ml vials. The D-values calculated from the first-order model (50 to 72 °C) ranged from 0.16 to 14.57 min for MNV-1 and 0.15 to 17.39 min for FCV-9. Using the Weibull model, the tD for MNV-1 and FCV-F9 to destroy 1 log (D ≈ 1) at the same temperatures ranged from 0.22 to 15.26 and 0.27 to 20.71 min, respectively. The z-values determined for MNV-1 were 11.66 ± 0.42 °C using the Weibull model and 10.98 ± 0.58 °C for the first-order model and for FCV-F9 were 10.85 ± 0.67 °C and 9.89 ± 0.79 °C, respectively. There was no difference in D- or z-value using the two models (P > 0.05). Relative uncertainty for dilution factor, personal counting, and test volume were 0.005, 0.0004, and ca. 0.84%, respectively. The major contribution to total uncertainty was from the model selected. Total uncertainties for FCV-F9 for the Weibull and first-order models were 3.53 to 7.56% and 11.99 to 21.01%, respectively, and for MNV-1, 3.10 to 7.01% and 13.14 to 16.94%, respectively. Novel and precise information on thermal inactivation of human norovirus surrogates in spinach was generated, enabling more reliable thermal process calculations to control noroviruses. The results of this study may be useful to the frozen food industry in designing blanching processes for

  19. Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques.

    Directory of Open Access Journals (Sweden)

    John G Hattersley

    Full Text Available We evaluated the ability of simple and complex surrogate-indices to identify individuals from an overweight/obese cohort with hepatic insulin-resistance (HEP-IR. Five indices, one previously defined and four newly generated through step-wise linear regression, were created against a single-cohort sample of 77 extensively characterised participants with the metabolic syndrome (age 55.6 ± 1.0 years, BMI 31.5 ± 0.4 kg/m(2; 30 males. HEP-IR was defined by measuring endogenous-glucose-production (EGP with [6-6(2H(2] glucose during fasting and euglycemic-hyperinsulinemic clamps and expressed as EGP*fasting plasma insulin. Complex measures were incorporated into the model, including various non-standard biomarkers and the measurement of body-fat distribution and liver-fat, to further improve the predictive capability of the index. Validation was performed against a data set of the same subjects after an isoenergetic dietary intervention (4 arms, diets varying in protein and fiber content versus control. All five indices produced comparable prediction of HEP-IR, explaining 39-56% of the variance, depending on regression variable combination. The validation of the regression equations showed little variation between the different proposed indices (r(2 = 27-32% on a matched dataset. New complex indices encompassing advanced measurement techniques offered an improved correlation (r = 0.75, P<0.001. However, when validated against the alternative dataset all indices performed comparably with the standard homeostasis model assessment for insulin resistance (HOMA-IR (r = 0.54, P<0.001. Thus, simple estimates of HEP-IR performed comparable to more complex indices and could be an efficient and cost effective approach in large epidemiological investigations.

  20. Evaluating clinical periodontal measures as surrogates for bacterial exposure: The Oral Infections and Vascular Disease Epidemiology Study (INVEST)

    OpenAIRE

    Jacobs David R; Papapanou Panos N; Demmer Ryan T; Desvarieux Moïse

    2010-01-01

    Abstract Background Epidemiologic studies of periodontal infection as a risk factor for cardiovascular disease often use clinical periodontal measures as a surrogate for the underlying bacterial exposure of interest. There are currently no methodological studies evaluating which clinical periodontal measures best reflect the levels of subgingival bacterial colonization in population-based settings. We investigated the characteristics of clinical periodontal definitions that were most represen...

  1. 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.

  2. An Artificial Turf-Based Surrogate Surface Collector for the Direct Measurement of Atmospheric Mercury Dry Deposition

    Science.gov (United States)

    Hall, Naima L.; Dvonch, Joseph Timothy; Marsik, Frank J.; Barres, James A.; Landis, Matthew S.

    2017-01-01

    This paper describes the development of a new artificial turf surrogate surface (ATSS) sampler for use in the measurement of mercury (Hg) dry deposition. In contrast to many existing surrogate surface designs, the ATSS utilizes a three-dimensional deposition surface that may more closely mimic the physical structure of many natural surfaces than traditional flat surrogate surface designs (water, filter, greased Mylar film). The ATSS has been designed to overcome several complicating factors that can impact the integrity of samples with other direct measurement approaches by providing a passive system which can be deployed for both short and extended periods of time (days to weeks), and is not contaminated by precipitation and/or invalidated by strong winds. Performance characteristics including collocated precision, in-field procedural and laboratory blanks were evaluated. The results of these performance evaluations included a mean collocated precision of 9%, low blanks (0.8 ng), high extraction efficiency (97%–103%), and a quantitative matrix spike recovery (100%). PMID:28208603

  3. An Artificial Turf-Based Surrogate Surface Collector for the Direct Measurement of Atmospheric Mercury Dry Deposition

    Directory of Open Access Journals (Sweden)

    Naima L. Hall

    2017-02-01

    Full Text Available This paper describes the development of a new artificial turf surrogate surface (ATSS sampler for use in the measurement of mercury (Hg dry deposition. In contrast to many existing surrogate surface designs, the ATSS utilizes a three-dimensional deposition surface that may more closely mimic the physical structure of many natural surfaces than traditional flat surrogate surface designs (water, filter, greased Mylar film. The ATSS has been designed to overcome several complicating factors that can impact the integrity of samples with other direct measurement approaches by providing a passive system which can be deployed for both short and extended periods of time (days to weeks, and is not contaminated by precipitation and/or invalidated by strong winds. Performance characteristics including collocated precision, in-field procedural and laboratory blanks were evaluated. The results of these performance evaluations included a mean collocated precision of 9%, low blanks (0.8 ng, high extraction efficiency (97%–103%, and a quantitative matrix spike recovery (100%.

  4. Variable reliability of surrogate measures of insulin sensitivity after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Bojsen-Møller, Kirstine N; Dirksen, Carsten; Svane, Maria Saur

    2017-01-01

    with HEC-estimated peripheral insulin sensitivity (Rd or Rd/I, depending on how the index was originally validated) and the tracer-determined hepatic insulin sensitivity index (HISI) in patients with preoperative type 2 diabetes (n=10) and normal glucose tolerance (n=10) 1 week, 3 months and 1 year...... postoperatively. Post-RYGB changes in inverse-HOMA-IR and HOMA2-%S did not correlate with changes in Rd at any visit, but were comparable to changes in HISI at 1 week. Changes in QUICKI and revised-QUICKI correlated with Rd/I after surgery. Changes in Matsuda and Gutt did not correlate with changes in Rd/I and Rd......) are frequently used, but have not been validated after RYGB. Our aim was to evaluate whether surrogate indices reliably estimate changes in insulin sensitivity after RYGB. Four fasting (inverse-HOMA-IR, HOMA2-%S, QUICKI, revised-QUICKI) and three OGTT-derived surrogates (Matsuda, Gutt, OGIS) were compared...

  5. 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.

  6. Multiplexed measurement of serum antibodies using an array biosensor.

    Science.gov (United States)

    Moreno-Bondi, Maria C; Taitt, Chris Rowe; Shriver-Lake, Lisa C; Ligler, Frances S

    2006-04-15

    The array biosensor provides the capability for simultaneously measuring titers of antibody against multiple antigens. Human antibodies against four different targets, tetanus toxin, diphtheria toxin, staphylococcal enterotoxin B (SEB) and hepatitis B, were measured simultaneously in sera from eight different donors in a single assay and titers were determined. The assays could measure amounts of bound antibody as low as approximately 100 fg. Each individual serum exhibited a different pattern of reactivity against the four target antigens. Applications of this biosensor capability include monitoring for exposure to pathogens and for efficacy of vaccination.

  7. Surrogate gas prediction model as a proxy for Δ(14)C-based measurements of fossil fuel-CO2.

    Science.gov (United States)

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

    2016-06-27

    The measured (14)C:(12)C isotopic ratio of atmospheric CO2 (and its associated derived Δ(14)C 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 US fossil fuel-CO2 emissions should be possible. However, the number of Δ(14)C measurements is presently constrained by cost, available sample volume, and availability of mass spectrometer measurement facilities. Δ(14)C is therefore measured in just a small fraction of samples obtained by ask 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/ESRL Global Greenhouse Gas Reference Network (GGGRN). The surrogates consist of measured enhancements of various anthropogenic trace gases, including CO, SF6, and halo- and hydrocarbons acquired in vertical airborne sampling profiles near Cape May, NJ and Portsmouth, NH from 2005 through 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 Δ(14)C measurements in the NOAA GGGRN and building new PPR models at additional sites would improve our understanding of uncertainties and

  8. 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

  9. Estimation of incidences of infectious diseases based on antibody measurements

    DEFF Research Database (Denmark)

    Simonsen, J; Mølbak, K; Falkenhorst, G

    2009-01-01

    Owing to under-ascertainment it is difficult if not impossible to determine the incidence of a given disease based on cases notified to routine public health surveillance. This is especially true for diseases that are often present in mild forms as for example diarrhoea caused by foodborne...... bacterial infections. This study presents a Bayesian approach for obtaining incidence estimates by use of measurements of serum antibodies against Salmonella from a cross-sectional study. By comparing these measurements with antibody measurements from a follow-up study of infected individuals...

  10. Cell-free measurements of brightness of fluorescently labeled antibodies

    Science.gov (United States)

    Zhou, Haiying; Tourkakis, George; Shi, Dennis; Kim, David M.; Zhang, Hairong; Du, Tommy; Eades, William C.; Berezin, Mikhail Y.

    2017-02-01

    Validation of imaging contrast agents, such as fluorescently labeled imaging antibodies, has been recognized as a critical challenge in clinical and preclinical studies. As the number of applications for imaging antibodies grows, these materials are increasingly being subjected to careful scrutiny. Antibody fluorescent brightness is one of the key parameters that is of critical importance. Direct measurements of the brightness with common spectroscopy methods are challenging, because the fluorescent properties of the imaging antibodies are highly sensitive to the methods of conjugation, degree of labeling, and contamination with free dyes. Traditional methods rely on cell-based assays that lack reproducibility and accuracy. In this manuscript, we present a novel and general approach for measuring the brightness using antibody-avid polystyrene beads and flow cytometry. As compared to a cell-based method, the described technique is rapid, quantitative, and highly reproducible. The proposed method requires less than ten microgram of sample and is applicable for optimizing synthetic conjugation procedures, testing commercial imaging antibodies, and performing high-throughput validation of conjugation procedures.

  11. Measures of Residual Risk with Connections to Regression, Risk Tracking, Surrogate Models, and Ambiguity

    Science.gov (United States)

    2015-05-20

    classes of statistics. The latter situation is the standard setting of risk-averse stochastic programming; see for example [13, 26]. Due to incomplete ...measures of risk and related quantifiers, and a theorem about connections among such quantifiers under relaxed assumptions. Section 3 defines measures of... Theorem in [26] to the broader class of regular measures defined here and also include additional characterizations of deviation measures and statistics

  12. Use of speed profile as surrogate measure: Effect of traffic calming devices on crosstown road safety performance.

    Science.gov (United States)

    Moreno, Ana Tsui; García, Alfredo

    2013-12-01

    Urban road safety management is usually characterized by the lack of sufficient, good quality crash data and low budgets to obtain it even though many traffic accidents occur there. For example, 54 percent of road crashes in Spain take place in urban areas, and 10 percent of urban fatal crashes occur on crosstown roads, which are rural roads that traverse small communities. Traffic calming measures (TCMs) are often implemented on these parts of rural roads that traverse small communities in order to reduce both the frequency and severity of crashes by lowering speeds, but evaluation of their effectiveness has been limited. The objective of this study was to develop a methodology using continuous speed profiles to evaluate the safety effectiveness of TCMs on crosstown roads as part of an integrated system in the absence of historical data. Given the strong relationship between speed and crash experience, safety performance can be related to speed. Consequently, speed can be used indirectly as a surrogate safety measure in the absence of crash and speed data. Two indexes were defined in this study as surrogate safety measures based on the continuous speed profile: Ra and Ea. Ra represents the absolute accumulated speed variations relative to the average speed and is inversely related to accumulated speed uniformity; and Ea represents the accumulated speed variations above the speed limit and is directly related to accumulated speeding. Naturalistic data were collected using GPS trackers for 12 scenarios with different TCM spacings. Then, the indexes were applied to individual observed speed profiles (individual analysis) as well as the operating speed profile (global analysis). The values obtained from individual and global analysis were statistically different. Spacing lower than 110m, which was found optimal from previous research, did not allow drivers to modify their speeds as the accumulated speed uniformity was quite similar regardless of the average operating

  13. 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.

  14. Non-invasive Measurement of Skin Autofluorescence as a Beneficial Surrogate Marker for Atherosclerosis in Patients with Type 2 Diabetes.

    Science.gov (United States)

    Temma, Jin; Matsuhisa, Munehide; Horie, Toru; Kuroda, Akio; Mori, Hiroyasu; Tamaki, Motoyuki; Endo, Itsuro; Aihara, Ken-ichi; Abe, Masahiro; Matsumoto, Toshio

    2015-01-01

    Advanced glycation end-products (AGEs) are thought to play a major role in the pathogenesis of diabetic vascular complications. Skin autofluorescence (AF) was recently reported to represent tissue AGEs accumulation with a non-invasive method. The aim of the present study was to evaluate association between AF value and diabetic vascular complications, such as retinopathy, nephropathy and cervical atherosclerosis using the carotid intima-media thickness (IMT), an established marker of cardiovascular disease in patients with type 2 diabetes. A total of 68 patients with type 2 diabetes were enrolled in a cross-sectional manner. AGEs accumulation was measured with AF reader. Clinical parameters were collected at the time of AF and IMT measurement. Max-IMT was correlated with age and AF (r=0.407, p=0.001), but not with HbA1c, GA, and pentosidine. Also, AF was not correlated with HbA1c, GA and pentosidine, but was correlated with age (r=0.560, p<0.001), duration of diabetes (r=0.256, p<0.05). Multivariate regression analysis revealed that AF, but not age, was an independent determinant of max-IMT. In conclusion, AF might be a beneficial surrogate marker for evaluating carotid atherosclerosis in patients with type 2 diabetes non-invasively. J. Med. Invest. 62: 126-129, August, 2015.

  15. The different surrogate measures of adiposity in relation to semen quality and serum reproductive hormone levels among Estonian fertile men.

    Science.gov (United States)

    Ehala-Aleksejev, K; Punab, M

    2015-03-01

    The objective of this study was to investigate the relations of basic semen parameters and reproductive hormones with different surrogate measures of adiposity: body mass index (BMI), body fat percentage (BF%), waist circumference (WC) and waist-to-height ratio (WHtR). Standard semen analysis was performed and serum levels of reproductive hormones were measured in 260 male partners of pregnant women at a university hospital andrology centres in Estonia. Quartile analysis revealed that all adiposity markers were negatively related to sex hormone-binding globulin and total testosterone levels. After adjustment for covariates a high BF%, WC and WHtR were negatively associated with total sperm count. The BF% was also negatively related to semen volume. These significant changes occurred from a BF% ≥ 23.4%, WC > 98 cm and WHtR > 0.54. Next to these changes the BMI was not related to sperm parameters. This study shows that semen quality is affected by central adiposity and confirms earlier findings that adiposity markedly changes serum sex hormone levels. Further studies are required to find out what is the best body composition marker showing most clearly the relationships between adiposity, semen characteristics and sex hormone levels.

  16. Topological performance measures as surrogates for physical flow models for risk and vulnerability analysis for electric power systems.

    Science.gov (United States)

    LaRocca, Sarah; Johansson, Jonas; Hassel, Henrik; Guikema, Seth

    2015-04-01

    Critical infrastructure systems must be both robust and resilient in order to ensure the functioning of society. To improve the performance of such systems, we often use risk and vulnerability analysis to find and address system weaknesses. A critical component of such analyses is the ability to accurately determine the negative consequences of various types of failures in the system. Numerous mathematical and simulation models exist that can be used to this end. However, there are relatively few studies comparing the implications of using different modeling approaches in the context of comprehensive risk analysis of critical infrastructures. In this article, we suggest a classification of these models, which span from simple topologically-oriented models to advanced physical-flow-based models. Here, we focus on electric power systems and present a study aimed at understanding the tradeoffs between simplicity and fidelity in models used in the context of risk analysis. Specifically, the purpose of this article is to compare performance estimates achieved with a spectrum of approaches typically used for risk and vulnerability analysis of electric power systems and evaluate if more simplified topological measures can be combined using statistical methods to be used as a surrogate for physical flow models. The results of our work provide guidance as to appropriate models or combinations of models to use when analyzing large-scale critical infrastructure systems, where simulation times quickly become insurmountable when using more advanced models, severely limiting the extent of analyses that can be performed.

  17. Investigation of the 238U(d ,p ) surrogate reaction via the simultaneous measurement of γ -decay and fission probabilities

    Science.gov (United States)

    Ducasse, Q.; Jurado, B.; 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. M.; Renstrøm, T.; Roig, O.; Rose, S. J.; Sérot, O.; Siem, S.; Tsekhanovich, I.; Tveten, G. M.; Wiedeking, M.

    2016-08-01

    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 γ -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 method and the distorted-wave Born approximation (DWBA) were used to correct our data from detected protons originating from elastic and inelastic deuteron breakup. In the region where fission and γ emission compete, the corrected fission probability is in agreement with neutron-induced data, whereas the γ -decay probability is much higher than the neutron-induced data. We have performed calculations of the decay probabilities with the statistical model and of the average angular momentum populated in the 238U(d ,p ) reaction with the DWBA to interpret these results.

  18. Absolute and relative surrogate measurements of the uranium-236(n,f) cross section as a probe of angular momentum effects

    Science.gov (United States)

    Lyles, Bethany Faye

    The absolute surrogate technique and the Surrogate Ratio Method (SRM) were used to deduce the 236U(n,f) cross section over an equivalent neutron energy range of 0.1 to 20 MeV for the absolute measurement and 0.8 to 20 MeV for the relative measurement. A 42 MeV 3He2+ beam from the 88--Inch Cyclotron at Lawrence Berkeley National Laboratory was used to perform a (3He,alpha) pickup reaction on targets of 235U (Jpi=7/2 --) and 238U (Jpi=0+) and the fission decay probabilities were determined. The 235U( 3He,alphaf) and 238U(3He,alphaf) reactions were surrogates for 233U(n,f) and 236U(n,f), respectively. Using the absolute surrogate technique, the experimentally determined 238U(3He,alpha) fission probability was multiplied by a calculated neutron absorption cross section to obtain the 236 U(n,f) cross section. Using the SRM, a ratio of the experimentally determined fission probabilities, 238U(3He,alphaf) to 235U(3He,alphaf), was extracted and multiplied by the evaluated 233U(n,f) cross section to obtain the 236U(n,f) cross section. Neither the absolute surrogate nor the SRM used in this case explicitly accounted for Jpi-dependence of the fission probabilities. The cross sections extracted using the Surrogate Method were compared to directly measured cross sections and theoretical predictions. The absolute surrogate 236U(n,f) cross section trended well with the evaluated nuclear data below 3.3 MeV, but was beset with target contamination above this energy, whereas the SRM result agreed with the evaluated nuclear data to within 10% at neutron energies from 3.5 to 20 MeV and exhibited significant deviations in the low energy regime. The deduced surrogate 236U(n,f) cross section was determined as a function of the angle of the alpha particle ejectile in the direct reaction to explore different angular momentum population distributions in the compound nucleus and their effects on the extracted fission probabilities. The 236U(n,f) cross sections extracted using both the

  19. 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.

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

    Science.gov (United States)

    Cabiddu, Ramona; Pantoni, Camila B. F.; Mendes, Renata G.; Trimer, Renata; Catai, Aparecida M.; Borghi-Silva, Audrey

    2016-01-01

    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. PMID:26982454

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

    Directory of Open Access Journals (Sweden)

    Benstead J.

    2016-01-01

    Full Text Available 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,t90Zr reaction, and are compared against measured data at an incident proton energy of 28.56 MeV.

  2. Evaluating clinical periodontal measures as surrogates for bacterial exposure: The Oral Infections and Vascular Disease Epidemiology Study (INVEST

    Directory of Open Access Journals (Sweden)

    Jacobs David R

    2010-01-01

    Full Text Available Abstract Background Epidemiologic studies of periodontal infection as a risk factor for cardiovascular disease often use clinical periodontal measures as a surrogate for the underlying bacterial exposure of interest. There are currently no methodological studies evaluating which clinical periodontal measures best reflect the levels of subgingival bacterial colonization in population-based settings. We investigated the characteristics of clinical periodontal definitions that were most representative of exposure to bacterial species that are believed to be either markers, or themselves etiologic, of periodontal disease. Methods 706 men and women aged ≥ 55 years, residing in northern Manhattan were enrolled. Using DNA-DNA checkerboard hybridization in subgingival biofilms, standardized values for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia were averaged within mouth and summed to define "bacterial burden". Correlations of bacterial burden with clinical periodontal constructs defined by the severity and extent of attachment loss (AL, pocket depth (PD and bleeding on probing (BOP were assessed. Results Clinical periodontal constructs demonstrating the highest correlations with bacterial burden were: i percent of sites with BOP (r = 0.62; ii percent of sites with PD ≥ 3 mm (r = 0.61; and iii number of sites with BOP (r = 0.59. Increasing PD or AL severity thresholds consistently attenuated correlations, i.e., the correlation of bacterial burden with the percent of sites with PD ≥ 8 mm was only r = 0.16. Conclusions Clinical exposure definitions of periodontal disease should incorporate relatively shallow pockets to best reflect whole mouth exposure to bacterial burden.

  3. 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 ...

  4. Antibody Phage Library Screening Efficiency Measured by KD Values

    Institute of Scientific and Technical Information of China (English)

    WANG Hui-tang; SHAN Ya-ming; TANG Li-li; GAO Li-zeng; WANG Li-ping; LI Wei; LI Yu-xin

    2005-01-01

    An antibody phage library was screened with two target molecules, IFNα-2a and FGFR-GST, and the KD value of each round of panning was measured. It was found that the apparent KD values decreased along with each additional panning round, which indicates the increase of the binding affinity between the phage and the target molecules.This result shows that the KD value is a reliable intrinsic parameter and a new method for screening efficiency detection is thus provided.

  5. Absolute and Relative Surrogate Measurements of the 236U(n,f) Cross Section as a Probe for Angular Momentum Effects

    Energy Technology Data Exchange (ETDEWEB)

    Lyles, B; Bernstein, L; Burke, J; Escher, J; Thompson, I; Dietrich, F; Phair, L; Bleuel, D; Gibelin, J; Wiedeking, M; McMahan, M; Rodroguez-Vieitez, E; Clark, R; Macchiavelli, A; Lesher, S; Darakchieva, B; Evtimova, M; Beausang, C; Fallon, P

    2007-04-03

    Using both the absolute and relative surrogate techniques, the {sup 236}U(n,f) cross section was deduced over an equivalent neutron energy range of 0 to 20 MeV. A 42 MeV {sup 3}He beam from the 88-Inch Cyclotron at Lawrence Berkeley National Laboratory was used to perform a ({sup 3}He,{alpha}) pickup reaction on targets of {sup 235}U (J{sup {pi}}=7/2{sup -}) and {sup 238}U (J{sup {pi}}=0{sup +}) and the fission decay probabilities were determined. The {sup 235}U({sup 3}He,{alpha}f) and {sup 238}U({sup 3}He,{alpha}f) were surrogates for {sup 233}U(n,f) and {sup 236}U(n,f), respectively. The cross sections extracted using the Surrogate Method were compared to directly measured cross sections. The sensitivity of these cross sections to the J{sup {pi}}-population distributions was explored.

  6. Detection and Measurement of Antigen-Antibody Reactions

    Science.gov (United States)

    1963-09-30

    kaolin . With low titer serum, much of the antibody also is removed, so that high titer antibody is made even more necessary. The use of immunodiffusion...increase the antibody titer significantly. In addition, a series of animals has been started on injections of bovine serum albumin with Freund’s... bovine serum albumin (BSA) has been obtained. With this available, a comparison can be made with normal antibody to the same antigen. Since the

  7. 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.

  8. 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

  9. 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...

  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. Replacing surrogate measures by direct quantification of ultraviolet radiation exposure in registry-based analyses of seasonality of melanoma diagnoses.

    Science.gov (United States)

    Keller, Andrea K; Uter, Wolfgang; Pfahlberg, Annette B; Radespiel-Tröger, Martin; Mayer, Ingo; Gefeller, Olaf

    2015-12-01

    Seasonal variation in melanoma diagnoses has been observed in numerous studies that used calendar time indicators. Depending on the latitude (and altitude) of the study region, the magnitude of seasonal and year-to-year variation of ultraviolet radiation (UVR) is neglected in these studies. An alternative approach comprises the direct incorporation of UVR measurements into such analyses. The aim of this investigation is a comparative evaluation of these approaches. The population-based Bavarian cancer registry recorded 11 901 incident melanoma cases between 2003 and 2008 that were used for the analysis. UVR intensity data for the same period were available from the solar radiation station at Munich-Neuherberg. Negative binomial regression modelling yielded adjusted relative risks (RR) controlled for year of diagnosis and age in 16 subgroups defined by sex, Breslow thickness and localization. Overall, the analyses showed slightly differing yet consistent results for exposure effects in subgroups. Melanoma evolving on the extremities showed the most pronounced association with increasing level of the UV index among men [e.g. RR=1.086, 95% confidence interval (CI) 1.054-1.119, and RR=1.102, 95% CI 1.046-1.161, for thin and thick melanoma on the upper limbs, respectively] and women (e.g. RR=1.088, 95% CI 1.058-1.119, and RR=1.056, 95% CI 1.010-1.103, for thin and thick melanoma on the lower limbs, respectively). Our analysis provides a benchmark for international comparisons and synthesis of epidemiologic evidence of seasonal variability in melanoma diagnoses. Future studies should use direct UVR measures to enable pooling of risk estimates and resolve remaining inconsistencies potentially resulting from latitudinal differences in exposure between international studies.

  12. Antibody response to the lipopolysaccharide and protein antigens of Salmonella typhi during typhoid infection. I. Measurement of serum antibodies by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Tsang, R.S.W.; Chau, P.Y.; Lam, S.K. (Hong Kong Univ.); La Brooy, J.T.; Rowley, D. (Adelaide Univ. (Australia))

    1981-12-01

    Serum antibody responses to the lipopolysaccharide and protein antigens of S. typhi in typhoid patients were studied using a solid-phase radioimmunoassay technique with /sup 125/I labelled anti-immunoglobulin antibody. Sera from 24 adult typhoid patients and 20 non-typhoid adult controls were compared. As a group, sera from typhoid patients showed increased IgA, IgG and IgM immunoglobulin levels and gave significantly higher anti-LPS and anti-protein antibody titres in all three major immunoglobulin classes than did non-typhoid controls. Levels of antibodies against LPS or protein in sera of typhoid patients were highly variable with a skew distribution. A good correlation was found between antibody titres to the LPS antigen and those to a protein antigen. No correlation, however, was found between the anti-LPS antibody titres measured by radioimmunoassay and the anti-O antibody titres measured by the Widal agglutination test. Titration of anti-LPS or anti-protein antibodies by radioimmunoassay was found to be more sensitive and specific than Widal test for the serological diagnosis of typhoid fever. The advantages of measuring antibody response by radioimmunoassay over conventional Widal test are discussed.

  13. Suspended-sediment concentrations, bedload, particle sizes, surrogate measurements, and annual sediment loads for selected sites in the lower Minnesota River Basin, water years 2011 through 2016

    Science.gov (United States)

    Groten, Joel T.; Ellison, Christopher A.; Hendrickson, Jon S.

    2016-12-20

    Accurate measurements of fluvial sediment are important for assessing stream ecological health, calculating flood levels, computing sediment budgets, and managing and protecting water resources. Sediment-enriched rivers in Minnesota are a concern among Federal, State, and local governments because turbidity and sediment-laden waters are the leading impairments and affect more than 6,000 miles of rivers in Minnesota. The suspended sediment in the lower Minnesota River is deleterious, contributing about 75 to 90 percent of the suspended sediment being deposited into Lake Pepin. The Saint Paul District of the U.S. Army Corps of Engineers and the Lower Minnesota River Watershed District collaborate to maintain a navigation channel on the lower 14.7 miles of the Minnesota River through scheduled dredging operations. The Minnesota Pollution Control Agency has adopted a sediment-reduction strategy to reduce sediment in the Minnesota River by 90 percent by 2040.The U.S. Geological Survey, in cooperation with the U.S. Army Corps of Engineers, the Minnesota Pollution Control Agency, and the Lower Minnesota River Watershed District, collected suspended-sediment, bedload, and particle-size samples at five sites in the lower Minnesota River Basin during water years 2011 through 2014 and surrogate measurements of acoustic backscatter at one of these sites on the lower Minnesota River during water years 2012 through 2016 to quantify sediment loads and improve understanding of sediment-transport relations. Annual sediment loads were computed for calendar years 2011 through 2014.Data collected from water years 2011 through 2014 indicated that two tributaries, Le Sueur River and High Island Creek, had the highest sediment yield and concentrations of suspended sediment. These tributaries also had greater stream gradients than the sites on the Minnesota River. Suspended fines were greater than suspended sand at all sites in the study area. The range of median particle sizes matched

  14. Antibody response to the lipopolysaccharide and protein antigens of Salmonella typhi during typhoid infection. II. Measurement of intestinal antibodies by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Chau, P.Y.; Tsang, R.S.W.; Lam, S.K. (Hong Kong Univ.); La Brooy, J.T.; Rowley, D. (Adelaide Univ. (Australia))

    1981-12-01

    Antibodies to the lipopolysaccharide (LPS) and protein antigens of S. typhi in secretions of small intestine obtained from 12 typhoid patients, four typhoid carriers and 16 non-typhoid control subjects were measured by a solid-phase radioimmunoassay technique using /sup 125/I labelled anti-immunoglobulin antibody. Intestinal secretions obtained from typhoid patients as a group had significantly higher anti-LPS and anti-protein antibodies than those from the control group. These antibodies were both IgM and IgA classes. There was no correlation between the IgM or IgA antibody levels in serum and those in the intestinal secretions. In the intestinal secretions obtained from typhoid carriers, on the other hand, only IgA-class antibodies to the LPS and protein antigens of S. typhi were present at high levels.

  15. Temporal linear mode complexity as a surrogate measure of the effect of remifentanil on the central nervous system in healthy volunteers

    Science.gov (United States)

    Choi, Byung-Moon; Shin, Da-Huin; Noh, Moon-Ho; Kim, Young-Hac; Jeong, Yong-Bo; Lee, Soo-Han; Lee, Eun-Kyung; Noh, Gyu-Jeong

    2011-01-01

    AIMS Previously, electroencephalographic approximate entropy (ApEn) effectively described both depression of central nervous system (CNS) activity and rebound during and after remifentanil infusion. ApEn is heavily dependent on the record length. Linear mode complexity, which is algorithmatically independent of the record length, was investigated to characterize the effect of remifentanil on the CNS using the combined effect and tolerance, feedback and sigmoid Emax models. METHODS The remifentanil blood concentrations and electroencephalographic data obtained in our previous study were used. With the recording of the electroencephalogram, remifentanil was infused at a rate of 1, 2, 3, 4, 5, 6, 7 or 8 µg kg−1 min−1 for 15–20 min. The areas below (AUCeffect) or above (AACrebound) the effect vs. time curve of temporal linear mode complexity (TLMC) and ApEn were calculated to quantitate the decrease of the CNS activity and rebound. The coefficients of variation (CV) of median baseline (E0), maximal (Emax), and individual median E0 minus Emaxvalues of TLMC were compared with those of ApEn. The concentration–TLMC relationship was characterized by population analysis using non-linear mixed effects modelling. RESULTS Median AUCeffectand AACreboundwere 1016 and 5.3 (TLMC), 787 and 4.5 (ApEn). The CVs of individual median E0 minus Emax were 35.6, 32.5% (TLMC, ApEn). The combined effect and tolerance model demonstrated the lowest Akaike information criteria value and the highest positive predictive value of rebound in tolerance. CONCLUSIONS The combined effect and tolerance model effectively characterized the time course of TLMC as a surrogate measure of the effect of remifentanil on the CNS. PMID:21223358

  16. 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.

  17. 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 ...

  18. 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...

  19. Sequential measurement of anti-platelet antibodies in a patient who developed EDTA-dependent pseudothrombocytopenia.

    Science.gov (United States)

    Edelman, B; Kickler, T

    1993-01-01

    Ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia is the occurrence of a falsely low platelet count caused by antibodies that agglutinate platelets in the presence of EDTA. If unrecognized, it may result in the erroneous diagnosis of thrombocytopenia and possible inappropriate therapy. It has been noted that this phenomenon tends to appear in hospitalized patients after an initially normal platelet count, but sequential measurements of anti-platelet antibody have not been reported. The case of a patient who developed EDTA-dependent pseudothrombocytopenia approximately 1 week after being hospitalized for severe trauma is described. Anti-platelet antibodies were not detected on admission by a radiolabeled antiglobulin technique but were shown to increase in titer concurrent with the appearance of EDTA-dependent pseudothrombocytopenia.

  20. Combustion Kinetic Studies of Gasolines and Surrogates

    KAUST Repository

    Javed, Tamour

    2016-11-01

    Future thrusts for gasoline engine development can be broadly summarized into two categories: (i) efficiency improvements in conventional spark ignition engines, and (ii) development of advance compression ignition (ACI) concepts. Efficiency improvements in conventional spark ignition engines requires downsizing (and turbocharging) which may be achieved by using high octane gasolines, whereas, low octane gasolines fuels are anticipated for ACI concepts. The current work provides the essential combustion kinetic data, targeting both thrusts, that is needed to develop high fidelity gasoline surrogate mechanisms and surrogate complexity guidelines. Ignition delay times of a wide range of certified gasolines and surrogates are reported here. These measurements were performed in shock tubes and rapid compression machines over a wide range of experimental conditions (650 – 1250 K, 10 – 40 bar) relevant to internal combustion engines. Using the measured the data and chemical kinetic analyses, the surrogate complexity requirements for these gasolines in homogeneous environments are specified. For the discussions presented here, gasolines are classified into three categories: (i)\\tLow octane gasolines including Saudi Aramco’s light naphtha fuel (anti-knock index, AKI = (RON + MON)/2 = 64; Sensitivity (S) = RON – MON = 1), certified FACE (Fuels for Advanced Combustion Engines) gasoline I and J (AKI ~ 70, S = 0.7 and 3 respectively), and their Primary Reference Fuels (PRF, mixtures of n-heptane and iso-octane) and multi-component surrogates. (ii)\\t Mid octane gasolines including FACE A and C (AKI ~ 84, S ~ 0 and 1 respectively) and their PRF surrogates. Laser absorption measurements of intermediate and product species formed during gasoline/surrogate oxidation are also reported. (iii)\\t A wide range of n-heptane/iso-octane/toluene (TPRF) blends to adequately represent the octane and sensitivity requirements of high octane gasolines including FACE gasoline F and G

  1. Antithyroglobulin antibody

    Science.gov (United States)

    Thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Hypothyroidism - thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Graves disease - thyroglobulin antibody; Underactive thyroid - thyroglobulin antibody

  2. Surrogate Modeling for Geometry Optimization

    DEFF Research Database (Denmark)

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

    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....

  3. Measurement of antibodies to pneumococcal, meningococcal and haemophilus polysaccharides, and tetanus and diphtheria toxoids using a 19-plexed assay.

    Science.gov (United States)

    Whitelegg, Alison M E; Birtwistle, Jane; Richter, Alex; Campbell, John P; Turner, James E; Ahmed, Tarana M; Giles, Lynda J; Fellows, Mark; Plant, Tim; Ferraro, Alastair J; Cobbold, Mark; Drayson, Mark T; MacLennan, Calman A

    2012-03-30

    The measurement of antibody responses to vaccination is useful in the assessment of immune status in suspected immune deficiency. Previous reliance on enzyme-linked immunoabsorbent assays (ELISA) has been cumbersome, time-consuming and expensive. The availability of flow cytometry systems has led to the development of multiplexed assays enabling simultaneous measurement of antibodies to several antigens. We optimized a flow cytometric bead-based assay to measure IgG and IgM concentrations in serum to 19 antigens contained in groups of bacterial subunit vaccines: pneumococcal vaccines, meningococcal vaccines, Haemophilus influenzae b (Hib), and tetanus and diphtheria toxoid vaccines. 89-SF was employed as the standard serum. The assay was used to determine specific antibody levels in serum from 193 healthy adult donors. IgG and pneumococcal IgM antibody concentrations were measurable across 3 log10 ranges encompassing the threshold protective IgG antibody levels for each antigen. There was little interference between antibody measurements by the 19-plexed assay compared with monoplexed assays, and a lack of cross-reactive IgG antibody, but evidence for cross-reacting IgM antibody for 3/19 pneumococcal antigens. 90th centile values for 15/19 IgG concentrations and 12/12 IgM concentrations of the 193 adult sera were within these ranges and percentages of sera containing protective IgG antibody levels varied from 4% to 95% depending on antigen. This multiplexed assay can simultaneously measure antibody levels to 19 bacterial vaccine antigens. It is suitable for use in standard clinical practice to assess the in vivo immune response to test vaccinations and measure absolute antibody levels to these antigens.

  4. Aerosol Physics Considerations for Using Cerium Oxide CeO2 as a Surrogate for Plutonium Oxide PuO2 in Airborne Release Fraction Measurements for Storage Container Investigations

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Murray E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tao, Yong [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-02-16

    Cerium oxide (CeO2) dust is recommended as a surrogate for plutonium oxide (PuO2) in airborne release fraction experiments. The total range of applicable particle sizes for PuO2 extends from 0.0032 μm (the diameter of a single PuO2 molecule) to 10 μm (the defined upper boundary for respirable particles). For particulates with a physical particle diameter of 1.0 μm, the corresponding aerodynamic diameters for CeO2 and PuO2 are 2.7 μm and 3.4 μm, respectively. Cascade impactor air samplers are capable of measuring the size distributions of CeO2 or PuO2 particulates. In this document, the aerodynamic diameters for CeO2 and PuO2 were calculated for seven different physical diameters (0.0032, 0.02, 0.11, 0.27, 1.0, 3.2, and 10 μm). For cascade impactor measurements, CeO2 and PuO2 particulates with the same physical diameter would be collected onto the same or adjacent collection substrates. The difference between the aerodynamic diameter of CeO2 and PuO2 particles (that have the same physical diameter) is 39% of the resolution of a twelve-stage MSP Inc. 125 cascade impactor, and 34% for an eight-stage Andersen impactor. An approach is given to calculate the committed effective dose (CED) coefficient for PuO2 aerosol particles, compared to a corresponding aerodynamic diameter of CeO2 particles. With this approach, use of CeO2 as a surrogate for PuO2 material would follow a direct conversion based on a molar equivalent. In addition to the analytical information developed for this document, several US national labs have published articles about the use of CeO2 as a PuO2 surrogate. Different physical and chemical aspects were considered by these investigators, including thermal properties, ceramic formulations, cold pressing, sintering, molecular reactions, and mass loss in high temperature gas flows. All of those US national lab studies recommended the use of CeO2 as a surrogate material for PuO2.

  5. Dengue reporter virus particles for measuring neutralizing antibodies against each of the four dengue serotypes.

    Science.gov (United States)

    Mattia, Kimberly; Puffer, Bridget A; Williams, Katherine L; Gonzalez, Ritela; Murray, Meredith; Sluzas, Emily; Pagano, Dan; Ajith, Sandya; Bower, Megan; Berdougo, Eli; Harris, Eva; Doranz, Benjamin J

    2011-01-01

    The lack of reliable, high-throughput tools for characterizing anti-dengue virus (DENV) antibodies in large numbers of serum samples has been an obstacle in understanding the impact of neutralizing antibodies on disease progression and vaccine efficacy. A reporter system using pseudoinfectious DENV reporter virus particles (RVPs) was previously developed by others to facilitate the genetic manipulation and biological characterization of DENV virions. In the current study, we demonstrate the diagnostic utility of DENV RVPs for measuring neutralizing antibodies in human serum samples against all four DENV serotypes, with attention to the suitability of DENV RVPs for large-scale, long-term studies. DENV RVPs used against human sera yielded serotype-specific responses and reproducible neutralization titers that were in statistical agreement with Plaque Reduction Neutralization Test (PRNT) results. DENV RVPs were also used to measure neutralization titers against the four DENV serotypes in a panel of human sera from a clinical study of dengue patients. The high-throughput capability, stability, rapidity, and reproducibility of assays using DENV RVPs offer advantages for detecting immune responses that can be applied to large-scale clinical studies of DENV infection and vaccination.

  6. Dengue reporter virus particles for measuring neutralizing antibodies against each of the four dengue serotypes.

    Directory of Open Access Journals (Sweden)

    Kimberly Mattia

    Full Text Available The lack of reliable, high-throughput tools for characterizing anti-dengue virus (DENV antibodies in large numbers of serum samples has been an obstacle in understanding the impact of neutralizing antibodies on disease progression and vaccine efficacy. A reporter system using pseudoinfectious DENV reporter virus particles (RVPs was previously developed by others to facilitate the genetic manipulation and biological characterization of DENV virions. In the current study, we demonstrate the diagnostic utility of DENV RVPs for measuring neutralizing antibodies in human serum samples against all four DENV serotypes, with attention to the suitability of DENV RVPs for large-scale, long-term studies. DENV RVPs used against human sera yielded serotype-specific responses and reproducible neutralization titers that were in statistical agreement with Plaque Reduction Neutralization Test (PRNT results. DENV RVPs were also used to measure neutralization titers against the four DENV serotypes in a panel of human sera from a clinical study of dengue patients. The high-throughput capability, stability, rapidity, and reproducibility of assays using DENV RVPs offer advantages for detecting immune responses that can be applied to large-scale clinical studies of DENV infection and vaccination.

  7. 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

  8. The Surrogate Method: Past, Present and Future

    Energy Technology Data Exchange (ETDEWEB)

    Lesher, S R; Bernstein, L A; Burke, J T; Lyles, B F; Clark, R M; Fallon, P; Phair, L

    2008-01-09

    The STARS/LiBerACE collaboration has been exploring the surrogate technique with success in the actinide region. This method uses a direct reaction to measure the decay probability of the same compound nucleus produced via a neutron-induced channel. This paper serves as an overview of these activities. Using the STARS array at 88-inch Cyclotron at Lawrence Berkeley National Laboratory we have explored the following surrogate reactions: {sup 234}U({alpha}, {alpha}{prime}f), {sup 235}U({sup 3}He, {alpha}f), {sup 236}U({alpha}, {alpha}{prime}f), {sup 238}U ({alpha},{alpha}{prime}f), {sup 238}U({sup 3}He,{alpha}f), {sup 238}U({sup 3}He, tf) surrogates for {sup 233}U(n,f), {sup 233}U(n,f), {sup 235}U(n,f), {sup 237}U(n,f), {sup 236}U(n,f), and {sup 237}Np(n,f), respectively.

  9. Recent Experimental Progress on Surrogate Reactions

    Science.gov (United States)

    Beausang, Cornelius

    2014-09-01

    Reactions on unstable nuclei are important in a wide variety of nuclear physics scenarios. Cross sections for neutron (or light charged particle) induced reactions on target nuclei spanning the chart of the nuclei are important for nuclear astrophysics (r-process, s-process rp- and p-processes etc.), for nuclear energy generation and for national security applications. Many such reactions occur on short-lived unstable nuclei. Even with the present generation of radioactive beam facilities, many such reactions are difficult, if not impossible, to measure directly. For these reactions, often the surrogate reaction technique provides the only option to provide some experimental guidance for the calculations. The experimental and theoretical techniques required are described in some detail in the recent review article by Escher et al.. Originally introduced in the 1970's the last decade has seen a resurgence of interest in the surrogate technique. Various ratio techniques, external, internal and hybrid, have been developed to minimize the effect of target contamination. In the actinide region, a large number of surrogate (n,f) cross sections have been measured. In general, these show agreement to within 5--10%, with directly measured (n,f) data where these data exist (benchmarking), for equivalent neutron energies ranging from ~100 keV up to tens of MeV. For (n, γ) reactions, measurements have been attempted for select nuclei in various mass regions (A ~ 90, 150 and 235) and for these the agreement with directly measured data is less good. The various experimental techniques employed will be described as well as the current state of the experimental data. Some future directions will be described. Reactions on unstable nuclei are important in a wide variety of nuclear physics scenarios. Cross sections for neutron (or light charged particle) induced reactions on target nuclei spanning the chart of the nuclei are important for nuclear astrophysics (r-process, s

  10. Surrogate Markers of Abdominal Aortic Aneurysm Progression.

    Science.gov (United States)

    Wanhainen, Anders; Mani, Kevin; Golledge, Jonathan

    2016-02-01

    The natural course of many abdominal aortic aneurysms (AAA) is to gradually expand and eventually rupture and monitoring the disease progression is essential to their management. In this publication, we review surrogate markers of AAA progression. AAA diameter remains the most widely used and important marker of AAA growth. Standardized reporting of reproducible methods of measuring AAA diameter is essential. Newer imaging assessments, such as volume measurements, biomechanical analyses, and functional and molecular imaging, as well as circulating biomarkers, have potential to add important information about AAA progression. Currently, however, there is insufficient evidence to recommend their routine use in clinical practice.

  11. Estimation of True Serum Thyroglobulin Concentration Using Simultaneous Measurement of Serum Antithyroglobulin Antibody

    Directory of Open Access Journals (Sweden)

    Byeong-Cheol Ahn

    2013-01-01

    Full Text Available We investigated the analytical interference of antithyroglobulin antibody (TgAb to thyroglobulin (Tg measurement and tried to convert measured Tg concentration to true Tg concentration using a mathematical equation which includes a concentration of TgAb. Methods. Tg was measured by immunoradiometric assay and TgAb by radioimmunoassy. Experimental samples were produced by mixing Tg and TgAb standard solutions or mixing patients’ serum with high Tg or high TgAb. Mathematical equations for prediction of expected Tg concentration with measured Tg and TgAb concentrations were deduced. The Tg concentration calculated using the equations was compared with the expected Tg concentration. Results. Measured Tg concentrations of samples having high TgAb were significantly lower than their expected Tg concentration. Magnitude of TgAb interference with the Tg assay showed a positive correlation with concentration of TgAb. Mathematical equations for estimation of expected Tg concentration using measured Tg and TgAb concentrations were successfully deduced and the calculated Tg concentration showed excellent correlation with expected Tg concentration. Conclusions. A mathematic equation for estimation of true Tg concentration using measured Tg and TgAb concentration was deduced. Tg concentration calculated by use of the equation might be more valuable than measured Tg concentration in patients with differentiated thyroid cancer.

  12. Beyond multi-fractals: surrogate time series and fields

    Science.gov (United States)

    Venema, V.; Simmer, C.

    2007-12-01

    Most natural complex are characterised by variability on a large range of temporal and spatial scales. The two main methodologies to generate such structures are Fourier/FARIMA based algorithms and multifractal methods. The former is restricted to Gaussian data, whereas the latter requires the structure to be self-similar. This work will present so-called surrogate data as an alternative that works with any (empirical) distribution and power spectrum. The best-known surrogate algorithm is the iterative amplitude adjusted Fourier transform (IAAFT) algorithm. We have studied six different geophysical time series (two clouds, runoff of a small and a large river, temperature and rain) and their surrogates. The power spectra and consequently the 2nd order structure functions were replicated accurately. Even the fourth order structure function was more accurately reproduced by the surrogates as would be possible by a fractal method, because the measured structure deviated too strong from fractal scaling. Only in case of the daily rain sums a fractal method could have been more accurate. Just as Fourier and multifractal methods, the current surrogates are not able to model the asymmetric increment distributions observed for runoff, i.e., they cannot reproduce nonlinear dynamical processes that are asymmetric in time. Furthermore, we have found differences for the structure functions on small scales. Surrogate methods are especially valuable for empirical studies, because the time series and fields that are generated are able to mimic measured variables accurately. Our main application is radiative transfer through structured clouds. Like many geophysical fields, clouds can only be sampled sparsely, e.g. with in-situ airborne instruments. However, for radiative transfer calculations we need full 3-dimensional cloud fields. A first study relating the measured properties of the cloud droplets and the radiative properties of the cloud field by generating surrogate cloud

  13. [Clinical significance of antiphospholipid antibody measured by EliA anticardiolipin antibodies and anti-β2Glycoprotein I antibodies in antiphospholipid syndrome].

    Science.gov (United States)

    Fujieda, Yuichiro; Shida, Haruki; Oku, Kenji; Bohgaki, Toshiyuki; Amengual, Olga; Horita, Tetsuya; Yasuda, Shinsuke; Atsumi, Tatsuya

    2014-01-01

    Anticardiolipin antibodies (aCL-IgG/IgM) and anti-β2-glycoprotein I antibodies (aβ2GPI-IgG/IgM) are laboratory tests included in the current classification criteria for definite antiphospholipid syndrome (APS). However, not all of these assays have been commercially available in Japan. We investigated the efficacy of aCL-IgG/IgM and aβ2GPI-IgG/IgM assays using fluorescence enzyme immunoassay (Phadia:EliA(TM)) for the diagnosis of APS in Japan. This study comprised 229 sera from patients (100 with APS and 129 without APS). The diagnosis of APS was made according to Sydney revised Sapporo criteria. EliA(TM)Cardiolipin and EliA(TM)β2-Glycoprotein (Phadia AB. Uppsala Sweden) were used to detect aCL IgG/M and aβ2GPI IgG/M, respectively. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) were as follows; aCL-IgG (45%, 94%, 0.80), aCL-IgM (20%, 94%, 0.54), aβ2GPI-IgG (33%, 98%, 0.88) and aβ2GPI-IgM (16%, 99%, 0.64) respectively. aCL-IgM, aβ2GPI-IgG or aβ2GPI-IgM were detected in 10 patients (18%) with aCL-IgG negative. The use of Phadia:EliA(TM)antiphospholipid antibodies assays improve the diagnostic yield of thrombotic risk in APS patients.

  14. Multi-Dimensional Measurement of Antibody-Mediated Heterosubtypic Immunity to Influenza.

    Directory of Open Access Journals (Sweden)

    Jiong Wang

    Full Text Available The human immune response to influenza vaccination depends in part on preexisting cross-reactive (heterosubtypic immunity from previous infection by, and/or vaccination with, influenza strains that share antigenic determinants with the vaccine strains. However, current methods for assessing heterosubtypic antibody responses against influenza, including the hemagglutination-inhibition (HAI assay and ELISA, are time and labor intensive, and require moderate amounts of serum and reagents. To address these issues we have developed a fluorescent multiplex assay, mPlex-Flu, that rapidly and simultaneously measures strain specific IgG, IgA, and IgM antibodies against influenza hemagglutinin (HA from multiple viral strains. We cloned, expressed and purified HA proteins from 12 influenza strains, and coupled them to multiplex beads. Assay validation showed that minimal sample volumes (<5 μl of serum were needed, and the assay had a linear response over a four Log10 range. The assay detected nanogram levels of anti-influenza specific antibodies, had high accuracy and reproducibility, with an average percentage coefficient of variation (%CV of 9.06 for intra-assay and 12.94 for inter-assay variability. Pre- and post-intramuscular trivalent influenza vaccination levels of virus specific Ig were consistent with HAI titer and ELISA measurements. A significant advantage of the mPLEX-Flu assay over the HAI assay is the ability to perform antigenic cartography, determining the antigenic distances between influenza HA's, without mathematical correction for HAI data issues. For validation we performed antigenic cartography on 14 different post-influenza infection ferret sera assayed against 12 different influenza HA's. Results were in good agreement with a phylogenetic tree generated from hierarchical clustering of the genomic HA sequences. This is the first report of the use of a multiplex method for antigenic cartography using ferret sera. Overall, the m

  15. 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

    2010-01-05

    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.

