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Sample records for nonlinear dose response

  1. Confidence bounds for nonlinear dose-response relationships.

    Science.gov (United States)

    Baayen, C; Hougaard, P

    2015-11-30

    An important aim of drug trials is to characterize the dose-response relationship of a new compound. Such a relationship can often be described by a parametric (nonlinear) function that is monotone in dose. If such a model is fitted, it is useful to know the uncertainty of the fitted curve. It is well known that Wald confidence intervals are based on linear approximations and are often unsatisfactory in nonlinear models. Apart from incorrect coverage rates, they can be unreasonable in the sense that the lower confidence limit of the difference to placebo can be negative, even when an overall test shows a significant positive effect. Bootstrap confidence intervals solve many of the problems of the Wald confidence intervals but are computationally intensive and prone to undercoverage for small sample sizes. In this work, we propose a profile likelihood approach to compute confidence intervals for the dose-response curve. These confidence bounds have better coverage than Wald intervals and are more precise and generally faster than bootstrap methods. Moreover, if monotonicity is assumed, the profile likelihood approach takes this automatically into account. The approach is illustrated using a public dataset and simulations based on the Emax and sigmoid Emax models. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Confidence bounds for nonlinear dose-response relationships

    DEFF Research Database (Denmark)

    Baayen, C; Hougaard, P

    2015-01-01

    . It is well known that Wald confidence intervals are based on linear approximations and are often unsatisfactory in nonlinear models. Apart from incorrect coverage rates, they can be unreasonable in the sense that the lower confidence limit of the difference to placebo can be negative, even when an overall...... test shows a significant positive effect. Bootstrap confidence intervals solve many of the problems of the Wald confidence intervals but are computationally intensive and prone to undercoverage for small sample sizes. In this work, we propose a profile likelihood approach to compute confidence...... intervals for the dose-response curve. These confidence bounds have better coverage than Wald intervals and are more precise and generally faster than bootstrap methods. Moreover, if monotonicity is assumed, the profile likelihood approach takes this automatically into account. The approach is illustrated...

  3. Nonlinearity of dose-response functions for carcinogenicity.

    OpenAIRE

    Hoel, D G; Portier, C J

    1994-01-01

    Carcinogenesis data for 315 chemicals were obtained from the National Cancer Institute-National Toxicology Program (NCI-NTP) bioassay programs and were analyzed to examine the shape of carcinogenesis dose-response curves. Tumor site data were more often consistent with a quadratic response than with a linear response, suggesting that the routine use of linear dose-response models will often overestimate risk. Information from in vivo short-term mutagenicity and genotoxicity assays was also ob...

  4. Arsenite Effects on Mitochondrial Bioenergetics in Human and Mouse Primary Hepatocytes Follow a Nonlinear Dose Response

    Directory of Open Access Journals (Sweden)

    Hemantkumar Chavan

    2017-01-01

    Full Text Available Arsenite is a known carcinogen and its exposure has been implicated in a variety of noncarcinogenic health concerns. Increased oxidative stress is thought to be the primary cause of arsenite toxicity and the toxic effect is thought to be linear with detrimental effects reported at all concentrations of arsenite. But the paradigm of linear dose response in arsenite toxicity is shifting. In the present study we demonstrate that arsenite effects on mitochondrial respiration in primary hepatocytes follow a nonlinear dose response. In vitro exposure of primary hepatocytes to an environmentally relevant, moderate level of arsenite results in increased oxidant production that appears to arise from changes in the expression and activity of respiratory Complex I of the mitochondrial proton circuit. In primary hepatocytes the excess oxidant production appears to elicit adaptive responses that promote resistance to oxidative stress and a propensity to increased proliferation. Taken together, these results suggest a nonlinear dose-response characteristic of arsenite with low-dose arsenite promoting adaptive responses in a process known as mitohormesis, with transient increase in ROS levels acting as transducers of arsenite-induced mitohormesis.

  5. Low Doses of Traditional Nanophytomedicines for Clinical Treatment: Manufacturing Processes and Nonlinear Response Patterns.

    Science.gov (United States)

    Bell, Iris R; Sarter, Barbara; Standish, Leanna J; Banerji, Prasanta; Banerji, Pratip

    2015-06-01

    The purpose of the present paper is to (a) summarize evidence for the nanoparticle nature and biological effects of traditional homeopathically-prepared medicines at low and ultralow doses; (b) provide details of historically-based homeopathic green manufacturing materials and methods, relating them to top-down mechanical attrition and plant-based biosynthetic processes in modern nanotechnology; (c) outline the potential roles of nonlinear dose-responses and dynamical interactions with complex adaptive systems in generating endogenous amplification processes during low dose treatment. Possible mechanisms of low dose effects, for which there is evidence involving nanoparticles and/or homeopathically-manufactured medicines, include hormesis, time-dependent sensitization, and stochastic resonance. All of the proposed mechanisms depend upon endogenous nonlinear amplification processes in the recipient organism in interaction with the salient, albeit weak signal properties of the medicine. Conventional ligand-receptor mechanisms relevant to higher doses are less likely involved. Effects, especially for homeopathically-prepared nanophytomedicines, include bidirectional host state-dependent changes in function. Homeopathic clinicians report successful treatment of serious infections and cancers. Preclinical biological evidence is consistent with such claims. Controlled biological data on homeopathically-prepared medicines indicate modulation of gene expression and biological signaling pathways regulating cell cycles, immune reactions, and central nervous system function from studies on cells, animals, and human subjects. As a 200-year old system of traditional medicine used by millions of people worldwide, homeopathy offers a pulsed low dose treatment strategy and strong safety record to facilitate progress in translational nanomedicine with plants and other natural products. In turn, modern nanotechnology methods can improve homeopathic manufacturing procedures

  6. Confidence intervals for intraclass correlation coefficients in a nonlinear dose-response meta-analysis

    NARCIS (Netherlands)

    Demetrashvili, Nino; Van den Heuvel, Edwin R.

    This work is motivated by a meta-analysis case study on antipsychotic medications. The Michaelis-Menten curve is employed to model the nonlinear relationship between the dose and D2 receptor occupancy across multiple studies. An intraclass correlation coefficient (ICC) is used to quantify the

  7. Confidence intervals for intraclass correlation coefficients in a nonlinear dose-response meta-analysis

    NARCIS (Netherlands)

    Demetrashvili, Nino; Van den Heuvel, Edwin R.

    2015-01-01

    This work is motivated by a meta-analysis case study on antipsychotic medications. The Michaelis-Menten curve is employed to model the nonlinear relationship between the dose and D2 receptor occupancy across multiple studies. An intraclass correlation coefficient (ICC) is used to quantify the hetero

  8. Methylphenidate has nonlinear dose effects on cued response inhibition in adults but not adolescents.

    Science.gov (United States)

    Simon, Nicholas W; Moghaddam, Bita

    2017-01-01

    Ongoing development of the dopamine system during adolescence may provide a partial mechanism for behavioral and psychiatric vulnerabilities. Despite early evidence for a hyperactive adolescent dopaminergic system, recent data suggest that adolescent dopamine may be functionally hypoactive compared to in adults. While this distinction has been established in response to dopaminergic drugs and natural rewards, little is known about age-related differences in cognitive efficacy of dopaminergic drugs. Using a recently established Cued Response Inhibition Task, we tested the effects of acute systemic methylphenidate, commonly known as Ritalin, on response inhibition and response initiation in adolescent and adults rats. First, we replicated previous data that adolescents are able to inhibit a response to a cue on par with adults, but are slower to produce a rewarded response after a stop cue. Next, we observed that methylphenidate modulated response inhibition in adult rats, with low dose (0.3mg/kg) improving inhibition, and high dose (3mg/kg) impairing performance. This dose-response pattern is commonly observed with psychostimulant cognitive modulation. In adolescents, however, methylphenidate had no effect on response inhibition at any dose. Latency of response initiation after the stop cue was not affected by methylphenidate in either adult or adolescent rats. These data establish that dose-response of a commonly prescribed psychostimulant medication is different in adolescents and adults. They further demonstrate that healthy adolescent response inhibition is not as sensitive to psychostimulants as in adults, supporting the idea that the dopamine system is hypoactive in adolescence. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Confidence intervals for intraclass correlation coefficients in a nonlinear dose-response meta-analysis.