  16. Diesel Surrogate Fuels for Engine Testing and Chemical-Kinetic Modeling: Compositions and Properties

    Science.gov (United States)

    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 taken to assist in determining the minimum level of surrogate-fuel compositional accuracy that is required to adequately emulate the performance characteristics of the target fuel under different combustion modes. For each of the four surrogate fuels, an approximately 30 L batch was blended, and a number of the physical and chemical properties were measured. This work documents the surrogate-fuel creation process and the results of the property measurements. PMID:27330248

  17. 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...

  18. 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.

  19. Smartphone dongle for simultaneous measurement of hemoglobin concentration and detection of HIV antibodies.

    Science.gov (United States)

    Guo, Tiffany; Patnaik, Ritish; Kuhlmann, Kevin; Rai, Alex J; Sia, Samuel K

    2015-09-07

    It is traditionally difficult to incorporate two classes of diagnostic tests into a single platform. In this work, we demonstrate a microfluidic-based smartphone dongle that simultaneously measures concentration of hemoglobin and detects HIV antibodies. Specifically, we demonstrate how a previously published immunoassay device, which measured optical density of silver precipitation on gold colloids, can be expanded to quantitatively measure hemoglobin concentration via a colorimetric assay. By lysing whole blood components with CHAPS detergent, we achieved highly reproducible measurement of hemoglobin concentration with the device. We tested this dual test on 38 patient samples from Columbia University Medical Center. Compared with the Hemocue Hb 201+ analyzer, hemoglobin concentrations from our device were accurate within 1.2 g dL(-1), while the HIV immunoassay (in the presence of CHAPS detergent) showed 95% sensitivity and 95% specificity, comparable to our previous studies. This work demonstrates the feasibility of integrating two classes of diagnostic tests (a colorimetric-based quantitative measurement and an immunoassay based on silver precipitation on gold colloids) into a low-cost, fast, and low-power dongle that works with smartphones, and creates a novel dual panel with clinical utility for antenatal-care settings.

  20. Comparison of antibody responses to human papillomavirus vaccination as measured by three assays

    Directory of Open Access Journals (Sweden)

    Hilary Ann Robbins

    2014-01-01

    Full Text Available Background: Different assays, including the competitive Luminex immunoassay (cLIA, secreted alkaline phosphatase neutralization assay (SEAP-NA, and virus-like particle-based ELISA, are commonly used to measure antibody responses after human papillomavirus (HPV vaccination. Direct assay comparisons aid interpretation of immunogenicity data evaluated by different assays. Methods: We compared cLIA to SEAP-NA and ELISA among 51 HPV16/18-vaccinated women enrolled in the Costa Rica Vaccine Trial. We tested replicate serum samples collected at months 0, 1, and 12 by HPV16/18 cLIA, SEAP-NA, and ELISA. For a subset (N=10, we further tested month 24 and 36 samples. We calculated seroprevalence estimates and Spearman rank correlation coefficients comparing cLIA to SEAP-NA and ELISA.Results: After one vaccine dose, seroprevalence by SEAP-NA and ELISA was 100% (both HPV16 and HPV18, and by cLIA was 96% (95% CI 87%-100% for HPV16 and 71% (95% CI 56%-83% for HPV18. Seroprevalence was 100% by all assays after 3 doses. Correlation between assays was high after one vaccine dose (cLIA/SEAP-NA ρ=0.91 (HPV16 and ρ=0.86 (HPV18; cLIA/ELISA ρ=0.84 (HPV16 and ρ=0.74 (HPV18; all p<0.001 and remained high through month 36. Ratios of mean antibody levels to seropositivity cutoffs at month 36 were lower for cLIA than for SEAP-NA or ELISA, particularly for HPV18 (HPV18 ratio for cLIA 1.9, SEAP-NA 3.5, ELISA 3.4.Conclusion: Though correlation between cLIA and SEAP-NA/ELISA is high and stable after vaccination, the assays differ in scale and sensitivity, with notable differences after 1 vaccine dose and for HPV18. Our results demonstrate that comparisons of antibody responses to HPV vaccination measured by different assays are approximate, and must consider biological and technical differences between assays.

  1. 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.

  2. Surface plasmon resonance measurements of plasma antibody avidity during primary and secondary responses to anthrax protective antigen.

    Science.gov (United States)

    Lynch, Heather E; Stewart, Shelley M; Kepler, Thomas B; Sempowski, Gregory D; Alam, S Munir

    2014-02-01

    Establishment of humoral immunity against pathogens is dependent on events that occur in the germinal center and the subsequent induction of high-affinity neutralizing antibodies. Quantitative assays that allow monitoring of affinity maturation and duration of antibody responses can provide useful information regarding the efficacy of vaccines and adjuvants. Using an anthrax protective antigen (rPA) and alum model antigen/adjuvant system, we describe a methodology for monitoring antigen-specific serum antibody concentration and avidity by surface plasmon resonance during primary and secondary immune responses. Our analyses showed that following a priming dose in mice, rPA-specific antibody concentration and avidity increases over time and reaches a maximal response in about six weeks, but gradually declines in the absence of antigenic boost. Germinal center reactions were observed early with maximal development achieved during the primary response, which coincided with peak antibody avidity responses to primary immunization. Boosting with antigen resulted in a rapid increase in rPA-specific antibody concentration and five-fold increase in avidity, which was not dependent on sustained GC development. The described methodology couples surface plasmon resonance-based plasma avidity measurements with germinal center analysis and provides a novel way to monitor humoral responses that can play a role in facilitating vaccine and adjuvant development.

  3. ELISPOT Assay for Measurement of Antigen-Specific and Polyclonal Antibody Responses.

    Science.gov (United States)

    Lycke, Nils; Coico, Richard

    2015-02-02

    The enzyme-linked immunospot (ELISPOT) assay for detection of antigen-specific and polyclonal antibody responses by single antibody-secreting cells has become the method of choice due to its cell-based quantitative value. Antigen stability and specificity and the diversity of antigens that can be used in the assay have contributed to the translational application of ELISPOT as demonstrated by many FDA-approved clinical tests that employ this technique. In addition, the ELISPOT assay can be used to detect two antigenically different secreted antibodies simultaneously by two-color analysis and offers the unique possibility of quantifying the number of antibody molecules secreted per cell.

  4. Measuring Immunoglobulin G Antibodies to Tetanus Toxin, Diphtheria Toxin, and Pertussis Toxin with Single-Antigen Enzyme-Linked Immunosorbent Assays and a Bead-Based Multiplex Assay▿

    OpenAIRE

    Reder, Sabine; Riffelmann, Marion; Becker, Christian; Wirsing von König, Carl Heinz

    2008-01-01

    Bead-based assay systems offer the possibility of measuring several specific antibodies in one sample simultaneously. This study evaluated a vaccine panel of a multianalyte system that measures antibodies to tetanus toxin, diphtheria toxin, and pertussis toxin (PT) from Bordetella pertussis. The antibody concentrations of human immunoglobulin G (IgG) to PT, tetanus toxin, and diphtheria toxin were measured in 123 serum pairs (total of 246 sera) from a vaccine study. The multianalyte bead assa...

  5. Validity of inner canthus temperature recorded by infrared thermography as a non-invasive surrogate measure for core temperature at rest, during exercise and recovery.

    Science.gov (United States)

    Fernandes, Alex Andrade; Moreira, Danilo Gomes; Brito, Ciro José; da Silva, Cristiano Diniz; Sillero-Quintana, Manuel; Pimenta, Eduardo Mendonça; Bach, Aaron J E; Garcia, Emerson Silami; Bouzas Marins, João Carlos

    2016-12-01

    Research into obtaining a fast, valid, reliable and non-invasive measure of core temperature is of interest in many disciplinary fields. Occupational and sports medicine research has attempted to determine a non-invasive proxy for core temperature particularly when access to participants is limited and thermal safety is of a concern due to protective encapsulating clothing, hot ambient environments and/or high endogenous heat production during athletic competition. This investigation aimed to determine the validity of inner canthus of the eye temperature (TEC) as an alternate non-invasive measure of intestinal core temperature (TC) during rest, exercise and post-exercise conditions. Twelve physically active males rested for 30min prior to exercise, performed 60min of aerobic exercise at 60% V̇O2max and passively recovered a further 60min post-exercise. TEC and TC were measured at 5min intervals during each condition. Mean differences between TEC and TC were 0.61°C during pre-exercise, -1.78°C during exercise and -1.00°C during post-exercise. The reliability between the methods was low in the pre-exercise (ICC=0.49 [-0.09 to 0.82]), exercise (ICC=-0.14 [-0.65 to 0.44]) and post-exercise (ICC=-0.25 [-0.70 to 0.35]) conditions. In conclusion, poor agreement was observed between the TEC values measured through IRT and TC measured through a gastrointestinal telemetry pill. Therefore, TEC is not a valid substitute measurement to gastrointestinal telemetry pill in sports and exercise science settings.

  6. Sensitive measurement of thrombopoietin by a monoclonal antibody based sandwich enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Folman, C C; von dem Borne, A E; Rensink, I H; Gerritsen, W; van der Schoot, C E; de Haas, M; Aarden, L

    1997-10-01

    In this report a sensitive enzyme-linked immunosorbent assay (ELISA) for the measurement of plasma thrombopoietin (Tpo) is described that is solely based on monoclonal antibodies (MoAbs). The assay has an intra and inter-assay variance of 5-7% and 7-13%, respectively. Native and recombinant human Tpo (rhTpo) were recognized equally well, no cross reactivity with other cytokines was found and rhTpo added to plasma and serum was completely recovered. With the ELISA, Tpo concentrations in EDTA-anticoagulated plasma of all controls (n = 193) could be determined, since the limit of detection (2 +/- 0.8 A.U./ml, mean +/- sd) was lower than the concentration found in controls (11 +/- 8 A.U./ml, mean +/- sd; 2.5th-97.5th percentile: 4-32 A.U./ml). Tpo levels in serum were on average 3.4 times higher than in plasma. We showed in vivo that Tpo is bound by platelets, as in thrombocytopenic patients (n = 5) a platelet transfusion immediately led to a drop in plasma Tpo level, whereas in patients receiving chemotherapy the induced thrombocytopenia was followed by a rise in plasma Tpo levels. In summary, these results indicate that this ELISA is a reliable tool for Tpo measurements and is applicable for large scale studies.

  7. Measuring Single-Domain Antibody Interactions with Epitopes in Jet Fuel Using Microscale Thermophoresis

    Science.gov (United States)

    2015-01-01

    J. G. Renisio, J. J. Prompers, C. J. van Platerink, C. Cambillau, H. Darbonand, and L. G. Frenken. 2001. Thermal unfolding of a llama antibody...K. Srivastava, W. Haasnoot, et al. 2011. A broad set of different llama antibodies specific for a 16 kDa heat shock protein of Mycobacterium

  8. Statistical evaluation of an improved quantitative immunofluorescence method of measuring serum antibody levels directed against intestinal bacteria

    NARCIS (Netherlands)

    Jansen, G.J.; Wilkinson, M.H.F.; Deddens, B.; Waaij, D. van der

    1993-01-01

    The accuracy of an improved quantitative immunofluorescence method to measure the antibody binding capacity of intestinal bacteria was assessed. The improvements comprise: calibration on a non-fading fluorescence standard (uranyl glass), prolonged camera exposure time (over 4 s) and shading correcti

  9. 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.

  10. 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.

  11. 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-...... the 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....

  12. 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

    a 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...

  13. Surrogate Analysis and Index Developer (SAID) tool

    Science.gov (United States)

    Domanski, Marian M.; Straub, Timothy D.; Landers, Mark N.

    2015-10-01

    The use of acoustic and other parameters as surrogates for suspended-sediment concentrations (SSC) in rivers has been successful in multiple applications across the Nation. Tools to process and evaluate the data are critical to advancing the operational use of surrogates along with the subsequent development of regression models from which real-time sediment concentrations can be made available to the public. Recent developments in both areas are having an immediate impact on surrogate research and on surrogate monitoring sites currently (2015) in operation.

  14. Oral immunoglobulin levels are not a good surrogate for cervical immunoglobulin levels

    Directory of Open Access Journals (Sweden)

    Troy J. Kemp

    2012-06-01

    Full Text Available Background: We sought to determine whether oral secretions could be used as a surrogate for cervical secretions for monitoring cervical immunoglobulin (Ig levels. To do so, we examined 1 whether oral IgG and IgA levels correlated with those observed at the cervix, and 2 whether time of menstrual cycle and other factors previously reported to influence cervical Ig levels were associated with oral IgG and IgA levels. Methods: We obtained oral samples from a group of 85 Costa Rican woman 25-35 years of age measured at three time points during one menstrual cycle. Total IgG and IgA levels were measured by ELISA. Generalized estimating equations (GEE methods that account for repeated measures were used to evaluate the association between oral and cervical Ig levels and to evaluate the association between various covariates and oral IgA and IgG levels. Results: We did not observe an association between oral and cervical IgG (linear regression coefficient (LRC 0.01; 95% CI, -0.05 to 0.07 and IgA levels (LRC 0.02; 95% CI, -0.04 to 0.08. Oral IgG and IgA levels were not influenced by phase of menstrual cycle, in contrast to what has previously been observed for cervical Ig levels. Conclusions: Our data suggest that oral IgG and IgA measures are not a good surrogate for cervical IgG and IgA levels. Future studies should examine whether antigen-specific antibody responses induced by vaccination correlate across mucosal sites.

  15. Hepatitis C virus resistance to broadly neutralizing antibodies measured using replication-competent virus and pseudoparticles.

    Science.gov (United States)

    Wasilewski, Lisa N; Ray, Stuart C; Bailey, Justin R

    2016-11-01

    A better understanding of natural variation in neutralization resistance and fitness of diverse hepatitis C virus (HCV) envelope (E1E2) variants will be critical to guide rational development of an HCV vaccine. This work has been hindered by inadequate genetic diversity in viral panels and by a lack of standardization of HCV entry assays. Neutralization assays generally use lentiviral pseudoparticles expressing HCV envelope proteins (HCVpp) or chimeric full-length viruses that are replication competent in cell culture (HCVcc). There have been few systematic comparisons of specific infectivities of E1E2-matched HCVcc and HCVpp, and to our knowledge, neutralization of E1E2-matched HCVpp and HCVcc has never been compared using a diverse panel of human broadly neutralizing monoclonal antibodies (bNAbs) targeting distinct epitopes. Here, we describe an efficient method for introduction of naturally occurring E1E2 genes into a full-length HCV genome, producing replication-competent chimeric HCVcc. We generated diverse panels of E1E2-matched HCVcc and HCVpp and measured the entry-mediating fitness of E1E2 variants using the two systems. We also compared neutralization of E1E2-matched HCVcc and HCVpp by a diverse panel of human bNAbs targeting epitopes across E1E2. We found no correlation between specific infectivities of E1E2-matched HCVcc versus HCVpp, but found a very strong positive correlation between relative neutralization resistance of these same E1E2-matched HCVcc and HCVpp variants. These results suggest that quantitative comparisons of neutralization resistance of E1E2 variants can be made with confidence using either HCVcc or HCVpp, allowing the use of either or both systems to maximize diversity of neutralization panels.

  16. Imaging Seeker Surrogate for IRCM evaluation

    NARCIS (Netherlands)

    Schleijpen, H.M.A.; Carpenter, S.R.; Mellier, B.; Dimmeler, A.

    2007-01-01

    NATO-SCI-139 and its predecessor groups have more than a decade of history in the evaluation and recommendation of EO and IR Countermeasures against anti-aircraft missiles. Surrogate Seekers have proven to be a valuable tool for this work. The use of surrogate seekers in international co-operations

  17. 77 FR 34788 - Surrogate Foreign Corporations

    Science.gov (United States)

    2012-06-12

    ... Internal Revenue Service 26 CFR Part 1 RIN 1545-BF47 Surrogate Foreign Corporations AGENCY: Internal... regulations regarding whether a foreign corporation is treated as a surrogate foreign corporation. The final ] regulations affect certain domestic corporations and partnerships (and certain parties related thereto),...

  18. 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.

  19. 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

  20. 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

  1. Kinetics of Antibody Binding to Membranes of Living Bacteria Measured by a Photonic Crystal-Based Biosensor

    Science.gov (United States)

    Rostova, Ekaterina; Ben Adiba, Carine; Dietler, Giovanni; Sekatskii, Sergey K.

    2016-01-01

    Optical biosensors based on photonic crystal surface waves (PC SWs) offer a possibility to study binding interactions with living cells, overcoming the limitation of rather small evanescent field penetration depth into a sample medium that is characteristic for typical optical biosensors. Besides this, simultaneous excitation of s- and p-polarized surface waves with different penetration depths is realized here, permitting unambiguous separation of surface and volume contributions to the measured signal. PC-based biosensors do not require a bulk signal correction, compared to widely used surface plasmon resonance-based devices. We developed a chitosan-based protocol of PC chip functionalization for bacterial attachment and performed experiments on antibody binding to living bacteria measured in real time by the PCSW-based biosensor. Data analysis reveals specific binding and gives the value of the dissociation constant for monoclonal antibodies (IgG2b) against bacterial lipopolysaccharides equal to KD = 6.2 ± 3.4 nM. To our knowledge, this is a first demonstration of antibody-binding kinetics to living bacteria by a label-free optical biosensor. PMID:27727183

  2. Utility of measuring serum concentrations of anti-TNF agents and anti-drug antibodies in inflammatory bowel disease.

    Science.gov (United States)

    Guerra, Iván; Chaparro, María; Bermejo, Fernando; Gisbert, Javier P

    2011-07-01

    Tumor necrosis factor alpha (TNFα) is a cytokine with a critical role in the pathogenesis of some chronic inflammatory diseases, such as inflammatory bowel diseases. Anti-TNF agents, which neutralize the biological activity of TNFα, are widely used among the different therapeutic options for the treatment of patients with inflammatory bowel diseases. These drugs are very useful in clinical practice, but some patients experience lack and loss of response during the treatment. Drug serum concentration, antibodies against anti-TNF agents, clearance of the drug, formation of immune complexes, a more severe disease and probably other unknown factors can influence the treatment's efficacy. Nowadays, the management of patients with lack or loss of response is empirical. The measurement of drug concentrations and antibodies against anti-TNF agents might be useful for improving the selection of patients that will benefit from the maintenance treatment. In clinical practice, these methods may help us decide which strategy will be used in cases of loss of response: treatment intensification, shortening the infusion interval, increasing the dose, switching to another anti-TNF agent or to a drug with another mechanism of action. The optimal strategy in the future may be comprised of an early detection of loss of response to the treatment by assessing clinical symptoms and finding evidence of activity of the disease on endoscopic or radiological examinations when necessary, as well as a better management of anti-TNF treatment aided by measuring the serum concentration of the drug and antibodies against the drug.

  3. Effect of exogenous circulating anti-bPL antibodies on bovine placental lactogen measurements in foetal samples

    Directory of Open Access Journals (Sweden)

    Taverne Marcel AM

    2010-02-01

    Full Text Available Abstract Background The involvement of placental lactogen (PL in the regulation of foetal growth has been investigated in different species by in vivo immunomodulation techniques. However, when circulating antibodies are present together with the hormone, the procedure for hormonal measurement becomes considerably complex. The aim of this study was the immunoneutralization of bovine placental lactogen (bPL concentrations in bovine foetal circulation by direct infusion of rabbit anti-bPL purified immunoglobulins (IgG via a foetal catheter (in vivo study. The ability of a RIA based on guinea pig anti-bPL antiserum, for the measurement of bPL concentrations in samples containing exogenous rabbit anti-bPL immunoglobulins, was also analyzed in in vitro and in vivo conditions. Methods Six bovine foetuses were chronic cannulated on the aorta via the medial tarsal artery. Infusion of rabbit anti-bPL IgG was performed during late gestation. Pooled rabbit anti-bPL antisera had a maximal neutralization capacity of 25 μg bPL/mL of immunoglobulin. Interference of rabbit anti-bPL immunoglobulin with radioimmunoassay measurement using guinea pig anti-bPL as primary antibody was first evaluated in vitro. Polyclonal anti-bPL antibodies raised in rabbit were added in foetal sera to produce 100 samples with known antibodies titers (dilutions ranging from 1:2,500 till 1:1,280,000. Result(s Assessment of the interference of rabbit anti-bPL antibody showed that bPL concentrations were significantly lower (P Conclusion(s The use of a bPL RIA using a guinea pig anti-bPL as primary antiserum allowed for the measurement of bPL concentrations in foetal plasma in presence of rabbit anti-bPL IgG into the foetal circulation. Long-term foetal catheterization allowed for the study of the influence of direct infusion of anti-bPL IgG on peripheral bPL concentrations in bovine foetuses.

  4. Prevalence of antibodies against Entamoeba histolytica in Mexico measured by ELISA

    Science.gov (United States)

    González, C. R.; Isibasi, A.; Ortiz-Navarrete, V.; Paniagua, J.; García, J. A.; Ramirez, A.; Salvatierra, B.; Tapia, R.; Sepúlveda, J.; Gutiérrez, G.; Kumate, J.

    1995-01-01

    The prevalence of antibodies against Entamoeba histolytica was studied in the Mexican population using an immunoenzyme assay in solid phase (ELISA) and semiautomatic equipment. The antigen was a mixture of membrane proteins obtained by Triton X-100 extraction from an axenic culture of Entamoeba histolytica HM1-IMSS. The method was standardized by comparing serum samples from amoebic liver abscess patients with healthy volunteers. From the 60538 samples supplied by the National Seroepidemiology Survey, antibodies were found in 4·49% (4·32—4·65% at 95% confidence limit). More significant titres occurred in the central region of the country. The ratio female to male was 1·25:1. The population living in metropolitan areas had probably been infected at a younger age than those living in the country. Important differences were found in the seroprevalence obtained by ELISA compared with a study which used indirect haemagglutination (IHA) in the same sample frame. PMID:8557086

  5. Prevalence of antibodies against Entamoeba histolytica in Mexico measured by ELISA

    OpenAIRE

    González, C. R.; Isibasi, A.; Ortiz-Navarrete, V.; Paniagua, J; García, J. A.; Ramirez, A.; Salvatierra, B.; Tapia, R.; J. Sepúlveda; Gutiérrez, G.; Kumate, J

    1995-01-01

    The prevalence of antibodies against Entamoeba histolytica was studied in the Mexican population using an immunoenzyme assay in solid phase (ELISA) and semiautomatic equipment. The antigen was a mixture of membrane proteins obtained by Triton X-100 extraction from an axenic culture of Entamoeba histolytica HM1-IMSS. The method was standardized by comparing serum samples from amoebic liver abscess patients with healthy volunteers. From the 60538 samples supplied by the National Seroepidemiolog...

  6. Surrogate mobility and orientation affect the early neurobehavioral development of infant rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Dettmer, Amanda M; Ruggiero, Angela M; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2008-05-01

    A biological mother's movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard stationary rocking surrogates (RS) and to 9-15 infants reared with their biological mothers (MR) for early developmental outcome. We predicted that MS infants would develop more similarly to MR infants than RS infants. In neonatal assessments conducted at Day 30, both MS and MR infants showed more highly developed motor activity than RS infants on measures of grasping (p = .009), coordination (p = .038), spontaneous crawl (p = .009), and balance (p = .003). At 2-3 months of age, both MS and MR infants displayed higher levels of exploration in the home cage than RS infants (p = .016). In a novel situation in which only MS and RS infants were tested, MS infants spent less time near their surrogates in the first five minutes of the test session than RS infants (p = .05), indicating a higher level of comfort. Collectively, these results suggest that when nursery-rearing of infant monkeys is necessary, a mobile hanging surrogate may encourage more normative development of gross motor skills and exploratory behavior and may serve as a useful alternative to stationary or rocking surrogates.

  7. 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.

  8. A Rapid Zika Diagnostic Assay to Measure Neutralizing Antibodies in Patients

    Directory of Open Access Journals (Sweden)

    Chao Shan

    2017-03-01

    Full Text Available The potential association of microcephaly and other congenital abnormalities with Zika virus (ZIKV infection during pregnancy underlines the critical need for a rapid and accurate diagnosis. Due to the short duration of ZIKV viremia in infected patients, a serologic assay that detects antibody responses to viral infection plays an essential role in diagnosing patient specimens. The current serologic diagnosis of ZIKV infection relies heavily on the labor-intensive Plaque Reduction Neutralization Test (PRNT that requires more than one-week turnaround time and represents a major bottleneck for patient diagnosis. To overcome this limitation, we have developed a high-throughput assay for ZIKV and dengue virus (DENV diagnosis that can attain the “gold standard” of the current PRNT assay. The new assay is homogeneous and utilizes luciferase viruses to quantify the neutralizing antibody titers in a 96-well format. Using 91 human specimens, we showed that the reporter diagnostic assay has a higher dynamic range and maintains the relative specificity of the traditional PRNT assay. Besides the improvement of assay throughput, the reporter virus technology has also shortened the turnaround time to less than two days. Collectively, our results suggest that, along with the viral RT-PCR assay, the reporter virus-based serologic assay could be potentially used as the first-line test for clinical diagnosis of ZIKV infection as well as for vaccine clinical trials.

  9. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy.

    Science.gov (United States)

    Kanigicherla, Durga; Gummadova, Jennet; McKenzie, Edward A; Roberts, Stephen A; Harris, Shelley; Nikam, Milind; Poulton, Kay; McWilliam, Lorna; Short, Colin D; Venning, Michael; Brenchley, Paul E

    2013-05-01

    Antibodies to the phospholipase A2 receptor 1 (PLA2R1) have been reported in 70% of cases of idiopathic membranous nephropathy (IMN). The genetic susceptibility of IMN has been accounted for by HLA DQA1 and PLA2R1 genes. Here we retrospectively quantified PLA2R antibodies by ELISA, and genotyped DQ alleles and PLA2R1 single-nucleotide polymorphisms for association with clinical criteria for disease activity at the time of first sample and with outcome over a median total follow-up of 90 months. In 90 prevalent patients with biopsy-proven IMN, anti-PLA2R antibodies were present in 75% of patients with IMN with active disease and were significantly higher than in patients in partial or complete remission at the time of antibody measurement. There was a differential IgG subclass response (4>2>3>1) at an early stage, i.e., within 6 months of biopsy. Levels of PLA2R antibodies were significantly linked to DQA1*05:01 and DQB1*02:01. Survival analysis of patients with IMN showed that PLA2R antibodies are significantly linked with outcome. Thus, high levels of PLA2R antibodies are linked with active disease and a higher risk of declining renal function during follow-up. Future therapeutic trials in IMN should monitor anti-PLA2R, as patients with a high antibody burden may benefit from earlier therapeutic intervention.

  10. Design, development, and analysis of a surrogate for pulmonary injury prediction.

    Science.gov (United States)

    Danelson, Kerry A; Gayzik, F Scott; Stern, Amber Rath; Hoth, J Jason; Stitzel, Joel D

    2011-10-01

    Current anthropomorphic test devices (ATDs) measure chest acceleration and deflection to assess risk of injury to the thorax. This study presents a lung surrogate prototype designed to expand the injury assessment capabilities of ATDs to include a risk measure for pulmonary contusion (PC). The surrogate augments these existing measures by providing pressure data specific to the lung and its lobes. The prototype was created from a rendering of a 50th percentile male lung inflated to normal inspiration, obtained from clinical CT data. Surrogate size, lobe volume, and airway cross sections were selected to match the morphology of the lung. Elastomeric urethane was molded via rapid prototyping to create a functional prototype. Pressure sensors in each of the five terminal airways independently monitored pressure traces in the lobes during impacts to the surrogate. Software was created to analyze the surrogate impact pressure data, determine the lobe with the greatest pressure rise for a particular impact, and estimate the initial speed of surface deformation. Calibration testing indicates an approximately linear relationship between peak lobe pressure and surface impact speed. No type I or II errors were demonstrated during lobe detection testing. During repeatability testing, the standard deviation was between 2 and 4% of the mean peak pressure. Ongoing research will focus on correlating surrogate data, pressure pulses, or surface deformation, to risk functions for PC.

  11. 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

    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...... = 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......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...

  12. Measurement of Ki-67 antigen in 159 pituitary adenomas using the MIB-1 monoclonal antibody

    Directory of Open Access Journals (Sweden)

    C.B. Pizarro

    2004-02-01

    Full Text Available Pituitary adenomas sometimes show rapid growth and recurrence, and about one third invade the structures surrounding the sella turcica. In an attempt to determine aggressive behavior at an early stage, we used the MIB-1 antibody to identify the Ki-67 antigen. The present study was designed to evaluate pituitary adenomatous tissue in terms of secretion and proliferation and to correlate the Ki-67 index with hormone phenotype and invasive behavior. Material from 159 patients submitted to one or more resections of pituitary adenomas was evaluated. Forty-two non-secretory adenomas and 43 adenomas immunoreactive for growth hormone, 19 for prolactin, 18 for growth hormone and prolactin, 16 for adrenocorticotropic hormone (ACTH, and 21 cases of plurihormonal/gonadotropin adenomas were detected by immunohistochemistry. The MIB-1 antibody was positive in 139 samples and the Ki-67 index ranged from 0.16 to 15.48% (mean = 1.22 ± 2.09%, with no significant difference between genders, age groups, or secretory and non-secretory status. The Ki-67 index was higher in ACTH-secreting adenomas. Invasive pituitary adenomas had a significantly higher Ki-67 index (2.01 ± 3.15% than macroadenomas with or without supra-sellar extension (1.12 ± 1.87%; P = 0.02. The index was not significantly different in the subgroup of adenomas with invasion of the cavernous sinus compared to groups with other types of invasion. We conclude that tumoral proliferative activity evaluated by the detection of the Ki-67 antigen is significantly higher in invasive than noninvasive adenomas, information which can be useful in therapeutic postoperative management since index cut-off values associated with aggressive behavior can be established.

  13. Development and application of a GuHCl-modified ELISA to measure the avidity of anti-HPV L1 VLP antibodies in vaccinated individuals.

    Science.gov (United States)

    Dauner, Joseph G; Pan, Yuanji; Hildesheim, Allan; Kemp, Troy J; Porras, Carolina; Pinto, Ligia A

    2012-04-01

    Antibody responses against infectious agents are an important component in the prevention of disease. The avidity of antibodies for their antigens relates to their functional efficiency, and is a fundamental aspect in the investigation of humoral responses. Modified ELISAs are used to estimate avidity through the use of chaotropic agents and the measurement of the degree to which they disrupt the interaction between antibody and antigen. The theory behind the assay is the higher the avidity of an interaction the less susceptible it is to the effects of the chaotropic agent. The goal of this study was to generate a modified ELISA where a complex, multimeric coating-antigen, human papillomavirus (HPV) virus-like particles (VLP), was used to measure the avidity of anti-HPV antibodies generated following vaccination with HPV VLPs. A series of chaotropic agents were evaluated in the assay for their effectiveness in measuring avidity. Guanidine hydrochloride (GuHCl) was selected as a chaotropic reagent with the ability to disrupt antibody and antigen interactions, while not affecting the integrity of the plate-bound VLP. Two methods of determining the avidity index were assessed and shown to be comparable. This assay was then successfully applied to measure the avidity of anti-HPV VLP serum antibodies in samples from an HPV L1 VLP vaccine clinical trial. Overall, the assay was highly reproducible and captured a wide range of antibody avidities. Therefore, a GuHCl-modified ELISA is an acceptable method that can be used to determine HPV-specific antibody avidity indices within a clinical trial setting.

  14. An integrated microfluidic system for measurement of glycated hemoglobin levels by using an aptamer-antibody assay on magnetic beads.

    Science.gov (United States)

    Chang, Ko-Wei; Li, Jinglun; Yang, Ching-Hsuan; Shiesh, Shu-Chu; Lee, Gwo-Bin

    2015-06-15

    Blood glycated hemoglobin (HbA1c), reflecting the average blood glucose level in the proceeding 2-3 months, is recommended for screening/diagnosing and patient management of diabetes. However, accurate measurement of the HbA1c level at the point of care is hampered by costly, large-scale instruments (such as high-performance liquid chromatography) or reagent instability of classical immunologic methods, which involve antibody-based immunoturbidimetry. In this work, an integrated microfluidic system using aptamer-based testing to measure HbA1c in blood samples is therefore presented. This measuring system used nucleic-acid aptamers that exhibited high sensitivity and high specificity for hemoglobin and HbA1c to perform a stable and robust testing. The compact microfluidic system consumed less samples and reagents and significantly shortened the detection time. Combining the advantages of microfluidics and aptamers, this integrated microsystem presents a promising tool for accurate and point-of-case HbA1c detection. To demonstrate its clinical utility, whole blood samples with clinically-relevant concentrations of HbA1c and Hb were automatically measured on the integrated microfluidic system. Experimental data showed that the developed aptamer-based microfluidic system is capable of detecting HbA1c and Hb with a good linear response. The entire process was completed within 25 min. The aptamer-antibody on-chip sandwich immunoassay may be further refined to allow diabetes screening and diagnosis at lower cost and earlier phase to minimize the risk of diabetic complications.

  15. Full validation of therapeutic antibody sequences by middle-up mass measurements and middle-down protein sequencing.

    Science.gov (United States)

    Resemann, Anja; Jabs, Wolfgang; Wiechmann, Anja; Wagner, Elsa; Colas, Olivier; Evers, Waltraud; Belau, Eckhard; Vorwerg, Lars; Evans, Catherine; Beck, Alain; Suckau, Detlev

    2016-01-01

    The regulatory bodies request full sequence data assessment both for innovator and biosimilar monoclonal antibodies (mAbs). Full sequence coverage is typically used to verify the integrity of the analytical data obtained following the combination of multiple LC-MS/MS datasets from orthogonal protease digests (so called "bottom-up" approaches). Top-down or middle-down mass spectrometric approaches have the potential to minimize artifacts, reduce overall analysis time and provide orthogonality to this traditional approach. In this work we report a new combined approach involving middle-up LC-QTOF and middle-down LC-MALDI in-source decay (ISD) mass spectrometry. This was applied to cetuximab, panitumumab and natalizumab, selected as representative US Food and Drug Administration- and European Medicines Agency-approved mAbs. The goal was to unambiguously confirm their reference sequences and examine the general applicability of this approach. Furthermore, a new measure for assessing the integrity and validity of results from middle-down approaches is introduced - the "Sequence Validation Percentage." Full sequence data assessment of the 3 antibodies was achieved enabling all 3 sequences to be fully validated by a combination of middle-up molecular weight determination and middle-down protein sequencing. Three errors in the reference amino acid sequence of natalizumab, causing a cumulative mass shift of only -2 Da in the natalizumab Fd domain, were corrected as a result of this work.

  16. Surrogates for herbicide removal in stormwater biofilters.

    Science.gov (United States)

    Zhang, Kefeng; Deletic, Ana; Page, Declan; McCarthy, David T

    2015-09-15

    Real time monitoring of suitable surrogate parameters are critical to the validation of any water treatment processes, and is of particularly high importance for validation of natural stormwater treatment systems. In this study, potential surrogates for herbicide removal in stormwater biofilters (also known as stormwater bio-retention or rain-gardens) were assessed using field challenge tests and matched laboratory column experiments. Differential UV absorbance at 254mn (ΔUVA254), total phosphorus (ΔTP), dissolved phosphorus (ΔDP), total nitrogen (ΔTN), ammonia (ΔNH3), nitrate and nitrite (ΔNO3+NO2), dissolved organic carbon (ΔDOC) and total suspended solids (ΔTSS) were compared with glyphosate, atrazine, simazine and prometryn removal rates. The influence of different challenge conditions on the performance of each surrogate was studied. Differential TP was significantly and linearly related to glyphosate reduction (R(2) = 0.75-0.98, P biofilters.

  17. Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease

    Directory of Open Access Journals (Sweden)

    Hyemi Kwon

    2016-06-01

    Full Text Available BackgroundHyperthyroidism relapse in Graves disease after antithyroid drug (ATD withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb and thyrotropin-binding inhibitory immunoglobulin (TBII at ATD withdrawal to predict relapse.MethodsThis retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35 or TBII (TBII group; n=39 every 3 to 6 months for 2 years after ATD withdrawal.ResultsTwenty-eight patients (38% relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67% than patients with negative TSAb (17%; P=0.007. Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%.ConclusionTSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

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

    KAUST Repository

    Elwardani, Ahmed Elsaid

    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.

  19. Best practice recommendations for the transfer of cell-based assays for the measurement of neutralizing anti-drug antibodies.

    Science.gov (United States)

    Belouski, Shelley S; Born, Danika; Jacques, Susan; Harder, Brandon; Reynhardt, Kai; Kaliyaperumal, Arunan; Gupta, Shalini

    2016-09-01

    We recommend the application of a strategically designed step-wise approach to transfer cell-based assays that includes assessing analytical performance (through a fit for purpose validation and/or design of experiment robustness characterization), clinical performance (i.e., concordance) and performance or proficiency testing for long-term method monitoring. Here we focus on the application of this strategy to cell-based assays for the measurement of neutralizing anti-drug antibodies. This application is unique in that it requires a custom cell-based assay to be used over a long period of time (potentially phase 1a through the life of a marketed product) with the confidence of consistent method performance and result reporting. But, the process is adaptable to a variety of assay types and applications. We present lessons learned from two cell-based assay transfers that met relevant challenges while implementing alternative permutations of the recommended method transfer process.

  20. 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.

  1. Antimitochondrial antibody

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003529.htm Antimitochondrial antibody To use the sharing features on this page, please enable JavaScript. Antimitochondrial antibodies (AMA) are substances ( antibodies ) that form against mitochondria. ...

  2. 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

  3. Videotrees: Improving video surrogate presentation using hierarchy

    NARCIS (Netherlands)

    Jansen, Michel; Heeren, Willemijn; Dijk, van Betsy

    2008-01-01

    As the amount of available video content increases, so does the need for better ways of browsing all this material. Because the nature of video makes it hard to process, the need arises for adequate surrogates for video that can readily be skimmed and browsed. In this paper, the effects of the use o

  4. 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.

  5. 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

    which can be present in both blood and synovial fluid. RF is present in some arthritic diseases as well as in some other medical conditions. When present, especially RF IgM is known to interfere with the immunometric measurements. A possible and affordable solution to diminish this interference is PEG...

  6. A qualitative investigation of selecting surrogate decision-makers

    NARCIS (Netherlands)

    Edwards, S.J.L.; Brown, P.; Twyman, M.A.; Christie, D.; Rakow, T.

    2011-01-01

    Background Empirical studies of surrogate decision-making tend to assume that surrogates should make only a 'substituted judgement'—that is, judge what the patient would want if they were mentally competent. Objectives To explore what people want in a surrogate decision-maker whom they themselves se

  7. Preparation and validation of radio iodinated recombinant human IL-10 for the measurement of natural human antibodies against IL-10

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia; Svenson, Morten;

    2009-01-01

    activity of 75 cpm/pg. Validation of the tracer confirmed preserved antibody epitopes and receptor binding ability. A robust Radio Immuno Assay (RIA) was developed and validated to detect natural human anti-IL-10 antibodies based on the formation of (125)I-labeled IL-10-IgG complexes in solution...

  8. Measurement of HNE-protein adducts in human plasma and serum by ELISA—Comparison of two primary antibodies

    Directory of Open Access Journals (Sweden)

    Daniela Weber

    2013-01-01

    After modification and validation of the protocol for both antibodies, samples of two groups were analyzed: apparently healthy obese (n=62 and non-obese controls (n=15. Although the detected absolute values of HNE–protein adducts were different, depending on the antibody used, both ELISA methods showed significantly higher values of HNE–protein adducts in the obese group.

  9. 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.

  10. Validating (d,pγ as a Surrogate for Neutron Capture

    Directory of Open Access Journals (Sweden)

    Ratkiewicz A.

    2015-01-01

    Full Text Available 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.

  11. 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.

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ratkiewicz, A. [Rutgers University; Cizewski, J. A. [Rutgers University; Pain, S. [Oak Ridge National Laboratory (ORNL); Adekola, A. S. [Rutgers University; Burke, J. T. [Lawrence Livermore National Laboratory (LLNL); Casperson, R.J. [Lawrence Livermore National Laboratory (LLNL); Fotiades, N. [Los Alamos National Laboratory (LANL); McCleskey, M. [Texas A& M University; Burcher, S. [Rutgers University; Shand, C. M. [Rutgers Univ./Univ. of Surrey, UK; Austin, R. A. E. [Saint Mary’s University, Halifa, Canada; Baugher, T. [Rutgers University; Carpenter, M. P. [Argonne National Laboratory (ANL); Devlin, M. [Los Alamos National Laboratory (LANL); Escher, J. E. [Lawrence Livermore National Laboratory (LLNL); Hardy, S. [Rutgers Univ./Univ. of Surrey, UK; Hatarik, R. [Lawrence Livermore National Laboratory (LLNL); Howard, M. [Rutgers University; Hughes, R. [University of Richmond, VA; Jones, K. L. [University of Tennessee, Knoxville (UTK); Kozub, R. L. [Tennessee Technological University (TTU); Lister, C. J. [University of Massachusetts, Lowell; Manning, B. [Rutgers University; O' Donnell, J. M. [Los Alamos National Laboratory (LANL); Peters, W. A. [Oak Ridge Associated Universities (ORAU); Ross, T.J. [University of Richmond, VA; Scielzo, N.D. [Lawrence Livermore National Laboratory (LLNL); Seweryniak, D. [Argonne National Laboratory (ANL); Zhu, S. [Argonne National Laboratory (ANL)

    2015-01-01

    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 rprocess 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,py) reaction at low energies was identified as a promising surrogate for the (n,y) reaction, as both reactions share many characteristics. We report on a program to validate (d,py) as a surrogate for (n,y) using 95Mo as a target. The experimental campaign includes direct measurements of the y-ray intensities from the decay of excited states populated in the 95Mo(n,y) and 95Mo(d,py) reactions.

  14. Measuring immunoglobulin g antibodies to tetanus toxin, diphtheria toxin, and pertussis toxin with single-antigen enzyme-linked immunosorbent assays and a bead-based multiplex assay.

    Science.gov (United States)

    Reder, Sabine; Riffelmann, Marion; Becker, Christian; Wirsing von König, Carl Heinz

    2008-05-01

    Bead-based assay systems offer the possibility of measuring several specific antibodies in one sample simultaneously. This study evaluated a vaccine panel of a multianalyte system that measures antibodies to tetanus toxin, diphtheria toxin, and pertussis toxin (PT) from Bordetella pertussis. The antibody concentrations of human immunoglobulin G (IgG) to PT, tetanus toxin, and diphtheria toxin were measured in 123 serum pairs (total of 246 sera) from a vaccine study. The multianalyte bead assay was compared to a standardized in-house IgG- anti-PT enzyme-linked immunosorbent assay (ELISA) of the German reference laboratory for bordetellae, as well as to various commercially available ELISAs for anti-PT IgG, anti-tetanus IgG, and anti-diphtheria IgG. The results of the multiplex assay regarding the antibodies against diphtheria toxin compared favorably with a regression coefficient of 0.938 for values obtained with an ELISA from the same manufacturer used as a reference. Similarly, antibodies to tetanus toxin showed a correlation of 0.910 between the reference ELISA and the multianalyte assay. A correlation coefficient of 0.905 was found when an "in-house" IgG anti-PT and the multiplex assay were compared. Compared to single ELISA systems from two other manufacturers, the multiplex assay performed similarly well or better. The multianalyte assay system was a robust system with fast and accurate results, analyzing three parameters simultaneously in one sample. The system was well suited to quantitatively determine relevant vaccine induced antibodies compared to in-house and commercially available single-antigen ELISA systems.

  15. Automated in situ measurement of cell-specific antibody secretion and laser-mediated purification for rapid cloning of highly-secreting producers.

    Science.gov (United States)

    Hanania, Elie G; Fieck, Annabeth; Stevens, Janine; Bodzin, Leon J; Palsson, Bernhard Ø; Koller, Manfred R

    2005-09-30

    Cloning of highly-secreting recombinant cells is critical for biopharmaceutical manufacturing, but faces numerous challenges including the fact that secreted protein does not remain associated with the producing cell. A fundamentally new approach was developed combining in situ capture and measurement of individual cell protein secretion followed by laser-mediated elimination of all non- and poorly-secreting cells, leaving only the highest-secreting cell in a well. Recombinant cells producing humanized antibody were cultured serum-free on a capture matrix, followed by staining with fluorescently-labeled anti-human antibody fragment. A novel, automated, high-throughput instrument (called LEAP) was used to image and locate every cell, quantify the cell-associated and secreted antibody (surrounding each cell), eliminate all undesired cells from a well via targeted laser irradiation, and then track clone outgrowth and stability. Temporarily sparing an island of helper cells around the clone of interest improved cloning efficiency (particularly when using serum-free medium), and helper cells were easily eliminated with the laser after several days. The in situ nature of this process allowed several serial sub-cloning steps to be performed within days of one another, resulting in rapid generation of clonal populations with significantly increased and more stable, homogeneous antibody secretion. Cell lines with specific antibody secretion rates of > 50 pg/cell per day (in static batch culture) were routinely obtained as a result of this cloning approach, often times representing up to 20% of the clones screened.

  16. Measurement of anti-TNF agents and anti-drug antibodies serum levels in patients with inflammatory bowel disease.

    Science.gov (United States)

    Guerra, Iván; Chaparro, María; Bermejo, Fernando; Gisbert, Javier P

    2014-01-01

    Despite its undoubted benefit in patients with inflammatory bowel disease, anti-TNF therapy has some limitations including the lack of primary response and the loss of response to treatment in some patients. An empirical approach to these problems is frequently used based on clinical outcome. The measurement of anti-TNF drug serum levels and anti-drug antibodies (ADAb) levels has been proposed for improving the management of anti-TNF drugs. Although their role in routine clinical practice has not been clearly defined, current data support their relationship with clinical outcomes and suggest their clinical utility primarily in patients with loss of response to anti-TNF agents. The presence of pre-existing ADAb before starting the anti-TNF therapy has recently been described. Transient ADAb, non-neutralizing ADAb and some cut-offs points have been proposed, extending the knowledge about this topic. A standardized and widely available test with cut-off points for each anti-TNF agent and the definition of the most appropriate actions to be taken given the serum concentration of the drugs and ADAb are needed before recommending their routine use.

  17. 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.

  18. 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

  19. 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

  20. Characterisation of non-toxigenic Clostridium spp. strains, to use as surrogates for non-proteolytic Clostridium botulinum in chilled food challenge testing.

    Science.gov (United States)

    Parker, M D; Barrett, P I; Shepherd, J; Price, L J; Bull, S D

    2015-01-01

    Under many of the conditions studied, a two-strain cocktail of non-toxigenic Clostridium spp. was found to be suitable as a surrogate for non-proteolytic Clostridium botulinum, and has the potential for use in chilled food challenge tests measuring growth. Non-toxigenic surrogates could also be used in thermal process screening studies.

  1. 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

  2. Using serum urate as a validated surrogate end point for flares in patients with gout

    DEFF Research Database (Denmark)

    Morillon, Melanie B; Stamp, Lisa; Taylor, William;

    2016-01-01

    INTRODUCTION: Gout is the most common inflammatory arthritis in men over 40 years of age. Long-term urate-lowering therapy is considered a key strategy for effective gout management. The primary outcome measure for efficacy in clinical trials of urate-lowering therapy is serum urate levels......, effectively acting as a surrogate for patient-centred outcomes such as frequency of gout attacks or pain. Yet it is not clearly demonstrated that the strength of the relationship between serum urate and clinically relevant outcomes is sufficiently strong for serum urate to be considered an adequate surrogate...

  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. Development and validation of a homogeneous mobility shift assay for the measurement of infliximab and antibodies-to-infliximab levels in patient serum.

    Science.gov (United States)

    Wang, Shui-Long; Ohrmund, Linda; Hauenstein, Scott; Salbato, Jared; Reddy, Rukmini; Monk, Patrick; Lockton, Steven; Ling, Nicholas; Singh, Sharat

    2012-08-31

    Antibody-based drugs such as infliximab (IFX) are effective for the treatment of inflammatory bowel disease (IBD) and other immune-mediated disorders. The development of antibodies against these drugs may result in unfavorable consequences, including the loss of drug efficacy, hypersensitivity reactions, and other adverse events. Therefore, accurate monitoring of serum drug and anti-drug antibody levels should be an important part of therapy for patients being treated with an antibody-based drug. Current methods for the assessment of anti-drug antibodies and drug levels, involving various bridging ELISA and radioimmunoassay techniques, are limited by their sensitivity, interference, and/or complexity. To overcome these limitations, we have developed a non-radiolabeled homogeneous mobility shift assay (HMSA) to measure the antibodies-to-infliximab (ATI) and IFX levels in serum samples. Full method validation was performed on both the ATI- and IFX-HMSA, and the clinical sample test results were also compared with those obtained from a bridging ELISA method to evaluate the difference in performance between the two assays. Validation of the ATI-HMSA revealed a lower limit of quantitation of 0.012 μg/mL in serum. The linear range of quantitation was 0.029-0.54 μg/mL. The intra- and inter-assay precision was less than 20% of coefficient of variation (CV), and the accuracy (% error) of the assay was less than 20%. In serum samples, ATI as low as 0.036 μg/mL can be measured, even in the presence of 60 μg/mL of IFX in the serum. Sera from 100 healthy subjects were tested to determine the cut point of the assay. ATI-positive samples that had been previously analyzed by using a bridging ELISA from 100 patients were also measured by the new method. There was a high correlation between the two methods for ATI levels (pELISA method. Validation of the mobility shift IFX assay also showed high assay sensitivity, precision and accuracy. The HMSA method may also be applied to

  5. Compositions, antibodies, asthma diagnosis methods, and methods for preparing antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hongjun; Zangar, Richard C.

    2017-01-17

    Methods for preparing an antibody are provided with the method including incorporating 3-bromo-4-hydroxy-benzoic acid into a protein to form an antigen, immunizing a mammalian host with the antigen, and recovering an antibody having an affinity for the antigen from the host. Antibodies having a binding affinity for a monohalotyrosine are provided as well as composition comprising an antibody bound with monohalotyrosine. Compositions comprising a protein having a 3-bromo-4-hydroxy-benzoic acid moiety are also provided. Methods for evaluating the severity of asthma are provide with the methods including analyzing sputum of a patient using an antibody having a binding affinity for monohalotyrosine, and measuring the amount of antibody bound to protein. Methods for determining eosinophil activity in bodily fluid are also provided with the methods including exposing bodily fluid to an antibody having a binding affinity for monohalotyrosine, and measuring the amount of bound antibody to determine the eosinophil activity.

  6. An Innovative Pseudotypes-Based Enzyme-Linked Lectin Assay for the Measurement of Functional Anti-Neuraminidase Antibodies.