    Science.gov (United States)

    Demetrashvili, Nino; Van den Heuvel, Edwin R

    2015-06-01

    This work is motivated by a meta-analysis case study on antipsychotic medications. The Michaelis-Menten curve is employed to model the nonlinear relationship between the dose and D2 receptor occupancy across multiple studies. An intraclass correlation coefficient (ICC) is used to quantify the heterogeneity across studies. To interpret the size of heterogeneity, an accurate estimate of ICC and its confidence interval is required. The goal is to apply a recently proposed generic beta-approach for construction the confidence intervals on ICCs for linear mixed effects models to nonlinear mixed effects models using four estimation methods. These estimation methods are the maximum likelihood, second-order generalized estimating equations and two two-step procedures. The beta-approach is compared with a large sample normal approximation (delta method) and bootstrapping. The confidence intervals based on the delta method and the nonparametric percentile bootstrap with various resampling strategies failed in our settings. The beta-approach demonstrates good coverages with both two-step estimation methods and consequently, it is recommended for the computation of confidence interval for ICCs in nonlinear mixed effects models for small studies.

  10. Performance comparison of various maximum likelihood nonlinear mixed-effects estimation methods for dose-response models.

    Science.gov (United States)

    Plan, Elodie L; Maloney, Alan; Mentré, France; Karlsson, Mats O; Bertrand, Julie

    2012-09-01

    Estimation methods for nonlinear mixed-effects modelling have considerably improved over the last decades. Nowadays, several algorithms implemented in different software are used. The present study aimed at comparing their performance for dose-response models. Eight scenarios were considered using a sigmoid E(max) model, with varying sigmoidicity and residual error models. One hundred simulated datasets for each scenario were generated. One hundred individuals with observations at four doses constituted the rich design and at two doses, the sparse design. Nine parametric approaches for maximum likelihood estimation were studied: first-order conditional estimation (FOCE) in NONMEM and R, LAPLACE in NONMEM and SAS, adaptive Gaussian quadrature (AGQ) in SAS, and stochastic approximation expectation maximization (SAEM) in NONMEM and MONOLIX (both SAEM approaches with default and modified settings). All approaches started first from initial estimates set to the true values and second, using altered values. Results were examined through relative root mean squared error (RRMSE) of the estimates. With true initial conditions, full completion rate was obtained with all approaches except FOCE in R. Runtimes were shortest with FOCE and LAPLACE and longest with AGQ. Under the rich design, all approaches performed well except FOCE in R. When starting from altered initial conditions, AGQ, and then FOCE in NONMEM, LAPLACE in SAS, and SAEM in NONMEM and MONOLIX with tuned settings, consistently displayed lower RRMSE than the other approaches. For standard dose-response models analyzed through mixed-effects models, differences were identified in the performance of estimation methods available in current software, giving material to modellers to identify suitable approaches based on an accuracy-versus-runtime trade-off.

  11. Non-Linear Dose-Response Relationships in Biology, Toxicology and Medicine - An International Conference

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, Edward J.; Kostecki, Paul T.

    2002-05-28

    Conference abstract book contains seven sections: Plenary-4 abstracts; Chemical-9 abstracts; Radiation-7 abstracts; Ultra Low Doses and Medicine-6 abstracts; Biomedical-11 abstracts; Risk Assessment-5 abstracts and Poster Sessions-25 abstracts. Each abstract was provided by the author/presenter participating in the conference.