    Directory of Open Access Journals (Sweden)

    Marua Prevato

    Full Text Available Antibodies (Ab to neuraminidase (NA play a role in limiting influenza infection and might help reduce the disease impact. The most widely used serological assay to measure functional anti-NA immune responses is the Enzyme-Linked Lectin Assay (ELLA which relies on hemagglutinin (HA mismatched virus reassortants, or detergent treated viruses as the NA source to overcome interference associated with steric hindrance of anti-HA Ab present in sera. The difficulty in producing and handling these reagents, which are not easily adapted for screening large numbers of samples, limits the routine analysis of functional anti-NA Ab in clinical trials. In this study, we produced influenza lentiviral pseudoparticles (PPs containing only the NA antigen (NA-PPs with a simple two-plasmid co-transfection system. NA-PPs were characterized and tested as an innovative source of NA in the NA inhibition (NI assay. Both swine A/California/07/2009 (H1N1 and avian A/turkey/Turkey/01/2005 (H5N1 N1s within NA-PPs retained their sialidase activity and were specifically inhibited by homologous and N1 subtype-specific, heterologous sheep sera. Moreover, A/California/07/2009 N1-PPs were a better source of NA compared to whole live and detergent treated H1N1 viruses in ELLA, likely due to lack of interference by anti-HA Ab, and absence of possible structural modifications caused by treatment with detergent. This innovative assay is safer and applicable to all NAs. Taken together, these results highlight the potential of NA-PPs-based NI assays to be developed as sensitive, flexible, easy to handle and scalable serological tests for routine NA immune response analysis.

  7. Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long‐Term Treatment Response in Rheumatoid Arthritis

    Science.gov (United States)

    Jani, Meghna; Chinoy, Hector; Warren, Richard B.; Griffiths, Christopher E. M.; Plant, Darren; Fu, Bo; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, KimmeL.; Prouse, P. J.; Moitra, R. K.; Shawe, D. J.; Nisar, M.; Fairburn, K.; Nixon, J.; Barnes, T.; Hui, M.; Coady, D.; Wright, D.; Morley, C.; Raftery, G.; Bracewell, C.; Bridges, M.; Armstrong, D.; Chuck, A. J.; Hailwood, S.; Kumar, N.; Ashok, D.; Reece, R.; O'Reilly, S. C.; Ding, T.; Badcock, L. J.; Deighton, C. M.; Raj, N.; Regan, M. R.; Summers, G. D.; Williams, R. A.; Lambert, J. R.; Stevens, R.; Wilkinson, C.; Kelly, C. A.; Hamilton, J.; Heycock, C. R.; Saravanan, V.; Cope, A.; Garrood, T.; Ng, N.; Kirkham, B.; Green, M.; Gough, A.; Lawson, C.; Das, D.; Borbas, E.; Wazir, T.; Emery, P.; Bingham, S.; Bird, H. A.; Conaghan, P.G.; Pease, C. T.; Wakefield, R. J.; Buch, M.; Bruce, I.; Gorodkin, R.; Ho, P.; Parker, B.; Smith, W.; Jenkins, E.; Mukhtyar, C.; Gaffney, K.; Macgregor, A. J.; Marshall, T.; Merry, P.; DeSilva, C.; Birrell, F. N.; Crook, P. R.; Szebenyi, B.; Bates, D.; James, D.; Gillott, T.; Alvi, A.; Grey, C.; Browning, J.; McHale, J. F.; Gaywood, I.C.; Jones, A. C.; Lanyon, P.; Pande, I.; Doherty, M.; Gupta, A.; Courtney, P. A.; Srikanth, A.; Abhishek, A.; Das, L.; Pattrick, M.; Snowden, H. N.; Bowden, A. P.; Smith, E. E.; Klimiuk, P.; Speden, D. J.; Naz, S.; Ledingham, J. M.; Hull, R. G.; McCrae, F.; Cooper, A.; Young‐Min, S. A.; Wong, E.; Shaban, R.; Woolf, A. D.; Davis, M.; Hutchinson, D.; Endean, A.; Mewar, D.; Tunn, E. J.; Nelson, K.; Kennedy, T. D.; Dubois, C.; Pauling, J.; Korendowych, E.; Jenkinson, T.; Sengupta, R.; Bhalla, A.; McHugh, N.; O'Neil, T.; Herrick, A. L.; Jones, A. K.; Cooper, R. G.; Dixon, W. G.; Harrison, B.; Buckley, C. D.; Carruthers, D. C.; Elamanchi, R.; Gordon, P. C.; Grindulis, K. A.; Khattak, F.; Raza, K.; Situnayake, K.; Akil, M.; Till, S.; Dunkley, L.; Tattersall, R.; Kilding, R.; Tait, T.; Maxwell, J.; Till, S.; Kuet, K.-P.; Plant, M. J.; Clarke, F.; Fordham, J. N.; Tuck, S.; Pathare, S. K.; Paul, A.; Marguerie, C. P.; Rigby, S. P.; Dunn, N.; Abbas, I.; Filer, C.; Abernethy, V. E.; Clewes, A. R.; Dawson, J. K.; Kitas, G.; Erb, N.; Klocke, R.; Whallett, A. J.; Douglas, K.; Pace, A.; Sandhu, R.; John, H.; Shand, L.; Lane, S.; Foster, H.; Griffiths, B.; Griffiths, I.; Kay, L.; Ng, W.-F.; Platt, P. N.; Walker, D. J.; Peterson, P.; Lorenzi, A.; Friswell, M.; Thompson, B.; Lee, M.; Pratt, A.; Hopkinson, N. D.; Dunne, C. A.; Quilty, B.; Marks, J.; Mukherjee, S.; Mulherin, D.; Chalam, S. V.; Price, T.; Sheeran, T.; Venkatachalam, S.; Baskar, S.; Al- Allaf, W.; McKenna, F.; Shah, P.; Filer, A.; Bowman, S. J.; Jobanputra, P.; Rankin, E. C.; Allen, M.; Chaudhuri, K.; Dubey, S.; Price‐Forbes, A.; Ravindran, J.; Samanta, A.; Sheldon, P.; Hassan, W.; Francis, J.; Kinder, A.; Neame, R.; Moorthy, A.; Bukhari, M.; Ottewell, L.; Palkonyai, E.; Hider, S.; Hassell, A.; Menon, A.; Dowson, C.; Kamath, S.; Packham, J.; Dutta, S.; Price, S.; Roddy, E.; Paskins, Z.; O'Reilly, D. T.; Rajagopal, V.; Bhagat, S.; Chattopadhyay, C. B.; Green, M.; Quinn, D.; Isdale, A.; Brown, A.; Saleem, B.; Foo, B.; Al Saffar, Z.; Koduri, G.

    2015-01-01

    Objective To investigate whether antidrug antibodies and/or drug non‐trough levels predict the long‐term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions. Methods A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme‐linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non‐trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated. Results Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment

  8. [Evaluation of the Fundamental Performance of 4 Latex Agglutination Reagents to Measure Anti-TP Antibody Concentration and Detailed Investigation of Decision-Mismatched Samples].

    Science.gov (United States)

    Ito, Atsushi; Niizeki, Noriyasu; Kurose, Hitomi; Yonezawa, Takatoshi; Sasaki, Rie; Tachibana, Mineji; Tomoda, Yutaka; Kino, Shuichi; Fujii, Satoshi

    2015-01-01

    Serological diagnosis of syphilis can be made by using the serological test for syphilis (STS) method for detecting a lipid antibody and Treponema pallidum (TP) method for detecting the anti-TP-specific antibody. In STS and TP methods, the basis using latex agglutination reaction has been used in many facilities. However, in latex agglutination, false-positive results due to non-specific reaction have sometimes been obtained in reactions of a routine laboratory test reagent detecting the anti-TP antibody used in our medical laboratory. We evaluated the fundamental performance of 4 reagents to measure anti-TP antibody concentration using latex agglutination: Reagents A, B, C and D produced by SEKISUI MEDICAL, FUJI REBIO, DENKA SEIKEN and SHINO TEST, respectively. We examined the correlations between Reagent A (routine laboratory test reagent) and Reagents B, C, and D in sera from 68 patients, and we performed additional investigation by using a neutralization test, immunochromatography, Western blotting, FTA-ABS (IgG), and STS method by an automatic analyzer for 13 decision-mismatched samples. The fundamental performance of each reagent was as good as that previously reported. Eight of the 13 decision-mismatched samples were false positives due to non-specific reaction of Reagent A. In latex agglutination non-specific reaction is inevitable. However, this study strongly suggests that using a neutralization test and immunochromatography that can be performed quickly is sufficient to verify whether positive reactions are true or false.

  9. Vertical Flume Testing of WIPP Surrogate Waste Materials

    Science.gov (United States)

    Herrick, C. G.; Schuhen, M.; Kicker, D.

    2013-12-01

    The Waste Isolation Pilot Plant (WIPP) is a U.S. Department of Energy geological repository for the permanent disposal of defense-related transuranic (TRU) waste. The waste is emplaced in rooms excavated in the bedded Salado salt formation at a depth of 655 m below ground surface. After emplacement of the waste, the repository will be sealed and decommissioned. The DOE demonstrates compliance with 40 CFR 194 by means of performance assessment (PA) calculations conducted by Sandia National Laboratories. WIPP PA calculations estimate the probability and consequences of radionuclide releases for a 10,000 year regulatory period. Human intrusion scenarios include cases in which a future borehole is drilled through the repository. Drilling mud flowing up the borehole will apply a hydrodynamic shear stress to the borehole wall which could result in erosion of the waste and radionuclides being carried up the borehole. WIPP PA uses the parameter TAUFAIL to represent the shear strength of the degraded waste. The hydrodynamic shear strength can only be measured experimentally by flume testing. Flume testing is typically performed horizontally, mimicking stream or ocean currents. However, in a WIPP intrusion event, the drill bit would penetrate the degraded waste and drilling mud would flow up the borehole in a predominantly vertical direction. In order to simulate this, a flume was designed and built so that the eroding fluid enters an enclosed vertical channel from the bottom and flows up past a specimen of surrogate waste material. The sample is pushed into the current by a piston attached to a step motor. A qualified data acquisition system controls and monitors the fluid's flow rate, temperature, pressure, and conductivity and the step motor's operation. The surrogate materials used correspond to a conservative estimate of degraded TRU waste at the end of the regulatory period. The recipes were previously developed by SNL based on anticipated future states of the waste

  10. 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 ...

  11. Priority wetland invertebrates as conservation surrogates.

    Science.gov (United States)

    Ormerod, S J; Durance, Isabelle; Terrier, Aurelie; Swanson, Alisa M

    2010-04-01

    Invertebrates are important functionally in most ecosystems, but seldom appraised as surrogate indicators of biological diversity. Priority species might be good candidates; thus, here we evaluated whether three freshwater invertebrates listed in the U.K. Biodiversity Action Plan indicated the richness, composition, and conservation importance of associated wetland organisms as defined respectively by their alpha diversity, beta diversity, and threat status. Sites occupied by each of the gastropods Segmentina nitida, Anisus vorticulus, and Valvata macrostoma had greater species richness of gastropods and greater conservation importance than other sites. Each also characterized species assemblages associated with significant variations between locations in alpha or beta diversity among other mollusks and aquatic macrophytes. Because of their distinct resource requirements, conserving the three priority species extended the range of wetland types under management for nature conservation by 18% and the associated gastropod niche-space by around 33%. Although nonpriority species indicated variations in richness, composition, and conservation importance among other organisms as effectively as priority species, none characterized such a wide range of high-quality wetland types. We conclude that priority invertebrates are no more effective than nonpriority species as indicators of alpha and beta diversity or conservation importance among associated organisms. Nevertheless, conserving priority species can extend the array of distinct environments that are protected for their specialized biodiversity and environmental quality. We suggest that this is a key role for priority species and conservation surrogates more generally, and, on our evidence, can best be delivered through multiple species with contrasting habitat requirements.

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

    Energy Technology Data Exchange (ETDEWEB)

    Malinowski, Kathleen T. [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); McAvoy, Thomas J. [Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); Department of Chemical and Biomolecular Engineering and Institute of Systems Research, University of Maryland, College Park, MD (United States); George, Rohini [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Dieterich, Sonja [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); D' Souza, Warren D., E-mail: wdsou001@umaryland.edu [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States)

    2012-04-01

    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.

  13. 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...

  14. Comparison of competitive ligand-binding assay and bioassay formats for the measurement of neutralizing antibodies to protein therapeutics.

    Science.gov (United States)

    Finco, Deborah; Baltrukonis, Daniel; Clements-Egan, Adrienne; Delaria, Kathy; Gunn, George R; Lowe, John; Maia, Mauricio; Wong, Teresa

    2011-01-25

    Administration of biological therapeutic proteins can lead to unwanted immunogenicity in recipients of these products. The assessment and characterization of such immune reactions can be helpful to better understand their clinical relevance and how they relate to patient safety and therefore, have become an integral part of a product development program for biological therapeutics. Testing for anti-drug antibodies (ADA) to biological/biotechnology-derived therapeutic proteins generally follows a tiered approach. Samples are initially screened for binding antibodies; presumptive positives are then confirmed in a confirmatory assay; subsequently, confirmed-positive samples may be further characterized by titration and with a neutralizing antibody (NAb) assay. Regulatory guidances on immunogenicity state that assessing the neutralizing capacity of antibodies should preferably be done using functional bioassays, while recognizing that competitive ligand-binding (CLB) assays may be substituted when neutralizing bioassays are inadequate or not feasible. This manuscript describes case studies from four companies in which CLB assays and functional bioassays were compared for their ability to detect neutralizing ADA against a variety of biotechnology-derived therapeutic proteins. Our findings indicate that CLB assays are comparable to bioassays for the detection of NAbs, in some cases offering better detection sensitivity, lower variability, and less matrix interference.

  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. A Method of Surrogate Model Construction which Leverages Lower-Fidelity Information using Space Mapping Techniques

    Science.gov (United States)

    2014-03-27

    errors found using the polynomial response surrogate (LS PRM ) overlaid on the data from the space-mapped (SM) surrogate...nonlinear space-mapped surrogate responses, with the least-squares PRM surrogate response plotted for comparison . . . . . . . . . . . . . . . . . 65 42...Percent error comparison between the least-squares space-mapping and the PRM surrogate models derived from samples in the second dataset

  17. Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gwon Jun; Hong, Key Sak; Choi, Kang Won; Lee, Kyu; Koh, Chang Soon; Lee, Mun Ho; Park, Sung Hoe; Chi, Je Geun; Lee, Sang Kook [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    The authors investigated the incidence of antithyroglobulin antibodies and antibodies and antimicrosomal antibodies measured by tanned red cell hemagglutination method in subjects suffering from various thyroid disorders. 1) In 15 normal patients, neither suffering from any thyroid diseases nor from any other autoimmune disorders, the antithyroglobulin antibodies were all negative, but the antimicrosomal antibody was positive only in one patient (6.7%). 2) The antithyroglobulin antibodies were positive in 31.5% (34 patients) of 108 patients with various thyroid diseases, and the antimicrosomal antibodies were positive in 37.0% (40 patients). 3) of the 25 patients with Graves' diseases, 7 patients (28.0%) showed positive for the antithyroglobulin antibodies, and 9 (36.0%) for the antimicrosomal antibodies. There was no definite differences in clinical and thyroid functions between the groups with positive and negative results. 4) Both antibodies were positive in 16 (88.9%) and 17 (94.4%) patients respectively among 18 patients with Hashimoto's thyroiditis, all of them were diagnosed histologically. 5) Three out of 33 patients with thyroid adenoma showed positive antibodies, and 3 of 16 patients with thyroid carcinoma revealed positive antibodies. 6) TRCH antibodies demonstrated negative results in 2 patients with subacute thyroiditis, but positive in one patient with idiopathic primary myxedema. 7) The number of patients with high titers(>l:802) was 16 for antithyroglobulin antibody, and 62.5% (10 patients) of which was Hashimoto's thyroiditis. Thirteen (65.0) of 20 patients with high titers (>l:802) for antimicrosomal antibody was Hashimoto's thyroiditis. TRCH test is a simple, sensitive method, and has high reliability and reproducibility. The incidences and titers of antithyroglobulin antibody and antimicrosomal antibody are especially high in Hashimoto's thyroiditis.

  18. Term clouds as surrogates for user generated speech

    NARCIS (Netherlands)

    M. Tsagkias; M. Larson; M. de Rijke

    2008-01-01

    User generated spoken audio remains a challenge for Automatic Speech Recognition (ASR) technology and content-based audio surrogates derived from ASR-transcripts must be error robust. An investigation of the use of term clouds as surrogates for podcasts demonstrates that ASR term clouds closely appr

  19. 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.

  20. Human surrogate neck response to +Gz vertical impact

    NARCIS (Netherlands)

    Rooij, L. van; Uittenbogaard, J.

    2011-01-01

    For the evaluation of impact scenarios with a substantial vertical component, the performance of current human surrogates - the RID 3D hardware dummy and two numerical human models - was evaluated. Volunteer tests with 10G and 6G pulses were compared to reconstructed tests with human surrogates. Add

  1. 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 ...

  2. 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.;

    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)...

  3. Surrogates of plutonium for detection equipment testing

    Science.gov (United States)

    Peerani, Paolo; Tomanin, Alice

    2011-10-01

    Fight against illicit trafficking of nuclear material relies on the possibility to detect nuclear material concealed in vehicles, people or cargo containers. This is done by equipping and training law enforcement and security staff in border stations or other points of access to strategic places and critical infrastructures with radiation detection equipment. The design, development, testing and evaluation of these instruments ideally require the use of real nuclear material to assess, verify and certify their detection performance. Availability of special nuclear material may be an issue, especially for industry, since only few specialized laboratories are licensed for such material. This paper tries to analyse and describe the possibility to use suitable surrogates that may replace the use of real nuclear material in testing the detection capabilities of instruments used in nuclear security.

  4. 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.

  5. Preclinical and human surrogate models of itch

    DEFF Research Database (Denmark)

    Hoeck, Emil August; Marker, Jens Broch; Gazerani, Parisa;

    2016-01-01

    Pruritus, or simply itch, is a debilitating symptom that significantly decreases the quality of life in a wide range of clinical conditions. While histamine remains the most studied mediator of itch in humans, treatment options for chronic itch, in particular antihistamine-resistant itch, are lim...... currently applied in animals and humans. This article is protected by copyright. All rights reserved.......Pruritus, or simply itch, is a debilitating symptom that significantly decreases the quality of life in a wide range of clinical conditions. While histamine remains the most studied mediator of itch in humans, treatment options for chronic itch, in particular antihistamine-resistant itch......, are limited. Relevant preclinical and human surrogate models of non-histaminergic itch are needed to accelerate the development of novel antipruritics and diagnostic tools. Advances in basic itch research have facilitated the development of diverse models of itch and associated dysesthesiae. While...

  6. Sheet metal forming optimization by using surrogate modeling techniques

    Science.gov (United States)

    Wang, Hu; Ye, Fan; Chen, Lei; Li, Enying

    2017-01-01

    Surrogate assisted optimization has been widely applied in sheet metal forming design due to its efficiency. Therefore, to improve the efficiency of design and reduce the product development cycle, it is important for scholars and engineers to have some insight into the performance of each surrogate assisted optimization method and make them more flexible practically. For this purpose, the state-of-the-art surrogate assisted optimizations are investigated. Furthermore, in view of the bottleneck and development of the surrogate assisted optimization and sheet metal forming design, some important issues on the surrogate assisted optimization in support of the sheet metal forming design are analyzed and discussed, involving the description of the sheet metal forming design, off-line and online sampling strategies, space mapping algorithm, high dimensional problems, robust design, some challenges and potential feasible methods. Generally, this paper provides insightful observations into the performance and potential development of these methods in sheet metal forming design.

  7. 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...

  8. Environmental diversity as a surrogate for species representation.

    Science.gov (United States)

    Beier, Paul; de Albuquerque, Fábio Suzart

    2015-10-01

    Because many species have not been described and most species ranges have not been mapped, conservation planners often use surrogates for conservation planning, but evidence for surrogate effectiveness is weak. Surrogates are well-mapped features such as soil types, landforms, occurrences of an easily observed taxon (discrete surrogates), and well-mapped environmental conditions (continuous surrogate). In the context of reserve selection, the idea is that a set of sites selected to span diversity in the surrogate will efficiently represent most species. Environmental diversity (ED) is a rarely used surrogate that selects sites to efficiently span multivariate ordination space. Because it selects across continuous environmental space, ED should perform better than discrete surrogates (which necessarily ignore within-bin and between-bin heterogeneity). Despite this theoretical advantage, ED appears to have performed poorly in previous tests of its ability to identify 50 × 50 km cells that represented vertebrates in Western Europe. Using an improved implementation of ED, we retested ED on Western European birds, mammals, reptiles, amphibians, and combined terrestrial vertebrates. We also tested ED on data sets for plants of Zimbabwe, birds of Spain, and birds of Arizona (United States). Sites selected using ED represented European mammals no better than randomly selected cells, but they represented species in the other 7 data sets with 20% to 84% effectiveness. This far exceeds the performance in previous tests of ED, and exceeds the performance of most discrete surrogates. We believe ED performed poorly in previous tests because those tests considered only a few candidate explanatory variables and used suboptimal forms of ED's selection algorithm. We suggest future work on ED focus on analyses at finer grain sizes more relevant to conservation decisions, explore the effect of selecting the explanatory variables most associated with species turnover, and investigate

  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. 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.

  11. Anthropometric surrogates for screening of low birth weight newborns: a community-based study.

    Science.gov (United States)

    Rustagi, Neeti; Prasuna, J G; Taneja, D K

    2012-03-01

    In developing countries, where about 75% of births occur at home or in the community, logistic problems prevent the weighing of every newborn child. This study compares various anthropometric surrogates for identification of low birth weight neonates. A longitudinal community based study was done in an urban resettlement colony and 283 singleton neonates within 7 days of birth were examined for the anthropometric measurements such as head, chest, mid upper arm circumference and foot length as a screening tool for low birth weight. Chest circumference measured within 7 days of birth appeared to be the most appropriate surrogate of low birth weight with highest sensitivity (75.4%), specificity (78.4%), and positive predictive value (48.9%) as compared with other anthropometric parameters. Low birth weight neonates in absence of weighing scales can be early identified by using simple anthropometric measurements for enhanced home-based care and timely referral.

  12. Impact of a Decision Aid on Surrogate Decision-makers’ Perceptions of Feeding Options for Patients with Dementia

    Science.gov (United States)

    Snyder, E. Amanda; Caprio, Anthony J.; Wessell, Kathryn; Lin, Feng Chang; Hanson, Laura C.

    2012-01-01

    Objective In advanced dementia, feeding problems are nearly universal, and families face difficult decisions about feeding options. Initial interviews for a randomized trial were used to describe surrogates’ perceptions feeding options, and to determine if a decision aid on feeding options in advanced dementia would improve knowledge, reduce expectation of benefit from tube feeding, and reduce conflict over treatment choices for persons with advanced dementia. Design Semi-structured interview with pre-post study design for surrogates in the intervention group. Setting Twenty-four skilled nursing facilities across North Carolina participating in a cluster randomized trial. Participants Two hundred fifty-five surrogate decision-makers for nursing home residents with advanced dementia and feeding problems, in control (n=129) and intervention (n=126) groups. Intervention For intervention surrogates only, an audiovisual-print decision aid provided information on dementia, feeding problems in dementia, advantages and disadvantages of feeding tubes or assisted oral feeding options and the role of surrogates in making these decisions. Measurements The interview included open-ended items asking surrogates to report advantages and disadvantages of tube feeding and assisted oral feeding. Knowledge of feeding options was measured with 19 true-false items, and items measuring expectation of benefit from tube feeding. Surrogates reported which of these two feeding options they preferred for the person with dementia, and how confident they were in this choice; their level of conflict about the choice was measured using the Decisional Conflict Scale. Results Prior to the decision aid, surrogates described advantages and disadvantages of assisted oral feeding and tube feeding in practical, ethical and medical terms. After review of the decision aid, intervention surrogates had improved knowledge scores (15.5 vs. 16.8; p<0.001), decreased expectation of benefits from tube feeding

  13. Characterization of monoclonal antibodies to an antigenic protein from Stachybotrys chartarum and its measurement in house dust.

    Science.gov (United States)

    Xu, Jianping; Liang, Yinan; Belisle, Donald; Miller, J David

    2008-03-20

    Using sera from atopic patients we have isolated an extracellular protein, which is antigenic in humans, from Stachybotrys chartarum sesu lato. Here we report the production of monoclonal antibodies to the protein and the development of a sensitive and specific assay to the target protein as well as analyses in house dust samples spiked with spores. The detection limit for the target antigen in house dust was approximately 0.2 ng/g dry weight house dust. This detection limit is comparable to those for house dust mite allergen and the allergen of the fungus Aspergillus fumigatus but lower than that for the fungus Alternaria alternata.

  14. Surrogate motherhood as a medical treatment procedure for women's infertility.

    Science.gov (United States)

    Jovic, Olga S

    2011-03-01

    The content of this work is conceived on the research of the consequences of surrogate motherhood as a process of assisted procreation, which represent a way of parenthood in cases when it is not possible to realize parenthood through a natural way. Surrogate motherhood is a process in which a woman (surrogate mother) agrees to carry a pregnancy with the intent to give the child to the couple with whom she has made a contract on surrogate maternity after the birth. This process of conception and birth makes the determination of the child's origin on its mother's side hard to determine, because of the distinction of the genetic and gestation phases of the two women. The concept of surrogate motherhood is to appear in two forms, depending on the existence or the non-existence of the genetic link between the surrogate mother and the child she gives birth to. There are gestation (full) and genetic (partial) surrogates each with different modalities and legal and ethical implications. In Serbia, Infertility Treatment and the Bio-medically Assisted Procreation Act from 2009 explicitly forbids surrogate motherhood, despite the fact that an infertile couple decides to use it, as a rule, after having tried all other treatment procedures, in cases when there is a diagnosis but the conventional treatment applied has not produced the desired results. Given the fact that no one has the right to ignore the sufferings of people who cannot procreate naturally, the medical practice and legal science in our country plead for a formulation of a legal framework in which to apply surrogate motherhood as an infertility treatment, under particular conditions.

  15. Development and validation of cell-based luciferase reporter gene assays for measuring neutralizing anti-drug antibodies against interferon beta

    DEFF Research Database (Denmark)

    Hermanrud, Christina; Ryner, Malin; Luft, Thomas

    2016-01-01

    Neutralizing anti-drug antibodies (NAbs) against therapeutic interferon beta (IFNβ) in people with multiple sclerosis (MS) are measured with cell-based bioassays. The aim of this study was to redevelop and validate two luciferase reporter-gene bioassays, LUC and iLite, using a cut-point approach...... was validated at Innsbruck Medical University (LUCIMU) and at Rigshospitalet (LUCRH) Copenhagen, and the iLite assay at Karolinska Institutet, Stockholm. For both assays, the optimal serum sample concentration in relation to sensitivity and recovery was 2.5% (v/v) in assay media. A Shapiro-Wilk test indicated...

  16. 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.

  17. Laboratory Testing of Waste Isolation Pilot Plant Surrogate Waste Materials

    Science.gov (United States)

    Broome, S.; Bronowski, D.; Pfeifle, T.; Herrick, C. G.

    2011-12-01

    The Waste Isolation Pilot Plant (WIPP) is a U.S. Department of Energy geological repository for the permanent disposal of defense-related transuranic (TRU) waste. The waste is emplaced in rooms excavated in the bedded Salado salt formation at a depth of 655 m below the ground surface. After emplacement of the waste, the repository will be sealed and decommissioned. WIPP Performance Assessment modeling of the underground material response requires a full and accurate understanding of coupled mechanical, hydrological, and geochemical processes and how they evolve with time. This study was part of a broader test program focused on room closure, specifically the compaction behavior of waste and the constitutive relations to model this behavior. The goal of this study was to develop an improved waste constitutive model. The model parameters are developed based on a well designed set of test data. The constitutive model will then be used to realistically model evolution of the underground and to better understand the impacts on repository performance. The present study results are focused on laboratory testing of surrogate waste materials. The surrogate wastes correspond to a conservative estimate of the degraded containers and TRU waste materials after the 10,000 year regulatory period. Testing consists of hydrostatic, uniaxial, and triaxial 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. Axial, lateral, and volumetric strain and axial and lateral 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

  18. 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.

  19. Thyroid Antibodies

    Science.gov (United States)

    ... e.g., at regular intervals after thyroid cancer treatment) Thyroid stimulating hormone receptor antibody, Thyroid Stimulating Immunoglobulin TRAb, TSHR Ab, TSI Graves disease When a person has symptoms of hyperthyroidism If a pregnant woman has a known autoimmune ...

  20. 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.

  1. Fernald Silos 1 & 2 Accelerated Waste Retrieval Program Surrogate Development

    Energy Technology Data Exchange (ETDEWEB)

    Mullen, O Dennis; Erian, Fadel F.

    2002-09-01

    Whitepaper describing the rationale and methodology for development of surrogates to be used for testing retrieval and processing systems for the DOE Fernald Silos 1 & 2 wastes. One significant updating/revision is expected.

  2. Using (d,pγ) as a Surrogate for Neutron Capture with ^75As

    Science.gov (United States)

    Peters, W. A.; Cizewski, J. A.; Hatarik, R.; O'Malley, P.; Vieira, D. J.; Jandel, M.; Wilhelmy, J. B.; Matei, C.; Bardayan, D. W.; Smith, M. S.; Pain, S. D.; Jones, K. L.; Moazen, B. H.; Chae, K. Y.; Kozub, R. L.; Shriner, J.; Blackmon, J. C.

    2008-10-01

    Arsenic is used as a radiochemical neutron fluence detector for nuclear reactions and other applications. The abundances of the residual isotopes ^73,74As allow one to calculate the total neutron activity through (n,2n) or (n,γ) reactions along the isotopic network chain. The neutron capture reaction cross sections used for these calculations cannot be directly measured for the radioactive isotopes, but the (d,pγ) reaction as a surrogate for the (n,γ) reaction can be measured. An experiment at Oak Ridge National Laboratory using As beams in inverse kinematics and a deuterated target will first measure the ^75As(d,pγ) reaction with stable beam to test the efficacy of our surrogate experimental techniques. With a tight geometry, eight ORRUBA silicon-strip detectors will detect recoil protons in coincidence with γ-rays detected by four high-purity segmented Ge clover detectors. Status and future goals for the As(d,pγ) surrogate campaign will be presented.

  3. Human surrogate models of neuropathic pain: validity and limitations.

    Science.gov (United States)

    Binder, Andreas

    2016-02-01

    Human surrogate models of neuropathic pain in healthy subjects are used to study symptoms, signs, and the hypothesized underlying mechanisms. Although different models are available, different spontaneous and evoked symptoms and signs are inducible; 2 key questions need to be answered: are human surrogate models conceptually valid, ie, do they share the sensory phenotype of neuropathic pain states, and are they sufficiently reliable to allow consistent translational research?

  4. Surrogate nutrition markers, malnutrition, and adequacy of nutrition support.

    Science.gov (United States)

    Seres, David S

    2005-06-01

    Surrogate nutrition markers are used to assess adequacy of nourishment and to define malnutrition despite evidence that fails to link nourishment, surrogate markers, and outcomes. Markers such as serum levels of albumin, prealbumin, transferrin, and IGF-1 and delayed hypersensitivity and total lymphocyte count may be valid to help stratify risk. However, it is not appropriate to consider these as markers of adequacy of nourishment in the sick patient.

  5. 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...

  6. THE SURROGATE COLONIZATION OF PALESTINE, 1917-1939

    OpenAIRE

    Atran, Scott

    1989-01-01

    The "surrogate colonization" of Palestine had a foreign power giving to a nonnative group rights over land occupied by an indigenous people. It thus brought into play the complementary and conflicting agendas of three culturally distinguishable parties: British, Jews and Arabs. Each party had both "externalist" [those with no sustained practical experience of day to day life in Palestine] and "internalist" representatives. The surrogate idea was based on a "strategic consensus" involving each...

  7. Financial Surrogate Decision Making: Lessons from Applied Experimental Philosophy.

    Science.gov (United States)

    Feltz, Adam

    2016-09-20

    An estimated 1 in 4 elderly Americans need a surrogate to make decisions at least once in their lives. With an aging population, that number is almost certainly going to increase. This paper focuses on financial surrogate decision making. To illustrate some of the empirical and moral implications associated with financial surrogate decision making, two experiments suggest that default choice settings can predictably influence some surrogate financial decision making. Experiment 1 suggested that when making hypothetical financial decisions, surrogates tended to stay with default settings (OR = 4.37, 95% CI 1.52, 12.48). Experiment 2 replicated and extended this finding suggesting that in a different context (OR = 2.27, 95% CI 1.1, 4.65). Experiment 2 also suggested that those who were more numerate were less likely to be influenced by default settings than the less numerate, but only when the decision is whether to "opt in" (p = .05). These data highlight the importance of a recent debate about "nudging." Defaults are common methods to nudge people to make desirable choices while allowing the liberty to choose otherwise. Some of the ethics of using default settings to nudge surrogate decision makers are discussed.

  8. 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.

  9. 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.

  10. Safety surrogate histograms (SSH): A novel real-time safety assessment of dilemma zone related conflicts at signalized intersections.

    Science.gov (United States)

    Ghanipoor Machiani, Sahar; Abbas, Montasir

    2016-11-01

    Drivers' indecisiveness in dilemma zones (DZ) could result in crash-prone situations at signalized intersections. DZ is to the area ahead of an intersection in which drivers encounter a dilemma regarding whether to stop or proceed through the intersection when the signal turns yellow. An improper decision to stop by the leading driver, combined with the following driver deciding to go, can result in a rear-end collision, unless the following driver recognizes a collision is imminent and adjusts his or her behavior at or shortly after the onset of yellow. Considering the significance of DZ-related crashes, a comprehensive safety measure is needed to characterize the level of safety at signalized intersections. In this study, a novel safety surrogate measure was developed utilizing real-time radar field data. This new measure, called safety surrogate histogram (SSH), captures the degree and frequency of DZ-related conflicts at each intersection approach. SSH includes detailed information regarding the possibility of crashes, because it is calculated based on the vehicles conflicts. An example illustrating the application of the new methodology at two study sites in Virginia is presented and discussed, and a comparison is provided between SSH and other DZ-related safety surrogate measures mentioned in the literature. The results of the study reveal the efficacy of the SSH as complementary to existing surrogate measures.

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

    Science.gov (United States)

    Peters, W. A.; Cizewski, J. A.; Hatarik, R.; O'Malley, P. D.; Jones, K. L.; Schmitt, K.; Moazen, B. H.; Chae, K. Y.; Pittman, S. T.; Kozub, R. L.; Vieira, D.; Jandel, M.; Wilhelmy, J. B.; Matei, C.; Escher, J.; Bardayan, D. W.; Pain, S. D.; Smith, M. S.

    2010-03-01

    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.

  12. Neutron Capture Surrogate Reaction on 75As in Inverse Kinematics Using (d,p(gamma))

    Energy Technology Data Exchange (ETDEWEB)

    Peters, W A; Cizewski, J A; Hatarik, R; O?Malley, P D; Jones, K L; Schmitt, K; Moazen, B H; Chae, K Y; Pittman, S T; Kozub, R L; Vieira, D; Jandel, M; Wilhelmy, J B; Matei, C; Escher, J; Bardayan, D W; Pain, S D; Smith, M S

    2009-11-09

    The {sup 75}As(d,p{gamma}) 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 {gamma}-ray from {sup 76}As in coincidence with ejected protons, from exciting {sup 76}As above the neutron separation energy populating a compound state, was measured. A tight geometry of four segmented germanium clover {gamma}-ray detectors together with eight ORRUBA-type silicon-strip charged-particle detectors was used to optimize geometric acceptance. The preliminary analysis of the {sup 75}As experiment, and the efficacy and future plans of the (d,p{gamma}) surrogate campaign in inverse kinematics, are discussed.

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

    Energy Technology Data Exchange (ETDEWEB)

    Peters, W. A. [Rutgers University; Cizewski, J. A. [Rutgers University; Hatarik, Robert [Rutgers University; O' Malley, Patrick [Rutgers University; Jones, K. L. [University of Tennessee; Schmitt, Kyle [University of Tennessee; Moazen, Brian [University of Tennessee; Chae, K. Y. [University of Tennessee; Pittman, S. T. [University of Tennessee, Knoxville (UTK); Kozub, R. L. [Tennessee Technological University; Vieira, D. J. [Los Alamos National Laboratory (LANL); Jandel, M. [Los Alamos National Laboratory (LANL); Wilhelmy, J. B. [Los Alamos National Laboratory (LANL); Matei, Catalin [Oak Ridge Associated Universities (ORAU); Escher, J. [Lawrence Livermore National Laboratory (LLNL); Bardayan, Daniel W [ORNL; Pain, Steven D [ORNL; Smith, Michael Scott [ORNL

    2010-01-01

    The 75As(d,p ) 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 -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 -ray detectors together with eight ORRUBA-type silicon-strip charged-particle detectors were used to optimize geometric acceptance. The preliminary analysis of the 75As experiment and the ecacy and future plans of the (d,p ) surrogate campaign in inverse kinematics are discussed.

  14. 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.

  15. Early change in proteinuria as a surrogate end point for kidney disease progression

    DEFF Research Database (Denmark)

    Inker, Lesley A; Levey, Andrew S; Pandya, Kruti;

    2014-01-01

    BACKGROUND: It is controversial whether proteinuria is a valid surrogate end point for randomized trials in chronic kidney disease. STUDY DESIGN: Meta-analysis of individual patient-level data. SETTING & POPULATION: Individual patient data for 9,008 patients from 32 randomized trials evaluating 5...... intervention types. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials of kidney disease progression until 2007 with measurements of proteinuria both at baseline and during the first year of follow-up, with at least 1 further year of follow-up for the clinical outcome. PREDICTOR: Early change...... statistical power for many chronic kidney disease clinical trials. CONCLUSIONS: These results provide new evidence supporting the use of an early reduction in proteinuria as a surrogate end point, but do not provide sufficient evidence to establish its validity in all settings....

  16. 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.

  17. 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.

  18. First steps in the standardization of immunoglobulin IgG myeloperoxidase-anti-neutrophil cytoplasmic antibody measurements.

    Science.gov (United States)

    Hutu, D P; Tuddenham, E; Monogioudi, E; Meroni, P; Schimmel, H; Sheldon, J; Zegers, I

    2016-02-01

    The standardization of immunoassays for immunoglobulin (Ig)G myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA) could contribute to a more accurate diagnosis and follow-up of small vessels-associated vasculitis, a systemic autoimmune disorder that leads to necrosis of blood vessel walls. Despite significant efforts by different groups, the level of comparability of results from commercially available immunoassays used for IgG MPO-ANCA detection is still poor. Therefore, the potential for improvement using reference materials was assessed. The evaluation of a set of 30 patient samples with 11 assays showed that differences between assays result in different interpretations for individual patients. Only 10 of 30 patient samples had the same clinical interpretation among 11 assays applying the cut-off values provided by each respective manufacturer. The correlation between results from 13 different assays was assessed in a pairwise manner. The correlation between results from patient samples was systematically very good for combinations of seven of those assays. The correlation of results ranged from reasonable to good for combinations with four other assays, therefore it should be possible to improve the comparability of results using a commutable reference material for calibration. Feasibility studies were conducted in order to find a reference material format most suitable for a calibrator. Two sets of candidate reference materials were produced from different raw materials, and assessed according to their suitability. A final format was selected, and a candidate reference material was produced.

  19. Evaluation of Humoral Immune Response of Cats to the Experimental Infection with the different Clonal Types of Toxoplasma gondii by Measurement of IgG Antibodies

    Directory of Open Access Journals (Sweden)

    Hosseininejad, M.

    2014-11-01

    Full Text Available Toxoplasma gondii is one of the most prevalent parasitic infections in world. Rh, NED and Me49 are of the most prevalent clonal types of the parasite isolated till now. Differences in pathogenicity and virulence of different types have been investigated in different studies. No controlled study was performed to compare the ability of different types to initiate humoral immune response. We investigated IgG antibody responses of kittens infected with each of these three clonal types. For this, experimental infection was performed using ME49 clonal type of T. gondii and humoral immune response (by measurement of IgG was detected and compared with the other two clonal types of the parasite. No antibodies were detectable at least until 7 days post infection for types Rh and NED while this period of no response was 19 days for ME49. Serum ELISA indices were significantly higher in kittens infected with Rh and NED tpes in comparison with ME49. The results of this study showed that humoral immune response of cats to ME49 starts with delay and are weaker than two other clonal types.

  20. Parameter identification and calibration of the Xin'anjiang model using the surrogate modeling approach

    Science.gov (United States)

    Ye, Yan; Song, Xiaomeng; Zhang, Jianyun; Kong, Fanzhe; Ma, Guangwen

    2014-06-01

    Practical experience has demonstrated that single objective functions, no matter how carefully chosen, prove to be inadequate in providing proper measurements for all of the characteristics of the observed data. One strategy to circumvent this problem is to define multiple fitting criteria that measure different aspects of system behavior, and to use multi-criteria optimization to identify non-dominated optimal solutions. Unfortunately, these analyses require running original simulation models thousands of times. As such, they demand prohibitively large computational budgets. As a result, surrogate models have been used in combination with a variety of multi-objective optimization algorithms to approximate the true Pareto-front within limited evaluations for the original model. In this study, multi-objective optimization based on surrogate modeling (multivariate adaptive regression splines, MARS) for a conceptual rainfall-runoff model (Xin'anjiang model, XAJ) was proposed. Taking the Yanduhe basin of Three Gorges in the upper stream of the Yangtze River in China as a case study, three evaluation criteria were selected to quantify the goodness-of-fit of observations against calculated values from the simulation model. The three criteria chosen were the Nash-Sutcliffe efficiency coefficient, the relative error of peak flow, and runoff volume (REPF and RERV). The efficacy of this method is demonstrated on the calibration of the XAJ model. Compared to the single objective optimization results, it was indicated that the multi-objective optimization method can infer the most probable parameter set. The results also demonstrate that the use of surrogate-modeling enables optimization that is much more efficient; and the total computational cost is reduced by about 92.5%, compared to optimization without using surrogate modeling. The results obtained with the proposed method support the feasibility of applying parameter optimization to computationally intensive simulation

  1. Surrogate Modeling of Deformable Joint Contact using Artificial Neural Networks

    Science.gov (United States)

    Eskinazi, Ilan; Fregly, Benjamin J.

    2016-01-01

    Deformable joint contact models can be used to estimate loading conditions for cartilage-cartilage, implant-implant, human-orthotic, and foot-ground interactions. However, contact evaluations are often so expensive computationally that they can be prohibitive for simulations or optimizations requiring thousands or even millions of contact evaluations. To overcome this limitation, we developed a novel surrogate contact modeling method based on artificial neural networks (ANNs). The method uses special sampling techniques to gather input-output data points from an original (slow) contact model in multiple domains of input space, where each domain represents a different physical situation likely to be encountered. For each contact force and torque output by the original contact model, a multi-layer feed-forward ANN is defined, trained, and incorporated into a surrogate contact model. As an evaluation problem, we created an ANN-based surrogate contact model of an artificial tibiofemoral joint using over 75,000 evaluations of a fine-grid elastic foundation (EF) contact model. The surrogate contact model computed contact forces and torques about 1000 times faster than a less accurate coarse grid EF contact model. Furthermore, the surrogate contact model was seven times more accurate than the coarse grid EF contact model within the input domain of a walking motion. For larger input domains, the surrogate contact model showed the expected trend of increasing error with increasing domain size. In addition, the surrogate contact model was able to identify out-of-contact situations with high accuracy. Computational contact models created using our proposed ANN approach may remove an important computational bottleneck from musculoskeletal simulations or optimizations incorporating deformable joint contact models. PMID:26220591

  2. 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.

  3. 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.

  4. Clinical implications of measuring drug and anti-drug antibodies by different assays when optimizing infliximab treatment failure in Crohn's disease

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Bendtzen, Klaus; Brynskov, Jørn;

    2014-01-01

    classifications. The four different assays did not differ in terms of the ability to predict response to interventions defined by the algorithm. CONCLUSIONS: Despite variable analytical properties, common assays result in similar classifications and interventions in patients with IFX treatment failure......OBJECTIVES: Cost-effective guidance of therapeutic strategy in Crohn's disease patients with secondary infliximab (IFX) treatment failure may be achieved by serum IFX and anti-IFX antibody (Ab) measurements by radioimmunoassay (RIA). This study investigated implications of using other techniques...... on classification of underlying mechanism for treatment failure in most cases (79-94%). The majority (74-88%) failed IFX owing to pharmacodynamic problems, or had noninflammatory pathophysiology for symptoms resembling relapse. Applied threshold for therapeutic vs. subtherapeutic IFX level influenced...

  5. Searching for Dynamical Earthquake Precursors with Surrogate Data

    Science.gov (United States)

    Lynch, J.; Revenaugh, J.; Georgopoulos, A.

    2007-12-01

    Surrogate data methods are resampling techniques related to the modern statistical bootstrap. The nonlinear dynamics community has promoted surrogate data as a useful tool for establishing the presence of nonlinear dynamics in experimental observations before applying more specific techniques such as nonlinear prediction. We propose to use surrogate data tests to search for evidence of transient nonlinear dynamics in seismographic data that act as a proxy for earthquake triggering mechanisms, such as fluid flow in the fault zone, failure cascades and slow prefatory slip, that signal changes in the coupling between geological boundaries. We will analyze the vertical component of broadband seismographic data recorded at 20Hz by the CI network of approximately 100 stations located throughout Southern California. We will focus on a period of six hours prior to seismic events of magnitude 4-5 located inside the CI network. Each seismographic record will be scanned for short, non-overlapping segments that pass a moderate stationarity criterion. We will then apply surrogate tests to each qualifying segment using three discriminating statistics: time reversal asymmetry, delay vector variance and zeroth-order nonlinear prediction error. We will correlate the results with known seismic activity and examine the spatial and temporal distribution of the surrogate test results for potential dynamical earthquake precursors.

  6. Biodegradation of naphthenic acid surrogates by axenic cultures.

    Science.gov (United States)

    Yue, Siqing; Ramsay, Bruce A; Ramsay, Juliana A

    2015-07-01

    This is the first study to report that bacteria from the genera Ochrobactrum, Brevundimonas and Bacillus can be isolated by growth on naphthenic acids (NAs) extracted from oil sands process water (OSPW). These pure cultures were screened for their ability to use a range of aliphatic, cyclic and aromatic NA surrogates in 96-well microtiter plates using water-soluble tetrazolium redox dyes (Biolog Redox Dye H) as the indicator of metabolic activity. Of the three cultures, Ochrobactrum showed most metabolic activity on the widest range of NA surrogates. Brevundomonas and especially Ochrobactrum had higher metabolic activity on polycyclic aromatic compounds than other classes of NA surrogates. Bacillus also oxidized a wide range of NA surrogates but not as well as Ochrobactrum. Using this method to characterize NA utilisation, one can identify which NAs or NA classes in OSPW are more readily degraded. Since aromatic NAs have been shown to have an estrogenic effect and polycyclic monoaromatic compounds have been suggested to pose the greatest environmental threat among the NAs, these bacterial genera may play an important role in detoxification of OSPW. Furthermore, this study demonstrates that bacteria belonging to the genera Ochrobactrum and Bacillus can also degrade surrogates of tricyclic NAs.

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

    Science.gov (United States)

    Bilicz, S.; Lambert, M.; Gyimóthy, Sz

    2010-07-01

    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.

  8. Asymptotic ideal observers and surrogate figures of merit for signal detection with list-mode data.

    Science.gov (United States)

    Clarkson, Eric

    2012-10-01

    The asymptotic form for the likelihood ratio is derived for list-mode data generated by an imaging system viewing a possible signal in a randomly generated background. This calculation provides an approximation to the likelihood ratio that is valid in the limit of large number of list entries, i.e., a large number of photons. These results are then used to derive surrogate figures of merit, quantities that are correlated with ideal-observer performance on detection tasks, as measured by the area under the receiver operating characteristic curve, but are easier to compute. A key component of these derivations is the determination of asymptotic forms for the Fisher information for the signal amplitude in the limit of a large number of counts or a long exposure time. This quantity is useful in its own right as a figure of merit (FOM) for the task of estimating the signal amplitude. The use of the Fisher information in detection tasks is based on the fact that it provides an approximation for ideal-observer detectability when the signal is weak. For both the fixed-count and fixed-time cases, four surrogate figures of merit are derived. Two are based on maximum likelihood reconstructions; one uses the characteristic functional of the random backgrounds. The fourth surrogate FOM is identical in the two cases and involves an integral over attribute space for each of a randomly generated sequence of backgrounds.

  9. Economic Statistical Design of Variable Sampling Interval X¯$\\overline X $ Control Chart Based on Surrogate Variable Using Genetic Algorithms

    Directory of Open Access Journals (Sweden)

    Lee Tae-Hoon

    2016-12-01

    Full Text Available In many cases, a X¯$\\overline X $ control chart based on a performance variable is used in industrial fields. Typically, the control chart monitors the measurements of a performance variable itself. However, if the performance variable is too costly or impossible to measure, and a less expensive surrogate variable is available, the process may be more efficiently controlled using surrogate variables. In this paper, we present a model for the economic statistical design of a VSI (Variable Sampling Interval X¯$\\overline X $ control chart using a surrogate variable that is linearly correlated with the performance variable. We derive the total average profit model from an economic viewpoint and apply the model to a Very High Temperature Reactor (VHTR nuclear fuel measurement system and derive the optimal result using genetic algorithms. Compared with the control chart based on a performance variable, the proposed model gives a larger expected net income per unit of time in the long-run if the correlation between the performance variable and the surrogate variable is relatively high. The proposed model was confined to the sample mean control chart under the assumption that a single assignable cause occurs according to the Poisson process. However, the model may also be extended to other types of control charts using a single or multiple assignable cause assumptions such as VSS (Variable Sample Size X¯$\\overline X $ control chart, EWMA, CUSUM charts and so on.

  10. An efficient surrogate-based simulation-optimization method for calibrating a regional MODFLOW model

    Science.gov (United States)

    Chen, Mingjie; Izady, Azizallah; Abdalla, Osman A.

    2017-01-01

    Simulation-optimization method entails a large number of model simulations, which is computationally intensive or even prohibitive if the model simulation is extremely time-consuming. Statistical models have been examined as a surrogate of the high-fidelity physical model during simulation-optimization process to tackle this problem. Among them, Multivariate Adaptive Regression Splines (MARS), a non-parametric adaptive regression method, is superior in overcoming problems of high-dimensions and discontinuities of the data. Furthermore, the stability and accuracy of MARS model can be improved by bootstrap aggregating methods, namely, bagging. In this paper, Bagging MARS (BMARS) method is integrated to a surrogate-based simulation-optimization framework to calibrate a three-dimensional MODFLOW model, which is developed to simulate the groundwater flow in an arid hardrock-alluvium region in northwestern Oman. The physical MODFLOW model is surrogated by the statistical model developed using BMARS algorithm. The surrogate model, which is fitted and validated using training dataset generated by the physical model, can approximate solutions rapidly. An efficient Sobol' method is employed to calculate global sensitivities of head outputs to input parameters, which are used to analyze their importance for the model outputs spatiotemporally. Only sensitive parameters are included in the calibration process to further improve the computational efficiency. Normalized root mean square error (NRMSE) between measured and simulated heads at observation wells is used as the objective function to be minimized during optimization. The reasonable history match between the simulated and observed heads demonstrated feasibility of this high-efficient calibration framework.

  11. Antiparietal cell antibody test

    Science.gov (United States)

    APCA; Anti-gastric parietal cell antibody; Atrophic gastritis - anti-gastric parietal cell antibody; Gastric ulcer - anti-gastric parietal cell antibody; Pernicious anemia - anti-gastric parietal cell antibody; ...