  12. Molecular Mechanisms of Nonlinearity in Response to Low Dose Ionizing Radiation

    Science.gov (United States)

    2007-10-12

    endogenous and cultured human skin. Radiat Rex 2004:161:739-45. effects on humans in radiation therapy patients. Radiat exogenous response modifiers...0.2 gtg/ml final concentration, typically a 1:1000 dilution. The secondary antibody (donkey anti-goat-hrp, sc-2020 or donkey anti- rabbit , sc-2004, SCB

  13. An update on modeling dose-response relationships: Accounting for correlated data structure and heterogeneous error variance in linear and nonlinear mixed models.

    Science.gov (United States)

    Gonçalves, M A D; Bello, N M; Dritz, S S; Tokach, M D; DeRouchey, J M; Woodworth, J C; Goodband, R D

    2016-05-01

    Advanced methods for dose-response assessments are used to estimate the minimum concentrations of a nutrient that maximizes a given outcome of interest, thereby determining nutritional requirements for optimal performance. Contrary to standard modeling assumptions, experimental data often present a design structure that includes correlations between observations (i.e., blocking, nesting, etc.) as well as heterogeneity of error variances; either can mislead inference if disregarded. Our objective is to demonstrate practical implementation of linear and nonlinear mixed models for dose-response relationships accounting for correlated data structure and heterogeneous error variances. To illustrate, we modeled data from a randomized complete block design study to evaluate the standardized ileal digestible (SID) Trp:Lys ratio dose-response on G:F of nursery pigs. A base linear mixed model was fitted to explore the functional form of G:F relative to Trp:Lys ratios and assess model assumptions. Next, we fitted 3 competing dose-response mixed models to G:F, namely a quadratic polynomial (QP) model, a broken-line linear (BLL) ascending model, and a broken-line quadratic (BLQ) ascending model, all of which included heteroskedastic specifications, as dictated by the base model. The GLIMMIX procedure of SAS (version 9.4) was used to fit the base and QP models and the NLMIXED procedure was used to fit the BLL and BLQ models. We further illustrated the use of a grid search of initial parameter values to facilitate convergence and parameter estimation in nonlinear mixed models. Fit between competing dose-response models was compared using a maximum likelihood-based Bayesian information criterion (BIC). The QP, BLL, and BLQ models fitted on G:F of nursery pigs yielded BIC values of 353.7, 343.4, and 345.2, respectively, thus indicating a better fit of the BLL model. The BLL breakpoint estimate of the SID Trp:Lys ratio was 16.5% (95% confidence interval [16.1, 17.0]). Problems with

  14. Dose-response-a challenge for allelopathy?

    Science.gov (United States)

    Belz, Regina G; Hurle, Karl; Duke, Stephen O

    2005-04-01

    The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions.

  15. Distributed nonlinear optical response

    DEFF Research Database (Denmark)

    Nikolov, Nikola Ivanov

    2005-01-01

    The purpose of the research presented here is to investigate basic physical properties in nonlinear optical materials with delayed or nonlocal nonlinearity. Soliton propagation, spectral broadening and the influence of the nonlocality or delay of the nonlinearity are the main focusses in the work...

  16. Dose response problems in carcinogenesis.

    Science.gov (United States)

    Crump, K S

    1979-03-01

    The estimation of risks from exposure to carcinogens is an important problem from the viewpoint of protection of human health. It also poses some very difficult dose-response problems. Two dose-response models may fit experimental data about equally well and yet predict responses that differ by many orders of magnitude at low doses. Mechanisms of carcinogenesis are not sufficiently understood so that the shape of the dose-response curve at low doses can be satisfactorily predicted. Mathematical theories of carcinogenesis and statistical procedures can be of use with dose-reponse problems such as this and, in addition, can lead to a better understanding of the mechanisms of carcinogenesis. In this paper, mathematical dose-response models of carcinogenesis are considered as well as various proposed dose-response procedures for estimating carcinogenic risks at low doses. Areas are suggested in which further work may be useful. These areas include experimental design problems, statistical procedures for use with time-to-occurrence data, and mathematical models that incorporate such biological features as pharmacokinetics of carcinogens, synergistic effects, DNA repair, susceptible subpopulations, and immune reactions.

  17. Description of dose response curve

    OpenAIRE

    Al-Samarai, Firas

    2011-01-01

    The book included several methods to estimate LD50, in addition to explain how to use several programs to estimate LD50. Moreover the book illustrate the description of the dose response curves. Firas Al-Samarai

  18. Intrinsic nonlinear response of surface plasmon polaritons

    CERN Document Server

    Im, Song-Jin; Kim, Gum-Hyok

    2015-01-01

    We offer a model to describe the intrinsic nonlinear response of surface plasmon polaritons (SPPs). Relation of the complex nonlinear coefficient of SPPs to the third-order nonlinear susceptibility of the metal is provided. As reported in a recent study, gold is highly lossy and simultaneously highly nonlinear due to interband absorption and interband thermo-modulation at a wavelength shorter than 700 nm. The effect of the high loss of the metal on the SPP nonlinear propagation is taken into account in our model. With the model we show difference in sign of real and imaginary parts between the nonlinear propagation coefficient and the nonlinear susceptibility of component material for the first time to our knowledge. Our model could have practical importance in studying plasmonic devices utilizing the nonlinear phase modulation and the nonlinear absorption of SPPs. For example, it allows one to extract the complex nonlinear susceptibility of gold through a measurement of SPP nonlinear propagation at the visib...

  19. Metamaterials with tailored nonlinear optical response.

    Science.gov (United States)

    Husu, Hannu; Siikanen, Roope; Mäkitalo, Jouni; Lehtolahti, Joonas; Laukkanen, Janne; Kuittinen, Markku; Kauranen, Martti

    2012-02-08

    We demonstrate that the second-order nonlinear optical response of noncentrosymmetric metal nanoparticles (metamolecules) can be efficiently controlled by their mutual ordering in an array. Two samples with minor change in ordering have nonlinear responses differing by a factor of up to 50. The results arise from polarization-dependent plasmonic resonances modified by long-range coupling associated with metamolecular ordering. The approach opens new ways for tailoring the nonlinear responses of metamaterials and their tensorial properties.

  20. The Effective AC Response of Nonlinear Composites

    Institute of Scientific and Technical Information of China (English)

    WEI En-Bo; GU Guo-Qing

    2001-01-01

    A perturbative approach is used to study the AC response of nonlinear composite media, which obey a current-field relation of the form J = σ E + χ|E|2 E with components having nonlinear response at finite frequencies. For a sinusoidal applied field, we extend the local potential in terms of sinusoidal components at fundamental frequency and high-order harmonic frequencies to treat the nonlinear composites. For nonlinear composite media vith a low concentrations of spherical inclusions, we give the formulae of the nonlinear effective AC susceptibility χ*3ω at the third harmonic frequency.

  1. Structural optimization for nonlinear dynamic response.

    Science.gov (United States)

    Dou, Suguang; Strachan, B Scott; Shaw, Steven W; Jensen, Jakob S

    2015-09-28

    Much is known about the nonlinear resonant response of mechanical systems, but methods for the systematic design of structures that optimize aspects of these responses have received little attention. Progress in this area is particularly important in the area of micro-systems, where nonlinear resonant behaviour is being used for a variety of applications in sensing and signal conditioning. In this work, we describe a computational method that provides a systematic means for manipulating and optimizing features of nonlinear resonant responses of mechanical structures that are described by a single vibrating mode, or by a pair of internally resonant modes. The approach combines techniques from nonlinear dynamics, computational mechanics and optimization, and it allows one to relate the geometric and material properties of structural elements to terms in the normal form for a given resonance condition, thereby providing a means for tailoring its nonlinear response. The method is applied to the fundamental nonlinear resonance of a clamped-clamped beam and to the coupled mode response of a frame structure, and the results show that one can modify essential normal form coefficients by an order of magnitude by relatively simple changes in the shape of these elements. We expect the proposed approach, and its extensions, to be useful for the design of systems used for fundamental studies of nonlinear behaviour as well as for the development of commercial devices that exploit nonlinear behaviour.