  12. Surrogate modeling for initial rotational stiffness of welded tubular joints

    Directory of Open Access Journals (Sweden)

    M.R. Garifullin

    2016-10-01

    Full Text Available Recently, buildings and structures erected in Russia and abroad have to comply with stringent economic requirements. Buildings should not only be reliable and safe, have a beautiful architectural design, but also meet the criteria of rationality and energy efficiency. In practice, this usually means the need for additional comparative analysis in order to determine the optimal solution to the engineering task. Usually such an analysis is time-consuming and requires huge computational efforts. In this regard, surrogate modeling can be an effective tool for solving such problems. This article provides a brief description of surrogate models and the basic techniques of their construction, describes the construction process of a surrogate model to calculate initial rotational stiffness of welded RHS joints made of high strength steel (HSS.

  13. Love as a regulative ideal in surrogate decision making.

    Science.gov (United States)

    Stonestreet, Erica Lucast

    2014-10-01

    This discussion aims to give a normative theoretical basis for a "best judgment" model of surrogate decision making rooted in a regulative ideal of love. Currently, there are two basic models of surrogate decision making for incompetent patients: the "substituted judgment" model and the "best interests" model. The former draws on the value of autonomy and responds with respect; the latter draws on the value of welfare and responds with beneficence. It can be difficult to determine which of these two models is more appropriate for a given patient, and both approaches may seem inadequate for a surrogate who loves the patient. The proposed "best judgment" model effectively draws on the values incorporated in each of the traditional standards, but does so because these values are important to someone who loves a patient, since love responds to the patient as the specific person she is.

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

    DEFF Research Database (Denmark)

    Søndergaard, Jacob

    2003-01-01

    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...... 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...

  15. 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

  16. 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.

  17. 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

  18. Using patient management as a surrogate for patient health outcomes in diagnostic test evaluation

    Directory of Open Access Journals (Sweden)

    Staub Lukas P

    2012-02-01

    Full Text Available Abstract Background Before a new test is introduced in clinical practice, evidence is needed to demonstrate that its use will lead to improvements in patient health outcomes. Studies reporting test accuracy may not be sufficient, and clinical trials of tests that measure patient health outcomes are rarely feasible. Therefore, the consequences of testing on patient management are often investigated as an intermediate step in the pathway. There is a lack of guidance on the interpretation of this evidence, and patient management studies often neglect a discussion of the limitations of measuring patient management as a surrogate for health outcomes. Methods We discuss the rationale for measuring patient management, describe the common study designs and provide guidance about how this evidence should be reported. Results Interpretation of patient management studies relies on the condition that patient management is a valid surrogate for downstream patient benefits. This condition presupposes two critical assumptions: the test improves diagnostic accuracy; and the measured changes in patient management improve patient health outcomes. The validity of this evidence depends on the certainty around these critical assumptions and the ability of the study design to minimise bias. Three common designs are test RCTs that measure patient management as a primary endpoint, diagnostic before-after studies that compare planned patient management before and after testing, and accuracy studies that are extended to report on the actual treatment or further tests received following a positive and negative test result. Conclusions Patient management can be measured as a surrogate outcome for test evaluation if its limitations are recognised. The potential consequences of a positive and negative test result on patient management should be pre-specified and the potential patient benefits of these management changes clearly stated. Randomised comparisons will provide

  19. 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."

  20. Alternative cokriging model for variable-fidelity surrogate modeling

    DEFF Research Database (Denmark)

    Han, Zhong Hua; Zimmermann, Ralf; Goertz, Stefan

    2012-01-01

    An alternative approach for the construction of the cokriging covariance matrix is developed and a more practical cokriging method in the context of surrogate-based analysis and optimization is proposed. The developed cokriging method is validated against an analytical problem and applied to cons...

  1. 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.

  2. Bending testing and characterization of surrogate nuclear fuel rods made of Zircaloy-4 cladding and aluminum oxide pellets

    Science.gov (United States)

    Wang, Hong; Wang, Jy-An John

    2016-10-01

    Behavior of surrogate nuclear fuel rods made of Zircaloy-4 (Zry-4) cladding with alumina pellets under reversed cyclic bending was studied. Tests were performed under load or moment control at 5 Hz. The surrogate rods fractured under moment amplitudes greater than 10.16 Nm with fatigue lives between 2.4 × 103 and 2.2 × 106 cycles. Fatigue response of Zry-4 cladding was characterized by using flexural rigidity. Degradation of flexural rigidity was shown to depend on the moment and the prefatigue condition of specimens. Pellet-to-pellet interface (PPI), pellet-to-cladding interface (PCI), and pellet condition affect surrogate rod failure. Both debonding of PPI/PCI and pellet fracturing contribute to surrogate rod bending fatigue. The effect of sensor spacing on curvature measurement using three-point deflections was studied; the method based on effective gauge length is effective in sensor spacing correction. The database developed and the understanding gained in this study can serve as input to analysis of SNF (spent nuclear fuel) vibration integrity.

  3. 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.

  4. 装备采购招标代理工作管理%Management of Equipment Procurement Tendering Surrogate Work

    Institute of Scientific and Technical Information of China (English)

    周静; 李晓松; 刘杰

    2016-01-01

    The paper defines the concept of equipment procurement tendering surrogate and analyzes the necessity of introducing tendering surrogate into equipment procurement.Combined with the main prac-tices and existing problems,it puts forward the general ideas and specific measures on how to strengthen the management of equipment procurement tendering surrogate work,which provides reference for the sci-entific management of equipment procurement tendering surrogate organizations.%界定了装备采购招标代理的概念,分析了装备采购引入招标代理的必要性,结合目前装备采购招标代理的主要做法及存在问题,提出了加强装备采购招标代理工作管理的总体思路与具体举措,为实现装备采购招标代理机构的科学管理提供参考。

  5. 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

  6. 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

  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. 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.

  9. Comparison of antibody-conjugated magnetic immunoassay and liquid chromatography-tandem mass spectrometry for the measurement of cyclosporine and tacrolimus in whole blood.

    Science.gov (United States)

    Cangemi, G; Barco, S; Bonifazio, P; Maffia, A; Agazzi, A; Melioli, G

    2013-01-01

    The aim of this work is to compare the results of a commercially available liquid chromatography tandem mass spectrometry (LC-MS/MS) method in a clinical pathology laboratory for routine Therapeutic Drug Monitoring (TDM) of cyclosporine (CsA) and tacrolimus (Tacr) in pediatric patients with those obtained with the current antibody-conjugated magnetic immunoassay (ACMIA). Whole blood levels of CsA (n= 135) and Tacr (n=100) were sequentially analyzed by using ACMIA and LC-MS/MS on pediatric transplanted patients. The differences were analyzed by using the Passing Bablok regression analysis and the Bland and Altman test. The LC-MS/MS method showed excellent reproducibility and lower limits of quantification compared to the ACMIA. A linear relationship between ACMIA and LC-MS/MS was obtained for both CsA Tacr. No significant inter-method biases were observed. The analytical performances of the LC-MS/MS method make it suitable for the accurate measurement of CsA and Tacr in pediatric transplanted patients. However ACMIA results are also accurate and reliable. For this reason the choice of the method to be used in a routine clinical pathology laboratory can be made on the bases of non-analytical considerations such as costs, organization, availability of skilled personnel.

  10. On the use of abiotic surrogates to describe marine benthic biodiversity

    Science.gov (United States)

    McArthur, M. A.; Brooke, B. P.; Przeslawski, R.; Ryan, D. A.; Lucieer, V. L.; Nichol, S.; McCallum, A. W.; Mellin, C.; Cresswell, I. D.; Radke, L. C.

    2010-06-01

    A growing need to manage marine biodiversity sustainably at local, regional and global scales cannot be met by applying existing biological data. Abiotic surrogates of biodiversity are thus increasingly valuable in filling the gaps in our knowledge of biodiversity patterns, especially identification of hotspots, habitats needed by endangered or commercially valuable species and systems or processes important to the sustained provision of ecosystem services. This review examines the use of abiotic variables as surrogates for patterns in benthic biodiversity with particular regard to how variables are tied to processes affecting species richness and how easily those variables can be measured at scales relevant to resource management decisions. Direct gradient variables such as salinity, oxygen concentration and temperature can be strong predictive variables for larger systems, although local stability of water quality may prevent usefulness of these factors at fine spatial scales. Biological productivity has complex relationships with benthic biodiversity and although the development of local and regional models cannot accurately predict outside the range of their biological sampling, remote sensing may provide useful information. Indeed, interpolated values are available for much of the world's seas, and these are continually being refined by the collection of remote sensing and field data. Sediment variables often exhibit complex relationships with benthic biodiversity. The strength of the relationship between any one sediment variable and biodiversity may depend on the state of another sediment variable in that system. Percentage mud, percentage gravel, rugosity and compaction hold the strongest independent predictive power. Rugosity and the difference between gravel and finer sediments can be established using acoustic methods, but to quantify grain size and measure compaction, a sample is necessary. Pure spatial variables such as latitude, longitude and depth

  11. Developing the (d,p γ) reaction as a surrogate for (n, γ) in inverse kinematics

    Science.gov (United States)

    Lepailleur, Alexandre; Baugher, Travis; Cizewski, Jolie; Ratkiewicz, Andrew; Walter, David; Pain, Steven; Smith, Karl; Garland, Heather; Goddess Collaboration

    2016-09-01

    The r-process that proceeds via (n, γ) reactions on neutron-rich nuclei is responsible for the synthesis of about half of the elements heavier than iron. Because (n, γ) measurements on short-lived isotopes are not possible, the (d,p γ) reaction is being investigated as a surrogate for (n, γ). Of particular importance is validating a surrogate in inverse kinematics. Therefore, the 95Mo(d,p γ) reaction was measured in inverse kinematics with stable beams from ATLAS and CD2 targets. Reaction protons were measured in coincidence with gamma rays with GODDESS - Gammasphere ORRUBA: Dual Detectors for Experimental Structure Studies. The Oak Ridge Rutgers University Barrel Array (ORRUBA) of position-sensitive silicon strip detectors was augmented with annular arrays of segmented strip detectors at backward and forward angles, resulting in a high-angular coverage for light ejectiles. Preliminary results from the 95Mo(d,p γ) study will be presented. This work was supported in part by the U.S. Department of Energy and National Science Foundation.

  12. Amount and avidity of antibody to Escherichia coli O antigen measured with the ammonium sulphate precipitation technique in children with urinary tract infections.

    Science.gov (United States)

    Ahlstedt, S; Jodal, U; Hanson, L A

    1975-01-01

    The antibody amounts and avidities were analyzed in 13 patients with acute primary pyelonephritis, 11 patients with acute primary cystitis, and one with ureterocele and recurrent infections, using the ammonium sulphate precipitation (ASP) technique. The ASP titrations did not discriminate as well between pyelonephritis and cystitis as do the determinations with the indirect hemagglutination technique. The increase of antibody titer and avidity detected by the ASP method in some of the cystitis patients suggested a deeper tissue involvement in some cases resulting in antibodies demonstrable with this technique. Since control patients also showed a somewhat heterogenous antibody response regarding titer and avidity it cannot be excluded that stimulation by Escherichia coli antigens in the gut is detected by the ASP method.

  13. 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 PSC...

  14. Ion chemistry of VX surrogates and ion energetics properties of VX: new suggestions for VX chemical ionization mass spectrometry detection.

    Science.gov (United States)

    Midey, Anthony J; Miller, Thomas M; Viggiano, A A; Bera, Narayan C; Maeda, Satoshi; Morokuma, Keiji

    2010-05-01

    Room temperature rate constants and product ion branching ratios have been measured for the reactions of numerous positive and negative ions with VX chemical warfare agent surrogates representing the amine (triethylamine) and organophosphonate (diethyl methythiomethylphosphonate (DEMTMP)) portions of VX. The measurements have been supplemented by theoretical calculations of the proton affinity, fluoride affinity, and ionization potential of VX and the simulants. The results show that many proton transfer reactions are rapid and that the proton affinity of VX is near the top of the scale. Many proton transfer agents should detect VX selectively and sensitively in chemical ionization mass spectrometers. Charge transfer with NO(+) should also be sensitive and selective since the ionization potential of VX is small. The surrogate studies confirm these trends. Limits of detection for commercial and research grade CIMS instruments are estimated at 80 pptv and 5 ppqv, respectively.

  15. 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.

  16. 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.

  17. Thermal measurements and computational simulations of three-phase (CeO2-MgAl2O4-CeMgAl11O19) and four-phase (3Y-TZP-Al2O3-MgAl2O4-LaPO4) composites as surrogate inert matrix nuclear fuel

    Science.gov (United States)

    Angle, Jesse P.; Nelson, Andrew T.; Men, Danju; Mecartney, Martha L.

    2014-11-01

    This study investigates the temperature dependent thermal conductivity of multiphase ceramic composites for simulated inert matrix nuclear fuel. Fine grained composites were made of CeO2-MgAl2O4-CeMgAl11O19 or 3Y-TZP-Al2O3-MgAl2O4-LaPO4. CeO2 and 3Y-TZP are used as UO2 surrogates due to their similar structures and low thermal conductivities. Laser flash analysis from room temperature to 1273 K (1000 °C) was used to determine the temperature dependent thermal conductivity. A computational approach using Object Oriented Finite Element Analysis Version 2 (OOF2) was employed to simulate the composite thermal conductivity based on the microstructure. Observed discrepancies between experimental and simulated thermal conductivities at low temperature may be due to Kapitza resistance; however, there is less than 3% deviation between models and experiments above 673 K (400 °C) for both compositions. When the surrogate phase was replaced with UO2 in the computational model for the four-phase composite, a 12-16% increase in thermal conductivity resulted compared to single phase UO2, in the range of 673-1273 K (400-1000 °C). This computational approach may be potentially viable for the high-throughput evaluation of composite systems and the strategic selection of inert phases without extensive sample fabrication during the initial development stages of composite nuclear fuel design.

  18. 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.

  19. 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.

  20. 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.

  1. The effectiveness of marine reserve systems constructed using different surrogates of biodiversity.

    Science.gov (United States)

    Sutcliffe, P R; Klein, C J; Pitcher, C R; Possingham, H P

    2015-06-01

    Biological sampling in marine systems is often limited, and the cost of acquiring new data is high. We sought to assess whether systematic reserves designed using abiotic domains adequately conserve a comprehensive range of species in a tropical marine inter-reef system. We based our assessment on data from the Great Barrier Reef, Australia. We designed reserve systems aiming to conserve 30% of each species based on 4 abiotic surrogate types (abiotic domains; weighted abiotic domains; pre-defined bioregions; and random selection of areas). We evaluated each surrogate in scenarios with and without cost (cost to fishery) and clumping (size of conservation area) constraints. To measure the efficacy of each reserve system for conservation purposes, we evaluated how well 842 species collected at 1155 sites across the Great Barrier Reef seabed were represented in each reserve system. When reserve design included both cost and clumping constraints, the mean proportion of species reaching the conservation target was 20-27% higher for reserve systems that were biologically informed than reserves designed using unweighted environmental data. All domains performed substantially better than random, except when there were no spatial or economic constraints placed on the system design. Under the scenario with no constraints, the mean proportion of species reaching the conservation target ranged from 98.5% to 99.99% across all surrogate domains, whereas the range was 90-96% across all domains when both cost and clumping were considered. This proportion did not change considerably between scenarios where one constraint was imposed and scenarios where both cost and clumping constraints were considered. We conclude that representative reserve systems can be designed using abiotic domains; however, there are substantial benefits if some biological information is incorporated.

  2. 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.

  3. Biopolicies and biotechnologies: reflections on surrogate maternity in India

    OpenAIRE

    Mónica Amador

    2010-01-01

    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,19...

  4. Surrogate fuel assembly multi-axis shaker tests to simulate normal conditions of rail and truck transport

    Energy Technology Data Exchange (ETDEWEB)

    McConnell, Paul E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Koenig, Greg John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Uncapher, William Leonard [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Grey, Carissa [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Engelhardt, Charles [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Saltzstein, Sylvia J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Sorenson, Ken B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-05-01

    This report describes the third set of tests (the “DCLa shaker tests”) of an instrumented surrogate PWR fuel assembly. The purpose of this set of tests was to measure strains and accelerations on Zircaloy-4 fuel rods when the PWR assembly was subjected to rail and truck loadings simulating normal conditions of transport when affixed to a multi-axis shaker. This is the first set of tests of the assembly simulating rail normal conditions of transport.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. [Antinuclear antibodies].

    Science.gov (United States)

    Cabiedes, Javier; Núñez-Álvarez, Carlos A

    2010-01-01

    Anti-nuclear antibodies (ANA) are immunoglobulin directed against autologous cell nuclear and cytoplasmic components. Besides the autoimmune ANA there are other ANA that can be detected in circulation, like natural and infectious ANA. Because of its high sensibility, detection of the ANA must be done by indirect immunofluorescence (IIF) as screening test and all of those positive samples are convenient to confirm its specificity by ELISA, western blot or other techniques. Positive ANA detected by IIF must be evaluated taking in to account the pattern and titer. The following recommended step is the specificity characterization (reactivity against extractable nuclear antigens [ENA], dsDNA, etc.) which is useful for the diagnosis and follow up of patients with autoimmune diseases, and by such reasoning, its detection must be performed in an orderly and reasonable way using guides or strategies focused to the good use and interpretation of the autoantibodies. The objective of this review is to present a compilation of the literature and our experience in the detection and study of the ANA.

  11. Effectiveness of biological surrogates for predicting patterns of marine biodiversity: a global meta-analysis.

    Directory of Open Access Journals (Sweden)

    Camille Mellin

    Full Text Available The use of biological surrogates as proxies for biodiversity patterns is gaining popularity, particularly in marine systems where field surveys can be expensive and species richness high. Yet, uncertainty regarding their applicability remains because of inconsistency of definitions, a lack of standard methods for estimating effectiveness, and variable spatial scales considered. We present a Bayesian meta-analysis of the effectiveness of biological surrogates in marine ecosystems. Surrogate effectiveness was defined both as the proportion of surrogacy tests where predictions based on surrogates were better than random (i.e., low probability of making a Type I error; P and as the predictability of targets using surrogates (R(2. A total of 264 published surrogacy tests combined with prior probabilities elicited from eight international experts demonstrated that the habitat, spatial scale, type of surrogate and statistical method used all influenced surrogate effectiveness, at least according to either P or R(2. The type of surrogate used (higher-taxa, cross-taxa or subset taxa was the best predictor of P, with the higher-taxa surrogates outperforming all others. The marine habitat was the best predictor of R(2, with particularly low predictability in tropical reefs. Surrogate effectiveness was greatest for higher-taxa surrogates at a <10-km spatial scale, in low-complexity marine habitats such as soft bottoms, and using multivariate-based methods. Comparisons with terrestrial studies in terms of the methods used to study surrogates revealed that marine applications still ignore some problems with several widely used statistical approaches to surrogacy. Our study provides a benchmark for the reliable use of biological surrogates in marine ecosystems, and highlights directions for future development of biological surrogates in predicting biodiversity.

  12. Measurement of serum antibodies against NY-ESO-1 by ELISA: A guide for the treatment of specific immunotherapy for patients with advanced colorectal cancer.

    Science.gov (United States)

    Long, Yan-Yan; Wang, Yu; Huang, Qian-Rong; Zheng, Guang-Shun; Jiao, Shun-Chang

    2014-10-01

    NY-ESO-1 has been identified as one of the most immunogenic antigens; thus, is a highly attractive target for cancer immunotherapy. The present study analyzed the expression of serum antibodies (Abs) against NY-ESO-1 in patients with advanced colorectal cancer (CRC), with the aim of guiding the treatment of NY-ESO-1-based specific-immunotherapy for these patients. Furthermore, the present study was the first to evaluate the kinetic expression of anti-NY-ESO-1 Abs and investigate the possible influencing factors. A total of 239 serum samples from 155 pathologically confirmed patients with advanced CRC (stages III and IV) were collected. The presence of spontaneous Abs against NY-ESO-1 was analyzed using an enzyme-linked immunosorbent assay (ELISA). The results demonstrated that 24.5% (38/155) of the investigated patients were positive for NY-ESO-1-specific Abs. No statistically significant correlations were identified between the expression of anti-NY-ESO-1 Abs and clinicopathological parameters, including age and gender, location, grading, local infiltration, lymph node status, metastatic status and K-ras mutation status (P>0.05). In 59 patients, the kinetic expression of anti-NY-ESO-1 Abs was analyzed, of which 14 patients were initially positive and 45 patients were initially negative. Notably, 16/59 (27.1%) patients changed their expression status during the study period, and the initially positive patients were more likely to change compared with the initially negative patients (85.7 vs. 8.8%; PESO-1 by ELISA is an easy and feasible method. The high expression rate of NY-ESO-1-specific Abs in CRC patients indicates that measuring the levels of serum Abs against NY-ESO-1 may guide the treatment of NY-ESO-1-based specific immunotherapy for patients with advanced CRC.

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

    Science.gov (United States)

    Laine, Juha; Jokiranta, T Sakari; Eklund, Kari K; Väkeväinen, Merja; Puolakka, Kari

    2016-01-01

    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 exceeded in real-life clinical practice. This study indicates that routine monitoring of drug level and ADAbs is cost-beneficial in clinical practice, thereby improving the decision-making process in using TNF-α blockers.

  14. Deducing the 236Pu(n,f) and 237Pu(n,f) cross sections via the surrogate ratio method

    Science.gov (United States)

    Hughes, R. O.; Beausang, C. W.; Ross, T. J.; Burke, J. T.; Casperson, R. J.; McCleskey, M.; Cooper, N.; Escher, J. E.; Gell, K. B.; Good, E.; Humby, P.; Saastimoinen, A.; Tarlow, T. D.

    2013-10-01

    The short half-lives associated with certain minor actinide nuclei that are relevant to stockpile stewardship pursuits and the development of next-generation nuclear reactors make direct neutron measurements very challenging. In certain cases, a stable beam and target ``surrogate reaction'' can be used in lieu of the neutron-induced reaction, and the (n,f) cross section can then be deduced indirectly. Agreement between surrogate and direct measurements for (n,f) cross sections in actinide nuclei is usually within 10%. The present work reports on the measurement of the 236Pu(n,f) and 237Pu(n,f) cross sections via 239Pu(p,tf) and 239Pu(p,df) surrogate reactions, respectively. The experiment was performed at the Texas A&M University Cyclotron Facility using a 28.5 MeV proton beam to bombard 239Pu and 235U targets. Outgoing light ions were detected in coincidence with fission fragments using the STAR-LiTe detector array. Results of the analysis will be presented. This work was supported by DoE Grant Numbers: DE-FG52-09NA29454 and DE-FG02-05ER41379 (Richmond), DE-AC52-07NA27344 (LLNL) and DE-FG52-09NA29467 (TAMU).

  15. Inactivation of the Tulane Virus, a Novel Surrogate for the Human Norovirus

    Science.gov (United States)

    TIAN, PENG; YANG, DAVID; QUIGLEY, CHRISTINA; CHOU, MARISSA; JIANG, XI

    2014-01-01

    Human noroviruses (HuNoVs) are the major cause of nonbacterial gastroenteritis epidemics. The culturable feline calicivirus and murine norovirus have been used extensively as surrogates to study HuNoV biology, as HuNoV does not grow in vitro. Additional efforts to identify new surrogates are needed, because neither of these common surrogates are truly intestinal pathogens. The newly described Tulane virus (TV) is a typical calicivirus, it is isolated from macaque stools, is cultivable in vitro, and recognizes human histo-blood group antigens. Therefore, TV is a promising surrogate for HuNoVs. In this study, we evaluated the resistance or stability of TV under various physical and environmental conditions by measuring a 50% reduction of tissue culture infective dose (TCID50) by using a TV cell culture system. Due to the nature of this virus, it is hard to produce a high-titer stock through tissue culture. In our study, the maximal reduction in virus titers was 5 D (D = 1 log) in heat-denaturation and EtOH experiments, and 4 D in UV, chlorine, and pH-stability experiments. Therefore in this study, we defined the inactivation of TV as reaching a TCID50/ml of 0 (a 4- to 5-D reduction in TCID50, depending on the detection limit). TV was inactivated after incubation at 63°C for 5 min, incubation at 56°C for 30 min (5 D), exposure to 60 mJ/cm2 of UVC radiation (4 D), or incubation at 300 ppm of free chlorine for 10 min (4 D). TV was shown to be stable from pH 3.0 to 8.0, though an obvious reduction in virus titer was observed at pH 2.5 and 9.0, and was inactivated at pH 10.0 (4 D). TV was resistant to a low concentration of EtOH (40% or lower) but was fully inactivated (5 D) by 50 to 70% EtOH after a short exposure (20 s). In contrast, quantitative real-time PCR was unable to detect, or poorly detected, virus titer reductions between treated and untreated samples described in this study. PMID:23575140

  16. 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

  17. Surface plasmon resonance-enhanced fluorescence implementation of a single-step competition assay: demonstration of fatty acid measurement using an anti-fatty acid monoclonal antibody and a Cy5-labeled fatty acid.

    Science.gov (United States)

    Vareiro, Margarida M L M; Tranchant, Isabelle; Maplin, Sandra; Zak, Kris; Gani, M M; Slevin, Christopher J; Hailes, Helen C; Tabor, Alethea B; Cameron, Petra J; Jenkins, A Toby A; Williams, David E

    2008-06-15

    The development of a single-step, separation-free method for measurement of low concentrations of fatty acid using a surface plasmon resonance-enhanced fluorescence competition assay with a surface-bound antibody is described. The assay behavior was unexpectedly complex. A nonlinear coverage-dependent self-quenching of emission from surface-bound fluorescent label was deduced from the response kinetics and attributed to a surface plasmon-mediated energy transfer between adsorbed fluorophores, modified by the effects of plasmon interference. Principles of assay design to avoid complications from such effects are discussed. An anti-fatty acid mouse monoclonal antibody reacting to the alkyl chain was prepared and supported on a gold chip at a spacing appropriate for surface-plasmon field-enhanced fluorescence spectroscopy (SPEFS), by applying successively a self-assembled biotinylated monolayer, then streptavidin, then biotinylated protein A, and then the antibody, which was crosslinked to the protein A. Synthesis of a fluorescently (Cy5) tagged C-11 fatty acid is reported. SPEFS was used to follow the kinetics of the binding of the labeled fatty acid to the antibody, and to implement a competition assay with free fatty acid (undecanoic acid), sensitive at the 1 microM scale, a sensitivity limit caused by the low affinity of antibodies for free fatty acids, rather than the SPEFS technique itself. Free fatty acid concentration in human serum is in the range 0.1-1mM, suggesting that this measurement approach could be applied in a clinical diagnostic context. Finally, a predictive, theoretical model of fatty acid binding was developed that accounted for the observed "overshoot" kinetics.

  18. 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.

  19. Indoor radon, geogenic radon surrogates and geology - Investigations on their correlation.

    Science.gov (United States)

    Friedmann, H; Baumgartner, A; Bernreiter, M; Gräser, J; Gruber, V; Kabrt, F; Kaineder, H; Maringer, F J; Ringer, W; Seidel, C; Wurm, G

    2017-01-01

    The indoor radon concentration was measured in most houses in a couple of municipalities in Austria. At the same time the activity concentration of radium in soil, the soil gas radon concentration, the permeability of the ground and the ambient dose equivalent rate were also measured and the geological situations (geological units) were recorded too. From the indoor radon concentration and different house and living parameters a radon potential (Austrian radon potential) was derived which should represent the radon concentration in a standard room. Another radon potential (Neznal radon potential) was calculated from the soil gas radon concentration and the permeability. The aim of the investigation was to correlate all the different variables and to test if the use of surrogate data (e.g. geological information, ambient dose equivalent rate, etc.) can be used to judge the radon risk for an area without performing numerous indoor measurements.

  20. 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

  1. Selection of antibodies from synthetic antibody libraries.

    Science.gov (United States)

    Harel Inbar, Noa; Benhar, Itai

    2012-10-15

    More than 2 dozen years had passed since the field of antibody engineering was established, with the first reports of bacterial [1-3] and mammalian cells [4] expression of recombinant antibody fragments, and in that time a lot of effort was dedicated to the development of efficient technological means, intended to assist in the creation of therapeutic monoclonal antibodies (mAbs). Research focus was given to two intertwined technological aspects: the selection platform and the recombinant antibody repertoires. In accordance with these areas of interest, it is the goal of this chapter to describe the various selection tools and antibody libraries existing, with emphasis on the later, and their applications. This chapter gives a far from exhaustive, subjective "historic account" of the field, describing the selection platforms, the different formats of antibody repertoires and the applications of both for selecting recombinant antibodies. Several excellent books provide detailed protocols for constructing antibody libraries and selecting antibodies from those libraries [5-13]. Such books may guide a newcomer to the field in the fine details of antibody engineering. We would like to offer advice to the novice: although seemingly simple, effective library construction and antibody isolation provide best benefits in the hands of professionals. It is an art as much as it is science.

  2. Optimisation of sandwich ELISA based on monoclonal antibodies for the specific measurement of pregnancy-associated plasma protein (PAPP-A) in acute coronary syndrome

    DEFF Research Database (Denmark)

    Rossen, Marie; Iversen, Kasper; Teisner, Ane

    2007-01-01

    by introduction of F(ab')(2)-fragment of the indicator antibody. This modified ELISA revealed that serum PAPP-A levels in ACS were statistically significantly higher than in controls (p... with acute coronary syndrome (ACS). The aims of the present study were to demonstrate (i) the importance of antibody specificity, (ii) the potential pitfalls in changing assay technology, (iii) the importance of strict definition of technology, and (iv) the application of a well-defined assay technology...... on sera from patients with ACS. DESIGN AND METHODS: Candidate monoclonal antibodies (Mab) were identified by immunohistochemistry, Western blot and the absence of positive signals (ELISA) with normal, non-pregnant serum as antigen source. The ELISA technology was standardized against the original PAPP...

  3. Generation of monoclonal antibodies against highly conserved antigens.

    Directory of Open Access Journals (Sweden)

    Hongzhe Zhou

    Full Text Available BACKGROUND: Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generating high-quality monoclonal antibodies against a given therapeutic target is very crucial for the success of the drug development. However, due to immune tolerance, some proteins that are highly conserved between mice and humans are not very immunogenic in mice, making it difficult to generate antibodies using a conventional approach. METHODOLOGY/PRINCIPAL FINDINGS: In this report, the impaired immune tolerance of NZB/W mice was exploited to generate monoclonal antibodies against highly conserved or self-antigens. Using two highly conserved human antigens (MIF and HMGB1 and one mouse self-antigen (TNF-alpha as examples, we demonstrate here that multiple clones of high affinity, highly specific antibodies with desired biological activities can be generated, using the NZB/W mouse as the immunization host and a T cell-specific tag fused to a recombinant antigen to stimulate the immune system. CONCLUSIONS/SIGNIFICANCE: We developed an efficient and universal method for generating surrogate or therapeutic antibodies against "difficult antigens" to facilitate the development of therapeutic antibodies.

  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.

  5. 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.

  6. 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)

    Matthew N Davies

    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.

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

    Science.gov (United States)

    Davies, Matthew N; Lawn, Sarah; Whatley, Steven; Fernandes, Cathy; Williams, Robert W; 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 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.

  8. 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

  9. 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...

  10. Surrogate model based iterative ensemble smoother for subsurface flow data assimilation

    Science.gov (United States)

    Chang, Haibin; Liao, Qinzhuo; Zhang, Dongxiao

    2017-02-01

    Subsurface geological formation properties often involve some degree of uncertainty. Thus, for most conditions, uncertainty quantification and data assimilation are necessary for predicting subsurface flow. The surrogate model based method is one common type of uncertainty quantification method, in which a surrogate model is constructed for approximating the relationship between model output and model input. Based on the prediction ability, the constructed surrogate model can be utilized for performing data assimilation. In this work, we develop an algorithm for implementing an iterative ensemble smoother (ES) using the surrogate model. We first derive an iterative ES scheme using a regular routine. In order to utilize surrogate models, we then borrow the idea of Chen and Oliver (2013) to modify the Hessian, and further develop an independent parameter based iterative ES formula. Finally, we establish the algorithm for the implementation of iterative ES using surrogate models. Two surrogate models, the PCE surrogate and the interpolation surrogate, are introduced for illustration. The performances of the proposed algorithm are tested by synthetic cases. The results show that satisfactory data assimilation results can be obtained by using surrogate models that have sufficient accuracy.

  11. Antibody response to measles immunization in India*

    OpenAIRE

    Job, J. S.; John, T J; Joseph, A.

    1984-01-01

    Antibody response to measles vaccine was measured in 238 subjects aged 6-15 months. Seroconversion rates ranged from 74% at 6 months of age to 100% at 13-15 months; the differences in age-specific rates were not statistically significant. The postimmunization antibody titres increased with increasing age of the vaccinee. Seroconversion rates and antibody titres in 49 subjects with grades I and II malnutrition were not significantly different from those in the 189 normal subjects.

  12. 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.

  13. 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.

  14. Association of Helicobacter pylori infection and giardiasis: Results from a study of surrogate markers for fecal exposure among children

    Institute of Scientific and Technical Information of China (English)

    Edson Duarte Moreira Jr; Victor Bastos Nassri; Rafaela Sousa Santos; Junísia Ferraz Matos; Wilson Andrade de Carvalho; Célia Stolve Silvani; Círia Santana e Sant'Ana

    2005-01-01

    AIM: To investigate whether Helicobacter pylori (H pykori)infection is associated with hepatitis A virus (HAV) infection, presence of enteroparasites, and other surrogates of fecal exposure.METHODS: We conducted a cross-sectional study in 121 children consecutively admitted at a pediatric hospital inSalvador, Brazil.H pylori and HAV infection were identified by the presence of serum antibodies. Stool specimens were examined for the presence of ova and parasites. A structured questionnaire inquiring about sanitary conditions and life style was applied to each subject. RESULTS: Fifty-one of the 121 children (42.1%) werefound to be seropositive for H pylori, and 45 (37.2%) for HAV. The seroprevalence ofHpyloriand HAV both increased significantly with age. Cross-tabulation of data showed that 26 (21.5%) were seropositive and 51 (42.1%) were negative for bothHpyloriand HAV antibodies (χ2 = 7.18,OR = 2.8, CI 1.30-5.97). The age adjusted OR for an HAV-infected child being H pylori positive was 2.3 (CI1.02-5.03). The agreement between H pylori and HAVseropositivity was fair (κ = 0.24). After controlling for possible confounding, the variables remaining independently associated with seropositivity to H pyloriwere age,presence of Giardia lamblia in feces (OR = 3.2, 95%CI, 1.1-9.5) and poor garbage disposal quality (OR = 2.4,95%CI, 1.1-5.1).CONCLUSION: Our data suggest that H pylori infection is associated with surrogate markers of fecal exposure. Thus, we conclude that the fecal-oral route is relevant in the transmission of HP among children in an urban setting of a developing country. The association observed between G. lamblia and H pylori infection may have several explanations. Further studies to investigate this relationship are warranted.

  15. 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

  16. 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...

  17. A semi-automated multiplex high-throughput assay for measuring IgG antibodies against Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) domains in small volumes of plasma

    DEFF Research Database (Denmark)

    Cham, Gerald K K; Kurtis, Jonathan; Lusingu, John;

    2008-01-01

    BACKGROUND: The level of antibodies against PfEMP1 is routinely quantified by the conventional microtitre enzyme-linked immunosorbent assay (ELISA). However, ELISA only measures one analyte at a time and requires a relatively large plasma volume if the complete antibody profile of the sample...... of twenty nine PfEMP1 domains were PCR amplified from 3D7 genomic DNA, expressed in the Baculovirus system and purified by metal-affinity chromatography. The antibody reactivity level to the recombinant PfEMP1 proteins in human hyper-immune plasma was measured by ELISA. In parallel, these recombinant PfEMP1......-based assay was sensitive, accurate and reproducible. Four recombinant PfEMP1 proteins C17, D5, D9 and D12, selected on the basis that they showed a spread of median fluorescent intensity (MFI) values from low to high when analysed by the bead-based assay were analysed by ELISA and the results from both...

  18. Unsteady Extinction of Opposed Jet Ethylene/Methane HIFiRE Surrogate Fuel Mixtures vs Air

    Science.gov (United States)

    Vaden, Sarah N.; Debes, Rachel L.; Lash, E. Lara; Burk, Rachel S.; Boyd, C. Merritt; Wilson, Lloyd G.; Pellett, Gerald L.

    2009-01-01

    A unique idealized study of the subject fuel vs. air systems was conducted using an Oscillatory-input Opposed Jet Burner (OOJB) system and a newly refined analysis. Extensive dynamic-extinction measurements were obtained on unanchored (free-floating) laminar Counter Flow Diffusion Flames (CFDFs) at 1-atm, stabilized by steady input velocities (e.g., U(sub air)) and perturbed by superimposed in-phase sinusoidal velocity inputs at fuel and air nozzle exits. Ethylene (C2H4) and methane (CH4), and intermediate 64/36 and 15/85 molar percent mixtures were studied. The latter gaseous surrogates were chosen earlier to mimic ignition and respective steady Flame Strengths (FS = U(sub air)) of vaporized and cracked, and un-cracked, JP-7 "like" kerosene for a Hypersonic International Flight Research Experimentation (HIFiRE) scramjet. For steady idealized flameholding, the 100% C2H4 flame is respectively approx. 1.3 and approx.2.7 times stronger than a 64/36 mix and CH4; but is still 12.0 times weaker than a 100% H2-air flame. Limited Hot-Wire (HW) measurements of velocity oscillations at convergent-nozzle exits, and more extensive Probe Microphone (PM) measurements of acoustic pressures, were used to normalize Dynamic FSs, which decayed linearly with pk/pk U(sub air) (velocity magnitude, HW), and also pk/pk P (pressure magnitude, PM). Thus Dynamic Flame Weakening (DFW) is defined as % decrease in FS per Pascal of pk/pk P oscillation, namely, DFW = -100 d(U(sub air)/U(sub air),0Hz)/d(pkpk P). Key findings are: (1) Ethylene flames are uniquely strong and resilient to extinction by oscillating inflows below 150 Hz; (2) Methane flames are uniquely weak; (3) Ethylene / methane surrogate flames are disproportionately strong with respect to ethylene content; and (4) Flame weakening is consistent with limited published results on forced unsteady CFDFs. Thus from 0 to approx. 10 Hz and slightly higher, lagging diffusive responses of key species led to progressive phase lags (relative

  19. Surrogate Mobility and Orientation Affect the Early Neurobehavioral Development of Infant Rhesus Macaques (Macaca mulatta)

    OpenAIRE

    Amanda M Dettmer; Ruggerio, Angela M.; Novak, Melinda A.; Meyer, Jerrold S.; Suomi, Stephen J.

    2008-01-01

    A biological mother’s movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard...

  20. Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China

    OpenAIRE

    Feiling Yang; Jinming Hu; Ruidong Wu

    2016-01-01

    Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that end...

  1. Cell-penetrating Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate Cancer

    Science.gov (United States)

    2014-10-01

    AR441 antibody or control antibodies. Changes in the levels of PSA mRNA were measured by real time PCR (Fig. 1). The bispecific antibody...depending on which capture antibody was used). These values are very compatible with expected affinities for monoclonal antibodies. Interestingly

  2. 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.

  3. Kinetics of and atmospheric effects on gallium removal from a CeO{sub 2} based mixed oxide surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Park, Y.S.; Taylor, T.N.; Atencio, A.; Butt, D.P.

    1998-12-31

    This paper describes preliminary experimental results on the kinetics of Ga removal from Ga{sub 2}O{sub 3}-doped CeO{sub 2{minus}x}, a surrogate for weapons grade PuO{sub 2{minus}x}. Ga is removed from the surrogate feedstock material using thermal techniques. An Ar-6% H{sub 2} gas was used in order to reduce the oxide to gaseous Ga{sub 2}O. Experiments were done in the temperature range of 600--1,200 C as a function of time, gas flow rate, and sample geometry. Samples were analyzed through measurements of weight change, scanning electron microscopy/energy dispersive spectroscopy, x-ray photoelectron spectroscopy, proton induced x-ray emission, and direct current plasma analysis. Gallium levels were reduced by as much as 98% (130 ppm Ga residue) of that in the starting material. Studies to date have shown CeO{sub 2{minus}x} is a very good surrogate for PuO{sub 2{minus}x}.

  4. 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.

  5. The use of surrogate endpoints in regulating medicines for cardio-renal disease: opinions of stakeholders.

    Directory of Open Access Journals (Sweden)

    Bauke Schievink

    Full Text Available AIM: There is discussion whether medicines can be authorized on the market based on evidence from surrogate endpoints. We assessed opinions of different stakeholders on this topic. METHODS: We conducted an online questionnaire that targeted various stakeholder groups (regulatory agencies, pharmaceutical industry, academia, relevant public sector organisations and medical specialties (cardiology or nephrology vs. other. Participants were enrolled through purposeful sampling. We inquired for conditions under which surrogate endpoints can be used, the validity of various cardio-renal biomarkers and new approaches for biomarker use. RESULTS: Participants agreed that surrogate endpoints can be used when the surrogate is scientifically valid (5-point Likert response format, mean score: 4.3, SD: 0.9 or when there is an unmet clinical need (mean score: 3.8, SD: 1.2. Industry participants agreed to a greater extent than regulators and academics. However, out of four proposed surrogates (blood pressure (BP, HbA1c, albuminuria, CRP for cardiovascular outcomes or end-stage renal disease, only use of BP for cardiovascular outcomes was deemed moderately accurate (mean: 3.6, SD: 1.1. Specialists in cardiology or nephrology tended to be more positive about the use of surrogate endpoints. CONCLUSION: Stakeholders in drug development do not oppose to the use of surrogate endpoints in drug marketing authorization, but most surrogates are not considered valid. To solve this impasse, increased efforts are required to validate surrogate endpoints and to explore alternative ways to use them.

  6. Evaluation of the use of surrogate Laminaria digitata in eco-hydraulic laboratory experiments

    Institute of Scientific and Technical Information of China (English)

    PAUL Maike; HENRY Pierre-Yves T

    2014-01-01

    Inert surrogates can avoid husbandry and adaptation problems of live vegetation in laboratories. Surrogates are generally used for experiments on vegetation-hydrodynamics interactions, but it is unclear how well they replicate field conditions. Here, surrogates for the brown macroalgae Laminaria digitata were developed to reproduce its hydraulic roughness. Plant shape, stiffness and buoyancy of L. digitata were evaluated and compared to the properties of inert materials. Different surrogate materials and shapes were exposed to unidirectional flow. It is concluded that buoyancy is an important factor in low flow conditions and a basic shape might be sufficient to model complex shaped plants resulting in the same streamlined shape.

  7. Simple and Efficient Method for Measuring Anti-Toxoplasma Immunoglobulin Antibodies in Human Sera Using Complement-Mediated Lysis of Transgenic Tachyzoites Expressing β-Galactosidase

    Science.gov (United States)

    Dando, Caroline; Gabriel, Katie E.; Remington, Jack S.; Parmley, Stephen F.

    2001-01-01

    A simple and efficient method using transgenic Toxoplasma gondii tachyzoites expressing β-galactosidase was developed for detection of specific antibodies against the parasite in sera of patients. The titers obtained with the new test were similar to those obtained with the Sabin-Feldman dye test run in parallel. Although significant changes in endpoint titers were not observed when sera drawn sequentially at 2- to 3-week intervals were tested with both procedures, apparent differences in antibody affinity were observed with the new test which were not perceptible with the Sabin-Feldman dye test. Like the Sabin-Feldman dye test, the new test is based on complement lysis of tachyzoites, but it is much easier to perform and the reaction is read colorimetrically instead of visually. PMID:11376045

  8. Premixed flame chemistry of a gasoline primary reference fuel surrogate

    KAUST Repository

    Selim, Hatem

    2017-03-10

    Investigating the combustion chemistry of gasoline surrogate fuels promises to improve detailed reaction mechanisms used for simulating their combustion. In this work, the combustion chemistry of one of the simplest, but most frequently used gasoline surrogates – primary reference fuel 84 (PRF 84, 84 vol% iso-octane and 16 vol% n-heptane), has been examined in a stoichiometric premixed laminar flame. Time-of-flight mass spectrometry coupled with a vacuum ultraviolet (VUV) synchrotron light source for species photoionization was used. Reactants, major end-products, stable intermediates, free radicals, and isomeric species were detected and quantified. Numerical simulations were conducted using a detailed chemical kinetic model with the most recently available high temperature sub-mechanisms for iso-octane and heptane, built on the top of an updated pentane isomers model and AramcoMech 2.0 (C0C4) base chemistry. A detailed interpretation of the major differences between the mechanistic pathways of both fuel components is given. A comparison between the experimental and numerical results is depicted and rate of production and sensitivity analyses are shown for the species with considerable disagreement between the experimental and numerical findings.

  9. Bayesian Calibration of the Community Land Model using Surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Ray, Jaideep; Hou, Zhangshuan; Huang, Maoyi; Sargsyan, K.; Swiler, Laura P.

    2015-01-01

    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, conditioned 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 accurate surrogate models can be created for CLM in most cases. The posterior distributions lead to better prediction 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 potentially be used to identify physical processes that could be contributing to it. While the calibrated CLM has a higher predictive skill, the calibration is under-dispersive.

  10. Bayesian calibration of the Community Land Model using surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Ray, Jaideep; Hou, Zhangshuan; Huang, Maoyi; Swiler, Laura Painton

    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.

  11. 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.

  12. 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.

  13. Fractional flow reserve as a surrogate for inducible myocardial ischaemia.

    Science.gov (United States)

    van de Hoef, Tim P; Meuwissen, Martijn; Escaned, Javier; Davies, Justin E; Siebes, Maria; Spaan, Jos A E; Piek, Jan J

    2013-08-01

    Documentation of inducible myocardial ischaemia, related to the coronary stenosis of interest, is of increasing importance in lesion selection for percutaneous coronary intervention (PCI). Fractional flow reserve (FFR) is an easily understood, routine diagnostic modality that has become part of daily clinical practice, and is used as a surrogate technique for noninvasive assessment of myocardial ischaemia. However, the application of a single, discrete, cut-off value for FFR-guided lesion selection for PCI, and its adoption in contemporary revascularization guidelines, has limited the requirement for a thorough understanding of the physiological basis of FFR. This limitation constitutes an obstacle for the adequate use and interpretation of this technique, and also for the understanding of new and future modalities of physiological functional intracoronary testing. In this Review, we revisit the fundamental elements of coronary physiology in the absence or presence of coronary artery disease. We provide insight into three essential characteristics of FFR as a diagnostic tool in contemporary clinical practice--the theoretical framework of FFR and its associated limitations; the characteristics and role of FFR as a surrogate for noninvasively assessed myocardial ischaemia; and the requirement and associated caveats of potent vasodilatory drugs to induce maximal vasodilatation of the coronary vascular bed.

  14. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Herbinet, O; Pitz, W J; Westbrook, C K

    2007-09-20

    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.

  15. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Herbinet, O; Pitz, W J; Westbrook, C K

    2007-09-17

    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.

  16. 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.

  17. Proper Orthogonal Decomposition as Surrogate Model for Aerodynamic Optimization

    Directory of Open Access Journals (Sweden)

    Valentina Dolci

    2016-01-01

    Full Text Available A surrogate model based on the proper orthogonal decomposition is developed in order to enable fast and reliable evaluations of aerodynamic fields. The proposed method is applied to subsonic turbulent flows and the proper orthogonal decomposition is based on an ensemble of high-fidelity computations. For the construction of the ensemble, fractional and full factorial planes together with central composite design-of-experiment strategies are applied. For the continuous representation of the projection coefficients in the parameter space, response surface methods are employed. Three case studies are presented. In the first case, the boundary shape of the problem is deformed and the flow past a backward facing step with variable step slope is studied. In the second case, a two-dimensional flow past a NACA 0012 airfoil is considered and the surrogate model is constructed in the (Mach, angle of attack parameter space. In the last case, the aerodynamic optimization of an automotive shape is considered. The results demonstrate how a reduced-order model based on the proper orthogonal decomposition applied to a small number of high-fidelity solutions can be used to generate aerodynamic data with good accuracy at a low cost.

  18. 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

  19. Benchmarking the External Surrogate Ratio Method using the (alpha,alpha' f) reaction at STARS

    Energy Technology Data Exchange (ETDEWEB)

    Lesher, S R; Bernstein, L A; Ai, H; Beausang, C W; Bleuel, D; Burke, J T; Clark, R M; Fallon, P; Gibelin, J; Lee, I Y; Lyles, B F; Macchiavelli, A O; McMahan, M A; Moody, K J; Norman, E B; Phair, L; Rodriguez-Vieitez, E; Wiedeking, M

    2008-01-09

    We measured the ratio of the fission probabilities of {sup 234}U* relative to {sup 236}U* formed via an ({alpha},{alpha}{prime}) direct reactions using the STARS array at the 88-inch cyclotron at the Lawrence Berkeley National Laboratory. This ratio has a shape similar to the ratio of neutron capture probabilities from {sup 233}U(n; f) and {sup 235}U(n; f), indicating the alpha reactions likely formed a compound nucleus. This result indicates that the ratios of fission exit channel probabilities for two actinide nuclei populated via ({alpha}, {alpha}{prime}) can be used to determine an unknown fission cross section relative to a known one. The validity of the External Surrogate Ratio Method (ESRM) is tested and the results support the conclusions of Burke et al. [1].

  20. Acetylcholine receptor antibody

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood ...

  1. Antinuclear antibody panel

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003535.htm Antinuclear antibody panel To use the sharing features on this page, please enable JavaScript. The antinuclear antibody panel is a blood test that looks at ...

  2. Lyme disease antibody

    Science.gov (United States)

    ... JavaScript. The Lyme disease blood test looks for antibodies in the blood to the bacteria that causes ... needed. A laboratory specialist looks for Lyme disease antibodies in the blood sample using the ELISA test . ...

  3. Anthropometric surrogates to identify low birth weight Nepalese newborns: a hospital-based study

    Directory of Open Access Journals (Sweden)

    Singh Dela

    2008-04-01

    Full Text Available Abstract Background In Nepal, more than 90% of the deliveries take place at home where birth weight is often not recorded. In developing countries, low birth weight (LBW, Methods A cross-sectional study was carried out in Western Regional Hospital, Pokhara between April and June, 2006. All consecutive full-term, singleton, live born babies were included. To ensure reliability and avoid inter-observer bias one of the investigators weighed all the newborns and carried out anthropometric measurements within 24 hours after birth. Circumferences of head, chest, mid-upper arm, thigh and calf were measured according to standard techniques. Non-parametric receiver operating characteristic (ROC curve analyses were carried out using bootstrap to calculate 95% confidence intervals of areas under the curve (AUC. The cut-points with lowest total misclassification rate were chosen to identify LBW babies. Results Out of 400 newborns studied, 204 (51% were males and 196 (49% were females. The mean birth weight was 3029 ± 438 grams and 34 (8.5% newborns were LBW. By ROC-AUC analyses, head circumference (AUC = 0.89, 95% CI 0.85 to 0.93 and chest circumference (AUC = 0.86, 95% CI 0.80 to 0.91 were identified as the optimal surrogate indicators of LBW babies. The optimal cut-points for head circumference and chest circumference to identify LBW newborns were ≥ 33.5 cm and ≥ 30.8 cm respectively. Conclusion Head and chest circumferences were the best anthropometric surrogates of LBW among Nepalese newborns. Further studies are needed in the field to cross-validate our results.

  4. 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 ...

  5. Antibody-Mediated Rejection: A Review

    Science.gov (United States)

    Garces, Jorge Carlos; Giusti, Sixto; Staffeld-Coit, Catherine; Bohorquez, Humberto; Cohen, Ari J.; Loss, George E.