  2. Modeling Dose-response at Low Dose: A Systems Biology Approach for Ionization Radiation.

    Science.gov (United States)

    Zhao, Yuchao; Ricci, Paolo F

    2010-03-18

    For ionization radiation (IR) induced cancer, a linear non-threshold (LNT) model at very low doses is the default used by a number of national and international organizations and in regulatory law. This default denies any positive benefit from any level of exposure. However, experimental observations and theoretical biology have found that both linear and J-shaped IR dose-response curves can exist at those very low doses. We develop low dose J-shaped dose-response, based on systems biology, and thus justify its use regarding exposure to IR. This approach incorporates detailed, molecular and cellular descriptions of biological/toxicological mechanisms to develop a dose-response model through a set of nonlinear, differential equations describing the signaling pathways and biochemical mechanisms of cell cycle checkpoint, apoptosis, and tumor incidence due to IR. This approach yields a J-shaped dose response curve while showing where LNT behaviors are likely to occur. The results confirm the hypothesis of the J-shaped dose response curve: the main reason is that, at low-doses of IR, cells stimulate protective systems through a longer cell arrest time per unit of IR dose. We suggest that the policy implications of this approach are an increasingly correct way to deal with precautionary measures in public health.

  3. Single toxin dose-response models revisited

    Science.gov (United States)

    Glaholt, SP; Kyker-Snowman, E; Shaw, JR; Chen, CY

    2016-01-01

    The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of four models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 hours) toxicity tests with mortality as a function of NiCl or CuSO4 toxin. PMID:27847315

  4. Structural optimization for nonlinear dynamic response

    DEFF Research Database (Denmark)

    Dou, Suguang; Strachan, B. Scott; Shaw, Steven W.

    2015-01-01

    condition, thereby providing a means for tailoring its nonlinear response. The method is applied to the fundamental nonlinear resonance of a clamped–clamped beam and to the coupled mode response of a frame structure, and the results show that one can modify essential normal form coefficients by an order...... resonant behaviour is being used for a variety of applications in sensing and signal conditioning. In this work, we describe a computational method that provides a systematic means for manipulating and optimizing features of nonlinear resonant responses of mechanical structures that are described...... by a single vibrating mode, or by a pair of internally resonant modes. The approach combines techniques from nonlinear dynamics, computational mechanics and optimization, and it allows one to relate the geometric and material properties of structural elements to terms in the normal form for a given resonance...

  5. Effective ac response in weakly nonlinear composites

    Energy Technology Data Exchange (ETDEWEB)

    Wei Enbo [Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071 (China); Yang Zidong [College of Power Engineering, University of Shanghai Science and Technology, Shanghai 200093 (China); Gu Guoqing [Information College of Science and Technology, East China Normal University, Shanghai 200062 (China)

    2004-01-07

    The perturbation method is developed to deal with the problem of determining the effective nonlinear conductivity of Kerr-like nonlinear media under an external ac electric field. As an example, we have considered the cylindrical inclusion embedded in a host under the sinusoidal external field E{sub 1} sin (<{omega}t) + E{sub 3} sin (3<{omega}t) with frequencies{omega} and 3{omega}. The potentials of composites at higher harmonics are derived in both local inclusion particle and host regions. The effective responses of bulk nonlinear composites at basic frequency and harmonics are given for cylindrical composites in the dilute limit. Moreover, the relationships between the nonlinear effective responses at the basic frequency and the third harmonics are derived.

  6. Optimal design for nonlinear response models

    CERN Document Server

    Fedorov, Valerii V

    2013-01-01

    Optimal Design for Nonlinear Response Models discusses the theory and applications of model-based experimental design with a strong emphasis on biopharmaceutical studies. The book draws on the authors' many years of experience in academia and the pharmaceutical industry. While the focus is on nonlinear models, the book begins with an explanation of the key ideas, using linear models as examples. Applying the linearization in the parameter space, it then covers nonlinear models and locally optimal designs as well as minimax, optimal on average, and Bayesian designs. The authors also discuss ada