    2017-01-01

    Background: Chronic antibody injury is a serious threat to allograft outcomes and is therefore the center of active research. In the continuum of allograft rejection, the development of antibodies plays a critical role. In recent years, an increased recognition of molecular and histologic changes has provided a better understanding of antibody-mediated rejection (AMR), as well as potential therapeutic interventions. However, several pathways are still unknown, which accounts for the lack of efficacy of some of the currently available agents that are used to treat rejection. Methods: We review the current diagnostic criteria for AMR; AMR paradigms; and desensitization, treatment, and prevention strategies. Results: Chronic antibody-mediated endothelial injury results in transplant glomerulopathy, manifested as glomerular basement membrane duplication, double contouring, or splitting. Clinical manifestations of AMR include proteinuria and a rise in serum creatinine. Current strategies for the treatment of AMR include antibody depletion with plasmapheresis (PLEX), immunoadsorption (IA), immunomodulation with intravenous immunoglobulin (IVIG), and T cell– or B cell–depleting agents. Some treatment benefits have been found in using PLEX and IA, and some small nonrandomized trials have identified some benefits in using rituximab and the proteasome inhibitor-based therapy bortezomib. More recent histologic follow-ups of patients treated with bortezomib have not shown significant benefits in terms of allograft outcomes. Furthermore, no specific treatment approaches have been approved by the US Food and Drug Administration. Other agents used for more difficult rejections include bortezomib and eculizumab (an anti-C5 monoclonal antibody). Conclusion: AMR is a fascinating field with ample opportunities for research and progress in the future. Despite the use of advanced techniques for the detection of human leukocyte antigen (HLA) or non-HLA donor-specific antibodies

  6. 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.

  7. The development and validation of an immunoassay for the measurement of anti-thymidine phosphorylase antibodies in mouse and dog sera.

    Science.gov (United States)

    Gasson, Charlotte; Levene, Michelle; Bax, Bridget E

    2013-01-01

    Erythrocyte encapsulated thymidine phosphorylase (EE-TP) is under development as an enzyme replacement therapy for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a fatal metabolic disorder resulting from an inherited deficiency of the enzyme thymidine phosphorylase. We report here the development and validation of a sensitive electrochemiluminescent (ECL) bridging immunoassay to support Good Laboratory Practice (GLP)-compliant preclinical safety studies of EE-TP in the mouse and dog. Affinity-purified rabbit anti-E. coli thymidine phosphorylase (TP) antibody was used as a calibrator standard with an effective working range of 2.5-7500 ng/mL. The minimum required dilution (MRD) for both mouse and dog sera was 1:10. The mean analytical recoveries for anti-TP antibodies spiked into serum at 70 ng/mL and 7000 ng/mL were 117.9% and 93.2%, respectively for mouse, and 112.0% and 104.3%, respectively for dog. The intra-assay precision (coefficient of variation, CV) ranged between 1.1% and 8.0% in mouse serum, and 1.9% and 2.5% in dog serum. Inter-assay precision ranged between -1.6% and 6.7% in mouse serum, and -13.0% and -2.5% in dog serum. Assay cut-point/screening cut-point correction factors were 201.37 and 44.4, respectively for mouse and dog sera. For future analysis of positive test samples, less than 37.12% (mouse) and 31.41% (dog) inhibition of the assay signal in the confirmation assay will confer anti-TP antibody specificity. Assay drift and hook effects (prozone) were not observed. The intra-assay and inter-assay accuracy for robustness were within ±20%.

  8. 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.

  9. Top predators: hot or not? A call for systematic assessment of biodiversity surrogates

    NARCIS (Netherlands)

    Cabeza, M.; Arponen, A.; Teeffelen, van A.J.A.

    2008-01-01

    argue that top predators are justified conservation surrogates based on a case study where raptor presence is associated with high species richness of birds, butterflies and trees. 2. We question the methodology as well as the applicability of their results, and clarify differences between surrogate

  10. Somatic coliphages as surrogates for enteroviruses in sludge hygienization treatments.

    Science.gov (United States)

    Martín-Díaz, Julia; Casas-Mangas, Raquel; García-Aljaro, Cristina; Blanch, Anicet R; Lucena, Francisco

    2016-01-01

    Conventional bacterial indicators present serious drawbacks giving information about viral pathogens persistence during sludge hygienization treatments. This calls for the search of alternative viral indicators. Somatic coliphages' (SOMCPH) ability for acting as surrogates for enteroviruses was assessed in 47 sludge samples subjected to novel treatment processes. SOMCPH, infectious enteroviruses and genome copies of enteroviruses were monitored. Only one of these groups, the bacteriophages, was present in the sludge at concentrations that allowed the evaluation of treatment's performance. An indicator/pathogen relationship of 4 log10 (PFU/g dw) was found between SOMCPH and infective enteroviruses and their detection accuracy was assessed. The obtained results and the existence of rapid and standardized methods encourage the inclusion of SOMCPH quantification in future sludge directives. In addition, an existing real-time quantitative polymerase chain reaction (RT-qPCR) for enteroviruses was adapted and applied.

  11. Sparse polynomial surrogates for aerodynamic computations with random inputs

    CERN Document Server

    Savin, Eric; Peter, Jacques

    2015-01-01

    This paper deals with some of the methodologies used to construct polynomial surrogate models based on generalized polynomial chaos (gPC) expansions for applications to uncertainty quantification (UQ) in aerodynamic computations. A core ingredient in gPC expansions is the choice of a dedicated sampling strategy, so as to define the most significant scenarios to be considered for the construction of such metamodels. A desirable feature of the proposed rules shall be their ability to handle several random inputs simultaneously. Methods to identify the relative "importance" of those variables or uncertain data shall be ideally considered as well. The present work is more particularly dedicated to the development of sampling strategies based on sparsity principles. Sparse multi-dimensional cubature rules based on general one-dimensional Gauss-Jacobi-type quadratures are first addressed. These sets are non nested, but they are well adapted to the probability density functions with compact support for the random in...

  12. Argan oil improves surrogate markers of CVD in humans.

    Science.gov (United States)

    Sour, Souad; Belarbi, Meriem; Khaldi, Darine; Benmansour, Nassima; Sari, Nassima; Nani, Abdelhafid; Chemat, Farid; Visioli, Francesco

    2012-06-01

    Limited - though increasing - evidence suggests that argan oil might be endowed with potential healthful properties, mostly in the areas of CVD and prostate cancer. We sought to comprehensively determine the effects of argan oil supplementation on the plasma lipid profile and antioxidant status of a group of healthy Algerian subjects, compared with matched controls. A total of twenty healthy subjects consumed 15 g/d of argan oil - with toasted bread - for breakfast, during 4 weeks (intervention group), whereas twenty matched controls followed their habitual diet, but did not consume argan oil. The study lasted 30 d. At the end of the study, argan oil-supplemented subjects exhibited higher plasma vitamin E concentrations, lower total and LDL-cholesterol, lower TAG and improved plasma and cellular antioxidant profile, when compared with controls. In conclusion, we showed that Algerian argan oil is able to positively modulate some surrogate markers of CVD, through mechanisms which warrant further investigation.

  13. A Rigorous Framework for Optimization of Expensive Functions by Surrogates

    Science.gov (United States)

    Booker, Andrew J.; Dennis, J. E., Jr.; Frank, Paul D.; Serafini, David B.; Torczon, Virginia; Trosset, Michael W.

    1998-01-01

    The goal of the research reported here is to develop rigorous optimization algorithms to apply to some engineering design problems for which design application of traditional optimization approaches is not practical. This paper presents and analyzes a framework for generating a sequence of approximations to the objective function and managing the use of these approximations as surrogates for optimization. The result is to obtain convergence to a minimizer of an expensive objective function subject to simple constraints. The approach is widely applicable because it does not require, or even explicitly approximate, derivatives of the objective. Numerical results are presented for a 31-variable helicopter rotor blade design example and for a standard optimization test example.

  14. High-Temperature Oxidation of Plutonium Surrogate Metals and Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Sparks, Joshua C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Krantz, Kelsie E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Christian, Jonathan H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Washington, II, Aaron L. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-07-27

    The Plutonium Management and Disposition Agreement (PMDA) is a nuclear non-proliferation agreement designed to remove 34 tons of weapons-grade plutonium from Russia and the United States. While several removal options have been proposed since the agreement was first signed in 2000, processing the weapons-grade plutonium to mixed-oxide (MOX) fuel has remained the leading candidate for achieving the goals of the PMDA. However, the MOX program has received its share of criticisms, which causes its future to be uncertain. One alternative pathway for plutonium disposition would involve oxidizing the metal followed by impurity down blending and burial in the Waste Isolation Pilot Plant (WIPP) in Carlsbad, New Mexico. This pathway was investigated by use of a hybrid microwave and a muffle furnace with Fe and Al as surrogate materials. Oxidation occurred similarly in the microwave and muffle furnace; however, the microwave process time was significantly faster.

  15. Cholesterol paradox: a correlate does not a surrogate make.

    Science.gov (United States)

    DuBroff, Robert

    2017-03-01

    The global campaign to lower cholesterol by diet and drugs has failed to thwart the developing pandemic of coronary heart disease around the world. Some experts believe this failure is due to the explosive rise in obesity and diabetes, but it is equally plausible that the cholesterol hypothesis, which posits that lowering cholesterol prevents cardiovascular disease, is incorrect. The recently presented ACCELERATE trial dumbfounded many experts by failing to demonstrate any cardiovascular benefit of evacetrapib despite dramatically lowering low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol in high-risk patients with coronary disease. This clinical trial adds to a growing volume of knowledge that challenges the validity of the cholesterol hypothesis and the utility of cholesterol as a surrogate end point. Inadvertently, the cholesterol hypothesis may have even contributed to this pandemic. This perspective critically reviews this evidence and our reluctance to acknowledge contradictory information.

  16. Potential cryptosporidium surrogates and evaluation of compressible oocysts

    Energy Technology Data Exchange (ETDEWEB)

    Li, S.Y.; Goodrich, J.A.; Owens, J.H. [Environmental Protection Agency, Cincinnati, OH (United States)] [and others

    1995-10-01

    Cryptosporidium has been recognized as an important waterborne agent of gastroenteritis and a biological contaminant in drinking water. The widespread presence of Cryptosporidium in surface source water and either untreated or insufficiently treated drinking water has led to Cryptosporidium outbreaks in the United States and worldwide. Among the conventional control practices, filtration and high temperature distillation appear to be the potentially viable technologies for protection against Cryptosporidium in drinking water. As employed in many water plants, filtration is likely to be the most practical treatment technology utilized for Cryptosporidium removal in the near future. Consequently, accurate and reliable methods for evaluation of Cryptosporidium removal rates for filtration-based systems are necessary to assist States in determining drinking water quality and complying with the up-coming national standard for Cryptosporidium in drinking water. Furthermore, searching for reliable and non-hazardous surrogates for evaluation of treatment plant efficiency has been intensified because of the potential health risk associated with Cryptosporidium. Additionally, during the filtration procedure Cryptosporidium may squeeze and fold through pores size of the filtration systems that are smaller than the diameter of the organism; a fraction of these Cryptosporidium oocysts may still remain a certain degree of viability. These uncertainties are critical for the evaluation and optimization of filtration-based physical treatment systems. The in-house research studies described below consist of two parts. One is a potential surrogate study using bag filtration systems at the US EPA Test & Evaluation Facility in Cincinnati, Ohio. The second is Cryptosporidium compressibility and viability investigation.

  17. Effectiveness of chitosan on the inactivation of enteric viral surrogates.

    Science.gov (United States)

    Davis, Robert; Zivanovic, Svetlana; D'Souza, Doris H; Davidson, P Michael

    2012-10-01

    Chitosan is known to have bactericidal and antifungal activity. Although human noroviruses are the leading cause of non-bacterial gastroenteritis, information on the efficacy of chitosan against foodborne viruses is very limited. The objective of this work was to determine the effectiveness of different molecular weight chitosans against the cultivable human norovirus and enteric virus surrogates, feline calicivirus, FCV-F9, murine norovirus, MNV-1, and bacteriophages, MS2 and phiX174. Five purified chitosans (53, 222, 307, 421, ~1150 kDa) were dissolved in water, 1% acetic acid, or aqueous HCl pH = 4.3, sterilized by membrane filtration, and mixed with equal volume of virus to obtain a final concentration of 0.7% chitosan and 5 log(10) PFU/ml virus. Virus-chitosan suspensions were incubated for 3 h at 37 °C. Untreated viruses in PBS, in PBS with acetic acid, and in PBS with HCl were tested as controls. Each experiment was run in duplicate and replicated at least twice. Water-soluble chitosan (53 kDa) reduced phiX174, MS2, FCV-F9 and MNV-1 titers by 0.59, 2.44, 3.36, and 0.34 log(10) PFU/ml respectively. Chitosans in acetic acid decreased phiX174 by 1.19-1.29, MS2 by 1.88-5.37, FCV-F9 by 2.27-2.94, and MNV-1 by 0.09-0.28 log(10) PFU/ml, respectively. Increasing the MW of chitosan corresponded with an increasing antiviral effect on MS2, but did not appear to play a role for the other three tested viral surrogates. Overall, chitosan treatments showed the greatest reduction for FCV-F9, and MS2 followed by phiX174, and with no significant effect on MNV-1.

  18. Pan masala advertisements are surrogate for tobacco products

    Directory of Open Access Journals (Sweden)

    Sushma C

    2005-01-01

    Full Text Available BACKGROUND: Pan masala is a comparatively recent habit in India and is marketed with and without tobacco. Advertisements of tobacco products have been banned in India since 1st May 2004. The advertisements of plain pan masala, which continue in Indian media, have been suspected to be surrogate for tobacco products bearing the same name. The study was carried out to assess whether these advertisements were for the intended product, or for tobacco products with same brand name. MATERIALS AND METHODS: The programme of a popular television Hindi news channel was watched for a 24-h period. Programmes on the same channel and its English counterpart were watched on different days to assess whether the advertisements were repeated. The total duration of telecast of a popular brand of plain pan masala (Pan Parag was multiplied by the rate charged by the channel to provide the cost of advertisement of this product. The total sale value of the company was multiplied by the proportion of usage of plain pan masala out of gutka plus pan masala habit as observed from a different study, to provide the annual sale value of plain pan masala product under reference. RESULTS: The annual sale value of plain Pan Parag was estimated to be Rs. 67.1 million. The annual cost of the advertisement of the same product on two television channels was estimated at Rs. 244.6 million. CONCLUSION: The advertisements of plain pan masala seen on Indian television are a surrogate for the tobacco products bearing the same name.

  19. Learning image based surrogate relevance criterion for atlas selection in segmentation

    Science.gov (United States)

    Zhao, Tingting; Ruan, Dan

    2016-06-01

    Picking geometrically relevant atlases from the whole training set is crucial to multi-atlas based image segmentation, especially with extensive data of heterogeneous quality in the Big Data era. Unfortunately, there is very limited understanding of how currently used image similarity criteria reveal geometric relevance, let alone the optimization of them. This paper aims to develop a good image based surrogate relevance criterion to best reflect the underlying inaccessible geometric relevance in a learning context. We cast this surrogate learning problem into an optimization framework, by encouraging the image based surrogate to behave consistently with geometric relevance during training. In particular, we desire a criterion to be small for image pairs with similar geometry and large for those with significantly different segmentation geometry. Validation experiments on corpus callosum segmentation demonstrate the improved quality of the learned surrogate compared to benchmark surrogate candidates.

  20. [VGKC-complex antibodies].

    Science.gov (United States)

    Watanabe, Osamu

    2013-04-01

    Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease).

  1. Anti-DNA antibodies--quintessential biomarkers of SLE.

    Science.gov (United States)

    Pisetsky, David S

    2016-02-01

    Antibodies that recognize and bind to DNA (anti-DNA antibodies) are serological hallmarks of systemic lupus erythematosus (SLE) and key markers for diagnosis and disease activity. In addition to common use in the clinic, anti-DNA antibody testing now also determines eligibility for clinical trials, raising important questions about the nature of the antibody-antigen interaction. At present, no 'gold standard' for serological assessment exists, and anti-DNA antibody binding can be measured with a variety of assay formats, which differ in the nature of the DNA substrates and in the conditions for binding and detection of antibodies. A mechanism called monogamous bivalency--in which high avidity results from simultaneous interaction of IgG Fab sites with a single polynucleotide chain--determines anti-DNA antibody binding; this mechanism might affect antibody detection in different assay formats. Although anti-DNA antibodies can promote pathogenesis by depositing in the kidney or driving cytokine production, they are not all alike, pathologically, and anti-DNA antibody expression does not necessarily correlate with active disease. Levels of anti-DNA antibodies in patients with SLE can vary over time, distinguishing anti-DNA antibodies from other pathogenic antinuclear antibodies. Elucidation of the binding specificities and the pathogenic roles of anti-DNA antibodies in SLE should enable improvements in the design of informative assays for both clinical and research purposes.

  2. 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.

  3. Gaseous Surrogate Hydrocarbons for a Hifire Scramjet that Mimic Opposed Jet Extinction Limits for Cracked JP Fuels

    Science.gov (United States)

    Pellett, Gerald L.; Vaden, Sarah N.; Wilson, Lloyd G.

    2008-01-01

    FS and nearly equal molecular weights; this could be useful when systematically varying the fuel composition. However, the mixture liquefies at much lower pressure, which limits on-board storage of gaseous fuel; (5) Dynamic Flame Weakening results that show how oscillations in OJB input flow (and composition) can weaken (extinguish) surrogate flames up to 200 Hz, but the weakening is 2.5x smaller compared to pure methane; and finally, (6) FS limits at 1-atm that compare with three published 1-D numerical OJB extinction results using four chemical kinetic models. The methane kinetics generally agree closely at 1-atm, whereas, the various ethylene models predict extinction limits that average 45% high, which represents a significant problem for numerical simulation of surrogate-based flameholding in a scramjet cavity. Finally, we continue advocating the FS approach as more direct and fundamental for assessing idealized scramjet flameholding potentials than measurements of "unstrained" premixed laminar burning velocity or blowout in a Perfectly Stirred Reactor.

  4. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...... endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...

  5. Flume-based calibration of different surrogate devices for bedload monitoring

    Science.gov (United States)

    Mao, Luca; Escauriaza, Cristian; Gordo, Fernanda; Carrillo, Ricardo

    2014-05-01

    Bedload assessment is important for geomorphological, engineering, and ecological studies of gravel-bed rivers. Bedload is usually assessed using portable traps, which allows measuring instantaneous transport rates, but at a single point and at high costs and operational risks. Slot traps or other fixed devices allow measuring bedload rate for longer periods, but require expensive maintenance. The need of measuring continuously bedload intensity and dynamics has therefore increased the use and enhancement of surrogate methods, such as geophones, hydrophones, and acoustic sensors. However, converting the signals recorded by these instruments to actual bedload fluxes, direct bedload measurements are needed to obtain a calibration relationship. Even if some noticeable examples are available in literature, only few flume experiments have been undertaken to calibrate rate and grain size of transported sediments, and to explore rigorously the sensitivity and signal dampening effects of various surrogate devices. Here we present some preliminary results obtained from a set of flume experiments on which different devices have been used. We have tested a 1m-long Japanese acoustic pipe sensor, a 150×130×6 mm steel plate linked to an accelerometer and a count input data logger, and a hydrophone. Experiments were made in a 0.8m-wide flume, using 4 homogeneous (4, 8, 32, and 45 mm) sediment mixtures. These fractions were then combined in order to obtain 3 further heterogeneous mixtures. Experiments with different discharges and slopes were performed, allowing to observe a wide range of shear stresses and transport rates. All transported sediments were captured with traps, weighted, and then manually recirculated at the upstream end of the flume. Preliminary results show that devices have different sensitivity to lower grain size that could be detected, being the transport of 4 mm particles detected relatively well only by the impact plates. Intense transport of 8 mm particles

  6. Evaluation of multiple-frequency, active and passive acoustics as surrogates for bedload transport

    Science.gov (United States)

    Wood, Molly S.; Fosness, Ryan L.; Pachman, Gregory; Lorang, Mark; Tonolla, Diego

    2015-01-01

    The use of multiple-frequency, active acoustics through deployment of acoustic Doppler current profilers (ADCPs) shows potential for estimating bedload in selected grain size categories. The U.S. Geological Survey (USGS), in cooperation with the University of Montana (UM), evaluated the use of multiple-frequency, active and passive acoustics as surrogates for bedload transport during a pilot study on the Kootenai River, Idaho, May 17-18, 2012. Four ADCPs with frequencies ranging from 600 to 2000 kHz were used to measure apparent moving bed velocities at 20 stations across the river in conjunction with physical bedload samples. Additionally, UM scientists measured the sound frequencies of moving particles with two hydrophones, considered passive acoustics, along longitudinal transects in the study reach. Some patterns emerged in the preliminary analysis which show promise for future studies. Statistically significant relations were successfully developed between apparent moving bed velocities measured by ADCPs with frequencies 1000 and 1200 kHz and bedload in 0.5 to 2.0 mm grain size categories. The 600 kHz ADCP seemed somewhat sensitive to the movement of gravel bedload in the size range 8.0 to 31.5 mm, but the relation was not statistically significant. The passive hydrophone surveys corroborated the sample results and could be used to map spatial variability in bedload transport and to select a measurement cross-section with moving bedload for active acoustic surveys and physical samples.

  7. HIV-1 resistance to neutralizing antibodies: Determination of antibody concentrations leading to escape mutant evolution.

    Science.gov (United States)

    Magnus, Carsten; Reh, Lucia; Trkola, Alexandra

    2016-06-15

    Broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) are considered vital components of novel therapeutics and blueprints for vaccine research. Yet escape to even the most potent of these antibodies is imminent in natural infection. Measures to define antibody efficacy and prevent mutant selection are thus urgently needed. Here, we derive a mathematical framework to predict the concentration ranges for which antibody escape variants can outcompete their viral ancestors, referred to as mutant selection window (MSW). When determining the MSW, we focus on the differential efficacy of neutralizing antibodies against HIV-1 in two canonical infection routes, free-virus infection and cell-cell transmission. The latter has proven highly effective in vitro suggesting its importance for both in vivo spread as well as for escaping targeted intervention strategies. We observed a range of MSW patterns that highlight the potential of mutants to arise in both transmission pathways and over wide concentration ranges. Most importantly, we found that only when the arising mutant has both, residual sensitivity to the neutralizing antibody and reduced infectivity compared to the parental virus, antibody dosing outside of the MSW to restrict mutant selection is possible. Emergence of mutants that provide complete escape and have no considerable fitness loss cannot be prevented by adjusting antibody doses. The latter may in part explain the ubiquitous resistance to neutralizing antibodies observed in natural infection and antibody treatment. Based on our findings, combinations of antibodies targeting different epitopes should be favored for antibody-based interventions as this may render complete resistance less likely to occur and also increase chances that multiple escapes result in severe fitness loss of the virus making longer-term antibody treatment more feasible.

  8. A general framework to learn surrogate relevance criterion for atlas based image segmentation.

    Science.gov (United States)

    Zhao, Tingting; Ruan, Dan

    2016-09-07

    Multi-atlas based image segmentation sees great opportunities in the big data era but also faces unprecedented challenges in identifying positive contributors from extensive heterogeneous data. To assess data relevance, image similarity criteria based on various image features widely serve as surrogates for the inaccessible geometric agreement criteria. This paper proposes a general framework to learn image based surrogate relevance criteria to better mimic the behaviors of segmentation based oracle geometric relevance. The validity of its general rationale is verified in the specific context of fusion set selection for image segmentation. More specifically, we first present a unified formulation for surrogate relevance criteria and model the neighborhood relationship among atlases based on the oracle relevance knowledge. Surrogates are then trained to be small for geometrically relevant neighbors and large for irrelevant remotes to the given targets. The proposed surrogate learning framework is verified in corpus callosum segmentation. The learned surrogates demonstrate superiority in inferring the underlying oracle value and selecting relevant fusion set, compared to benchmark surrogates.

  9. A general framework to learn surrogate relevance criterion for atlas based image segmentation

    Science.gov (United States)

    Zhao, Tingting; Ruan, Dan

    2016-09-01

    Multi-atlas based image segmentation sees great opportunities in the big data era but also faces unprecedented challenges in identifying positive contributors from extensive heterogeneous data. To assess data relevance, image similarity criteria based on various image features widely serve as surrogates for the inaccessible geometric agreement criteria. This paper proposes a general framework to learn image based surrogate relevance criteria to better mimic the behaviors of segmentation based oracle geometric relevance. The validity of its general rationale is verified in the specific context of fusion set selection for image segmentation. More specifically, we first present a unified formulation for surrogate relevance criteria and model the neighborhood relationship among atlases based on the oracle relevance knowledge. Surrogates are then trained to be small for geometrically relevant neighbors and large for irrelevant remotes to the given targets. The proposed surrogate learning framework is verified in corpus callosum segmentation. The learned surrogates demonstrate superiority in inferring the underlying oracle value and selecting relevant fusion set, compared to benchmark surrogates.

  10. Not all Laminaria digitata are the same! Phenotypic plasticity and the selection of appropriate surrogate macroalgae for ecohydraulic experimentation

    Science.gov (United States)

    Thomas, Robert E.; McLelland, Stuart J.; Henry, Pierre-Yves T.; Paul, Maike; Eiff, Olivier; Evertsen, Antti-Jussi O.; Aberle, Jochen; Teacă, Adrian

    2015-04-01

    Whilst early physical modelling and theoretical studies of the interactions between vegetation and flowing water employed rigid structures such as wooden dowels, recent studies have progressed to flexible surrogate plants. However, even appropriately-scaled flexible surrogates fail to capture the variability in thallus morphology, flexibility and strength, both within and between individuals, and frontal or planform area over space and time. Furthermore, although there have been a number of field studies, measurements of hydraulic variables have generally been limited to time-averaged at-a-point measurements that aim to approximate the depth-mean velocity. This is problematic because in spatially heterogeneous flows, point measurements are dependent upon the sampling location. Herein, we describe research carried out by the participants in the PISCES work package of the HYDRALAB IV project that sought to address these limitations and assess the level of complexity needed to adequately reproduce the hydrodynamics of the natural system in physical models. We selected an 11 m long × 6 m wide region of a tidal inlet, the Hopavågen Bay, Sør-Trøndelag, Norway, that contained 19 Laminaria digitata thalli and 101 other macroalgae thalli. Two L. digitata specimens ~0.50 m apart were selected for detailed study and a 2 m long × 8 m wide frame was oriented around them by enforcing zero cross-stream discharge at its upstream edge. We then quantified: 1. the mean and turbulent flow field of the undisturbed condition (Case A); 2. the positions, geometrical and biomechanical properties of the macroalgae; and 3. the mean and turbulent flow field after the macroalgae were completely removed (Case B). Later, Case A was replicated in the same location (±0.025 m) before the 19 L. digitata thalli were replaced with 19 "optimized" surrogates (Case C). These three cases were then repeated in the Total Environment Simulator at the University of Hull, UK. Live macroalgae thalli could

  11. A comparative study of the oxidation characteristics of two gasoline fuels and an n-heptane/iso-octane surrogate mixture

    KAUST Repository

    Javed, Tamour

    2015-01-01

    Ignition delay times and CO, H2O, OH and CO2 time-histories were measured behind reflected shock waves for two FACE (Fuels for Advanced Combustion Engines) gasolines and one PRF (Primary Reference Fuel) blend. The FACE gasolines chosen for this work are primarily paraffinic and have the same octane rating (∼RON = 84) as the PRF blend, but contain varying amounts of iso- and n-paraffins. Species time-histories and ignition delay times were measured using laser absorption methods over a temperature range of 1350-1550 K and pressures near 2 atm. Measured species time-histories and ignition delay times of the PRF blend and the two FACE fuels agreed reasonably well. However, when compared to recent gasoline surrogate mechanisms, the simulations did not capture some of the kinetic trends found in the species profiles. To our knowledge, this work provides some of the first shock tube species time-history data for gasoline fuels and PRF surrogates and should enable further improvements in detailed kinetic mechanisms of gasoline fuels.

  12. 87Y(n,γ and 89,90Zr(n,γ cross sections from a surrogate reaction approach

    Directory of Open Access Journals (Sweden)

    Ota Shuya

    2015-01-01

    Full Text Available The surrogate reaction approach is an indirect method for determining nuclear reaction cross sections which cannot be measured directly or predicted reliably. While recent studies demonstrated the validity of the surrogate reaction approach for studying fission cross sections for short-lived actinides, its applicability for radiative neutron capture reactions ((n,γ is still under investigation. We studied the γ decay of excited 88Y and 90,91Zr nuclei produced by 89Y(p,d, 91Zr(p,d, and 92Zr(p,d reactions, respectively, in order to infer the 87Y(n,γ and 89, 90Zr(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 25-60° with the array of three segmented Micron S2 silicon detectors. The compound nuclei with energies up to a few MeV above the neutron separation thresholds were populated. The coincident γ-rays were measured with the array of five Compton-suppressed HPGe clover detectors.

  13. Label free checkerboard assay to determine overlapping epitopes of Ebola virus VP-40 antibodies using surface plasmon resonance.

    Science.gov (United States)

    Anderson, George P; Liu, Jinny L; Zabetakis, Dan; Legler, Patricia M; Goldman, Ellen R

    2017-03-01

    Immunoassay formats, in which antibodies provide sensitivity and specificity, are often utilized to provide rapid and simple diagnostic tests. Surface plasmon resonance is frequently used to evaluate the suitability of antibodies by determining binding kinetics to agents or surrogate antigens. We used SPR to evaluate a number of commercial monoclonal antibodies as well as single domain antibodies produced in-house. All the antibodies targeted the Ebola virus viral protein 40 (VP40). We determined the ability of each antibody to bind to immobilized VP40, and ensured they did not bind Ebola glycoprotein or the nucleoprotein. A subset of the monoclonal antibodies was immobilized to characterize antigen capture in solution. It can be advantageous to utilize antibodies that recognize distinct epitopes when choosing reagents for detection and diagnostic assays. We determined the uniqueness of the epitope recognized by the anti-VP40 antibodies using a checkerboard format that exploits the 6×6 array of interactions monitored by the Bio-Rad ProteOn XPR36 SPR instrument. The results demonstrate the utility of surface plasmon resonance to characterize monoclonal and recombinant antibodies. Additionally, the analysis presented here enabled the identification of pairs of anti-VP40 antibodies which could potentially be utilized in sandwich type immunoassays for the detection of Ebola virus.

  14. Results from Second Round of Remediated Nitrate Salt Surrogate Formulation and Testing

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Geoffrey Wayne [Los Alamos National Laboratory; Leonard, Philip [Los Alamos National Laboratory; Hartline, Ernest Leon [Los Alamos National Laboratory; Tian, Hongzhao [Los Alamos National Laboratory

    2016-04-04

    High Explosives and Technology (M-7) completed the second round of formulation and testing of Remediated Nitrate Salt (RNS) surrogates on March 17, 2016. This report summarizes the results of the work and also includes additional documentation required under test plan PLAN-TA9-2443 Rev B, "Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure", released February 16, 2016. All formulation and testing was carried out according to PLAN-TA9-2443 Rev B. Results from the first round of formulation and testing were documented in memorandum M7-16-6042, "Results from First Round of Remediated Nitrate Salt Surrogate Formulation and Testing."

  15. Latex Rubber Gloves as a Sampling Dosimeter Using a Novel Surrogate Sampling Device.

    Science.gov (United States)

    Sankaran, Gayatri; Lopez, Terry; Ries, Steve; Ross, John; Vega, Helen; Eastmond, David A; Krieger, Robert I

    2015-01-01

    Pesticide exposure during harvesting of crops occurs primarily to the workers' hands. When harvesters wear latex rubber gloves for personal safety and hygiene harvesting reasons, gloves accumulate pesticide residues. Hence, characterization of the gloves' properties may be useful for pesticide exposure assessments. Controlled field studies were conducted using latex rubber gloves to define the factors that influence the transfer of pesticides to the glove and that would affect their use as a residue monitoring device. A novel sampling device called the Brinkman Contact Transfer Unit (BCTU) was constructed to study the glove characteristics and residue transfer and accumulation under controlled conditions on turf. The effectiveness of latex rubber gloves as sampling dosimeters was evaluated by measuring the transferable pesticide residues as a function of time. The validation of latex rubber gloves as a residue sampling dosimeter was performed by comparing pesticide transfer and dissipation from the gloves, with the turf transferable residues sampled using the validated California (CA) Roller, a standard measure of residue transfer. The observed correlation (Pearson's correlation coefficient R(2)) between the two methods was .84 for malathion and .96 for fenpropathrin, indicating that the BCTU is a useful, reliable surrogate tool for studying available residue transfer to latex rubber gloves under experimental conditions. Perhaps more importantly, these data demonstrate that latex gloves worn by workers may be useful quantifiable matrices for measuring pesticide exposure.

  16. Numerical investigation for erratic behavior of Kriging surrogate model

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hyun Gil; Yi, Seul Gi [KAIST, Daejeon (Korea, Republic of); Choi, Seong Im [Virginia Polytechnic Institute and State University, Blacksburg (United States)

    2014-09-15

    Kriging model is one of popular spatial/temporal interpolation models in engineering field since it could reduce the time resources for the expensive analysis. But generation of the Kriging model is hardly a sinecure because internal semi-variogram structure of the Kriging often reveals numerically unstable or erratic behaviors. In present study, the issues in the maximum likelihood estimation which are the vital-parts of the construction of the Kriging model, is investigated. These issues are divided into two aspects; Issue I is for the erratic response of likelihood function itself, and Issue II is for numerically unstable behaviors in the correlation matrix. For both issues, studies for specific circumstances which might raise the issue, and the reason of that are conducted. Some practical ways further are suggested to cope with them. Furthermore, the issue is studied for practical problem; aerodynamic performance coefficients of two-dimensional airfoil predicted by CFD analysis. Result shows that such erratic behavior of Kriging surrogate model can be effectively resolved by proposed solution. In conclusion, it is expected this paper could be helpful to prevent such an erratic and unstable behavior.

  17. Protected Gold Nanoparticles with Thioethers and Amines As Surrogate Ligands

    Directory of Open Access Journals (Sweden)

    M. Rafiq H. Siddiqui

    2013-01-01

    Full Text Available Dodecyl sulfide, dodecyl amine, and hexylamine were shown to act as surrogate ligands (L via metastable gold nanoparticles. By collating analytical and spectroscopic data obtained simultaneously, empirical formula Au24L was assigned. These impurity-free nanoparticles obtained in near quantitative yields showing exceptional gold assays (up to 98%Au were prepared by a modification of the two-phase method. Replacement reactions on the Au24L showed that Au:L ratios may be increased (up to Au55:L (L= (H25C122S or decreased (Au12:L (L= H2NC12H25 and H2NC6H13 as desired. This work encompassing the role of analytical techniques used, that is, elemental analysis, variable temperature 1H NMR, FAB mass spectrometry, UV-Vis spectroscopy, thin film X-ray diffraction, and high-resolution electron microscopy (HREM has implications in the study of size control, purity, stability, and metal assays of gold nanoparticles.

  18. Investigation of ethosomes as surrogate carriers for bioactives

    Directory of Open Access Journals (Sweden)

    Devina Verma

    2016-01-01

    Full Text Available Background: Ethosomal vesicular system delivering a bioactive phytochemical, chrysin, was developed for transdermal delivery to increase its permeability and penetrability. Materials and Methods: Ethosomal system was optimized by keeping lecithin and ethanol concentration as independent variable while size and size distribution were taken as dependent variables. The optimized formulation was then subjected to various in vitro characterization parameters. Results: Ethosomal vesicle with an optimum size and polydispersity index of 134 ± 35 nm and 0.153, respectively, and entrapment efficiency of 80.05 ± 2.6% was considered as optimized and subjected to characterization. The scanning electron microscopy and transmission electron microscopy showed spherical entities with uniform surface whereas in vitro permeation and retention study showed the sustained mode of drug release and better skin retention as compared to hydroethanolic solution of the drug. The confocal laser scanning microscopy study reiterated high penetrability of vesicles into the skin. Histopathological and Fourier transform infrared spectroscopy analysis revealed its mechanism of penetration. Conclusion : The study thus demonstrated the ability of the ethosomal vesicles as surrogate carriers for delivery of bioactive agents through the skin for better amelioration of skin inflammation and other diseases.

  19. Evaluation of the diagnostic value of measuring IgG, IgM, and IgA antibodies to mycobacterial A60 antigen in active tuberculosis.

    Science.gov (United States)

    Ben-selma, Walid; Harizi, Hedi; Marzouk, Manel; Ben Kahla, Imen; Ben Lazreg, Foued; Ferjeni, Asma; Boukadida, Jalel

    2010-09-01

    The purpose of the present study was to evaluate the clinical usefulness of detection of serum immunoglobulin A (IgA), IgG, and IgM antibodies raised against the mycobacterial A60 antigen for the diagnosis and discrimination of active tuberculosis (TB) from other pulmonary diseases. Three commercially available ELISA kits (IgA, IgG, and IgM) (ANDA Biologicals, Strasbourg, France) were evaluated simultaneously in 246 serum samples from 3 groups of patients: group I, 171 patients with active TB (128 pulmonary TB and 43 extrapulmonary TB); group II, 73 patients with pulmonary non-TB diseases; and group III, 2 leprosies patients. The sensitivities of tests ranged from 31.3% (IgA) to 94% (IgG) in pulmonary TB patients and from 21% (IgA) to 84% (IgG) in extrapulmonary TB patients. The specificities of assays varied from 92% (IgG) to 96% (IgA) in the pulmonary non-TB group. Combination of IgG with IgA and/or IgM does not improve its sensitivity. Clinical use of the A60-based serodiagnostic IgG assay is of great value for the rapid diagnosis and discrimination between active TB and pulmonary non-TB diseases. Moreover, this test could be used to increase diagnostic accuracy, especially for smear-negative TB cases, which are difficult to diagnose.

  20. Correlating excipient effects on conformational and storage stability of an IgG1 monoclonal antibody with local dynamics as measured by hydrogen/deuterium-exchange mass spectrometry.

    Science.gov (United States)

    Manikwar, Prakash; Majumdar, Ranajoy; Hickey, John M; Thakkar, Santosh V; Samra, Hardeep S; Sathish, Hasige A; Bishop, Steven M; Middaugh, C Russell; Weis, David D; Volkin, David B

    2013-07-01

    The effects of sucrose and arginine on the conformational and storage stability of an IgG1 monoclonal antibody (mAb) were monitored by differential scanning calorimetry (DSC) and size-exclusion chromatography (SEC), respectively. Excipient effects on protein physical stability were then compared with their effects on the local flexibility of the mAb in solution at pH 6, 25°C using hydrogen/deuterium-exchange mass spectrometry (H/D-MS). Compared with a 0.1 M NaCl control, sucrose (0.5 M) increased conformational stability (T(m) values), slowed the rate of monomer loss, reduced the formation of insoluble aggregates, and resulted in a global trend of small decreases in local flexibility across most regions of the mAb. In contrast, the addition of arginine (0.5 M) decreased the mAb's conformational stability, increased the rate of loss of monomer with elevated levels of soluble and insoluble aggregates, and led to significant increases in the local flexibility in specific regions of the mAb, most notably within the constant domain 2 of the heavy chain (C(H)2). These results provide new insights into the effect of sucrose and arginine on the local dynamics of IgG1 domains as well as preliminary correlations between local flexibility within specific segments of the C(H)2 domain (notably heavy chain 241-251) and the mAb's overall physical stability.

  1. SU-E-J-73: Generation of Volumetric Images with a Respiratory Motion Model Based On An External Surrogate Signal

    Energy Technology Data Exchange (ETDEWEB)

    Hurwitz, M; Williams, C; Mishra, P; Dhou, S; Lewis, J [Brigham and Women' s Hospital, Dana-Farber Cancer Center, Harvard Medical School, Boston, MA, Boston, MA (United States)

    2014-06-01

    Purpose: Respiratory motion during radiotherapy treatment can differ significantly from motion observed during imaging for treatment planning. Our goal is to use an initial 4DCT scan and the trace of an external surrogate marker to generate 3D images of patient anatomy during treatment. Methods: Deformable image registration is performed on images from an initial 4DCT scan. The deformation vectors are used to develop a patient-specific linear relationship between the motion of each voxel and the trajectory of an external surrogate signal. Correlations in motion are taken into account with principal component analysis, reducing the number of free parameters. This model is tested with digital phantoms reproducing the breathing patterns of ten measured patient tumor trajectories, using five seconds of data to develop the model and the subsequent thirty seconds to test its predictions. The model is also tested with a breathing physical anthropomorphic phantom programmed to reproduce a patient breathing pattern. Results: The error (mean absolute, 95th percentile) over 30 seconds in the predicted tumor centroid position ranged from (0.8, 1.3) mm to (2.2, 4.3) mm for the ten patient breathing patterns. The model reproduced changes in both phase and amplitude of the breathing pattern. Agreement between prediction and truth over the entire image was confirmed by assessing the global voxel intensity RMS error. In the physical phantom, the error in the tumor centroid position was less than 1 mm for all images. Conclusion: We are able to reconstruct 3D images of patient anatomy with a model correlating internal respiratory motion with motion of an external surrogate marker, reproducing the expected tumor centroid position with an average accuracy of 1.4 mm. The images generated by this model could be used to improve dose calculations for treatment planning and delivered dose estimates. This work was partially funded by a research grant from Varian Medical Systems.

  2. Oral priming with replicating adenovirus serotype 4 followed by subunit H5N1 vaccine boost promotes antibody affinity maturation and expands H5N1 cross-clade neutralization.

    Directory of Open Access Journals (Sweden)

    Surender Khurana

    Full Text Available 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.

  3. Expression of recombinant antibodies.

    Science.gov (United States)

    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 transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with "human-like" post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

  4. 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…

  5. Recombinant renewable polyclonal antibodies.

    Science.gov (United States)

    Ferrara, Fortunato; D'Angelo, Sara; Gaiotto, Tiziano; Naranjo, Leslie; Tian, Hongzhao; Gräslund, Susanne; Dobrovetsky, Elena; Hraber, Peter; Lund-Johansen, Fridtjof; Saragozza, Silvia; Sblattero, Daniele; Kiss, Csaba; Bradbury, Andrew R M

    2015-01-01

    Only a small fraction of the antibodies in a traditional polyclonal antibody mixture recognize the target of interest, frequently resulting in undesirable polyreactivity. Here, we show that high-quality recombinant polyclonals, in which hundreds of different antibodies are all directed toward a target of interest, can be easily generated in vitro by combining phage and yeast display. We show that, unlike traditional polyclonals, which are limited resources, recombinant polyclonal antibodies can be amplified over one hundred million-fold without losing representation or functionality. Our protocol was tested on 9 different targets to demonstrate how the strategy allows the selective amplification of antibodies directed toward desirable target specific epitopes, such as those found in one protein but not a closely related one, and the elimination of antibodies recognizing common epitopes, without significant loss of diversity. These recombinant renewable polyclonal antibodies are usable in different assays, and can be generated in high throughput. This approach could potentially be used to develop highly specific recombinant renewable antibodies against all human gene products.

  6. Endospore surface properties of commonly used Bacillus anthracis surrogates vary in aqueous solution

    Science.gov (United States)

    The hydrophobic character and electrophoretic mobility of microorganisms are vital aspects of understanding their interactions with the environment. These properties are fundamental in fate-and-transport, physiological, and virulence studies, and thus integral in surrogate select...

  7. Surrogate Models for Online Monitoring and Process Troubleshooting of NBR Emulsion Copolymerization

    Directory of Open Access Journals (Sweden)

    Chandra Mouli R. Madhuranthakam

    2016-03-01

    Full Text Available Chemical processes with complex reaction mechanisms generally lead to dynamic models which, while beneficial for predicting and capturing the detailed process behavior, are not readily amenable for direct use in online applications related to process operation, optimisation, control, and troubleshooting. Surrogate models can help overcome this problem. In this research article, the first part focuses on obtaining surrogate models for emulsion copolymerization of nitrile butadiene rubber (NBR, which is usually produced in a train of continuous stirred tank reactors. The predictions and/or profiles for several performance characteristics such as conversion, number of polymer particles, copolymer composition, and weight-average molecular weight, obtained using surrogate models are compared with those obtained using the detailed mechanistic model. In the second part of this article, optimal flow profiles based on dynamic optimisation using the surrogate models are obtained for the production of NBR emulsions with the objective of minimising the off-specification product generated during grade transitions.

  8. Midwest Surrogate Species and Prairie Reconstruction Funding Final Report, FY 2016

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Final report on funding received from the Natural Resources Program Center to support surrogate species planning and implementation and the Prairie Reconstruction...

  9. Trimethylsilylethynyl ketones as surrogates for ethynyl ketones in the double Michael reaction.

    Science.gov (United States)

    Holeman, Derrick S; Rasne, Ravindra M; Grossman, Robert B

    2002-05-01

    Trimethylsilylethynyl ketones can be desilylated in the presence of a tethered carbon diacid and induced to undergo a double Michael reaction in situ. The trimethylsilylethynyl ketones can serve as surrogates of ethynyl ketones that are difficult to prepare or isolate.

  10. 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.

  11. Using multiscale spatial models to assess potential surrogate habitat for an imperiled reptile.

    Directory of Open Access Journals (Sweden)

    Jennifer M Fill

    Full Text Available In evaluating conservation and management options for species, practitioners might consider surrogate habitats at multiple scales when estimating available habitat or modeling species' potential distributions based on suitable habitats, especially when native environments are rare. Species' dependence on surrogates likely increases as optimal habitat is degraded and lost due to anthropogenic landscape change, and thus surrogate habitats may be vital for an imperiled species' survival in highly modified landscapes. We used spatial habitat models to examine a potential surrogate habitat for an imperiled ambush predator (eastern diamondback rattlesnake, Crotalus adamanteus; EDB at two scales. The EDB is an apex predator indigenous to imperiled longleaf pine ecosystems (Pinus palustris of the southeastern United States. Loss of native open-canopy pine savannas and woodlands has been suggested as the principal cause of the species' extensive decline. We examined EDB habitat selection in the Coastal Plain tidewater region to evaluate the role of marsh as a potential surrogate habitat and to further quantify the species' habitat requirements at two scales: home range (HR and within the home range (WHR. We studied EDBs using radiotelemetry and employed an information-theoretic approach and logistic regression to model habitat selection as use vs.We failed to detect a positive association with marsh as a surrogate habitat at the HR scale; rather, EDBs exhibited significantly negative associations with all landscape patches except pine savanna. Within home range selection was characterized by a negative association with forest and a positive association with ground cover, which suggests that EDBs may use surrogate habitats of similar structure, including marsh, within their home ranges. While our HR analysis did not support tidal marsh as a surrogate habitat, marsh may still provide resources for EDBs at smaller scales.

  12. Flume and field-based calibration of surrogate sensors for monitoring bedload transport

    Science.gov (United States)

    Mao, L.; Carrillo, R.; Escauriaza, C.; Iroume, A.

    2016-01-01

    Bedload transport assessment is important for geomorphological, engineering, and ecological studies of gravel-bed rivers. Bedload can be monitored at experimental stations that require expensive maintenance or by using portable traps, which allows measuring instantaneous transport rates but at a single point and at high costs and operational risks. The need for continuously measuring bedload intensity and dynamics has therefore increased the use and enhancement of surrogate methods. This paper reports on a set of flume experiments in which a Japanese acoustic pipe and an impact plate have been tested using four well-sorted and three poorly sorted sediment mixtures. Additional data were collected in a glacierized high-gradient Andean stream (Estero Morales) using a portable Bunte-type bedload sampler. Results show that the data provided by the acoustic pipe (which is amplified on 6 channels having different gains) can be calibrated for the grain size and for the intensity of transported sediments coarser than 9 mm (R2 = 0.93 and 0.88, respectively). Even if the flume-based calibration is very robust, upscaling the calibration to field applications is more challenging, and the bedload intensity could be predicted better than the grain size of transported sediments (R2 = 0.61 and 0.43, respectively). The inexpensive impact plate equipped with accelerometer could be calibrated for bedload intensity quite well in the flume but only poorly in the field (R2 = 0.16) and could not provide information on the size of transported sediments.

  13. Modelling metal accumulation using humic acid as a surrogate for plant roots.

    Science.gov (United States)

    Le, T T Yen; Swartjes, Frank; Römkens, Paul; Groenenberg, Jan E; Wang, Peng; Lofts, Stephen; Hendriks, A Jan

    2015-04-01

    Metal accumulation in roots was modelled with WHAM VII using humic acid (HA) as a surrogate for root surface. Metal accumulation was simulated as a function of computed metal binding to HA, with a correction term (E(HA)) to account for the differences in binding site density between HA and root surface. The approach was able to model metal accumulation in roots to within one order of magnitude for 95% of the data points. Total concentrations of Mn in roots of Vigna unguiculata, total concentrations of Ni, Zn, Cu and Cd in roots of Pisum sativum, as well as internalized concentrations of Cd, Ni, Pb and Zn in roots of Lolium perenne, were significantly correlated to the computed metal binding to HA. The method was less successful at modelling metal accumulation at low concentrations and in soil experiments. Measured concentrations of Cu internalized in L. perenne roots were not related to Cu binding to HA modelled and deviated from the predictions by over one order of magnitude. The results indicate that metal uptake by roots may under certain conditions be influenced by conditional physiological processes that cannot simulated by geochemical equilibrium. Processes occurring in chronic exposure of plants grown in soil to metals at low concentrations complicate the relationship between computed metal binding to HA and measured metal accumulation in roots.

  14. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  15. Adaptive surrogate model based multi-objective transfer trajectory optimization between different libration points

    Science.gov (United States)

    Peng, Haijun; Wang, Wei

    2016-10-01

    An adaptive surrogate model-based multi-objective optimization strategy that combines the benefits of invariant manifolds and low-thrust control toward developing a low-computational-cost transfer trajectory between libration orbits around the L1 and L2 libration points in the Sun-Earth system has been proposed in this paper. A new structure for a multi-objective transfer trajectory optimization model that divides the transfer trajectory into several segments and gives the dominations for invariant manifolds and low-thrust control in different segments has been established. To reduce the computational cost of multi-objective transfer trajectory optimization, a mixed sampling strategy-based adaptive surrogate model has been proposed. Numerical simulations show that the results obtained from the adaptive surrogate-based multi-objective optimization are in agreement with the results obtained using direct multi-objective optimization methods, and the computational workload of the adaptive surrogate-based multi-objective optimization is only approximately 10% of that of direct multi-objective optimization. Furthermore, the generating efficiency of the Pareto points of the adaptive surrogate-based multi-objective optimization is approximately 8 times that of the direct multi-objective optimization. Therefore, the proposed adaptive surrogate-based multi-objective optimization provides obvious advantages over direct multi-objective optimization methods.

  16. Band-phase-randomized Surrogates to assess nonlinearity in non-stationary time series

    CERN Document Server

    Guarin, Diego; Orozco, Alvaro

    2011-01-01

    Testing for nonlinearity is one of the most important preprocessing steps in nonlinear time series analysis. Typically, this is done by means of the linear surrogate data methods. But it is a known fact that the validity of the results heavily depends on the stationarity of the time series. Since most physiological signals are non-stationary, it is easy to falsely detect nonlinearity using the linear surrogate data methods. In this document, we propose a methodology to extend the procedure for generating constrained surrogate time series in order to assess nonlinearity in non-stationary data. The method is based on the band-phase-randomized surrogates, which consists (contrary to the linear surrogate data methods) in randomizing only a portion of the Fourier phases in the high frequency band. Analysis of simulated time series showed that in comparison to the linear surrogate data method, our method is able to discriminate between linear stationarity, linear non-stationary and nonlinear time series. When apply...

  17. Laminar Burning Velocities of Fuels for Advanced Combustion Engines (FACE) Gasoline and Gasoline Surrogates with and without Ethanol Blending Associated with Octane Rating

    KAUST Repository

    Mannaa, Ossama A.

    2016-05-04

    Laminar burning velocities of fuels for advanced combustion engines (FACE) C gasoline and of several blends of surrogate toluene reference fuels (TRFs) (n-heptane, iso-octane, and toluene mixtures) of the same research octane number are presented. Effects of ethanol addition on laminar flame speed of FACE-C and its surrogate are addressed. Measurements were conducted using a constant volume spherical combustion vessel in the constant pressure, stable flame regime at an initial temperature of 358 K and initial pressures up to 0.6 MPa with the equivalence ratios ranging from 0.8 to 1.6. Comparable values in the laminar burning velocities were measured for the FACE-C gasoline and the proposed surrogate fuel (17.60% n-heptane + 77.40% iso-octane + 5% toluene) over the range of experimental conditions. Sensitivity of flame propagation to total stretch rate effects and thermo-diffusive instability was quantified by determining Markstein length. Two percentages of an oxygenated fuel of ethanol as an additive, namely, 60 vol% and 85 vol% were investigated. The addition of ethanol to FACE-C and its surrogate TRF-1 (17.60% n-heptane + 77.40% iso-octane + 5% toluene) resulted in a relatively similar increase in the laminar burning velocities. The high-pressure measured values of Markstein length for the studied fuels blended with ethanol showed minimal influence of ethanol addition on the flame’s response to stretch rate and thermo-diffusive instability. © 2016 Taylor & Francis.

  18. Composite Sampling Approaches for Bacillus anthracis Surrogate Extracted from Soil

    Science.gov (United States)

    France, Brian; Bell, William; Chang, Emily; Scholten, Trudy

    2015-01-01

    Any release of anthrax spores in the U.S. would require action to decontaminate the site and restore its use and operations as rapidly as possible. The remediation activity would require environmental sampling, both initially to determine the extent of contamination (hazard mapping) and post-decon to determine that the site is free of contamination (clearance sampling). Whether the spore contamination is within a building or outdoors, collecting and analyzing what could be thousands of samples can become the factor that limits the pace of restoring operations. To address this sampling and analysis bottleneck and decrease the time needed to recover from an anthrax contamination event, this study investigates the use of composite sampling. Pooling or compositing of samples is an established technique to reduce the number of analyses required, and its use for anthrax spore sampling has recently been investigated. However, use of composite sampling in an anthrax spore remediation event will require well-documented and accepted methods. In particular, previous composite sampling studies have focused on sampling from hard surfaces; data on soil sampling are required to extend the procedure to outdoor use. Further, we must consider whether combining liquid samples, thus increasing the volume, lowers the sensitivity of detection and produces false negatives. In this study, methods to composite bacterial spore samples from soil are demonstrated. B. subtilis spore suspensions were used as a surrogate for anthrax spores. Two soils (Arizona Test Dust and sterilized potting soil) were contaminated and spore recovery with composites was shown to match individual sample performance. Results show that dilution can be overcome by concentrating bacterial spores using standard filtration methods. This study shows that composite sampling can be a viable method of pooling samples to reduce the number of analysis that must be performed during anthrax spore remediation. PMID:26714315

  19. Composite Sampling Approaches for Bacillus anthracis Surrogate Extracted from Soil.

    Science.gov (United States)

    France, Brian; Bell, William; Chang, Emily; Scholten, Trudy

    2015-01-01

    Any release of anthrax spores in the U.S. would require action to decontaminate the site and restore its use and operations as rapidly as possible. The remediation activity would require environmental sampling, both initially to determine the extent of contamination (hazard mapping) and post-decon to determine that the site is free of contamination (clearance sampling). Whether the spore contamination is within a building or outdoors, collecting and analyzing what could be thousands of samples can become the factor that limits the pace of restoring operations. To address this sampling and analysis bottleneck and decrease the time needed to recover from an anthrax contamination event, this study investigates the use of composite sampling. Pooling or compositing of samples is an established technique to reduce the number of analyses required, and its use for anthrax spore sampling has recently been investigated. However, use of composite sampling in an anthrax spore remediation event will require well-documented and accepted methods. In particular, previous composite sampling studies have focused on sampling from hard surfaces; data on soil sampling are required to extend the procedure to outdoor use. Further, we must consider whether combining liquid samples, thus increasing the volume, lowers the sensitivity of detection and produces false negatives. In this study, methods to composite bacterial spore samples from soil are demonstrated. B. subtilis spore suspensions were used as a surrogate for anthrax spores. Two soils (Arizona Test Dust and sterilized potting soil) were contaminated and spore recovery with composites was shown to match individual sample performance. Results show that dilution can be overcome by concentrating bacterial spores using standard filtration methods. This study shows that composite sampling can be a viable method of pooling samples to reduce the number of analysis that must be performed during anthrax spore remediation.

  20. Composite Sampling Approaches for Bacillus anthracis Surrogate Extracted from Soil.

    Directory of Open Access Journals (Sweden)

    Brian France

    Full Text Available Any release of anthrax spores in the U.S. would require action to decontaminate the site and restore its use and operations as rapidly as possible. The remediation activity would require environmental sampling, both initially to determine the extent of contamination (hazard mapping and post-decon to determine that the site is free of contamination (clearance sampling. Whether the spore contamination is within a building or outdoors, collecting and analyzing what could be thousands of samples can become the factor that limits the pace of restoring operations. To address this sampling and analysis bottleneck and decrease the time needed to recover from an anthrax contamination event, this study investigates the use of composite sampling. Pooling or compositing of samples is an established technique to reduce the number of analyses required, and its use for anthrax spore sampling has recently been investigated. However, use of composite sampling in an anthrax spore remediation event will require well-documented and accepted methods. In particular, previous composite sampling studies have focused on sampling from hard surfaces; data on soil sampling are required to extend the procedure to outdoor use. Further, we must consider whether combining liquid samples, thus increasing the volume, lowers the sensitivity of detection and produces false negatives. In this study, methods to composite bacterial spore samples from soil are demonstrated. B. subtilis spore suspensions were used as a surrogate for anthrax spores. Two soils (Arizona Test Dust and sterilized potting soil were contaminated and spore recovery with composites was shown to match individual sample performance. Results show that dilution can be overcome by concentrating bacterial spores using standard filtration methods. This study shows that composite sampling can be a viable method of pooling samples to reduce the number of analysis that must be performed during anthrax spore remediation.

  1. Interactions between Human Norovirus Surrogates and Acanthamoeba spp.

    Science.gov (United States)

    Hsueh, Tun-Yun; Gibson, Kristen E

    2015-06-15

    Human noroviruses (HuNoVs) are the most common cause of food-borne disease outbreaks, as well as virus-related waterborne disease outbreaks in the United States. Here, we hypothesize that common free-living amoebae (FLA)-ubiquitous in the environment, known to interact with pathogens, and frequently isolated from water and fresh produce-could potentially act as reservoirs of HuNoV and facilitate the environmental transmission of HuNoVs. To investigate FLA as reservoirs for HuNoV, the interactions between two Acanthamoeba species, A. castellanii and A. polyphaga, as well as two HuNoV surrogates, murine norovirus type 1 (MNV-1) and feline calicivirus (FCV), were evaluated. The results showed that after 1 h of amoeba-virus incubation at 25°C, 490 and 337 PFU of MNV-1/ml were recovered from A. castellanii and A. polyphaga, respectively, while only few or no FCVs were detected. In addition, prolonged interaction of MNV-1 with amoebae was investigated for a period of 8 days, and MNV-1 was demonstrated to remain stable at around 200 PFU/ml from day 2 to day 8 after virus inoculation in A. castellanii. Moreover, after a complete amoeba life cycle (i.e., encystment and excystment), infectious viruses could still be detected. To determine the location of virus associated with amoebae, immunofluorescence experiments were performed and showed MNV-1 transitioning from the amoeba surface to inside the amoeba over a 24-h period. These results are significant to the understanding of how HuNoVs may interact with other microorganisms in the environment in order to aid in its persistence and survival, as well as potential transmission in water and to vulnerable food products such as fresh produce.

  2. Desorption of a methamphetamine surrogate from wallboard under remediation conditions

    Science.gov (United States)

    Poppendieck, Dustin; Morrison, Glenn; Corsi, Richard

    2015-04-01

    Thousands of homes in the United States are found to be contaminated with methamphetamine each year. Buildings used to produce illicit methamphetamine are typically remediated by removing soft furnishings and stained materials, cleaning and sometimes encapsulating surfaces using paint. Methamphetamine that has penetrated into paint films, wood and other permanent materials can be slowly released back into the building air over time, exposing future occupants and re-contaminating furnishings. The objective of this study was to determine the efficacy of two wallboard remediation techniques for homes contaminated with methamphetamine: 1) enhancing desorption by elevating temperature and relative humidity while ventilating the interior space, and 2) painting over affected wallboard to seal the methamphetamine in place. The emission of a methamphetamine surrogate, N-isopropylbenzylamine (NIBA), from pre-dosed wallboard chambers over 20 days at 32 °C and two values of relative humidity were studied. Emission rates from wallboard after 15 days at 32 °C ranged from 35 to 1400 μg h-1 m-2. Less than 22% of the NIBA was removed from the chambers over three weeks. Results indicate that elevating temperatures during remediation and latex painting of impacted wallboard will not significantly reduce freebase methamphetamine emissions from wallboard. Raising the relative humidity from 27% to 49% increased the emission rates by a factor of 1.4. A steady-state model of a typical home using the emission rates from this study and typical residential building parameters and conditions shows that adult inhalation reference doses for methamphetamine will be reached when approximately 1 g of methamphetamine is present in the wallboard of a house.

  3. Monoclonal antibody "gold rush".

    Science.gov (United States)

    Maggon, Krishan

    2007-01-01

    The market, sales and regulatory approval of new human medicines, during the past few years, indicates increasing number and share of new biologics and emergence of new multibillion dollar molecules. The global sale of monoclonal antibodies in 2006 were $20.6 billion. Remicade had annual sales gain of $1 billion during the past 3 years and five brands had similar increase in 2006. Rituxan with 2006 sales of $4.7 billion was the best selling monoclonal antibody and biological product and the 6th among the top selling medicinal brand. It may be the first biologic and monoclonal antibody to reach $10 billion annual sales in the near future. The strong demand from cancer and arthritis patients has surpassed almost all commercial market research reports and sales forecast. Seven monoclonal antibody brands in 2006 had sales exceeding $1 billion. Humanized or fully human monoclonal antibodies with low immunogenicity, enhanced antigen binding and reduced cellular toxicity provide better clinical efficacy. The higher technical and clinical success rate, overcoming of technical hurdles in large scale manufacturing, low cost of market entry and IND filing, use of fully human and humanized monoclonal antibodies has attracted funds and resources towards R&D. Review of industry research pipeline and sales data during the past 3 years indicate a real paradigm shift in industrial R&D from pharmaceutical to biologics and monoclonal antibodies. The antibody bandwagon has been joined by 200 companies with hundreds of new projects and targets and has attracted billions of dollars in R&D investment, acquisitions and licensing deals leading to the current Monoclonal Antibody Gold Rush.

  4. Novel 18650 lithium-ion battery surrogate cell design with anisotropic thermophysical properties for studying failure events

    Science.gov (United States)

    Spinner, Neil S.; Hinnant, Katherine M.; Mazurick, Ryan; Brandon, Andrew; Rose-Pehrsson, Susan L.; Tuttle, Steven G.

    2016-04-01

    Cylindrical 18650-type surrogate cells were designed and fabricated to mimic the thermophysical properties and behavior of active lithium-ion batteries. An internal jelly roll geometry consisting of alternating stainless steel and mica layers was created, and numerous techniques were used to estimate thermophysical properties. Surrogate cell density was measured to be 1593 ± 30 kg/m3, and heat capacity was found to be 727 ± 18 J/kg-K. Axial thermal conductivity was determined to be 5.1 ± 0.6 W/m-K, which was over an order of magnitude higher than radial thermal conductivity due to jelly roll anisotropy. Radial heating experiments were combined with numerical and analytical solutions to the time-dependent, radial heat conduction equation, and from the numerical method an additional estimate for heat capacity of 805 ± 23 J/kg-K was found. Using both heat capacities and analysis techniques, values for radial thermal conductivity were between 0.120 and 0.197 W/m-K. Under normal operating conditions, relatively low radial temperature distributions were observed; however, during extreme battery failure with a hexagonal cell package, instantaneous radial temperature distributions as high as 43-71 °C were seen. For a vertical cell package, even during adjacent cell failure, similar homogeneity in internal temperatures were observed, demonstrating thermal anisotropy.

  5. Antiphospholipid antibody syndrome.

    Science.gov (United States)

    Kutteh, William H; Hinote, Candace D

    2014-03-01

    Antiphospholipid antibodies (aPLs) are acquired antibodies directed against negatively charged phospholipids. Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings. Obstetric APS is one of the most commonly identified causes of recurrent pregnancy loss. Thus, obstetric APS is distinguished from APS in other organ systems where the most common manifestation is thrombosis. Several pathophysiologic mechanisms of action of aPLs have been described. This article discusses the diagnostic and obstetric challenges of obstetric APS, proposed pathophysiologic mechanisms of APS during pregnancy, and the management of women during and after pregnancy.

  6. A Laboratory Investigation of the Suspension, Transport, and Settling of Silver Carp Eggs Using Synthetic Surrogates.

    Science.gov (United States)

    Garcia, Tatiana; Zuniga Zamalloa, Carlo; Jackson, P Ryan; Murphy, Elizabeth A; Garcia, Marcelo H

    2015-01-01

    Asian carp eggs are semi-buoyant and must remain suspended in the water to survive, supported by the turbulence of the flow, until they hatch and develop the ability to swim. Analysis of the transport and dispersal patterns of Asian carp eggs will facilitate the development and implementation of control strategies to target the early life stages. Experimenting with Asian carp eggs is complicated due to practical issues of obtaining eggs in close proximity to experimental facilities and extensive handling of eggs tends to damage them. Herein, we describe laboratory experiments using styrene beads (4.85 mm diameter) as synthetic surrogate eggs to mimic the physical properties of water-hardened silver carp eggs. The first set of experiments was completed in a rectangular vertical column filled with salt water. The salinity of the water was adjusted in an iterative fashion to obtain a close approximation of the fall velocity of the styrene beads to the mean fall velocity of silver carp water-hardened eggs. The terminal fall velocity of synthetic eggs was measured using an image processing method. The second set of experiments was performed in a temperature-controlled recirculatory flume with a sediment bed. The flume was filled with salt water, and synthetic eggs were allowed to drift under different flow conditions. Drifting behavior, suspension conditions, and settling characteristics of synthetic eggs were observed. At high velocities, eggs were suspended and distributed through the water column. Eggs that touched the sediment bed were re-entrained by the flow. Eggs saltated when they touched the bed, especially at moderate velocities and with a relatively flat bed. At lower velocities, some settling of the eggs was observed. With lower velocities and a flat bed, eggs were trapped near the walls of the flume. When bedforms were present, eggs were trapped in the lee of the bedforms in addition to being trapped near the flume walls. Results of this research study

  7. A Laboratory Investigation of the Suspension, Transport, and Settling of Silver Carp Eggs Using Synthetic Surrogates.

    Directory of Open Access Journals (Sweden)

    Tatiana Garcia

    Full Text Available Asian carp eggs are semi-buoyant and must remain suspended in the water to survive, supported by the turbulence of the flow, until they hatch and develop the ability to swim. Analysis of the transport and dispersal patterns of Asian carp eggs will facilitate the development and implementation of control strategies to target the early life stages. Experimenting with Asian carp eggs is complicated due to practical issues of obtaining eggs in close proximity to experimental facilities and extensive handling of eggs tends to damage them. Herein, we describe laboratory experiments using styrene beads (4.85 mm diameter as synthetic surrogate eggs to mimic the physical properties of water-hardened silver carp eggs. The first set of experiments was completed in a rectangular vertical column filled with salt water. The salinity of the water was adjusted in an iterative fashion to obtain a close approximation of the fall velocity of the styrene beads to the mean fall velocity of silver carp water-hardened eggs. The terminal fall velocity of synthetic eggs was measured using an image processing method. The second set of experiments was performed in a temperature-controlled recirculatory flume with a sediment bed. The flume was filled with salt water, and synthetic eggs were allowed to drift under different flow conditions. Drifting behavior, suspension conditions, and settling characteristics of synthetic eggs were observed. At high velocities, eggs were suspended and distributed through the water column. Eggs that touched the sediment bed were re-entrained by the flow. Eggs saltated when they touched the bed, especially at moderate velocities and with a relatively flat bed. At lower velocities, some settling of the eggs was observed. With lower velocities and a flat bed, eggs were trapped near the walls of the flume. When bedforms were present, eggs were trapped in the lee of the bedforms in addition to being trapped near the flume walls. Results of this

  8. Flame ignition studies of conventional and alternative jet fuels and surrogate components

    Science.gov (United States)

    Liu, Ning

    Practical jet fuels are widely used in air-breathing propulsion, but the chemical mechanisms that control their combustion are not yet understood. Thousands of components are contained in conventional and alternative jet fuels, making thus any effort to model their combustion behavior a daunting task. That has been the motivation behind the development of surrogate fuels that contain typically a small number of neat components, whose physical properties and combustion behavior mimic those of the real jet fuel, and whose kinetics could be modeled with increased degree of confidence. Towards that end, a large number of experimental data are required both for the real fuels and the attendant surrogate components that could be used to develop and validate detailed kinetic models. Those kinetic models could be used then upon reduction to model a combustor and eventually optimize its performance. Among all flame phenomena, ignition is rather sensitive to the oxidative and pyrolytic propensity of the fuel as well as to its diffusivity. The counterflow configuration is ideal in probing both the fuel reactivity and diffusivity aspects of the ignition process and it was used in the present work to determine the ignition temperatures of premixed and non-premixed flames of a variety of fuels relevant to air-breathing propulsion. The experiments were performed at atmospheric pressure, elevated unburned fuel mixture temperatures, and various strain rates that were measured locally. Several recent kinetic models were used in direct numerical simulations of the experiments and the computed results were tested against the experimental data. Furthermore, through sensitivity, reaction path, and structure analyses of the computed flames, insight was provided into the dominant mechanisms that control ignition. It was found that ignition is primarily sensitive to fuel diffusion and secondarily sensitive to chemical kinetics and intermediate species diffusivities under the low fuel

  9. Coastal aquifer management under parameter uncertainty: Ensemble surrogate modeling based simulation-optimization

    Science.gov (United States)

    Janardhanan, S.; Datta, B.

    2011-12-01

    Surrogate models are widely used to develop computationally efficient simulation-optimization models to solve complex groundwater management problems. Artificial intelligence based models are most often used for this purpose where they are trained using predictor-predictand data obtained from a numerical simulation model. Most often this is implemented with the assumption that the parameters and boundary conditions used in the numerical simulation model are perfectly known. However, in most practical situations these values are uncertain. Under these circumstances the application of such approximation surrogates becomes limited. In our study we develop a surrogate model based coupled simulation optimization methodology for determining optimal pumping strategies for coastal aquifers considering parameter uncertainty. An ensemble surrogate modeling approach is used along with multiple realization optimization. The methodology is used to solve a multi-objective coastal aquifer management problem considering two conflicting objectives. Hydraulic conductivity and the aquifer recharge are considered as uncertain values. Three dimensional coupled flow and transport simulation model FEMWATER is used to simulate the aquifer responses for a number of scenarios corresponding to Latin hypercube samples of pumping and uncertain parameters to generate input-output patterns for training the surrogate models. Non-parametric bootstrap sampling of this original data set is used to generate multiple data sets which belong to different regions in the multi-dimensional decision and parameter space. These data sets are used to train and test multiple surrogate models based on genetic programming. The ensemble of surrogate models is then linked to a multi-objective genetic algorithm to solve the pumping optimization problem. Two conflicting objectives, viz, maximizing total pumping from beneficial wells and minimizing the total pumping from barrier wells for hydraulic control of

  10. Soot formation characteristics of gasoline surrogate fuels in counterflow diffusion flames

    KAUST Repository

    Choi, Byungchul

    2011-01-01

    The characteristics of polycyclic aromatic hydrocarbon (PAH) and soot for gasoline surrogate fuels have been investigated in counterflow diffusion flames by adopting laser-induced fluorescence (LIF) and laser-induced incandescence (LII) techniques for both soot formation and soot formation/oxidation flames. Tested fuels were three binary mixtures from the primary reference fuels of n-heptane, iso-octane, and toluene. The result showed that PAH and soot maintained near zero level for all mixtures of n-heptane/iso-octane case under present experimental conditions. For n-heptane/toluene and iso-octane/toluene mixtures, PAH initially increased and then decreased with the toluene ratio, exhibiting a synergistic effect. The soot formation increased monotonically with the toluene ratio, however the effect of toluene on soot formation was minimal for relatively small toluene ratios. These results implied that even though toluene had a dominant role in soot and PAH formations, small amount of toluene had a minimal effect on soot formation. Numerical simulations have also been conducted by adopting recently proposed two kinetic mechanisms. The synergistic behavior of aromatic rings was predicted similar to the experimental PAH measurement, however, the degree of the synergistic effect was over-predicted for the soot formation flame, indicating the need for refinements in the kinetic mechanisms. © 2010 Published by Elsevier Inc. on behalf of The Combustion Institute. All rights reserved.

  11. Utilisation of transparent synthetic soil surrogates in geotechnical physical models:A review

    Institute of Scientific and Technical Information of China (English)

    Abideen Adekunle Ganiyu; Ahmad Safuan A. Rashid; Mohd Hanim Osman

    2016-01-01

    Efforts to obtain non-intrusive measurement of deformations and spatial flow within soil mass prior to the advent of transparent soils have perceptible limitations. The transparent soil is a two-phase medium composed of both the synthetic aggregate and fluid components of identical refractive indices aiming at attaining transparency of the resulting soil. The transparency facilitates real life visualisation of soil continuum in physical models. When applied in conjunction with advanced photogrammetry and image processing techniques, transparent soils enable the quantification of the spatial deformation, displace-ment and multi-phase flow in physical model tests. Transparent synthetic soils have been successfully employed in geotechnical model tests as soil surrogates based on the testing results of their geotechnical properties which replicate those of natural soils. This paper presents a review on transparent synthetic soils and their numerous applications in geotechnical physical models. The properties of the aggregate materials are outlined and the features of the various transparent clays and sands available in the literature are described. The merits of transparent soil are highlighted and the need to amplify its application in geotechnical physical model researches is emphasised. This paper will serve as a concise compendium on the subject of transparent soils for future researchers in this field.

  12. Is Ceftizoxime an Appropriate Surrogate for Amikacin in Neonatal Sepsis Treatment? A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Peyman Salamati

    2011-08-01

    Full Text Available Neonatal sepsis, a life-threatening condition, presents with non-specific clinical manifestations and needs immediate empirical antimicrobial therapy. Choosing an appropriate antibiotic regimen covering the most probable pathogens is an important issue. In this study we compared the effectiveness of ceftizoxime and amikacin in the treatment of neonatal sepsis both in combination with ampicillin. In a randomized clinical trial, all term neonates with suspected sepsis referred to Bahrami hospital during March 2008 to March 2010 were evaluated. Patients were randomly recruited into two groups; one group receiving ampicillin and amikacin and the other ampicillin and ceftizoxime. Blood, urine and cerebrospinal fluid cultures, leukocyte count and C-reactive protein level were measured in all neonates. A total of 135 neonates were evaluated, 65 in amikacin group and 70 in ceftizoxime group. 60 neonates (85.7% in ceftizoxime group and 54 neonates (83.1% in amikacin group responded to the treatment (P= 0.673 and χ2 = 0.178. Only 24 (18% blood samples had a report of positive blood culture. The most frequent pathogen was coagulase negative staphylococcus with the frequency of 58.32% of all positive blood samples. Ceftizoxime in combination with ampicillin is an appropriate antimicrobial regimen for surrogating the combination of ampicillin and amikacin to prevent bacterial resistance against them.

  13. Foot-mediated incubation: Nazca booby (Sula granti) feet as surrogate brood patches.

    Science.gov (United States)

    Morgan, Stephanie M; Ashley-Ross, Miriam A; Anderson, David J

    2003-01-01

    Incubation in most avian species involves transferring heat from parent to egg through a highly vascularized brood patch. Some birds, however, do not develop a brood patch. Unusual among birds, these species hold their eggs under the webs of their feet, but the role of the feet in heat transfer is uncertain. Often the webs are positioned between the feathered abdomen and the egg during incubation, suggesting that either the abdomen, the feet, or both could transfer heat to the egg. We studied heat transfer from foot webs to eggs during incubation in Nazca boobies by spatially separating the feet from the abdomen using an oversized egg. We found that feet transfer heat to eggs independently of any heat that may be transferred from the abdomen. In addition, we found that incubating boobies had significantly greater vascularization in their foot webs, measured as a percentage of web area covered by vessels, than nonincubating boobies. We also found that males, whether incubating or nonincubating, had significantly less web vascularization than females. We concluded that vascularized Nazca booby feet function in the same way during incubation that vascularized brood patches do, acting as surrogate brood patches.

  14. Generation of hydroxyl radicals from ambient fine particles in a surrogate lung fluid solution.

    Science.gov (United States)

    Vidrio, Edgar; Phuah, Chin H; Dillner, Ann M; Anastasio, Cort

    2009-02-01

    While it has been hypothesized that the adverse health effects associated with ambient particulate matter (PM) are due to production of hydroxyl radical (*OH), few studies have quantified *OH production from PM. Here we report the amounts of *OH produced from ambient fine particles (PM2.5) collected in northern California and extracted in a cell-free surrogate lung fluid (SLF). On average, the extracted particles produced 470 nmol *OH mg(-1)-PM2.5 during our 15-month collection period. There was a clear seasonal pattern in the efficiency with which particles generated *OH, with highest production during spring and summer and lowest during winter. In addition, nighttime PM was typically more efficient than daytime PM at generating *OH. Transition metals played the dominant role in *OH production: on average (+/-sigma), the addition of desferoxamine (a chelator that prevents metals from forming *OH) to the SLF removed (90 +/- 5) % of *OH generation. Furthermore, based on the concentrations of Fe in the PM2.5 SLF extracts, and the measured yield of *OH as a function of Fe concentration, dissolved iron can account for the majority of *OH produced in most of our PM2.5 extracts.

  15. Homocysteine and C-Reactive Protein as Useful Surrogate Markers for Evaluating CKD Risk in Adults

    Directory of Open Access Journals (Sweden)

    Chung-Hsun Chuang

    2013-10-01

    Full Text Available Background/Aims: This study aimed to evaluate the effectiveness of homocysteine and C-reactive protein (CRP as potential markers for chronic kidney disease (CKD in adults in Taiwan, and to identify associations between these factors and CKD, stratifying by gender. Methods: This cross-sectional study analyzed multi-center data retrospectively. Data were collected from 22,043 adult Taiwanese at Chang-Gung Memorial Hospital from 2005 to 2011. Smoking/drinking history, personal medical/medication history, pregnancy, fasting times as well as laboratory parameters, including homocysteine and CRP were measured and analyzed. Results: Significant differences were observed between four homocysteine and CRP quartiles in eGFR and CKD. For males, only one model showed significant associations between plasma homocysteine and CKD, while in females, all three models showed significant associations with CKD. On the contrary, the gender difference in the case of CRP was opposite. Combined homocysteine and CRP were associated with CKD in males but not in females. Conclusion: Among Taiwanese adults, plasma homocysteine is associated with CKD in females and plasma hsCRP is associated with CKD in males. High hsCRP/high homocysteine is associated with elevated CKD risk in male. Our results suggest that homocysteine and hsCRP may be useful surrogate markers for evaluating CKD risk in adults.

  16. Utilisation of transparent synthetic soil surrogates in geotechnical physical models: A review

    Directory of Open Access Journals (Sweden)

    Abideen Adekunle Ganiyu

    2016-08-01

    Full Text Available Efforts to obtain non-intrusive measurement of deformations and spatial flow within soil mass prior to the advent of transparent soils have perceptible limitations. The transparent soil is a two-phase medium composed of both the synthetic aggregate and fluid components of identical refractive indices aiming at attaining transparency of the resulting soil. The transparency facilitates real life visualisation of soil continuum in physical models. When applied in conjunction with advanced photogrammetry and image processing techniques, transparent soils enable the quantification of the spatial deformation, displacement and multi-phase flow in physical model tests. Transparent synthetic soils have been successfully employed in geotechnical model tests as soil surrogates based on the testing results of their geotechnical properties which replicate those of natural soils. This paper presents a review on transparent synthetic soils and their numerous applications in geotechnical physical models. The properties of the aggregate materials are outlined and the features of the various transparent clays and sands available in the literature are described. The merits of transparent soil are highlighted and the need to amplify its application in geotechnical physical model researches is emphasised. This paper will serve as a concise compendium on the subject of transparent soils for future researchers in this field.

  17. Effect of surrogate aggregates on the thermal conductivity of concrete at ambient and elevated temperatures.

    Science.gov (United States)

    Yun, Tae Sup; Jeong, Yeon Jong; Youm, Kwang-Soo

    2014-01-01

    The accurate assessment of the thermal conductivity of concretes is an important part of building design in terms of thermal efficiency and thermal performance of materials at various temperatures. We present an experimental assessment of the thermal conductivity of five thermally insulated concrete specimens made using lightweight aggregates and glass bubbles in place of normal aggregates. Four different measurement methods are used to assess the reliability of the thermal data and to evaluate the effects of the various sensor types. The concrete specimens are also assessed at every 100 °C during heating to ~800 °C. Normal concrete is shown to have a thermal conductivity of ~2.25 W m(-1) K(-1). The surrogate aggregates effectively reduce the conductivity to ~1.25 W m(-1) K(-1) at room temperature. The aggregate size is shown not to affect thermal conduction: fine and coarse aggregates each lead to similar results. Surface contact methods of assessment tend to underestimate thermal conductivity, presumably owing to high thermal resistance between the transducers and the specimens. Thermogravimetric analysis shows that the stages of mass loss of the cement paste correspond to the evolution of thermal conductivity upon heating.

  18. Anti-cartilage antibody.

    Science.gov (United States)

    Greenbury, C L; Skingle, J

    1979-08-01

    Antibody to cartilage has been demonstrated by indirect immunofluorescence on rat trachea in the serum of about 3% of 1126 patients with rheumatoid arthritis. Titres ranged from 1:20 to 1:640. The antibody was not found in 284 patients with primary or secondary osteoarthritis or in 1825 blood donors, nor, with the exception of two weak reactors, in 1314 paraplegic patients. In most cases the antibody appears to be specific for native type II collagen. Using this as an antigen in a haemagglutination test 94% of anti-cartilage sera were positive, whereas among 100 rheumatoid control sera there were only three weak positives. More than 80% of patients with antibody had some erosion of articular cartilage, but there was no correlation with age, sex, duration of disease, nor any recognisable clinical event or change.

  19. Antithyroid microsomal antibody

    Science.gov (United States)

    ... to confirm the cause of thyroid problems, including Hashimoto thyroiditis . The test is also used to find ... positive test may be due to: Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also ...

  20. Serum herpes simplex antibodies

    Science.gov (United States)

    ... 2. HSV-1 most often causes cold sores (oral herpes). HSV-2 causes genital herpes. How the Test ... whether a person has ever been infected with oral or genital herpes . It looks for antibodies to herpes simplex virus ...

  1. Immune Dysfunction in Rett Syndrome Patients Revealed by High Levels of Serum Anti-N(Glc IgM Antibody Fraction

    Directory of Open Access Journals (Sweden)

    Anna Maria Papini

    2014-01-01

    Full Text Available Rett syndrome (RTT, a neurodevelopmental disorder affecting exclusively (99% female infants, is associated with loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2 and, more rarely, cyclin-dependent kinase-like 5 (CDKL5 and forkhead box protein G1 (FOXG1. In this study, we aimed to evaluate the function of the immune system by measuring serum immunoglobulins (IgG and IgM in RTT patients (n=53 and, by comparison, in age-matched children affected by non-RTT pervasive developmental disorders (non-RTT PDD (n=82 and healthy age-matched controls (n=29. To determine immunoglobulins we used both a conventional agglutination assay and a novel ELISA based on antibody recognition by a surrogate antigen probe, CSF114(Glc, a synthetic N-glucosylated peptide. Both assays provided evidence for an increase in IgM titer, but not in IgG, in RTT patients relative to both healthy controls and non-RTT PDD patients. The significant difference in IgM titers between RTT patients and healthy subjects in the CSF114(Glc assay (P=0.001 suggests that this procedure specifically detects a fraction of IgM antibodies likely to be relevant for the RTT disease. These findings offer a new insight into the mechanism underlying the Rett disease as they unveil the possible involvement of the immune system in this pathology.

  2. Primary Reference Fuels (PRFs) as Surrogates for Low Sensitivity Gasoline Fuels

    KAUST Repository

    Bhavani Shankar, Vijai Shankar

    2016-04-05

    Primary Reference Fuels (PRFs) - binary mixtures of n-heptane and iso-octane based on Research Octane Number (RON) - are popular gasoline surrogates for modeling combustion in spark ignition engines. The use of these two component surrogates to represent real gasoline fuels for simulations of HCCI/PCCI engines needs further consideration, as the mode of combustion is very different in these engines (i.e. the combustion process is mainly controlled by the reactivity of the fuel). This study presents an experimental evaluation of PRF surrogates for four real gasoline fuels termed FACE (Fuels for Advanced Combustion Engines) A, C, I, and J in a motored CFR (Cooperative Fuels Research) engine. This approach enables the surrogate mixtures to be evaluated purely from a chemical kinetic perspective. The gasoline fuels considered in this study have very low sensitivities, S (RON-MON), and also exhibit two-stage ignition behavior. The first stage heat release, which is termed Low Temperature Heat Release (LTHR), controls the combustion phasing in this operating mode. As a result, the performance of the PRF surrogates was evaluated by its ability to mimic the low temperature chemical reactivity of the real gasoline fuels. This was achieved by comparing the LTHR from the engine pressure histories. The PRF surrogates were able to consistently reproduce the amount of LTHR, closely match the phasing of LTHR, and the compression ratio for the start of hot ignition of the real gasoline fuels. This suggests that the octane quality of a surrogate fuel is a good indicator of the fuel’s reactivity across low (LTC), negative temperature coefficient (NTC), and high temperature chemical (HTC) reactivity regimes.

  3. Ovulation Statuses of Surrogate Gilts Are Associated with the Efficiency of Excellent Pig Cloning.

    Directory of Open Access Journals (Sweden)

    Yanjun Huan

    Full Text Available Somatic cell nuclear transfer (SCNT is an assisted reproductive technique that can produce multiple copies of excellent livestock. However, low cloning efficiency limits the application of SCNT. In this study, we systematically investigated the major influencing factors related to the overall cloning efficiency in pigs. Here, 13620 cloned embryos derived from excellent pigs were transferred into 79 surrogate gilts, and 119 live cloned piglets were eventually generated. During cloning, group of cloned embryos derived from excellent Landrace or Large white pigs presented no significant differences of cleavage and blastocyst rates, blastocyst cell numbers, surrogate pregnancy and delivery rates, average numbers of piglets born and alive and cloning efficiencies, and group of 101-150, 151-200 or 201-250 cloned embryos transferred per surrogate also displayed a similar developmental efficiency. When estrus stage of surrogate gilts was compared, group of embryo transfer on Day 2 of estrus showed significantly higher pregnancy rate, delivery rate, average number of piglets born, average alive piglet number or cloning efficiency than group on Day 1, Day 3, Day 4 or Day 5, respectively (P<0.05. And, in comparison with the preovulation and postovulation groups, group of surrogate gilts during periovulation displayed a significantly higher overall cloning efficiency (P<0.05. Further investigation of surrogate estrus stage and ovulation status displayed that ovulation status was the real factor underlying estrus stage to determine the overall cloning efficiency. And more, follicle puncture for preovulation, not transfer position shallowed for preovulation or deepened for postovulation, significantly improved the average number of piglets alive and cloning efficiency (P<0.05. In conclusion, our results demonstrated that ovulation status of surrogate gilts was the fundamental factor determining the overall cloning efficiency of excellent pigs, and follicle

  4. Real-time characterization of partially observed epidemics using surrogate models.

    Energy Technology Data Exchange (ETDEWEB)

    Safta, Cosmin; Ray, Jaideep; Lefantzi, Sophia; Crary, David (Applied Research Associates, Arlington, VA); Sargsyan, Khachik; Cheng, Karen (Applied Research Associates, Arlington, VA)

    2011-09-01

    We present a statistical method, predicated on the use of surrogate models, for the 'real-time' characterization of partially observed epidemics. Observations consist of counts of symptomatic patients, diagnosed with the disease, that may be available in the early epoch of an ongoing outbreak. Characterization, in this context, refers to estimation of epidemiological parameters that can be used to provide short-term forecasts of the ongoing epidemic, as well as to provide gross information on the dynamics of the etiologic agent in the affected population e.g., the time-dependent infection rate. The characterization problem is formulated as a Bayesian inverse problem, and epidemiological parameters are estimated as distributions using a Markov chain Monte Carlo (MCMC) method, thus quantifying the uncertainty in the estimates. In some cases, the inverse problem can be computationally expensive, primarily due to the epidemic simulator used inside the inversion algorithm. We present a method, based on replacing the epidemiological model with computationally inexpensive surrogates, that can reduce the computational time to minutes, without a significant loss of accuracy. The surrogates are created by projecting the output of an epidemiological model on a set of polynomial chaos bases; thereafter, computations involving the surrogate model reduce to evaluations of a polynomial. We find that the epidemic characterizations obtained with the surrogate models is very close to that obtained with the original model. We also find that the number of projections required to construct a surrogate model is O(10)-O(10{sup 2}) less than the number of samples required by the MCMC to construct a stationary posterior distribution; thus, depending upon the epidemiological models in question, it may be possible to omit the offline creation and caching of surrogate models, prior to their use in an inverse problem. The technique is demonstrated on synthetic data as well as

  5. A Development of a Human Cranial Bone Surrogate for Impact Studies

    Directory of Open Access Journals (Sweden)

    Jack C Roberts

    2013-10-01

    Full Text Available In order to replicate the fracture behavior of the intact human skull under impact it becomes necessary to develop a material having the mechanical properties of cranial bone. The most important properties to replicate in a surrogate human skull were found to be the fracture toughness and tensile strength of the cranial tables as well as the bending strength of the 3-layer (inner table-diplöe-outer table architecture of the human skull. The materials selected to represent the surrogate cranial tables consisted of two different epoxy resins systems with random milled glass fiber to enhance the strength and stiffness and the materials to represent the surrogate diplöe consisted of three low density foams. Forty-one three-point bending fracture toughness tests were performed on nine material combinations. The materials that best represented the fracture toughness of cranial tables were then selected and formed into tensile samples and tested. These materials were then used with the two surrogate diplöe foam materials to create the three layer surrogate cranial bone samples for three point bending tests. Drop tower tests were performed on flat samples created from these materials and the fracture patterns were very similar to the linear fractures seen in pendulum impacts of intact human skulls. The surrogate cranial tables had the quasi-static fracture toughness and tensile strength of 2.5 MPa√m and 53 ± 4.9 MPa, respectively, while the same properties of human compact bone were 3.1 ± 1.8 MPa√m and 68 ± 18 MPa, respectively. The cranial surrogate had a quasi-static bending strength of 68 ± 5.7 MPa, while that of cranial bone was 82 ± 26 MPa. This material/design is currently being used to construct spherical shell samples for drop tower and ballistic tests.

  6. Is Diaphragm Motion a Good Surrogate for Liver Tumor Motion?

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Juan [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); School of Information Science and Engineering, Shandong University, Jinan, Shandong (China); Cai, Jing [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Wang, Hongjun [School of Information Science and Engineering, Shandong University, Jinan, Shandong (China); Chang, Zheng; Czito, Brian G. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Bashir, Mustafa R. [Department of Radiology, Duke University Medical Center, Durham, North Carolina (United States); Palta, Manisha [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Yin, Fang-Fang, E-mail: fangfang.yin@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2014-11-15

    Purpose: To evaluate the relationship between liver tumor motion and diaphragm motion. Methods and Materials: Fourteen patients with hepatocellular carcinoma (10 of 14) or liver metastases (4 of 14) undergoing radiation therapy were included in this study. All patients underwent single-slice cine–magnetic resonance imaging simulations across the center of the tumor in 3 orthogonal planes. Tumor and diaphragm motion trajectories in the superior–inferior (SI), anterior–posterior (AP), and medial–lateral (ML) directions were obtained using an in-house-developed normalized cross-correlation–based tracking technique. Agreement between the tumor and diaphragm motion was assessed by calculating phase difference percentage, intraclass correlation coefficient, and Bland-Altman analysis (Diff). The distance between the tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between the 2 motions. Results: Of all patients, the mean (±standard deviation) phase difference percentage values were 7.1% ± 1.1%, 4.5% ± 0.5%, and 17.5% ± 4.5% in the SI, AP, and ML directions, respectively. The mean intraclass correlation coefficient values were 0.98 ± 0.02, 0.97 ± 0.02, and 0.08 ± 0.06 in the SI, AP, and ML directions, respectively. The mean Diff values were 2.8 ± 1.4 mm, 2.4 ± 1.1 mm, and 2.2 ± 0.5 mm in the SI, AP, and ML directions, respectively. Tumor and diaphragm motions had high concordance when the distance between the tumor and tracked diaphragm area was small. Conclusions: This study showed that liver tumor motion had good correlation with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be used as a reliable surrogate for liver tumor motion.

  7. Longitudinal Analysis of Tetanus- and Influenza-Specific IgG Antibodies in Myeloma Patients

    Directory of Open Access Journals (Sweden)

    Sebastian Kobold

    2012-01-01

    Full Text Available Background. Multiple myeloma (MM and its therapies may induce a severely compromised humoral immunity. We have performed a longitudinal analysis of IgG-antibody responses against influenza virus (FLU and tetanus toxoid (TT as surrogate markers for the B cell-mediated immunity in MM patients. Methods. 1094 serum samples of 190 MM patients and samples from 100 healthy donors were analyzed by ELISA for FLU- and TT-specific antibodies. Results. MM patients evidenced lower levels of FLU- and TT-specific antibodies than healthy controls (P<0.001. Immunoreactivity decreased with progressing disease and worsening clinical status. Levels of FLU- and TT-specific antibodies increased shortly (0-6 months after alloSCT (P<0.001, a time-period during which intravenous immunoglobulin (IVIG is routinely applied. Thereafter, antibody concentrations declined and remained suppressed for 3 years in the case of FLU-specific and for more than 5 years in the case of TT-specific antibodies. Conclusions. We found that MM is associated with a profound disease- and therapy-related immunosuppression, which is compensated for a few months after alloSCT, most likely by application of IVIG. This and the differences regarding the recovery of anti-FLU and anti-TT antibody titers during the following years need to be taken into account for optimizing IVIG application and immunization after alloSCT.

  8. Anti-cysticercus antibody detection in saliva as a potential diagnostic tool for neurocysticercosis

    Science.gov (United States)

    Saha, Rumpa; Roy, Priyamvada; Das, Shukla; Shah, Dheeraj; Agarwal, Sunil; Kaur, Iqbal Rajinder

    2016-01-01

    Objectives: This study was planned to determine the usefulness of anti-cysticercus IgG antibody detection in saliva for neurocysticercosis (NCC) diagnosis, along with serum C-reactive protein (CRP) level to serve as a surrogate marker. Materials and Methods: In this prospective study of 14 months duration, blood and saliva samples were collected from 40 patients suspected to be suffering from NCC and were subjected to anti-cysticercus IgG antibody detection by ELISA. Serum CRP levels were estimated as acute-phase reactant by high sensitivity CRP ELISA. Results: Anti-cysticercus IgG was detected in serum and saliva of 34 and 30 patients, respectively. Cases positive for salivary antibody were positive for serum antibody and their serum CRP level was higher than normal. Cases negative for salivary antibody had low serum CRP levels. Anti-cysticercus IgG detection in saliva was 88.24% sensitive, 100% specific, and had a positive predictive value of 100% and negative predictive value of 60%. Positive salivary anti-cysticercus IgG and high serum CRP level showed a significant association. Difference between CRP levels of patients positive for anti-cysticercus antibody in both serum and saliva, and patients positive for antibody in serum but not saliva was highly significant. Conclusions: Saliva, being painless and noninvasive, can be used as alternative to serum for NCC diagnosis. PMID:27570404

  9. Diagnosis of natural exposure to bovine viral diarrhea in a vaccinated herd by measuring extended antibody titers against bovine viral diarrhea virus

    OpenAIRE

    Ross, Jeremy

    2003-01-01

    Two abortions occurred in a 150-head commercial cow-calf herd. Bovine viral diarrhea was suspected and confirmed by measuring extended titers against bovine viral diarrhea virus (BVDV) in a sample of 15 breeding females. Fifteen were sero-positive and 11 had significantly high titers (1:972–1:8748), likely due to natural exposure to cattle persistently infected with BVDV.

  10. Heparin-Induced Thrombocytopenia Antibody Test

    Science.gov (United States)

    ... Global Sites Search Help? Heparin-induced Thrombocytopenia PF4 Antibody Share this page: Was this page helpful? Also known as: Heparin-PF4 Antibody; HIT Antibody; HIT PF4 Antibody; Heparin Induced Antibody; ...

  11. Pig and guinea pig skin as surrogates for human in vitro penetration studies: a quantitative review.

    Science.gov (United States)

    Barbero, Ana M; Frasch, H Frederick

    2009-02-01

    Both human and animal skin in vitro models are used to predict percutaneous penetration in humans. The objective of this review is a quantitative comparison of permeability and lag time measurements between human and animal skin, including an evaluation of the intra and inter species variability. We limit our focus to domestic pig and rodent guinea pig skin as surrogates for human skin, and consider only studies in which both animal and human penetration of a given chemical were measured jointly in the same lab. When the in vitro permeability of pig and human skin were compared, the Pearson product moment correlation coefficient (r) was 0.88 (Pskin permeability of 21% for pig and 35% for human, and an inter species average coefficient of variation of 37% for the set of studied compounds (n=41). The lag times of pig skin and human skin did not correlate (r=0.35, P=0.26). When the in vitro permeability of guinea pig and human skin were compared, r=0.96 (Phuman, and an inter species coefficient of variation of permeability of 41% for the set of studied compounds (n=15). Lag times of guinea pig and human skin correlated (r=0.90, Phuman skin was calculated for pig skin (n=50) and guinea pig skin (n=25). For pig skin, 80% of measurements fell within the range 0.3skin, 65% fell within that range. Both pig and guinea pig are good models for human skin permeability and have less variability than the human skin model. The skin model of choice will depend on the final purpose of the study and the compound under investigation.

  12. [New antibodies in cancer treatment].

    Science.gov (United States)

    Pestalozzi, B C; Knuth, A

    2004-09-22

    Since the development of hybridoma technology in 1975 monoclonal antibodies with pre-defined specificity can be produced. Only twenty years later did it become possible to make therapeutic use of monoclonal antibodies in oncology. To this end it was necessary to attach the antigen-binding site of a mouse antibody onto the scaffold of a human antibody molecule. Such chimeric or "humanized" antibodies may be used in passive immunotherapy without eliciting an immune response. Rituximab and trastuzumab are such humanized antibodies. They are used today routinely in the treatment of malignant lymphoma and breast cancer, respectively. These antibodies are usually used in combination with conventional cytostatic anticancer drugs.

  13. Engineering antibodies for cancer therapy.

    Science.gov (United States)

    Boder, Eric T; Jiang, Wei

    2011-01-01

    The advent of modern antibody engineering has led to numerous successes in the application of these proteins for cancer therapy in the 13 years since the first Food and Drug Administration approval, which has stimulated active interest in developing more and better drugs based on these molecules. A wide range of tools for discovering and engineering antibodies has been brought to bear on this challenge in the past two decades. Here, we summarize mechanisms of monoclonal antibody therapeutic activity, challenges to effective antibody-based treatment, existing technologies for antibody engineering, and current concepts for engineering new antibody formats and antibody alternatives as next generation biopharmaceuticals for cancer treatment.

  14. Development of a multi-objective optimization algorithm using surrogate models for coastal aquifer management

    Science.gov (United States)

    Kourakos, George; Mantoglou, Aristotelis

    2013-02-01

    SummaryThe demand for fresh water in coastal areas and islands can be very high due to increased local needs and tourism. A multi-objective optimization methodology is developed, involving minimization of economic and environmental costs while satisfying water demand. The methodology considers desalinization of pumped water and injection of treated water into the aquifer. Variable density aquifer models are computationally intractable when integrated in optimization algorithms. In order to alleviate this problem, a multi-objective optimization algorithm is developed combining surrogate models based on Modular Neural Networks [MOSA(MNNs)]. The surrogate models are trained adaptively during optimization based on a genetic algorithm. In the crossover step, each pair of parents generates a pool of offspring which are evaluated using the fast surrogate model. Then, the most promising offspring are evaluated using the exact numerical model. This procedure eliminates errors in Pareto solution due to imprecise predictions of the surrogate model. The method has important advancements compared to previous methods such as precise evaluation of the Pareto set and alleviation of propagation of errors due to surrogate model approximations. The method is applied to an aquifer in the Greek island of Santorini. The results show that the new MOSA(MNN) algorithm offers significant reduction in computational time compared to previous methods (in the case study it requires only 5% of the time required by other methods). Further, the Pareto solution is better than the solution obtained by alternative algorithms.

  15. Surrogate POD models for building forming limit diagrams of parameterized sheet metal forming applications

    Science.gov (United States)

    Hamdaoui, M.; Le Quilliec, Guénhaël; Breitkopf, Piotr; Villon, Pierre

    2013-05-01

    The aim of this work is to present a surrogate POD (Proper Orthogonal Decomposition) approach for building forming limit diagrams at minimum cost for parameterized sheet metal formed work-pieces. First, a Latin Hypercube Sampling is performed on the design parameter space. Then, at each design site, displacement fields are computed using the popular open-source finite element software Code_Aster. Then, the method of snapshots is used for POD mode determination. POD coefficients are interpolated using kriging. Furthermore, an error analysis of the surrogate POD model is performed on a validation set. It is shown that on the considered use case the accuracy of the surrogate POD model is excellent for the representation of finite element displacement fields. The validated surrogate POD model is then used to build forming limit diagrams (FLD) for any design parameter to assess the quality of stamped metal sheets. Using the surrogate POD model, the Green-Lagrange strain tensor is derived, then major and minor principal deformations are determined at Gauss points for each mesh element. Furthermore, a signed distance between the forming limit curve in rupture and the obtained cloud of points in the plane (ɛ2, ɛ1) is computed to assess the quality of the formed workpiece. The minimization of this signed distance allows determining the safest design for the chosen use case.