  7. Evaluating dose response from flexible dose clinical trials

    Directory of Open Access Journals (Sweden)

    Baron David

    2008-01-01

    Full Text Available Abstract Background The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related. Methods To evaluate dose effect in response on primary efficacy scales from 2 randomized, double-blind, flexible-dose trials of patients with bipolar mania who received olanzapine (N = 234, 5–20 mg/day, or patients with schizophrenia who received olanzapine (N = 172, 10–20 mg/day, we used marginal structural models, inverse probability of treatment weighting (MSM, IPTW methodology. Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model. To adjust for selection bias due to non-random dose assignment and dropouts, patient-specific time-dependent weights were determined as products of (i stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by (ii stable weights based on inverse probability of patient remaining on treatment by that time. Results were compared with those by unweighted analyses. Results While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses, the weighted analyses showed no strong dose effects and, in some cases, reversed the apparent "negative dose effect." Conclusion While naïve comparison of groups by last or modal dose in a flexible-dose trial may result in severely biased efficacy analyses, the MSM with IPTW estimators approach may be a valuable method of removing these biases and evaluating potential dose effect, which may prove useful for planning confirmatory trials.

  8. Simplified Warfarin Dose-response Pharmacodynamic Models

    OpenAIRE

    Kim, Seongho; Gaweda, Adam E.; Wu, Dongfeng; Li, Lang; Shesh N Rai; Brier, Michael E.

    2015-01-01

    Warfarin is a frequently used oral anticoagulant for long-term prevention and treatment of thromboembolic events. Due to its narrow therapeutic range and large inter-individual dose-response variability, it is highly desirable to personalize warfarin dosing. However, the complexity of the conventional kinetic-pharmacodynamic (K-PD) models hampers the development of the personalized dose management. To avert this challenge, we propose simplified PD models for warfarin dose-response relationshi...

  9. Dose-response meta-analysis of differences in means

    Directory of Open Access Journals (Sweden)

    Alessio Crippa

    2016-08-01

    Full Text Available Abstract Background Meta-analytical methods are frequently used to combine dose-response findings expressed in terms of relative risks. However, no methodology has been established when results are summarized in terms of differences in means of quantitative outcomes. Methods We proposed a two-stage approach. A flexible dose-response model is estimated within each study (first stage taking into account the covariance of the data points (mean differences, standardized mean differences. Parameters describing the study-specific curves are then combined using a multivariate random-effects model (second stage to address heterogeneity across studies. Results The method is fairly general and can accommodate a variety of parametric functions. Compared to traditional non-linear models (e.g. E max, logistic, spline models do not assume any pre-specified dose-response curve. Spline models allow inclusion of studies with a small number of dose levels, and almost any shape, even non monotonic ones, can be estimated using only two parameters. We illustrated the method using dose-response data arising from five clinical trials on an antipsychotic drug, aripiprazole, and improvement in symptoms in shizoaffective patients. Using the Positive and Negative Syndrome Scale (PANSS, pooled results indicated a non-linear association with the maximum change in mean PANSS score equal to 10.40 (95 % confidence interval 7.48, 13.30 observed for 19.32 mg/day of aripiprazole. No substantial change in PANSS score was observed above this value. An estimated dose of 10.43 mg/day was found to produce 80 % of the maximum predicted response. Conclusion The described approach should be adopted to combine correlated differences in means of quantitative outcomes arising from multiple studies. Sensitivity analysis can be a useful tool to assess the robustness of the overall dose-response curve to different modelling strategies. A user-friendly R package has been developed to facilitate

  10. Nonlinear frequency response analysis of structural vibrations

    Science.gov (United States)

    Weeger, Oliver; Wever, Utz; Simeon, Bernd

    2014-12-01

    In this paper we present a method for nonlinear frequency response analysis of mechanical vibrations of 3-dimensional solid structures. For computing nonlinear frequency response to periodic excitations, we employ the well-established harmonic balance method. A fundamental aspect for allowing a large-scale application of the method is model order reduction of the discretized equation of motion. Therefore we propose the utilization of a modal projection method enhanced with modal derivatives, providing second-order information. For an efficient spatial discretization of continuum mechanics nonlinear partial differential equations, including large deformations and hyperelastic material laws, we employ the concept of isogeometric analysis. Isogeometric finite element methods have already been shown to possess advantages over classical finite element discretizations in terms of higher accuracy of numerical approximations in the fields of linear vibration and static large deformation analysis. With several computational examples, we demonstrate the applicability and accuracy of the modal derivative reduction method for nonlinear static computations and vibration analysis. Thus, the presented method opens a promising perspective on application of nonlinear frequency analysis to large-scale industrial problems.