  16. Stochastic structural optimization using particle swarm optimization, surrogate models and Bayesian statistics

    Institute of Scientific and Technical Information of China (English)

    Jongbin Im; Jungsun Park

    2013-01-01

    This paper focuses on a method to solve structural optimization problems using particle swarm optimization (PSO),surrogate models and Bayesian statistics.PSO is a random/stochastic search algorithm designed to find the global optimum.However,PSO needs many evaluations compared to gradient-based optimization.This means PSO increases the analysis costs of structural optimization.One of the methods to reduce computing costs in stochastic optimization is to use approximation techniques.In this work,surrogate models are used,including the response surface method (RSM) and Kriging.When surrogate models are used,there are some errors between exact values and approximated values.These errors decrease the reliability of the optimum values and discard the realistic approximation of using surrogate models.In this paper,Bayesian statistics is used to obtain more reliable results.To verify and confirm the efficiency of the proposed method using surrogate models and Bayesian statistics for stochastic structural optimization,two numerical examples are optimized,and the optimization of a hub sleeve is demonstrated as a practical problem.

  17. Surrogate utility estimation by long-term partners and unfamiliar dyads

    Directory of Open Access Journals (Sweden)

    Richard J Tunney

    2015-03-01

    Full Text Available To what extent are people able to make predictions about other people’s preferences and values? We report two experiments that present a novel method assessing some of the basic processes in surrogate decision-making, namely surrogate-utility estimation. In each experiment participants formed dyads who were asked to assign utilities to health related items and commodity items, and to predict their partner’s utility judgments for the same items. In experiment one we showed that older adults in long-term relationships were able to accurately predict their partner’s wishes. In experiment two we showed that younger adults who were relatively unfamiliar with one another were also able to predict other people’s wishes. Crucially we demonstrated that these judgments were accurate even after partialling out each participant’s own preferences indicating that in order to make surrogate utility estimations people engage in perspective-taking rather than simple anchoring and adjustment, suggesting that utility estimation is not the cause of inaccuracy in surrogate decision-making. The data and implications are discussed with respect to theories of surrogate decision-making.

  18. Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China.

    Science.gov (United States)

    Yang, Feiling; Hu, Jinming; Wu, Ruidong

    2016-08-19

    Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that endangered plants had higher surrogacy values than endangered animals but that the two were not substitutable; coupled endangered plants and animals as surrogates yielded a higher surrogacy value than endangered plants or animals as surrogates; the plant-animal priority areas (PAPAs) was the optimal among the four types of PCAs for conserving both endangered plants and animals in Yunnan. PAPAs could well represent overall species diversity distribution patterns and overlap with critical biogeographical regions in Yunnan. Fourteen priority units in PAPAs should be urgently considered as optimizing Yunnan's protected area system. The spatial pattern of PAPAs at the 100% conservation level could be conceptualized into three connected conservation belts, providing a valuable reference for optimizing the layout of the in situ protected area system in Yunnan.

  19. Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China

    Science.gov (United States)

    Yang, Feiling; Hu, Jinming; Wu, Ruidong

    2016-08-01

    Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that endangered plants had higher surrogacy values than endangered animals but that the two were not substitutable; coupled endangered plants and animals as surrogates yielded a higher surrogacy value than endangered plants or animals as surrogates; the plant-animal priority areas (PAPAs) was the optimal among the four types of PCAs for conserving both endangered plants and animals in Yunnan. PAPAs could well represent overall species diversity distribution patterns and overlap with critical biogeographical regions in Yunnan. Fourteen priority units in PAPAs should be urgently considered as optimizing Yunnan’s protected area system. The spatial pattern of PAPAs at the 100% conservation level could be conceptualized into three connected conservation belts, providing a valuable reference for optimizing the layout of the in situ protected area system in Yunnan.

  20. Prediction of naphthenic acid species degradation by kinetic and surrogate models during the ozonation of oil sands process-affected water.

    Science.gov (United States)

    Islam, Md Shahinoor; Moreira, Jesús; Chelme-Ayala, Pamela; Gamal El-Din, Mohamed

    2014-09-15

    Oil sands process-affected water (OSPW) is a complex mixture of organic and inorganic contaminants, and suspended solids, generated by the oil sands industry during the bitumen extraction process. OSPW contains a large number of structurally diverse organic compounds, and due to variability of the water quality of different OSPW matrices, there is a need to select a group of easily measured surrogate parameters for monitoring and treatment process control. In this study, kinetic and surrogate correlation models were developed to predict the degradation of naphthenic acids (NAs) species during the ozonation of OSPW. Additionally, the speciation and distribution of classical and oxidized NA species in raw and ozonated OSPW were also examined. The structure-reactivity of NA species indicated that the reactivity of individual NA species increased as the carbon and hydrogen deficiency numbers increased. The kinetic parameters obtained in this study allowed calculating the evolution of the concentrations of the acid-extractable fraction (AEF), chemical oxygen demand (COD), and NA distributions for a given ozonation process. High correlations between the AEF and COD and NA species were found, suggesting that AEF and COD can be used as surrogate parameters to predict the degradation of NAs during the ozonation of OSPW.

  1. Evaluating the Efficacy of Three U.S. Department of Agriculture-Approved Antimicrobial Sprays for Reducing Shiga Toxin-Producing Escherichia coli Surrogate Populations on Bob Veal Carcasses.

    Science.gov (United States)

    2016-06-01

    Effective antimicrobial intervention strategies to reduce Shiga toxin-producing Escherichia coli (STEC) risks associated with veal are needed. This study evaluated the efficacy of lactic acid (4.5%, pH 2.0), Citrilow (pH 1.2), and Beefxide (2.25%, pH 2.3) for reducing STEC surrogates on prerigor and chilled bob veal carcasses and monitored the effects of these interventions on chilled carcass color. Dehided bob veal carcasses were inoculated with a five-strain cocktail of rifampin-resistant, surrogate E. coli bacteria.E. coli surrogates were enumerated after inoculation, after water wash, after prechill carcass antimicrobial spray application, after chilling for 24 h, and after postchill carcass antimicrobial spray application; carcass color was measured throughout the process. A standard carcass water wash (∼50°C) reduced the STEC surrogate population by 0.9 log CFU/cm(2) (P ≤ 0.05). All three antimicrobial sprays applied to prerigor carcasses delivered an additional ∼0.5-log reduction (P ≤ 0.05) of the surrogates. Chilling of carcasses for 24 h reduced (P ≤ 0.05) the surrogate population by an additional ∼0.4 log cycles. The postchill application of the antimicrobial sprays provided no further reductions. Carcass L*, a*, and b* color values were not different (P > 0.05) among carcass treatments. Generally, the types and concentrations of the antimicrobial sprays evaluated herein did not negatively impact visual or instrumental color of chilled veal carcasses. This study demonstrates that warm water washing, followed by a prechill spray treatment with a low-pH chemical intervention, can effectively reduce STEC risks associated with veal carcasses; this provides processors a validated control point in slaughter operations.

  2. Antibody-mediated resistance against plant pathogens.

    Science.gov (United States)

    Safarnejad, Mohammad Reza; Jouzani, Gholamreza Salehi; Tabatabaei, Meisam; Tabatabaie, Meisam; Twyman, Richard M; Schillberg, Stefan

    2011-01-01

    Plant diseases have a significant impact on the yield and quality of crops. Many strategies have been developed to combat plant diseases, including the transfer of resistance genes to crops by conventional breeding. However, resistance genes can only be introgressed from sexually-compatible species, so breeders need alternative measures to introduce resistance traits from more distant sources. In this context, genetic engineering provides an opportunity to exploit diverse and novel forms of resistance, e.g. the use of recombinant antibodies targeting plant pathogens. Native antibodies, as a part of the vertebrate adaptive immune system, can bind to foreign antigens and eliminate them from the body. The ectopic expression of antibodies in plants can also interfere with pathogen activity to confer disease resistance. With sufficient knowledge of the pathogen life cycle, it is possible to counter any disease by designing expression constructs so that pathogen-specific antibodies accumulate at high levels in appropriate sub-cellular compartments. Although first developed to tackle plant viruses and still used predominantly for this purpose, antibodies have been targeted against a diverse range of pathogens as well as proteins involved in plant-pathogen interactions. Here we comprehensively review the development and implementation of antibody-mediated disease resistance in plants.

  3. Are Surrogate Assumptions and Use of Diuretics Associated with Diagnosis and Staging of Acute Kidney Injury after Cardiac Surgery?

    Science.gov (United States)

    Hussein, Hayder K.; Prabhu, Mahesh; Kanagasundaram, N. Suren

    2012-01-01

    Summary Background and objectives This study measured the association between the Acute Kidney Injury Network (AKIN) diagnostic and staging criteria and surrogates for baseline serum creatinine (SCr) and body weight, compared urine output (UO) with SCr criteria, and assessed the relationships between use of diuretics and calibration between criteria and prediction of outcomes. Design, setting, participants, & measurements This was a retrospective cohort study using prospective measurements of SCr, hourly UO, body weight, and drug administration records from 5701 patients admitted, after cardiac surgery, to a cardiac intensive care unit between 1995 and 2006. Results More patients (n=2424, 42.5%) met SCr diagnostic criteria with calculated SCr assuming a baseline estimated GFR of 75 ml/min per 1.73 m2 than with known baseline SCr (n=1043, 18.3%). Fewer patients (n=484, 8.5%) met UO diagnostic criteria with assumed body weight (70 kg) than with known weight (n=624, 10.9%). Agreement between SCr and UO criteria was fair (κ=0.28; 95% confidence interval 0.25–0.31). UO diagnostic criteria were specific (0.95; 0.94–0.95) but insensitive (0.36; 0.33–0.39) compared with SCr. Intravenous diuretics were associated with higher probability of falling below the UO diagnostic threshold compared with SCr, higher 30-day mortality (relative risk, 2.27; 1.08–4.76), and the need for renal support (4.35; 1.82–10.4) compared with no diuretics. Conclusions Common surrogates for baseline estimated GFR and body weight were associated with misclassification of AKIN stage. UO criteria were insensitive compared with SCr. Intravenous diuretic use further reduced agreement and confounded association between AKIN stage and 30-day mortality or need for renal support. PMID:22246280

  4. Natural and Man-made Antibody Repertories for Antibody Discovery

    Directory of Open Access Journals (Sweden)

    Juan C eAlmagro

    2012-11-01

    Full Text Available Antibodies are the fastest-growing segment of the biologics market. The success of antibody-based drugs resides in their exquisite specificity, high potency, stability, solubility, safety and relatively inexpensive manufacturing process in comparison with other biologics. We outline here the structural studies and fundamental principles that define how antibodies interact with diverse targets. We also describe the antibody repertoires and affinity maturation mechanisms of human, mice and chickens, plus the use of novel single-domain antibodies in camelids and sharks. These species all utilize diverse evolutionary solutions to generate specific and high affinity antibodies and illustrate the plasticity of natural antibody repertoires. In addition, we discuss the multiple variations of man-made antibody repertoires designed and validated in the last two decades, which have served as tools to explore how the size, diversity and composition of a repertoire impact the antibody discovery process.

  5. Surrogate fuel formulation for light naphtha combustion in advanced combustion engines

    KAUST Repository

    Ahmed, Ahfaz

    2015-03-30

    Crude oil once recovered is further separated in to several distinct fractions to produce a range of energy and chemical products. One of the less processed fractions is light naphtha (LN), hence they are more economical to produce than their gasoline and diesel counterparts. Recent efforts have demonstrated usage of LN as transportation fuel for internal combustion engines with slight modifications. In this study, a multicomponent surrogate fuel has been developed for light naphtha fuel using a multi-variable nonlinear constrained optimization scheme. The surrogate, consisting of palette species n-pentane, 2-methylhexane, 2-methylbutane, n-heptane and toluene, was validated against the LN using ignition quality tester following ASTM D6890 methodology. Comparison of LN and the surrogate fuel demonstrated satisfactory agreement.

  6. Adaptive surrogate modeling for response surface approximations with application to bayesian inference

    KAUST Repository

    Prudhomme, Serge

    2015-09-17

    Parameter estimation for complex models using Bayesian inference is usually a very costly process as it requires a large number of solves of the forward problem. We show here how the construction of adaptive surrogate models using a posteriori error estimates for quantities of interest can significantly reduce the computational cost in problems of statistical inference. As surrogate models provide only approximations of the true solutions of the forward problem, it is nevertheless necessary to control these errors in order to construct an accurate reduced model with respect to the observables utilized in the identification of the model parameters. Effectiveness of the proposed approach is demonstrated on a numerical example dealing with the Spalart–Allmaras model for the simulation of turbulent channel flows. In particular, we illustrate how Bayesian model selection using the adapted surrogate model in place of solving the coupled nonlinear equations leads to the same quality of results while requiring fewer nonlinear PDE solves.

  7. Kinetic Modeling of Gasoline Surrogate Components and Mixtures under Engine Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Mehl, M; Pitz, W J; Westbrook, C K; Curran, H J

    2010-01-11

    Real fuels are complex mixtures of thousands of hydrocarbon compounds including linear and branched paraffins, naphthenes, olefins and aromatics. It is generally agreed that their behavior can be effectively reproduced by simpler fuel surrogates containing a limited number of components. In this work, an improved version of the kinetic model by the authors is used to analyze the combustion behavior of several components relevant to gasoline surrogate formulation. Particular attention is devoted to linear and branched saturated hydrocarbons (PRF mixtures), olefins (1-hexene) and aromatics (toluene). Model predictions for pure components, binary mixtures and multicomponent gasoline surrogates are compared with recent experimental information collected in rapid compression machine, shock tube and jet stirred reactors covering a wide range of conditions pertinent to internal combustion engines (3-50 atm, 650-1200K, stoichiometric fuel/air mixtures). Simulation results are discussed focusing attention on the mixing effects of the fuel components.

  8. A study of friction mechanisms between a surrogate skin (Lorica soft) and nonwoven fabrics.

    Science.gov (United States)

    Cottenden, David J; Cottenden, Alan M

    2013-12-01

    Hygiene products such as incontinence pads bring nonwoven fabrics into contact with users' skin, which can cause damage in various ways, including the nonwoven abrading the skin by friction. The aim of the work described here was to develop and use methods for understanding the origin of friction between nonwoven fabrics and skin by relating measured normal and friction forces to the nature and area of the contact (fibre footprint) between them. The method development work reported here used a skin surrogate (Lorica Soft) in place of skin for reproducibility. The work was primarily experimental in nature, and involved two separate approaches. In the first, a microscope with a shallow depth of field was used to determine the length of nonwoven fibre in contact with a facing surface as a function of pressure, from which the contact area could be inferred; and, in the second, friction between chosen nonwoven fabrics and Lorica Soft was measured at a variety of anatomically relevant pressures (0.25-32.1kPa) and speeds (0.05-5mms(-1)). Both techniques were extensively validated, and showed reproducibility of about 5% in length and force, respectively. Straightforward inspection of the data for Lorica Soft against the nonwovens showed that Amontons' law (with respect to load) was obeyed to high precision (R(2)>0.999 in all cases), though there was the suggestion of sub-linearity at low loads. More detailed consideration of the friction traces suggested that two different friction mechanisms are important, and comparison with the contact data suggests tentatively that they may correspond to adhesion between two different populations of contacts, one "rough" and one "smooth". This additional insight is a good illustration of how these techniques may prove valuable in studying other, similar interfaces. In particular, they could be used to investigate interfaces between nonwovens and skin, which was the primary motivation for developing them.

  9. Aerosolization of a Human Norovirus Surrogate, Bacteriophage MS2, during Simulated Vomiting.

    Directory of Open Access Journals (Sweden)

    Grace Tung-Thompson

    Full Text Available Human noroviruses (NoV are the leading cause of acute gastroenteritis worldwide. Epidemiological studies of outbreaks have suggested that vomiting facilitates transmission of human NoV, but there have been no laboratory-based studies characterizing the degree of NoV release during a vomiting event. The purpose of this work was to demonstrate that virus aerosolization occurs in a simulated vomiting event, and to estimate the amount of virus that is released in those aerosols. A simulated vomiting device was constructed at one-quarter scale of the human body following similitude principles. Simulated vomitus matrices at low (6.24 mPa*s and high (177.5 mPa*s viscosities were inoculated with low (108 PFU/mL and high (1010 PFU/mL concentrations of bacteriophage MS2 and placed in the artificial "stomach" of the device, which was then subjected to scaled physiologically relevant pressures associated with vomiting. Bio aerosols were captured using an SKC Biosampler. In low viscosity artificial vomitus, there were notable differences between recovered aerosolized MS2 as a function of pressure (i.e., greater aerosolization with increased pressure, although this was not always statistically significant. This relationship disappeared when using high viscosity simulated vomitus. The amount of MS2 aerosolized as a percent of total virus "vomited" ranged from 7.2 x 10-5 to 2.67 x 10-2 (which corresponded to a range of 36 to 13,350 PFU total. To our knowledge, this is the first study to document and measure aerosolization of a NoV surrogate in a similitude-based physical model. This has implications for better understanding the transmission dynamics of human NoV and for risk modeling purposes, both of which can help in designing effective infection control measures.

  10. Non-antibody protein-based biosensors

    Science.gov (United States)

    2016-01-01

    Biosensors that depend on a physical or chemical measurement can be adversely affected by non-specific interactions. For example, a biosensor designed to measure specifically the levels of a rare analyte can give false positive results if there is even a small amount of interaction with a highly abundant but irrelevant molecule. To overcome this limitation, the biosensor community has frequently turned to antibody molecules as recognition elements because they are renowned for their exquisite specificity. Unfortunately antibodies can often fail when immobilised on inorganic surfaces, and alternative biological recognition elements are needed. This article reviews the available non-antibody-binding proteins that have been successfully used in electrical and micro-mechanical biosensor platforms. PMID:27365032

  11. Total lymphocyte count is a reliable surrogate marker for CD4 cell counts after the first year of antiretroviral therapy: data from an Indonesian cohort study.

    Science.gov (United States)

    de Jong, Marrigje A; Wisaksana, Rudi; Meijerink, Hinta; Indrati, Agnes; van de Ven, Andre J A M; Alisjahbana, Bachti; van Crevel, Reinout

    2012-05-01

    Many studies have evaluated the total lymphocyte count (TLC) as a cheap surrogate marker for CD4 cells in HIV-infected patients not receiving antiretroviral therapy (ART). We assessed whether TLC can replace CD4 cell counts in evaluating the immunological response to ART. In a cohort of patients in Indonesia TLC, if measured after at least 1-year ART, correctly identified patients with <200 CD4 cells, and reliably excluded immunological failure, obviating the need for CD4 cell measurement in 43% of patients.

  12. Surrogate analysis and index developer (SAID) tool and real-time data dissemination utilities

    Science.gov (United States)

    Domanski, Marian M.; Straub, Timothy D.; Wood, Molly S.; Landers, Mark N.; Wall, Gary R.; Brady, Steven J.

    2015-01-01

    The use of acoustic and other parameters as surrogates for suspended-sediment concentrations (SSC) in rivers has been successful in multiple applications across the Nation. Critical to advancing the operational use of surrogates are tools to process and evaluate the data along with the subsequent development of regression models from which real-time sediment concentrations can be made available to the public. Recent developments in both areas are having an immediate impact on surrogate research, and on surrogate monitoring sites currently in operation. The Surrogate Analysis and Index Developer (SAID) standalone tool, under development by the U.S. Geological Survey (USGS), assists in the creation of regression models that relate response and explanatory variables by providing visual and quantitative diagnostics to the user. SAID also processes acoustic parameters to be used as explanatory variables for suspended-sediment concentrations. The sediment acoustic method utilizes acoustic parameters from fixed-mount stationary equipment. The background theory and method used by the tool have been described in recent publications, and the tool also serves to support sediment-acoustic-index methods being drafted by the multi-agency Sediment Acoustic Leadership Team (SALT), and other surrogate guidelines like USGS Techniques and Methods 3-C4 for turbidity and SSC. The regression models in SAID can be used in utilities that have been developed to work with the USGS National Water Information System (NWIS) and for the USGS National Real-Time Water Quality (NRTWQ) Web site. The real-time dissemination of predicted SSC and prediction intervals for each time step has substantial potential to improve understanding of sediment-related water-quality and associated engineering and ecological management decisions.

  13. Testing pairwise association between spatially autocorrelated variables: a new approach using surrogate lattice data.

    Directory of Open Access Journals (Sweden)

    Vincent Deblauwe

    Full Text Available BACKGROUND: Independence between observations is a standard prerequisite of traditional statistical tests of association. This condition is, however, violated when autocorrelation is present within the data. In the case of variables that are regularly sampled in space (i.e. lattice data or images, such as those provided by remote-sensing or geographical databases, this problem is particularly acute. Because analytic derivation of the null probability distribution of the test statistic (e.g. Pearson's r is not always possible when autocorrelation is present, we propose instead the use of a Monte Carlo simulation with surrogate data. METHODOLOGY/PRINCIPAL FINDINGS: The null hypothesis that two observed mapped variables are the result of independent pattern generating processes is tested here by generating sets of random image data while preserving the autocorrelation function of the original images. Surrogates are generated by matching the dual-tree complex wavelet spectra (and hence the autocorrelation functions of white noise images with the spectra of the original images. The generated images can then be used to build the probability distribution function of any statistic of association under the null hypothesis. We demonstrate the validity of a statistical test of association based on these surrogates with both actual and synthetic data and compare it with a corrected parametric test and three existing methods that generate surrogates (randomization, random rotations and shifts, and iterative amplitude adjusted Fourier transform. Type I error control was excellent, even with strong and long-range autocorrelation, which is not the case for alternative methods. CONCLUSIONS/SIGNIFICANCE: The wavelet-based surrogates are particularly appropriate in cases where autocorrelation appears at all scales or is direction-dependent (anisotropy. We explore the potential of the method for association tests involving a lattice of binary data and discuss its

  14. Two-dimensional surrogate contact modeling for computationally efficient dynamic simulation of total knee replacements.

    Science.gov (United States)

    Lin, Yi-Chung; Haftka, Raphael T; Queipo, Nestor V; Fregly, Benjamin J

    2009-04-01

    Computational speed is a major limiting factor for performing design sensitivity and optimization studies of total knee replacements. Much of this limitation arises from extensive geometry calculations required by contact analyses. This study presents a novel surrogate contact modeling approach to address this limitation. The approach involves fitting contact forces from a computationally expensive contact model (e.g., a finite element model) as a function of the relative pose between the contacting bodies. Because contact forces are much more sensitive to displacements in some directions than others, standard surrogate sampling and modeling techniques do not work well, necessitating the development of special techniques for contact problems. We present a computational evaluation and practical application of the approach using dynamic wear simulation of a total knee replacement constrained to planar motion in a Stanmore machine. The sample points needed for surrogate model fitting were generated by an elastic foundation (EF) contact model. For the computational evaluation, we performed nine different dynamic wear simulations with both the surrogate contact model and the EF contact model. In all cases, the surrogate contact model accurately reproduced the contact force, motion, and wear volume results from the EF model, with computation time being reduced from 13 min to 13 s. For the practical application, we performed a series of Monte Carlo analyses to determine the sensitivity of predicted wear volume to Stanmore machine setup issues. Wear volume was highly sensitive to small variations in motion and load inputs, especially femoral flexion angle, but not to small variations in component placements. Computational speed was reduced from an estimated 230 h to 4 h per analysis. Surrogate contact modeling can significantly improve the computational speed of dynamic contact and wear simulations of total knee replacements and is appropriate for use in design sensitivity

  15. Multimission Fuel-Burn Minimization in Aircraft Design: A Surrogate-Modeling Approach

    Science.gov (United States)

    Liem, Rhea Patricia

    Aerodynamic shape and aerostructural design optimizations that maximize the performance at a single flight condition result in designs with unacceptable off-design performance. While considering multiple flight conditions in the optimization improves the robustness of the designs, there is a need to develop a rational strategy for choosing the flight conditions and their relative emphases such that multipoint optimizations reflect the true objective function. In addition, there is a need to consider uncertain missions and flight conditions. In this thesis, the strategies to formulate the multipoint objective functions for aerodynamic shape and aerostructural optimization are presented. To determine the flight conditions and their corresponding weights, a novel surrogate-based mission analysis is developed to efficiently analyze hundreds of actual mission data to emulate their flight condition distribution. Using accurate and reliable surrogate models to approximate the aerodynamic coefficients used in the analysis makes this procedure computationally tractable. A mixture of experts (ME) approach is developed to overcome the limitations of conventional surrogate models in modeling the complex transonic drag profile. The ME approach combines multiple surrogate models probabilistically based on the divide-andconquer strategy. Using this model in the mission analysis significantly improves the range estimation accuracy, as compared to other conventional surrogate models. As expected, the multipoint aerodynamic shape and aerostructural optimizations demonstrate a consistent drag reduction, instead of the localized improvement by the single-point optimizations. The improved robustness in the multipoint optimized designs was also observed in terms of the improved range performance and more consistent fuel-burn reduction across the different missions. The results presented in this thesis show that the surrogate-model-assisted multipoint optimization produces a robust

  16. Calibration of an agricultural-hydrological model (RZWQM2) using surrogate global optimization

    Science.gov (United States)

    Xi, Maolong; Lu, Dan; Gui, Dongwei; Qi, Zhiming; Zhang, Guannan

    2017-01-01

    Robust calibration of an agricultural-hydrological model is critical for simulating crop yield and water quality and making reasonable agricultural management. However, calibration of the agricultural-hydrological system models is challenging because of model complexity, the existence of strong parameter correlation, and significant computational requirements. Therefore, only a limited number of simulations can be allowed in any attempt to find a near-optimal solution within an affordable time, which greatly restricts the successful application of the model. The goal of this study is to locate the optimal solution of the Root Zone Water Quality Model (RZWQM2) given a limited simulation time, so as to improve the model simulation and help make rational and effective agricultural-hydrological decisions. To this end, we propose a computationally efficient global optimization procedure using sparse-grid based surrogates. We first used advanced sparse grid (SG) interpolation to construct a surrogate system of the actual RZWQM2, and then we calibrate the surrogate model using the global optimization algorithm, Quantum-behaved Particle Swarm Optimization (QPSO). As the surrogate model is a polynomial with fast evaluation, it can be efficiently evaluated with a sufficiently large number of times during the optimization, which facilitates the global search. We calibrate seven model parameters against five years of yield, drain flow, and NO3-N loss data from a subsurface-drained corn-soybean field in Iowa. Results indicate that an accurate surrogate model can be created for the RZWQM2 with a relatively small number of SG points (i.e., RZWQM2 runs). Compared to the conventional QPSO algorithm, our surrogate-based optimization method can achieve a smaller objective function value and better calibration performance using a fewer number of expensive RZWQM2 executions, which greatly improves computational efficiency.

  17. Testing Pairwise Association between Spatially Autocorrelated Variables: A New Approach Using Surrogate Lattice Data

    Science.gov (United States)

    Deblauwe, Vincent; Kennel, Pol; Couteron, Pierre

    2012-01-01

    Background Independence between observations is a standard prerequisite of traditional statistical tests of association. This condition is, however, violated when autocorrelation is present within the data. In the case of variables that are regularly sampled in space (i.e. lattice data or images), such as those provided by remote-sensing or geographical databases, this problem is particularly acute. Because analytic derivation of the null probability distribution of the test statistic (e.g. Pearson's r) is not always possible when autocorrelation is present, we propose instead the use of a Monte Carlo simulation with surrogate data. Methodology/Principal Findings The null hypothesis that two observed mapped variables are the result of independent pattern generating processes is tested here by generating sets of random image data while preserving the autocorrelation function of the original images. Surrogates are generated by matching the dual-tree complex wavelet spectra (and hence the autocorrelation functions) of white noise images with the spectra of the original images. The generated images can then be used to build the probability distribution function of any statistic of association under the null hypothesis. We demonstrate the validity of a statistical test of association based on these surrogates with both actual and synthetic data and compare it with a corrected parametric test and three existing methods that generate surrogates (randomization, random rotations and shifts, and iterative amplitude adjusted Fourier transform). Type I error control was excellent, even with strong and long-range autocorrelation, which is not the case for alternative methods. Conclusions/Significance The wavelet-based surrogates are particularly appropriate in cases where autocorrelation appears at all scales or is direction-dependent (anisotropy). We explore the potential of the method for association tests involving a lattice of binary data and discuss its potential for

  18. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    surface expression of various antibody formats in the generated knockout strain. Functional scFv and scFab fragments were efficiently displayed on yeast whereas impaired chain assembly and heavy chain degradation was observed for display of full-length IgG molecules. To identify the optimal polypeptide...... linker for yeast surface display of scFv and scFab fragments, we compared a series of different Gly-Ser-based linkers in display and antigen binding proficiency. We show that these formats of the model antibody can accommodate linkers of different lengths and that introduction of alanine or glutamate...... fragments by in vivo homologous recombination large combinatorial antibody libraries can easily be generated. We have optimized ordered assembly of three CDR fragments into a gapped vector and observed increased transformation efficiency in a yeast strain carrying a deletion of the SGS1 helicase...

  19. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi;

    2014-01-01

    to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic...... infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

  20. Investigation of Antiphosphatidyl-Serine Antibody and Antiphosphatidyl-Inositol Antibody in Ischemic Stroke Patients

    Directory of Open Access Journals (Sweden)

    Hirohisa Okuma

    2010-01-01

    Full Text Available Antiphospholipid syndrome is characterized by arterial or venous thrombosis and the presence of antiphospholipid antibodies (aPL. We measured β2-GPI aCL, IgGaCL, LA, antiphosphatidyl-serine antibody (PS, and antiphosphatidyl-inositol antibody (PI in each patient at one month after the onset of stroke. In addition, carotid artery echography was performed in patients positive for PI or PS. Among the 250 patients, 13.6% (34/250 were positive for either PI or PS, and 6.8% (17/250 were positive for both. Carotid artery echography performed on these 34 patients showed that the frequencies of increased intimal-medial thickness (IMT of 1.1 mm or more, plaque, and carotid artery stenosis of 50% or more were all significantly higher in patients positive for antinuclear antibody than those negative for the antibody (P<.05. PI and PS are associated with antinuclear antibody and precipitation of atherosclerosis. Ischemic stroke patients with SLE frequently showed a variety of antiphospholipid-protein antibodies.

  1. A Bayesian Surrogate Model for Rapid Time Series Analysis and Application to Exoplanet Observations

    CERN Document Server

    Ford, Eric B; Veras, Dimitri

    2011-01-01

    We present a Bayesian surrogate model for the analysis of periodic or quasi-periodic time series data. We describe a computationally efficient implementation that enables Bayesian model comparison. We apply this model to simulated and real exoplanet observations. We discuss the results and demonstrate some of the challenges for applying our surrogate model to realistic exoplanet data sets. In particular, we find that analyses of real world data should pay careful attention to the effects of uneven spacing of observations and the choice of prior for the "jitter" parameter.

  2. Initial Results from the Third Round 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)

    2016-04-20

    High explosives science and technology (M-7) is currently working on the third round of formulation and testing of Remediated nitrate salt (RNS) surrogates. This report summarizes the calorimetry results from the 15% sWheat mixtures. All formulation and testing was carried out according to PLAN-TA9-2443 Rev B, "Remediated Nitrate Salt (RNS) surrogate formulation and testing standard procedure", released February 16, 2016. Results from the first and second rounds of formulation and testing were documented in memoranda M7-16-6042 and M7-16-6053.

  3. Religion and Spirituality in Surrogate Decision Making for Hospitalized Older Adults.

    Science.gov (United States)

    Geros-Willfond, Kristin N; Ivy, Steven S; Montz, Kianna; Bohan, Sara E; Torke, Alexia M

    2016-06-01

    We conducted semi-structured interviews with 46 surrogate decision makers for hospitalized older adults to characterize the role of spirituality and religion in decision making. Three themes emerged: (1) religion as a guide to decision making, (2) control, and (3) faith, death and dying. For religious surrogates, religion played a central role in end of life decisions. There was variability regarding whether God or humans were perceived to be in control; however, beliefs about control led to varying perspectives on acceptance of comfort-focused treatment. We conclude that clinicians should attend to religious considerations due to their impact on decision making.

  4. Prediction of Antibody Epitopes

    DEFF Research Database (Denmark)

    Nielsen, Morten; Marcatili, Paolo

    2015-01-01

    Antibodies recognize their cognate antigens in a precise and effective way. In order to do so, they target regions of the antigenic molecules that have specific features such as large exposed areas, presence of charged or polar atoms, specific secondary structure elements, and lack of similarity...... to self-proteins. Given the sequence or the structure of a protein of interest, several methods exploit such features to predict the residues that are more likely to be recognized by an immunoglobulin.Here, we present two methods (BepiPred and DiscoTope) to predict linear and discontinuous antibody...

  5. The investigation of relationship between preeclampsia and antiphospholipid antibody syndrome

    Directory of Open Access Journals (Sweden)

    Mehmet Tayyar

    2013-03-01

    Full Text Available Aim. The aim of this study was evaluate the relationship between preeclampsia and antiphospholipid antibodies. Methods. A total of 116 pregnant women between 20th and 40th weeks of gestation admitted to our department were investigated. 63 of them were allocated our preeclampsia group and 53 of them were allocated our control group. Lupus anticoagulant, anti-cardiolipin antibodies (IG G ve M and antiphosphatidylserine antibodies (IG G ve M were measured. Results. There was no statistical significance between preeclampsia and control group for antiphospholipid antibodies but these were two times higher in preeclamptic group compared to control group. (22.2% in preeclampsia, 11.3% in control group p=0.193. Conclusions. In an unselected population we were not able to demonstrate an association between preeclampsia and antiphospholipid antibody syndrome but antiphospholipid antibody ratio elevated in women with preeclampsia. These findings show that, there is a need for large scale studies.

  6. Anti-phospholipid antibodies in patients with Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; Morris-Jones, S D; Hviid, L;

    1993-01-01

    Plasma levels of antibodies against phosphatidylinositol (PI), phosphatidylcholine (PC) and cardiolipin (CL) were measured by enzyme-linked immunosorbent assay (ELISA) in patients from malaria endemic area of Sudan and The Gambia. Some Sudanese adults produced IgM antibodies against all three types...... of phospholipids (PL) during an acute Plasmodium falciparum infection. The anti-PL antibody titre returned to preinfection levels in most of the donors 30 days after the disease episode. IgG titres against PI, PC and CL were low. In Gambian children with malaria, IgM antibody titres against PI and PC were...... significantly higher in those with severe malaria than in those with mild malaria. These results show that a proportion of malaria patients produce anti-PL antibodies during infection and that titres of these antibodies are associated with the severity of disease....

  7. Anti-ganglioside antibodies induced in chickens by an alum-adsorbed anti-idiotype antibody targeting NeuGcGM3.

    Directory of Open Access Journals (Sweden)

    Marcelo David Guthmann

    2013-01-01

    Full Text Available Racotumomab is a murine anti-idiotype cancer vaccine targeting NeuGcGM3 on melanoma, breast and lung cancer. In order to characterize the immunogenicity of alum-adsorbed racotumomab in a non-clinical setting, Leghorn chickens were immunized in dose levels ranging from 25 µg to 1600 µg. Racotumomab was administered subcutaneously in the birds’ neck with three identical boosters and serum samples were collected before, during and after the immunization schedule. A strong antibody response was obtained across the evaluated dose range, confirming the immunogenicity of racotumomab even at dose levels as low as 25 µg. As previously observed when using Freund´s adjuvant, alum-adsorbed racotumomab induced an idiotype-specific response in all the immunized birds and ganglioside-specific antibodies in 60-100% of the animals. In contrast to the rapid induction anti-idiotype response, detection of ganglioside-specific antibodies in responsive animals may require repeated boosting. Kinetics of anti-NeuGcGM3 antibody titers showed a slight decline two weeks after each booster, arguing in favor of repeated immunizations in order to maintain antibody titer.Interestingly, the intensity of the anti-NeuGcGM3 response paralleled that of anti-mucin antibodies and anti-tumor antibodies, suggesting that the in vitro detection of anti-ganglioside antibodies might be a surrogate for an in vivo activity of racotumomab. Taken together, these results suggest that Leghorn chicken immunization might become the means to test the biological activity of racotumomab intended for clinical use.

  8. Immunological variation in Taenia solium porcine cysticercosis: measurement on the variation of the antibody immune response of naturally infected pigs against antigens extracted from their own cysticerci and from those of different pigs.

    Science.gov (United States)

    Ostoa-Saloma, Pedro; Esquivel-Velázquez, Marcela; Larralde, Carlos

    2013-10-18

    Although it is widely assumed that both antigen and host immunological variability are involved in the variable intensity of natural porcine infections by Taenia solium (T. solium) cysticercis and success of immunodiagnostic tests vaccines, the magnitude of such combined variability has not been studied or measured at all. In this paper we report statistical data on the variability of the antibody response of naturally infected pigs against the antigens extracted from the vesicular fluids of their own infecting cysts (variance within pigs) and against antigen samples extracted from cysts of other cysticercotic pigs (variance among pigs). The variation between pigs was greater than the inter-pigs variations, which suggests that a concomitant immunity process prevents the establishment of cysts coming from a subsequent challenge. In so doing, we found that there is not a single antigenic band that was recognized by all hosts and that antigens varied among the cysts within the same pigs as well as among pigs. Our results may be valuable for the improvement of immunodiagnostic tests and of effective vaccines against naturally acquired porcine T. solium cysticercosis.

  9. Evaluation of surrogate markers for human immunodeficiency virus infection among blood donors at the blood bank of "Hospital Universitário Regional Norte do Paraná", Londrina, PR, Brazil

    Directory of Open Access Journals (Sweden)

    Reiche Edna Maria Vissoci

    2003-01-01

    Full Text Available This study evaluated the usefulness of the anti-HBc, hepatitis C virus antibodies (anti-HCV, human T cell lymphotropic virus I and II antibodies (anti-HTLV I/II, serologic tests for syphilis, and surface antigen of hepatitis B virus (HBsAg as surrogate markers for the risk for HIV infection in 80,284 serum samples from blood donors from the Blood Bank of "Hospital Universitário Regional Norte do Paraná", Londrina, Paraná State, Brazil, analyzed from July 1994 to April 2001. Among 39 blood donors with positive serology for HIV, 12 (30.8% were anti-HBc positive, 10 (25.6% for anti-HCV, 1 (2.6% for anti-HTLV I/I, 1 (2.6% was positive for syphilis, and 1 (2.6% for HBsAg. Among the donors with negative serology for HIV, these markers were detected in 8,407 (10.5%, 441 (0.5%, 189 (0.2%, 464 (0.6%, and 473 (0.6% samples, respectively. The difference was statistically significant (p < 0.001 for anti-HBc and anti-HCV. Although the predictive positive value for these surrogate markers were low for HIV infection, the results confirmed the anti-HBc and anti-HCV as useful surrogate markers for HIV infection thus reinforcing the maintenance of them in the screening for blood donors contributing to the prevention of the small number of cases in which HIV is still transmitted by transfusion.

  10. Human germline antibody gene segments encode polyspecific antibodies.

    Science.gov (United States)

    Willis, Jordan R; Briney, Bryan S; DeLuca, Samuel L; Crowe, James E; Meiler, Jens

    2013-04-01

    Structural flexibility in germline gene-encoded antibodies allows promiscuous binding to diverse antigens. The binding affinity and specificity for a particular epitope typically increase as antibody genes acquire somatic mutations in antigen-stimulated B cells. In this work, we investigated whether germline gene-encoded antibodies are optimal for polyspecificity by determining the basis for recognition of diverse antigens by antibodies encoded by three VH gene segments. Panels of somatically mutated antibodies encoded by a common VH gene, but each binding to a different antigen, were computationally redesigned to predict antibodies that could engage multiple antigens at once. The Rosetta multi-state design process predicted antibody sequences for the entire heavy chain variable region, including framework, CDR1, and CDR2 mutations. The predicted sequences matched the germline gene sequences to a remarkable degree, revealing by computational design the residues that are predicted to enable polyspecificity, i.e., binding of many unrelated antigens with a common sequence. The process thereby reverses antibody maturation in silico. In contrast, when designing antibodies to bind a single antigen, a sequence similar to that of the mature antibody sequence was returned, mimicking natural antibody maturation in silico. We demonstrated that the Rosetta computational design algorithm captures important aspects of antibody/antigen recognition. While the hypervariable region CDR3 often mediates much of the specificity of mature antibodies, we identified key positions in the VH gene encoding CDR1, CDR2, and the immunoglobulin framework that are critical contributors for polyspecificity in germline antibodies. Computational design of antibodies capable of binding multiple antigens may allow the rational design of antibodies that retain polyspecificity for diverse epitope binding.

  11. Prediction of antibody persistency from antibody titres to natalizumab

    DEFF Research Database (Denmark)

    Jensen, Poul Erik H; Koch-Henriksen, Nils; Sellebjerg, Finn Thorup;

    2012-01-01

    In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients.......In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients....

  12. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    OBJECTIVE: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to d...

  13. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.;

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  14. Antibody Blood Tests

    Science.gov (United States)

    ... What do I do if I have a negative blood test (or panel) but I’m still having symptoms? While it is rare, it is possible for patients to have a negative antibody test results and still have celiac disease. ...

  15. RBC Antibody Screen

    Science.gov (United States)

    ... test also may be used to help diagnose autoimmune-related hemolytic anemia in conjunction with a DAT. This condition may be caused when a person produces antibodies against his or her own RBC antigens. This can happen with some autoimmune disorders , such as lupus , with diseases such as ...

  16. Effectiveness of vegetation-based biodiversity offset metrics as surrogates for ants.

    Science.gov (United States)

    Hanford, Jayne K; Crowther, Mathew S; Hochuli, Dieter F

    2017-02-01

    Biodiversity offset schemes are globally popular policy tools for balancing the competing demands of conservation and development. Trading currencies for losses and gains in biodiversity value at development and credit sites are usually based on several vegetation attributes combined to yield a simple score (multimetric), but the score is rarely validated prior to implementation. Inaccurate biodiversity trading currencies are likely to accelerate global biodiversity loss through unrepresentative trades of losses and gains. We tested a model vegetation multimetric (i.e., vegetation structural and compositional attributes) typical of offset trading currencies to determine whether it represented measurable components of compositional and functional biodiversity. Study sites were located in remnant patches of a critically endangered ecological community in western Sydney, Australia, an area representative of global conflicts between conservation and expanding urban development. We sampled ant fauna composition with pitfall traps and enumerated removal by ants of native plant seeds from artificial seed containers (seed depots). Ants are an excellent model taxon because they are strongly associated with habitat complexity, respond rapidly to environmental change, and are functionally important at many trophic levels. The vegetation multimetric did not predict differences in ant community composition or seed removal, despite underlying assumptions that biodiversity trading currencies used in offset schemes represent all components of a site's biodiversity value. This suggests that vegetation multimetrics are inadequate surrogates for total biodiversity value. These findings highlight the urgent need to refine existing offsetting multimetrics to ensure they meet underlying assumptions of surrogacy. Despite the best intentions, offset schemes will never achieve their goal of no net loss of biodiversity values if trades are based on metrics unrepresentative of total

  17. Postharvest Survival of Porcine Sapovirus, a Human Norovirus Surrogate, on Phytopathogen-Infected Leafy Greens.

    Science.gov (United States)

    Esseili, Malak A; Chin, Ashlina; Saif, Linda; Miller, Sally A; Qu, Feng; Lewis Ivey, Melanie L; Wang, Qiuhong

    2015-08-01

    Leafy greens are increasingly being recognized as an important vehicle for human noroviruses (HuNoV), which cause recurring gastroenteritis outbreaks. Leafy greens often become infected by phytopathogens in the field, which may cause symptoms on the edible parts. Whether plant pathogen infections enhance the survival of HuNoV on leafy greens is unknown. Lettuce and spinach plants were infected with a bacterium, Xanthomonas campestris pv. vitians strain 701a, and with Cucumber mosaic virus strain Fny, respectively. The survival rate of porcine sapovirus (SaV), a HuNoV surrogate, on infected and noninfected postharvest leaves was then assessed. In addition, acibenzolar-S-methyl, a commercial chemical elicitor of plant systemic defense, was used to assess whether stimulating the plant host defense affects the postharvest survival of SaV. Leaves harvested from control and treated plants were inoculated with SaV and incubated for 7 days at 4°C. The infectivity (tissue culture infectious dose affecting 50% of the culture [TCID50]/ml) and RNA (genomic equivalent/ml) titers of SaV were assayed using immunohistochemistry staining and SaV-specific TaqMan real-time reverse transcription PCR. Our results showed that cucumber mosaic virus Fny induced mild, nonnecrotic symptoms on spinach leaves and had no effect on SaV survival. In contrast, X. campestris pv. vitians 701a induced small localized necrotic lesions and significantly enhanced SaV survival on lettuce leaves. Treatment with acibenzolar-S-methyl was effective in reducing X. campestris pv. vitians 701a-induced lesions on infected lettuce plants but had no direct effect on SaV survival when used on healthy lettuce plants. These findings indicate that phytopathogen-induced necrotic lesions may enhance the postharvest survival of HuNoV on lettuce leaves. Therefore, preventive measures aiming to maintain healthy plants and minimize preharvest biological damage are expected to improve the safety of leafy greens.

  18. Effective NOx remediation from a surrogate flue gas using the US NRL Electra electron beam facility

    Science.gov (United States)

    Petrova, Tz. B.; Petrov, G. M.; Wolford, M. F.; Giuliani, J. L.; Ladouceur, H. D.; Hegeler, F.; Myers, M. C.; Sethian, J. D.

    2017-02-01

    Nitric oxide (NOx) emission is under restrictive federal regulations because of its negative impact on atmosphere, biosphere, and human health. Therefore, its removal has been a subject of extensive research to develop new efficient and cost effective techniques that can be applied on an industrial scale. In this work, we study both experimentally and theoretically an effective removal of NOx pollutants from a surrogate flue gas (SFG) using high power electron beam (e-beam) pulses. SFG is a simulant for exhaust from coal combustion power plants (82% N2, 6% O2, 12% CO2, and ˜100 ppm of NOx). The pulsed electron beam is generated using the United States Naval Research Laboratory Electra facility, which delivers e-beams with energies of ˜500 keV and a power pulse duration of ˜140 ns. During the e-beam irradiation, the energetic electrons generate a non-equilibrium plasma containing chemically active species, which then react with NOx to form harmless substances. A non-equilibrium time-dependent model is developed to describe NOx remediation from SFG. The model combines e-beam deposition rates obtained by solving the electron Boltzmann equation and extensive plasma chemistry modeling, which follows the species on a time scale from sub-nanoseconds to a few seconds. NOx decomposition as a function of electron beam parameters is studied. It is demonstrated experimentally that short (ns) pulses are the most efficient for NOx removal. A sharp reduction of NOx was measured with e-beam power deposition increasing, following the trend predicted by the model, achieving a 20 fold reduction to ˜5 ppm at energy deposition ˜20 J/l.

  19. What Is 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 ...

  20. Red Blood Cell Antibody Identification

    Science.gov (United States)

    ... ID, RBC; RBC Ab ID Formal name: Red Blood Cell Antibody Identification Related tests: Direct Antiglobulin Test ; RBC ... I should know? How is it used? Red blood cell (RBC) antibody identification is used as a follow- ...

  1. Lupus anticoagulants and antiphospholipid antibodies

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000547.htm Lupus anticoagulants and antiphospholipid antibodies To use the sharing features on this page, please enable JavaScript. Lupus anticoagulants are antibodies against substances in the lining ...

  2. Anti-smooth muscle antibody

    Science.gov (United States)

    ... gov/ency/article/003531.htm Anti-smooth muscle antibody To use the sharing features on this page, please enable JavaScript. Anti-smooth muscle antibody is a blood test that detects the presence ...

  3. Characteristics of spray from a GDI fuel injector for naphtha and surrogate fuels

    KAUST Repository

    Wang, Libing

    2016-11-18

    Characterization of the spray angle, penetration, and droplet size distribution is important to analyze the spray and atomization quality. In this paper, the spray structure development and atomization characterization of two naphtha fuels, namely light naphtha (LN) and whole naphtha (WN) and two reference fuel surrogates, i.e. toluene primary reference fuel (TPRF) and primary reference fuel (PRF) were investigated using a gasoline direct injection (GDI) fuel injector. The experimental setup included a fuel injection system, a high-speed imaging system, and a droplet size measurement system. Spray images were taken by using a high-speed camera for spray angle and penetration analysis. Sauter mean diameter, Dv(10), Dv(50), Dv(90), and particle size distribution were measured using a laser diffraction technique. Results show that the injection process is very consistent for different runs and the time averaged spray angles during the measuring period are 103.45°, 102.84°, 102.46° and 107.61° for LN, WN, TPRF and PRF, respectively. The spray front remains relatively flat during the early stage of the fuel injection process. The peak penetration velocities are 80 m/s, 75 m/s, 75 m/s and 79 m/s for LN, WN, TPRF and PRF, respectively. Then velocities decrease until the end of the injection and stay relatively stable. The transient particle size and the time-averaged particle size were also analyzed and discussed. The concentration weighted average value generally shows higher values than the arithmetic average results. The average data for WN is usually the second smallest except for Dv90, of which WN is the biggest. Generally the arithmetic average particle sizes of PRF are usually the smallest, and the sizes does not change much with the measuring locations. For droplet size distribution results, LN and WN show bimodal distributions for all the locations while TPRF and PRF shows both bimodal and single peak distribution patterns. The results imply that droplet size

  4. Oxidation of Alkane Rich Gasoline Fuels and their Surrogates in a Motored Engine

    KAUST Repository

    Shankar, Vijai S B

    2015-03-30

    The validation of surrogates formulated using a computational framework by Ahmed et al.[1]for two purely paraffinic gasoline fuels labelled FACE A and FACE C was undertaken in this study. The ability of these surrogate mixtures to be used in modelling LTC engines was accessed by comparison of their low temperature oxidation chemistry with that of the respective parent fuel as well as a PRF based on RON. This was done by testing the surrogate mixtures in a modified Cooperative Fuels Research (CFR) engine running in Controlled Autoignition Mode (CAI) mode. The engine was run at a constant speed of 600 rpm at an equivalence ratio of 0.5 with the intake temperature at 150 °C and a pressure of 98 kPa. The low temperature reactivity of the fuels were studied by varying the compression ratio of the engine from the point were very only small low temperature heat release was observed to a point beyond which auto-ignition of the fuel/air mixture occurred. The apparent heat release rates of different fuels was calculated from the pressure histories using first law analysis and the CA 50 times of the low temperature heat release (LTHR) were compared. The surrogates reproduced the cool flame behavior of the parent fuels better than the PRF across all compression ratios.

  5. Refined ambient PM2.5 exposure surrogates and the risk of myocardial infarction

    Science.gov (United States)

    Using a case-crossover study design and conditional logistic regression, we compared the relative odds of transmural (full-wall) myocardial infarction (MI) calculated using exposure surrogates that account for human activity patterns and the indoor transport of ambient PM2....

  6. A surrogate-based approach for post-genomic partner identification

    Directory of Open Access Journals (Sweden)

    Giordano Tony

    2001-09-01

    Full Text Available Abstract Background Modern drug discovery is concerned with identification and validation of novel protein targets from among the 30,000 genes or more postulated to be present in the human genome. While protein-protein interactions may be central to many disease indications, it has been difficult to identify new chemical entities capable of regulating these interactions as either agonists or antagonists. Results In this paper, we show that peptide complements (or surrogates derived from highly diverse random phage display libraries can be used for the identification of the expected natural biological partners for protein and non-protein targets. Our examples include surrogates isolated against both an extracellular secreted protein (TNFβ and intracellular disease related mRNAs. In each case, surrogates binding to these targets were obtained and found to contain partner information embedded in their amino acid sequences. Furthermore, this information was able to identify the correct biological partners from large human genome databases by rapid and integrated computer based searches. Conclusions Modified versions of these surrogates should provide agents capable of modifying the activity of these targets and enable one to study their involvement in specific biological processes as a means of target validation for downstream drug discovery.

  7. Developmental biotechnology for aquaculture, with special reference to surrogate production in teleost fishes

    Science.gov (United States)

    Yamaha, Etsuro; Saito, Taiju; Goto-Kazeto, Rie; Arai, Katsutoshi

    2007-07-01

    This review introduces surrogate production as a new technique for fish-seed production in aquaculture. Surrogate production in fish is a technique used to obtain the gametes of a certain genotype through the gonad of another genotype. It is achieved by inducing germ-line chimerism between different species during early development. Primordial germ cells (PGCs) are the key material of this technique to induce germ-line chimera. In several species, it has been reported that PGCs differentiated from the blastomeres inherited some maternally supplied mRNA located in the terminal regions of the early cleavage furrows. PGCs from donor species (or strains) are isolated and transplanted into host species to induce the germ-line chimera. Four methods for inducing germ-line chimera are described: blastomere transplantation, blastoderm-graft transplantation, transplantation of PGC from the genital ridge, and transplantation visualised PGC with GFP fluorescence. Several problems preventing the successful induction of germ-line chimera in various fish species are discussed. Surrogate production, however, opens the possibility of efficient fish-seed production and effective breeding and transfer of biodiversity to an aquaculture strain. Conservation and efficient utilisation of genetic resources will be achieved through surrogate production combined with the cryopreservation of PGCs.

  8. Comparative Numerical Study of Four Biodiesel Surrogates for Application on Diesel 0D Phenomenological Modeling

    Directory of Open Access Journals (Sweden)

    Claude Valery Ngayihi Abbe

    2016-01-01

    Full Text Available To meet more stringent norms and standards concerning engine performances and emissions, engine manufacturers need to develop new technologies enhancing the nonpolluting properties of the fuels. In that sense, the testing and development of alternative fuels such as biodiesel are of great importance. Fuel testing is nowadays a matter of experimental and numerical work. Researches on diesel engine’s fuel involve the use of surrogates, for which the combustion mechanisms are well known and relatively similar to the investigated fuel. Biodiesel, due to its complex molecular configuration, is still the subject of numerous investigations in that area. This study presents the comparison of four biodiesel surrogates, methyl-butanoate, ethyl-butyrate, methyl-decanoate, and methyl-9-decenoate, in a 0D phenomenological combustion model. They were investigated for in-cylinder pressure, thermal efficiency, and NOx emissions. Experiments were performed on a six-cylinder turbocharged DI diesel engine fuelled by methyl ester (MEB and ethyl ester (EEB biodiesel from wasted frying oil. Results showed that, among the four surrogates, methyl butanoate presented better results for all the studied parameters. In-cylinder pressure and thermal efficiency were predicted with good accuracy by the four surrogates. NOx emissions were well predicted for methyl butanoate but for the other three gave approximation errors over 50%.

  9. Thermal Inactivation of Foodborne Enteric Viruses and Their Viral Surrogates in Foods.

    Science.gov (United States)

    Bozkurt, Hayriye; D'Souza, Doris H; Davidson, P Michael

    2015-08-01

    Foodborne viruses, in particular human norovirus and hepatitis A virus, are the most common causes of food-associated infections and foodborne illness outbreaks around the world. Since it is currently not possible to cultivate human noroviruses and the wild-type strain of hepatitis A virus in vitro, the use of a variety of viral surrogates is essential to determine appropriate thermal processing conditions to reduce the risk associated with their contamination of food. Therefore, the objectives of this review are to (i) present pertinent characteristics of enteric foodborne viruses and their viral surrogates, (ii) discuss the viral surrogates currently used in thermal inactivation studies and their significance and value, (iii) summarize available data on thermal inactivation kinetics of enteric viruses, (iv) discuss factors affecting the efficacy of thermal treatment, (v) discuss suggested mechanisms of thermal inactivation, and (vi) provide insights on foodborne enteric viruses and viral surrogates for future studies and industrial applications. The overall goal of this review is to contribute to the development of appropriate thermal processing protocols to ensure safe food for human consumption.

  10. Identification of the first surrogate agonists for the G protein-coupled receptor GPR132

    DEFF Research Database (Denmark)

    Shehata, Mohamed A.; Christensen, Hanna Belcik; Isberg, Vignir;

    2015-01-01

    -arrestin recruitment assay, and thereby identified the first disclosed surrogate GPR132 agonist 1 with a potency of 3.4 μM. This constitutes the first available pharmacological tool for the in vitro characterization of the orphan receptor GPR132. The testing of 32 analogs furthermore identified a number of compounds...

  11. A spinal cord surrogate with nanoscale porosity for in vitro simulations of restorative neurosurgical techniques

    Science.gov (United States)

    Gillies, G. T.; Wilhelm, T. D.; Humphrey, J. A. C.; Fillmore, H. L.; Holloway, K. L.; Broaddus, W. C.

    2002-10-01

    The development of strategies for the regrowth of axons through a section of damaged spinal cord could benefit from the availability of an in vitro model in which the potential clinical utility of candidate techniques could be assessed preliminarily. We have designed a spinal cord surrogate for this purpose; it uses 0.6% agarose gel as the parenchymal component and has a fibrous-like longitudinal structure. At this concentration, the pore size distribution of the homogeneous gel ranges from less than 10 nm to more than 1000 nm while the average pore size ranges from 100 to 300 nm. The average pore size is larger than that of the extracellular space in the tissues of the central nervous system, which is of the order of 20 nm. However, the addition of fibres to the surrogate gel model significantly modifies its longitudinal permeability, as assessed by monitoring the distribution of marker dye material during direct infusion into the surrogate. This makes the model useful for evaluating infusion-based techniques that will ultimately be employed for the delivery of growth factors and other agents to the growing axonal processes in injured spinal cord. The role foreseen for this type of surrogate in investigations of the nanomechanics of restorative neurosurgical procedures is discussed.

  12. Testing for nonlinearity in time series: The method of surrogate data

    Energy Technology Data Exchange (ETDEWEB)

    Theiler, J.; Galdrikian, B.; Longtin, A. (Los Alamos National Lab., NM (United States)); Eubank, S.; Farmer, J.D. (Los Alamos National Lab., NM (United States) Santa Fe Inst., NM (United States))

    1991-01-01

    We describe a statistical approach for identifying nonlinearity in time series; in particular, we want to avoid claims of chaos when simpler models (such as linearly correlated noise) can explain the data. The method requires a careful statement of the null hypothesis which characterizes a candidate linear process, the generation of an ensemble of surrogate'' data sets which are similar to the original time series but consistent with the null hypothesis, and the computation of a discriminating statistic for the original and for each of the surrogate data sets. The idea is to test the original time series against the null hypothesis by checking whether the discriminating statistic computed for the original time series differs significantly from the statistics computed for each of the surrogate sets. We present algorithms for generating surrogate data under various null hypotheses, and we show the results of numerical experiments on artificial data using correlation dimension, Lyapunov exponent, and forecasting error as discriminating statistics. Finally, we consider a number of experimental time series -- including sunspots, electroencephalogram (EEG) signals, and fluid convection -- and evaluate the statistical significance of the evidence for nonlinear structure in each case. 56 refs., 8 figs.

  13. Space mapping interpolating surrogates for highly optimized EM-based design of microwave devices

    DEFF Research Database (Denmark)

    Bandler, John; Cheng, Qingsha; Dakroury, Sameh;

    2004-01-01

    A powerful optimization algorithm that incorporates Space Mapping (SM) and the new Output Space Mapping (OSM) to yield highly optimized results in a handful of fine model evaluations is presented. The new method employs an SM-based interpolating surrogate (SMIS) framework that aims at matching th...

  14. Evaluation and Development of Chemical Kinetic Mechanism Reduction Scheme for Biodiesel and Diesel Fuel Surrogates

    DEFF Research Database (Denmark)

    Poon, Hiew Mun; Ng, Hoon Kiat; Gan, Suyin

    2013-01-01

    The aim of this study is to evaluate the existing chemical kinetic mechanism reduction techniques. From here, an appropriate reduction scheme was developed to create compact yet comprehensive surrogate models for both diesel and biodiesel fuels for diesel engine applications. The reduction techni...

  15. ASYMPTOTIC SURROGATE CONSTRAINT METHOD AND ITS CONVERGENCEFOR A CLASS OF SEMI-INFINITE PROGRAMMING

    Institute of Scientific and Technical Information of China (English)

    WanZhongping; WuGuoming

    1999-01-01

    A class of constrained semi infinite minimax problem is transformed into a simpleconstrained problem, by means of discretization decoraposirion and maximum entropy method,making use of surrogate constraint, The paper deals with the convergence of this asymptotic aI-proach method.

  16. Permanent pixels : building blocks for the longevity of digital surrogates of historical photographs

    NARCIS (Netherlands)

    Van Horik, M.P.M.

    2005-01-01

    Within the context of long-term access to digital objects in general this dissertation takes the longevity of digital surrogates of historical photographs into consideration. For memory institutes digitisation of analogue source material, such as historical photographs, is an exciting way to open up

  17. PCA-derived respiratory motion surrogates from X-ray angiograms for percutaneous coronary interventions

    NARCIS (Netherlands)

    H. Ma (Hua); G. Dibildox (Gerardo); C. Schultz (Carl); E.S. Regar (Eveline); T.W. van Walsum (Theo)

    2015-01-01

    textabstractPurpose: Intraoperative coronary motion modeling with motion surrogates enables prospective motion prediction in X-ray angiograms (XA) for percutaneous coronary interventions. The motion of coronary arteries is mainly affected by patients breathing and heartbeat. Purpose of our work is t

  18. Family matters: effects of birth order, culture, and family dynamics on surrogate decision-making.

    Science.gov (United States)

    Su, Christopher T; McMahan, Ryan D; Williams, Brie A; Sharma, Rashmi K; Sudore, Rebecca L

    2014-01-01

    Cultural attitudes about medical decision-making and filial expectations may lead some surrogates to experience stress and family conflict. Thirteen focus groups with racially and ethnically diverse English and Spanish speakers from county and Veterans Affairs hospitals, senior centers, and cancer support groups were conducted to describe participants' experiences making serious or end-of-life decisions for others. Filial expectations and family dynamics related to birth order and surrogate decision-making were explored using qualitative, thematic content analysis, and overarching themes from focus group transcripts were identified. The mean age of the 69 participants was 69 ± 14, and 29% were African American, 26% were white, 26% were Asian or Pacific Islander, and 19% were Latino. Seventy percent of participants engaged in unprompted discussions about birth order and family dynamics. Six subthemes were identified within three overarching categories: communication (unspoken expectations and discussion of death as taboo), emotion (emotional stress and feelings of loneliness), and conflict (family conflict and potential solutions to prevent conflict). These findings suggest that birth order and family dynamics can have profound effects on surrogate stress and coping. Clinicians should be aware of potential unspoken filial expectations for firstborns and help facilitate communication between the patient, surrogate, and extended family to reduce stress and conflict.

  19. Ovulation Statuses of Surrogate Gilts Are Associated with the Efficiency of Excellent Pig Cloning.

    Science.gov (United States)

    Huan, Yanjun; Hu, Kui; Xie, Bingteng; Shi, Yongqian; Wang, Feng; Zhou, Yang; Liu, Shichao; Huang, Bo; Zhu, Jiang; Liu, Zhongfeng; He, Yilong; Li, Jingyu; Kong, Qingran; Liu, Zhonghua

    2015-01-01

    Somatic cell nuclear transfer (SCNT) is an assisted reproductive technique that can produce multiple copies of excellent livestock. However, low cloning efficiency limits the application of SCNT. In this study, we systematically investigated the major influencing factors related to the overall cloning efficiency in pigs. Here, 13620 cloned embryos derived from excellent pigs were transferred into 79 surrogate gilts, and 119 live cloned piglets were eventually generated. During cloning, group of cloned embryos derived from excellent Landrace or Large white pigs presented no significant differences of cleavage and blastocyst rates, blastocyst cell numbers, surrogate pregnancy and delivery rates, average numbers of piglets born and alive and cloning efficiencies, and group of 101-150, 151-200 or 201-250 cloned embryos transferred per surrogate also displayed a similar developmental efficiency. When estrus stage of surrogate gilts was compared, group of embryo transfer on Day 2 of estrus showed significantly higher pregnancy rate, delivery rate, average number of piglets born, average alive piglet number or cloning efficiency than group on Day 1, Day 3, Day 4 or Day 5, respectively (Pcloning efficiency (Pcloning efficiency. And more, follicle puncture for preovulation, not transfer position shallowed for preovulation or deepened for postovulation, significantly improved the average number of piglets alive and cloning efficiency (Pcloning efficiency of excellent pigs, and follicle puncture, not transfer position change, improved cloning efficiency. This work would have important implications in preserving and breeding excellent livestock and improving the overall cloning efficiency.

  20. Atmospheric cold plasma iactivation of norovirus surrogates and native microbiota on blueberries

    Science.gov (United States)

    Cold plasma (CP) is an emerging, novel, nonthermal technology that can be used for surface decontamination of foods. This study investigated CP technology for the nonthermal inactivation of the human norovirus surrogates, Tulane virus (TV) and Murine Norovirus (MNV), as well as for background microb...

  1. Antibody Engineering and Therapeutics Conference

    OpenAIRE

    Larrick, James W; Parren, Paul WHI; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A.; Burton, Dennis R.; Adams, Gregory P.; Weiner, Louis M.; Scott, Jamie K.; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M.

    2013-01-01

    The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Bi...

  2. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery...

  3. Inactivation Kinetics and Mechanism of a Human Norovirus Surrogate on Stainless Steel Coupons via Chlorine Dioxide Gas.

    Science.gov (United States)

    Yeap, Jia Wei; Kaur, Simran; Lou, Fangfei; DiCaprio, Erin; Morgan, Mark; Linton, Richard; Li, Jianrong

    2015-10-16

    Acute gastroenteritis caused by human norovirus is a significant public health issue. Fresh produce and seafood are examples of high-risk foods associated with norovirus outbreaks. Food contact surfaces also have the potential to harbor noroviruses if exposed to fecal contamination, aerosolized vomitus, or infected food handlers. Currently, there is no effective measure to decontaminate norovirus on food contact surfaces. Chlorine dioxide (ClO2) gas is a strong oxidizer and is used as a decontaminating agent in food processing plants. The objective of this study was to determine the kinetics and mechanism of ClO2 gas inactivation of a norovirus surrogate, murine norovirus 1 (MNV-1), on stainless steel (SS) coupons. MNV-1 was inoculated on SS coupons at the concentration of 10(7) PFU/coupon. The samples were treated with ClO2 gas at 1, 1.5, 2, 2.5, and 4 mg/liter for up to 5 min at 25°C and a relative humidity of 85%, and virus survival was determined by plaque assay. Treatment of the SS coupons with ClO2 gas at 2 mg/liter for 5 min and 2.5 mg/liter for 2 min resulted in at least a 3-log reduction in MNV-1, while no infectious virus was recovered at a concentration of 4 mg/liter even within 1 min of treatment. Furthermore, it was found that the mechanism of ClO2 gas inactivation included degradation of viral protein, disruption of viral structure, and degradation of viral genomic RNA. In conclusion, treatment with ClO2 gas can serve as an effective method to inactivate a human norovirus surrogate on SS contact surfaces.

  4. Effects of Abiotic and Biotic Stresses on the Internalization and Dissemination of Human Norovirus Surrogates in Growing Romaine Lettuce.

    Science.gov (United States)

    DiCaprio, Erin; Purgianto, Anastasia; Li, Jianrong

    2015-07-01

    Human norovirus (NoV) is the major causative agent of fresh-produce-related outbreaks of gastroenteritis; however, the ecology and persistence of human NoV in produce systems are poorly understood. In this study, the effects of abiotic and biotic stresses on the internalization and dissemination of two human NoV surrogates (murine norovirus 1 [MNV-1] and Tulane virus [TV]) in romaine lettuce were determined. To induce abiotic stress, romaine lettuce was grown under drought and flood conditions that mimic extreme weather events, followed by inoculation of soil with MNV-1 or TV. Independently, lettuce plants were infected with lettuce mosaic virus (LMV) to induce biotic stress, followed by inoculation with TV. Plants were grown for 14 days, and viral titers in harvested tissues were determined by plaque assays. It was found that drought stress significantly decreased the rates of both MNV-1 and TV internalization and dissemination. In contrast, neither flood stress nor biotic stress significantly impacted viral internalization or dissemination. Additionally, the rates of TV internalization and dissemination in soil-grown lettuce were significantly higher than those for MNV-1. Collectively, these results demonstrated that (i) human NoV surrogates can be internalized via roots and disseminated to shoots and leaves of romaine lettuce grown in soil, (ii) abiotic stress (drought) but not biotic stress (LMV infection) affects the rates of viral internalization and dissemination, and (iii) the type of virus affects the efficiency of internalization and dissemination. This study also highlights the need to develop effective measures to eliminate internalized viruses in fresh produce.

  5. Adsorption of monoclonal antibodies to glass microparticles.

    Science.gov (United States)

    Hoehne, Matthew; Samuel, Fauna; Dong, Aichun; Wurth, Christine; Mahler, Hanns-Christian; Carpenter, John F; Randolph, Theodore W

    2011-01-01

    Microparticulate glass represents a potential contamination to protein formulations that may occur as a result of processing conditions or glass types. The effect of added microparticulate glass to formulations of three humanized antibodies was tested. Under the three formulation conditions tested, all three antibodies adsorbed irreversibly at near monolayer surface coverages to the glass microparticles. Analysis of the secondary structure of the adsorbed antibodies by infrared spectroscopy reveal only minor perturbations as a result of adsorption. Likewise, front-face fluorescence quenching measurements reflected minimal tertiary structural changes upon adsorption. In contrast to the minimal effects on protein structure, adsorption of protein to suspensions of glass microparticles induced significant colloidal destabilization and flocculation of the suspension.

  6. Sensitive neutralization test for rubella antibody.

    Science.gov (United States)

    Sato, H; Albrecht, P; Krugman, S; Ennis, F A

    1979-01-01

    A modified rubella virus plaque neutralization test for measuring rubella antibody was developed based on the potentiation of the virus-antibody complex by heterologous anti-immunoglobulin. The test is highly sensitive, yielding titers on the average 50 to 100 times higher than the haemagglutination inhibition test or the conventional plaque neutralization test. The sensitivity of this enhanced neutralization test is somewhat limited by the existence of a prozone phenomenon which precludes testing of low-titered sera below a dilution of 1:16. No prozone effect was observed with cerebrospinal fluids. The specificity of the enhanced neutralization test was determined by seroconversion of individuals receiving rubella vaccine. Although the rubella hemagglutination inhibition test remains the test of choice in routine diagnostic and surveillance work, the enhanced rubella neutralization test is particularly useful in monitoring low-level antibody in the cerebrospinal fluid in patients with neurological disorders and in certain instances of vaccine failure. PMID:107192

  7. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the uni

  8. Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

    Directory of Open Access Journals (Sweden)

    Groot-Kormelink Paul J

    2012-10-01

    Full Text Available Abstract Background Alveolar macrophages are one of the first lines of defence against invading pathogens and play a central role in modulating both the innate and acquired immune systems. By responding to endogenous stimuli within the lung, alveolar macrophages contribute towards the regulation of the local inflammatory microenvironment, the initiation of wound healing and the pathogenesis of viral and bacterial infections. Despite the availability of protocols for isolating primary alveolar macrophages from the lung these cells remain recalcitrant to expansion in-vitro and therefore surrogate cell types, such as monocyte derived macrophages and phorbol ester-differentiated cell lines (e.g. U937, THP-1, HL60 are frequently used to model macrophage function. Methods The availability of high throughput gene expression technologies for accurate quantification of transcript levels enables the re-evaluation of these surrogate cell types for use as cellular models of the alveolar macrophage. Utilising high-throughput TaqMan arrays and focussing on dynamically regulated families of integral membrane proteins, we explore the similarities and differences in G-protein coupled receptor (GPCR and ion channel expression in alveolar macrophages and their widely used surrogates. Results The complete non-sensory GPCR and ion channel transcriptome is described for primary alveolar macrophages and macrophage surrogates. The expression of numerous GPCRs and ion channels whose expression were hitherto not described in human alveolar macrophages are compared across primary macrophages and commonly used macrophage cell models. Several membrane proteins known to have critical roles in regulating macrophage function, including CXCR6, CCR8 and TRPV4, were found to be highly expressed in macrophages but not expressed in PMA-differentiated surrogates. Conclusions The data described in this report provides insight into the appropriate choice of cell models for

  9. Compositional effects on PAH and soot formation in counterflow diffusion flames of gasoline surrogate fuels

    KAUST Repository

    Park, Sungwoo

    2017-02-05

    Gasoline surrogate fuels are widely used to understand the fundamental combustion properties of complex refinery gasoline fuels. In this study, the compositional effects on polycyclic aromatic hydrocarbons (PAHs) and soot formation were investigated experimentally for gasoline surrogate mixtures comprising n-heptane, iso-octane, and toluene in counterflow diffusion flames. A comprehensive kinetic model for the gasoline surrogate mixtures was developed to accurately predict the fuel oxidation along with the formation of PAHs and soot in flames. This combined model was first tested against ignition delay times and laminar burning velocities data. The proposed model for the formation and growth of PAHs up to coronene (C24H12) was based on previous studies and was tested against existing and present new experimental data. Additionally, in the accompanied soot model, PAHs with sizes larger than (including) pyrene were used for the inception of soot particles, followed by particle coagulations and PAH condensation/chemical reactions on soot surfaces. The major pathways for the formation of PAHs were also identified for the surrogate mixtures. The model accurately captures the synergistic PAH formation characteristics observed experimentally for n-heptane/toluene and iso-octane/toluene binary mixtures. Furthermore, the present experimental and modeling results also elucidated different trends in the formation of larger PAHs and soot between binary n-heptane/iso-octane and ternary n-heptane/iso-octane/toluene mixtures. Propargyl radicals (C3H3) were shown to be important in the formation and growth of PAHs for n-heptane/iso-octane mixtures when the iso-octane concentration increased; however, reactions involving benzyl radicals (C6H5CH2) played a significant role in the formation of PAHs for n-heptane/iso-octane/toluene mixtures. These results indicated that the formation of PAHs and subsequently soot was strongly affected by the composition of gasoline surrogate mixtures.

  10. 'Tissue surrogates' as a model for archival formalin-fixed paraffin-embedded tissues.

    Science.gov (United States)

    Fowler, Carol B; Cunningham, Robert E; O'Leary, Timothy J; Mason, Jeffrey T

    2007-08-01

    High-throughput proteomic studies of archival formalin-fixed paraffin-embedded (FFPE) tissues have the potential to be a powerful tool for examining the clinical course of disease. However, advances in FFPE tissue-based proteomics have been hampered by inefficient methods to extract proteins from archival tissue and by an incomplete knowledge of formaldehyde-induced modifications in proteins. To help address these problems, we have developed a procedure for the formation of 'tissue surrogates' to model FFPE tissues. Cytoplasmic proteins, such as lysozyme or ribonuclease A, at concentrations approaching the protein content in whole cells, are fixed with 10% formalin to form gelatin-like plugs. These plugs have sufficient physical integrity to be processed through graded alcohols, xylene, and embedded in paraffin according to standard histological procedures. In this study, we used tissue surrogates formed from one or two proteins to evaluate extraction protocols for their ability to quantitatively extract proteins from the surrogates. Optimal protein extraction was obtained using a combination of heat, a detergent, and a protein denaturant. The addition of a reducing agent did not improve protein recovery; however, recovery varied significantly with pH. Protein extraction of >80% was observed for pH 4 buffers containing 2% (w/v) sodium dodecyl sulfate (SDS) when heated at 100 degrees C for 20 min, followed by incubation at 60 degrees C for 2 h. SDS-polyacrylamide gel electrophoresis of the extracted proteins revealed that the surrogate extracts contained a mixture of monomeric and multimeric proteins, regardless of the extraction protocol employed. Additionally, protein extracts from surrogates containing carbonic anhydrase:lysozyme (1:2 mol/mol) had disproportionate percentages of lysozyme, indicating that selective protein extraction in complex multiprotein systems may be a concern in proteomic studies of FFPE tissues.

  11. Assessment of electrical conductivity as a surrogate measurement for water samples in a tracer injection experiment

    Science.gov (United States)

    The transport behavior of solutes in streams depends on chemical, physical, biological, and hydrodynamic processes. Although it is a very complex system, it is known that this behavior is greatly influenced by surface and subsurface flows. For this reason, tracer injection in the water flows is one ...

  12. Establishment of a quantitative ELISA for the measurement of allergen-specific IgE in dogs using anti-IgE antibody cross-reactive to mouse and dog IgE.

    Science.gov (United States)

    Okayama, Taro; Matsuno, Yukiko; Yasuda, Nobutaka; Tsukui, Toshihiro; Suzuta, Yasuyuki; Koyanagi, Masanori; Sakaguchi, Masahiro; Ishii, Yasuyuki; Olivry, Thierry; Masuda, Kenichi

    2011-02-15

    As IgE plays a pivotal role in type I hypersensitivity-mediated allergic diseases, it is valuable to measure absolute quantity of serum antigen-specific IgE for clinical and research purposes. Here we describe a novel ELISA system that enables quantification of antigen-specific IgE in ng/ml in dogs. A newly developed monoclonal antibody (CRE-DM) was shown to recognize canine and mouse IgE equally in a dose dependent manner, but it did not recognize canine IgG. The reactivity of CRE-DM to canine IgE was also confirmed by an inhibition ELISA using canine IgE as an inhibitor and the maximum inhibition rate was 91.3%. In order to know whether canine IgE specific to an allergen could be quantitatively measured with an ELISA using CRE-DM, we established a quantitative ELISA that could measure canine IgE recognizing Cry j 1, one of the major allergens of Japanese cedar pollen. In this ELISA, a standard curve was created by using concentration-predetermined Cry j 1-specific monoclonal mouse IgE. According to the standard curve, the concentration of Cry j 1-specific IgE in dogs that were experimentally sensitized to Japanese cedar pollen could be calculated and determined in ng/ml. The specificity of the Cry j 1-specific IgE ELISA using CRE-DM was also confirmed by inhibition ELISA using canine IgE as an inhibitor and the inhibition rate was 97.0%. Reproducibility of the ELISA in three independent assays was determined using groups of pooled canine sera whose Cry j 1-IgE titers ranged from 155.9 to 888.2 ng/ml. Intra- and inter-assay reproducibility was determined with coefficient of variation ranging between 3.1-5.2% and 2.2-8.0%, respectively. These results demonstrated that the ELISA utilizing CRE-DM was a specific, reliable and robust new laboratory test that could quantify absolute amount of antigen-specific IgE in canine serum. The ELISA will serve as a useful tool in the clinics to evaluate the change of serum IgE titers during anti-allergic treatments as well as

  13. ANTI-GM1 ANTIBODIES IN PATIENTS WITH GUILLAIN-BARRE-SYNDROME

    NARCIS (Netherlands)

    VANDENBERG, LH; MARRINK, J; DEJAGER, AEJ; DEJONG, HJ; VANIMHOFF, GW; LATOV, N; SADIQ, SA

    1992-01-01

    Anti-GM1 antibodies were measured in 22 patients with the Guillain-Barre syndrome (GBS) and compared with anti-GM1 antibody activity in patients with other neurological or immunological diseases and in normal subjects. Four out of 22 patients with GBS had raised IgM, IgG, or IgA anti-GM1 antibody ac

  14. Antiphospholipid Antibody and Antiphospholipid Syndrome

    Institute of Scientific and Technical Information of China (English)

    吴竞生

    2008-01-01

    @@ Antiphospholipid antibodies (APA) APA is a big category for all kinds of negative charge phospholipid or lecithin - a protein complex autoantibodies or the same antibody, through its recognition of antigen (target protein) different, and phospholipids or lecithin - protein complex combination of various rely on the interference Phospholipid clotting and anti-coagulation factor, and promote endothelial cells, platelets, complement activation and play a role. APA including lupus anticoagulant(LA) and anticardiolipin antibody (ACA), In addition, there are anti-β2 glycoprotein-I (β2-GPI) antibody, anti-prothrombin (a- PT) antibody, anti-lysophosphatidic acid antibody and anti-phosphatidylserine antibody, and so on. APA as the main target of phospholipid-binding protein, including β2-GPI, prothrombin, annexin, protein C (PC) and protein S (PS), plasminogen, and so on.

  15. Engineering antibodies by yeast display.

    Science.gov (United States)

    Boder, Eric T; Raeeszadeh-Sarmazdeh, Maryam; Price, J Vincent

    2012-10-15

    Since its first application to antibody engineering 15 years ago, yeast display technology has been developed into a highly potent tool for both affinity maturing lead molecules and isolating novel antibodies and antibody-like species. Robust approaches to the creation of diversity, construction of yeast libraries, and library screening or selection have been elaborated, improving the quality of engineered molecules and certainty of success in an antibody engineering campaign and positioning yeast display as one of the premier antibody engineering technologies currently in use. Here, we summarize the history of antibody engineering by yeast surface display, approaches used in its application, and a number of examples highlighting the utility of this method for antibody engineering.

  16. Clinical significance of co-measurement of three different serum antibodies in women with recurrent spontaneous abortion%复发性流产患者联合检测三种血清自身抗体及临床意义

    Institute of Scientific and Technical Information of China (English)

    郑建琼; 沈晓露; 朱雪琼; 郑加永; 徐芳

    2012-01-01

    目的:探讨血清抗心磷脂抗体(anticardiolipin antibody,ACL)、抗β2-糖蛋白Ⅰ抗体(anti-beta2-glycoproteinI antibody,抗β2-GPI抗体)和狼疮抗凝物(lupus anticoagulant antibody,LAC)联合检测对复发性流产(reeurrent spontaneous abortion,RSA)的预测意义.方法:选取85例RSA患者为实验组,50例正常经产妇作为对照组,检测两组血清ACL、抗β2-GP1抗体和LAC水平.结果:RSA组ACL阳性率为27.06%(23/85),而对照组为8%(4/50),差异有统计学意义(P<0.01);抗β2-GPI抗体阳性率为21.18%(18/85),而对照组2%(1/50),差异有统计学意义(P< 0.01);LAC阳性率为21.18%(18/85),而对照组为6%(3/50),差异有统计学意义(P<0.05).在确诊的40例抗磷脂抗体综合症患者中,ACL或抗β2-GPI抗体阳性率为95.00%(38/40),和ACL或LAC阳性组比较,差异有统计学意义(P<0.01);和抗β2-GPI抗体或LAC阳性组比较,差异有统计学意义(P<0.05).结论:(1) ACL、抗β2-GPI抗体和LAC均与RSA有关.(2)ACL和抗β2-GPI抗体联合检测可以提高RSA患者抗磷脂抗体综合症检出率,对于临床诊断和指导治疗有重要意义.%Objective To investigate the clinical value of co-measurement of anticardiolipin (ACL), anti-beta2-glycoprotein I, and lupus anticoagulant antibody (LAC) antibodies in women with recurrent spontaneous abortion (RSA). Methods Levels of ACL, anti-beta2-glycoprotein I and LAC antibodies in 85 women with RSA (RSA group) and 50 normal mukigravidas (control group) were detected. Results The positive rates of ACL, anti-beta2-glycoprotein I and LAC antibodies in RSA group and control group were 27.06% (23/85), 21.18% (18/85), 21.18% (18/85) and 8% (4/50), 2% (1 /50), 6% (3/50), respectively; And the differences between the two groups were significant (P < 0.01, P<0.01, P < 0.05). The positive rate of ACL or anti-beta2-glycoprotein I antibodies was 95.00% (38/40) in 40 women who were definitely diagnosed with antiphosphlipid syndrome (APS

  17. A Quantitative Method for Comparing the Brightness of Antibody-dye Reagents and Estimating Antibodies Bound per Cell.

    Science.gov (United States)

    Kantor, Aaron B; Moore, Wayne A; Meehan, Stephen; Parks, David R

    2016-01-01

    We present a quantitative method for comparing the brightness of antibody-dye reagents and estimating antibodies bound per cell. The method is based on complementary binding of test and fill reagents to antibody capture microspheres. Several aliquots of antibody capture beads are stained with varying amounts of the test conjugate. The remaining binding sites on the beads are then filled with a second conjugate containing a different fluorophore. Finally, the fluorescence of the test conjugate compared to the fill conjugate is used to measure the relative brightness of the test conjugate. The fundamental assumption of the test-fill method is that if it takes X molecules of one test antibody to lower the fill signal by Y units, it will take the same X molecules of any other test antibody to give the same effect. We apply a quadratic fit to evaluate the test-fill signal relationship across different amounts of test reagent. If the fit is close to linear, we consider the test reagent to be suitable for quantitative evaluation of antibody binding. To calibrate the antibodies bound per bead, a PE conjugate with 1 PE molecule per antibody is used as a test reagent and the fluorescence scale is calibrated with Quantibrite PE beads. When the fluorescence per antibody molecule has been determined for a particular conjugate, that conjugate can be used for measurement of antibodies bound per cell. This provides comparisons of the brightness of different conjugates when conducted on an instrument whose statistical photoelectron (Spe) scales are known. © 2016 by John Wiley & Sons, Inc.

  18. Neuroticism, cortisol reactivity, and antibody response to vaccination

    OpenAIRE

    Anna C. Phillips; Carroll, Douglas; Burns, Victoria E.; Drayson, Mark

    2005-01-01

    This study examined whether neuroticism was related to the antibody response to influenza vaccination and whether the relationship was mediated by cortisol reactions to an acute laboratory mental stress. Antibody status was assessed at baseline and to a trivalent influenza vaccination in 57 students at five-weeks and five-month follow-up. Neuroticism was also measured at baseline. Cortisol was measured at rest and in response to a pressurised mental arithmetic task. At both follow-ups, hi...

  19. The NASA Langley Research Center's Unmanned Aerial System Surrogate Research Aircraft

    Science.gov (United States)

    Howell, Charles T., III; Jessup, Artie; Jones, Frank; Joyce, Claude; Sugden, Paul; Verstynen, Harry; Mielnik, John

    2010-01-01

    Research is needed to determine what procedures, aircraft sensors and other systems will be required to allow Unmanned Aerial Systems (UAS) to safely operate with manned aircraft in the National Airspace System (NAS). The NASA Langley Research Center has transformed a Cirrus Design SR22 general aviation (GA) aircraft into a UAS Surrogate research aircraft to serve as a platform for UAS systems research, development, flight testing and evaluation. The aircraft is manned with a Safety Pilot and systems operator that allows for flight operations almost anywhere in the NAS without the need for a Federal Aviation Administration (FAA) Certificate of Authorization (COA). The UAS Surrogate can be controlled from a modular, transportable ground station like a true UAS. The UAS Surrogate is able to file and fly in the NAS with normal traffic and is a better platform for real world UAS research and development than existing vehicles flying in restricted ranges or other sterilized airspace. The Cirrus Design SR22 aircraft is a small, singleengine, four-place, composite-construction aircraft that NASA Langley acquired to support NASA flight-research programs like the Small Aircraft Transportation System (SATS) Project. Systems were installed to support flight test research and data gathering. These systems include: separate research power; multi-function flat-panel displays; research computers; research air data and inertial state sensors; video recording; data acquisition; data-link; S-band video and data telemetry; Common Airborne Instrumentation System (CAIS); Automatic Dependent Surveillance-Broadcast (ADS-B); instrumented surfaces and controls; and a systems operator work station. The transformation of the SR22 to a UAS Surrogate was accomplished in phases. The first phase was to modify the existing autopilot to accept external commands from a research computer that was connected by redundant data-link radios to a ground control station. An electro-mechanical auto

  20. Surrogate model approach for improving the performance of reactive transport simulations

    Science.gov (United States)

    Jatnieks, Janis; De Lucia, Marco; Sips, Mike; Dransch, Doris

    2016-04-01

    Reactive transport models can serve a large number of important geoscientific applications involving underground resources in industry and scientific research. It is common for simulation of reactive transport to consist of at least two coupled simulation models. First is a hydrodynamics simulator that is responsible for simulating the flow of groundwaters and transport of solutes. Hydrodynamics simulators are well established technology and can be very efficient. When hydrodynamics simulations are performed without coupled geochemistry, their spatial geometries can span millions of elements even when running on desktop workstations. Second is a geochemical simulation model that is coupled to the hydrodynamics simulator. Geochemical simulation models are much more computationally costly. This is a problem that makes reactive transport simulations spanning millions of spatial elements very difficult to achieve. To address this problem we propose to replace the coupled geochemical simulation model with a surrogate model. A surrogate is a statistical model created to include only the necessary subset of simulator complexity for a particular scenario. To demonstrate the viability of such an approach we tested it on a popular reactive transport benchmark problem that involves 1D Calcite transport. This is a published benchmark problem (Kolditz, 2012) for simulation models and for this reason we use it to test the surrogate model approach. To do this we tried a number of statistical models available through the caret and DiceEval packages for R, to be used as surrogate models. These were trained on randomly sampled subset of the input-output data from the geochemical simulation model used in the original reactive transport simulation. For validation we use the surrogate model to predict the simulator output using the part of sampled input data that was not used for training the statistical model. For this scenario we find that the multivariate adaptive regression splines

  1. “RéaNet”, the Internet utilization among surrogates of critically ill patients with sepsis

    Science.gov (United States)

    Porcher, Raphaël; Argaud, Laurent; Piquilloud, Lise; Guitton, Christophe; Tamion, Fabienne; Hraiech, Sami; Mira, Jean-Paul

    2017-01-01

    Context Health-related Internet utilization is common but its use by proxies of critically ill patients is unknown. Our objective was to describe the prevalence and the Internet utilization characteristics among surrogates of critically ill septic patients. We conducted a prospective observational study in French ICUs. Three survey instruments were used to describe ICU organization regarding information delivery, patients and surrogates characteristics. Results 169 surrogates of 146 septic patients hospitalized in 19 ICUs were included. One sixth of ICUs (n = 3, 16%) had their own website. Majority of patients were males (n = 100, 68%), aged 64±1 years old, with a SAPS2 score at 53±17 and required vasopressors (n = 117, 83%), mechanical ventilation (n = 116, 82%). More than one quarter required renal replacement therapy (n = 36, 26%). Majority of surrogates were female, in their fifties. Only one in five knew the word sepsis (n = 27, 16%). Majority of proxies internet users (n = 77; 55%) search on the internet about sepsis. The main motivation was curiosity. Majority of surrogates found the information online reliable, suitable for request and concordant. Prior use of health-related Internet (OR = 20.7 [4.30–100.1]), the presence of a nursing staff during family-physician meetings (OR = 3.33 [1.17–9.53]), a younger patient age (OR = 1.32 [1.01–1.72]) and renal replacement therapy requirement (OR = 2.58 [1.06–6.26]) were associated with health-related Internet use. Neither satisfaction with medical care or information provision, neither presence of anxiety-depression symptoms, were associated with health-related Internet use. Majority of surrogates (N = 76 (52%)) would have like receiving a list of selected websites on sepsis. Conclusions Majority of proxies of critically ill patients with sepsis use Internet to learn more about sepsis. Internet utilization is independent of satisfaction with global ICU care, perceived quality of information delivery by

  2. Development of Depletion Code Surrogate Models for Uncertainty Propagation in Scenario Studies

    Science.gov (United States)

    Krivtchik, Guillaume; Coquelet-Pascal, Christine; Blaise, Patrick; Garzenne, Claude; Le Mer, Joël; Freynet, David

    2014-06-01

    The result of transition scenario studies, which enable the comparison of different options of the reactor fleet evolution and management of the future fuel cycle materials, allow to perform technical and economic feasibility studies. The COSI code is developed by CEA and used to perform scenario calculations. It allows to model any fuel type, reactor fleet, fuel facility, and permits the tracking of U, Pu, minor actinides and fission products nuclides on a large time scale. COSI is coupled with the CESAR code which performs the depletion calculations based on one-group cross-section libraries and nuclear data. Different types of uncertainties have an impact on scenario studies: nuclear data and scenario assumptions. Therefore, it is necessary to evaluate their impact on the major scenario results. The methodology adopted to propagate these uncertainties throughout the scenario calculations is a stochastic approach. Considering the amount of inputs to be sampled in order to perform a stochastic calculation of the propagated uncertainty, it appears necessary to reduce the calculation time. Given that evolution calculations represent approximately 95% of the total scenario simulation time, an optimization can be done, with the development and implementation of a surrogate models library of CESAR in COSI. The input parameters of CESAR are sampled with URANIE, the CEA uncertainty platform, and for every sample, the isotopic composition after evolution evaluated with CESAR is stored. Then statistical analysis of the input and output tables allow to model the behavior of CESAR on each CESAR library, i.e. building a surrogate model. Several quality tests are performed on each surrogate model to insure the prediction power is satisfying. Afterward, a new routine implemented in COSI reads these surrogate models and using them in replacement of CESAR calculations. A preliminary study of the calculation time gain shows that the use of surrogate models allows stochastic

  3. Detection of cynomolgus monkey anti-protein XYZ antibody using immunocapture-LC/MS

    Directory of Open Access Journals (Sweden)

    David Roos

    2016-10-01

    Full Text Available Although enzyme-linked immunosorbent assays and electrochemiluminescence (ECL immunoassays are the most widely used platform for ADA detection, they may be compromised by drug interference. We describe here an alternate, free of drug interference, immunocapture-LC/MS methodology for detecting anti-protein XYZ antibody in cynomolgus monkey plasma. In our approach, ADA-protein XYZ complexes are captured by a mouse monoclonal anti-drug antibody on streptavidin magnetic beads and separated from monkey plasma by a magnet. After elution, ADA are digested with trypsin and detected by LC/MS using a surrogate peptide common to monkey IgG subclasses 1-4. The immunocapture-LC/MS assay was applied to support a toxicology study and results were in close agreement with those from a modified ECL immunoassay. To our knowledge, this is the first application of using LC/MS for monkey ADA detection.

  4. Fabrication and Characterization of Surrogate TRISO Particles Using 800μm ZrO2 Kernels

    Energy Technology Data Exchange (ETDEWEB)

    Jolly, Brian C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Helmreich, Grant [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cooley, Kevin M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dyer, John [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Terrani, Kurt [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-07-01

    In support of fully ceramic microencapsulated (FCM) fuel development, coating development work is ongoing at Oak Ridge National Laboratory (ORNL) to produce tri-structural isotropic (TRISO) coated fuel particles with both UN kernels and surrogate (uranium-free) kernels. The nitride kernels are used to increase fissile density in these SiC-matrix fuel pellets with details described elsewhere. The surrogate TRISO particles are necessary for separate effects testing and for utilization in the consolidation process development. This report focuses on the fabrication and characterization of surrogate TRISO particles which use 800μm in diameter ZrO2 microspheres as the kernel.

  5. How antibodies use complement to regulate antibody responses.

    Science.gov (United States)

    Sörman, Anna; Zhang, Lu; Ding, Zhoujie; Heyman, Birgitta

    2014-10-01

    Antibodies, forming immune complexes with their specific antigen, can cause complete suppression or several 100-fold enhancement of the antibody response. Immune complexes containing IgG and IgM may activate complement and in such situations also complement components will be part of the immune complex. Here, we review experimental data on how antibodies via the complement system upregulate specific antibody responses. Current data suggest that murine IgG1, IgG2a, and IgG2b upregulate antibody responses primarily via Fc-receptors and not via complement. In contrast, IgM and IgG3 act via complement and require the presence of complement receptors 1 and 2 (CR1/2) expressed on both B cells and follicular dendritic cells. Complement plays a crucial role for antibody responses not only to antigen complexed to antibodies, but also to antigen administered alone. Lack of C1q, but not of Factor B or MBL, severely impairs antibody responses suggesting involvement of the classical pathway. In spite of this, normal antibody responses are found in mice lacking several activators of the classical pathway (complement activating natural IgM, serum amyloid P component (SAP), specific intracellular adhesion molecule-grabbing non-integrin R1 (SIGN-R1) or C-reactive protein. Possible explanations to these observations will be discussed.

  6. Dry deposition of large, airborne particles onto a surrogate surface

    Science.gov (United States)

    Kim, Eugene; Kalman, David; Larson, Timothy

    Simultaneous measurements of particle dry deposition flux and airborne number concentration in the open atmosphere were made using three different types of artificially generated particles in the size range 10-100 μm - perlite, diatomaceous earth and glass beads. A combination of gravimetric analysis, automated microscopy and sonic anemometry provided size-resolved estimates of both the inertial and gravitational components of the quasi-laminar layer particle deposition velocity, ( Vd) b, as a function of size. Eddy inertial deposition efficiency ( ηdI) was determined as a function of dimensionless eddy Stokes number (Stk e). In the range 3PNL-SA-6721, Pacific Northwest Laboratories, Richland, WA), used in several regulatory models, significantly under-predicted (up to seven times) ( Vd) b for large particles ( da>10 μm).

  7. Testing of organic waste surrogate materials in support of the Hanford organic tank program. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Turner, D.A. [Westinghouse Hanford Co., Richland, WA (United States); Miron, Y. [Bureau of Mines (United States)

    1994-01-01

    To address safety issues regarding effective waste management efforts of underground organic waste storage tanks at the Hanford Site, the Bureau of Mines conducted a series of tests, at the request of the Westinghouse Hanford company. In this battery of tests, the thermal and explosive characteristics of surrogate materials, chosen by Hanford, were determined. The surrogate materials were mixtures of inorganic and organic sodium salts, representing fuels and oxidants. The oxidants were sodium nitrate and sodium nitrite. The fuels were sodium salts of oxalate, citrate and ethylenediamine tetraacetic acid (EDTA). Polyethylene powder was also used as a fuel with the oxidant(s). Sodium aluminate was used as a diluent. In addition, a sample of FeCN, supplied by Hanford was also investigated.

  8. Surrogate modelling and optimization using shape-preserving response prediction: A review

    Science.gov (United States)

    Leifsson, Leifur; Koziel, Slawomir

    2016-03-01

    Computer simulation models are ubiquitous in modern engineering design. In many cases, they are the only way to evaluate a given design with sufficient fidelity. Unfortunately, an added computational expense is associated with higher fidelity models. Moreover, the systems being considered are often highly nonlinear and may feature a large number of designable parameters. Therefore, it may be impractical to solve the design problem with conventional optimization algorithms. A promising approach to alleviate these difficulties is surrogate-based optimization (SBO). Among proven SBO techniques, the methods utilizing surrogates constructed from corrected physics-based low-fidelity models are, in many cases, the most efficient. This article reviews a particular technique of this type, namely, shape-preserving response prediction (SPRP), which works on the level of the model responses to correct the underlying low-fidelity models. The formulation and limitations of SPRP are discussed. Applications to several engineering design problems are provided.

  9. Efficient stochastic EMC/EMI analysis using HDMR-generated surrogate models

    KAUST Repository

    Yücel, Abdulkadir C.

    2011-08-01

    Stochastic methods have been used extensively to quantify effects due to uncertainty in system parameters (e.g. material, geometrical, and electrical constants) and/or excitation on observables pertinent to electromagnetic compatibility and interference (EMC/EMI) analysis (e.g. voltages across mission-critical circuit elements) [1]. In recent years, stochastic collocation (SC) methods, especially those leveraging generalized polynomial chaos (gPC) expansions, have received significant attention [2, 3]. SC-gPC methods probe surrogate models (i.e. compact polynomial input-output representations) to statistically characterize observables. They are nonintrusive, that is they use existing deterministic simulators, and often cost only a fraction of direct Monte-Carlo (MC) methods. Unfortunately, SC-gPC-generated surrogate models often lack accuracy (i) when the number of uncertain/random system variables is large and/or (ii) when the observables exhibit rapid variations. © 2011 IEEE.

  10. Determination of neutron-induced fission cross-sections of unstable nuclei via surrogate reaction method

    Indian Academy of Sciences (India)

    B K Nayak

    2014-11-01

    Heavy ion reaction studies around Coulomb barrier energies have been generally used to investigate the effect of the structure of projectile/target on reaction dynamics. Other than providing an understanding of basic physics of the reaction dynamics, some of these reactions have been used as tools to serve as surrogates of neutron-induced compound nuclear fission cross-sections involving unstable targets. In this paper, we report some of the recent results on the determination of neutron-induced fission cross-sections of unstable actinides present in Th–U and U–Pu fuel cycles by surrogate reaction method by employing transfer-induced fission studies with 6,7Li beams.

  11. Fast surrogate-assisted simulation-driven optimization of compact microwave hybrid couplers

    Science.gov (United States)

    Kurgan, Piotr; Koziel, Slawomir

    2016-07-01

    This work presents a robust methodology for expedited simulation-driven design optimization of compact microwave hybrid couplers. The technique relies on problem decomposition, and a bottom-up design strategy, starting from the level of basic building blocks of the coupler, and finishing with a tuning procedure that exploits a fast surrogate model of the entire structure. The latter is constructed by cascading local response surface approximations of coupler elementary elements. The cross-coupling effects within the structure are neglected in the first stage of the design process; however, they are accounted for in the tuning phase by means of space-mapping correction of the surrogate. The proposed approach is demonstrated through the design of a compact rat-race and two branch-line couplers. In all cases, the computational cost of the optimization process is very low and corresponds to just a few high-fidelity electromagnetic simulations of respective structures. Experimental validation is also provided.

  12. Determination of Diethyl Phthalate and Polyhexamethylene Guanidine in Surrogate Alcohol from Russia

    Directory of Open Access Journals (Sweden)

    Yulia B. Monakhova

    2011-01-01

    Full Text Available Analytical methods based on spectroscopic techniques were developed and validated for the determination of diethyl phthalate (DEP and polyhexamethylene guanidine (PHMG, which may occur in unrecorded alcohol. Analysis for PHMG was based on UV-VIS spectrophotometry after derivatization with Eosin Y and 1H NMR spectroscopy of the DMSO extract. Analysis of DEP was performed with direct UV-VIS and 1H NMR methods. Multivariate curve resolution and spectra computation methods were used to confirm the presence of PHMG and DEP in the investigated beverages. Of 22 analysed alcohol samples, two contained DEP or PHMG. 1H NMR analysis also revealed the presence of signals of hawthorn extract in three medicinal alcohols used as surrogate alcohol. The simple and cheap UV-VIS methods can be used for rapid screening of surrogate alcohol samples for impurities, while 1H NMR is recommended for specific confirmatory analysis if required.

  13. Quantum dynamics of a vibronically coupled linear chain using a surrogate Hamiltonian approach.

    Science.gov (United States)

    Lee, Myeong H; Troisi, Alessandro

    2016-06-07

    Vibronic coupling between the electronic and vibrational degrees of freedom has been reported to play an important role in charge and exciton transport in organic photovoltaic materials, molecular aggregates, and light-harvesting complexes. Explicitly accounting for effective vibrational modes rather than treating them as a thermal environment has been shown to be crucial to describe the effect of vibronic coupling. We present a methodology to study dissipative quantum dynamics of vibronically coupled systems based on a surrogate Hamiltonian approach, which is in principle not limited by Markov approximation or weak system-bath interaction, using a vibronic basis. We apply vibronic surrogate Hamiltonian method to a linear chain system and discuss how different types of relaxation process, intramolecular vibrational relaxation and intermolecular vibronic relaxation, influence population dynamics of dissipative vibronic systems.

  14. Multiobjective Optimization Design of Double-Row Blades Hydraulic Retarder with Surrogate Model

    Directory of Open Access Journals (Sweden)

    Liu Chunbao

    2015-02-01

    Full Text Available For the design of double-row blades hydraulic retarder involves too many parameters, the solution process of the optimal parameter combination is characterized by the large calculation load, the long calculation