  11. Bacteriorhodopsin: Tunable Optical Nonlinear Magnetic Response

    CERN Document Server

    Bovino, F A; Sibilia, C; Giardina, M; Váró, G; Gergely, C

    2011-01-01

    We report on a strong and tunable magnetic optical nonlinear response of Bacteriorhodopsin (BR) under "off resonance" femtosecond (fs) pulse excitation, by detecting the polarization map of the noncollinear second harmonic signal of an oriented BR film, as a function of the input beam power. BR is a light-driven proton pump with a unique photochemistry initiated by the all trans retinal chromophore embedded in the protein. An elegant application of this photonic molecular machine has been recently found in the new area of optogenetics, where genetic expression of BR in brain cells conferred a light responsivity to the cells enabling thus specific stimulation of neurons. The observed strong tunable magnetic nonlinear response of BR might trigger promising applications in the emerging area of pairing optogenetics and functional magnetic resonance imaging susceptible to provide an unprecedented complete functional mapping of neural circuits.

  12. BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants.

    Science.gov (United States)

    Aune, Dagfinn; Sen, Abhijit; Prasad, Manya; Norat, Teresa; Janszky, Imre; Tonstad, Serena; Romundstad, Pål; Vatten, Lars J

    2016-05-04

    To conduct a systematic review and meta-analysis of cohort studies of body mass index (BMI) and the risk of all cause mortality, and to clarify the shape and the nadir of the dose-response curve, and the influence on the results of confounding from smoking, weight loss associated with disease, and preclinical disease. PubMed and Embase databases searched up to 23 September 2015. Cohort studies that reported adjusted risk estimates for at least three categories of BMI in relation to all cause mortality. Summary relative risks were calculated with random effects models. Non-linear associations were explored with fractional polynomial models. 230 cohort studies (207 publications) were included. The analysis of never smokers included 53 cohort studies (44 risk estimates) with >738 144 deaths and >9 976 077 participants. The analysis of all participants included 228 cohort studies (198 risk estimates) with >3 744 722 deaths among 30 233 329 participants. The summary relative risk for a 5 unit increment in BMI was 1.18 (95% confidence interval 1.15 to 1.21; I(2)=95%, n=44) among never smokers, 1.21 (1.18 to 1.25; I(2)=93%, n=25) among healthy never smokers, 1.27 (1.21 to 1.33; I(2)=89%, n=11) among healthy never smokers with exclusion of early follow-up, and 1.05 (1.04 to 1.07; I(2)=97%, n=198) among all participants. There was a J shaped dose-response relation in never smokers (Pnon-linearity <0.001), and the lowest risk was observed at BMI 23-24 in never smokers, 22-23 in healthy never smokers, and 20-22 in studies of never smokers with ≥20 years' follow-up. In contrast there was a U shaped association between BMI and mortality in analyses with a greater potential for bias including all participants, current, former, or ever smokers, and in studies with a short duration of follow-up (<5 years or <10 years), or with moderate study quality scores. Overweight and obesity is associated with increased risk of all cause mortality and the nadir of the curve

  13. Optomechanical response of a nonlinear mechanical resonator

    Science.gov (United States)

    Shevchuk, Olga; Singh, Vibhor; Steele, Gary A.; Blanter, Ya. M.

    2015-11-01

    We investigate theoretically in detail the nonlinear effects in the response of an optical/microwave cavity coupled to a Duffing mechanical resonator. The cavity is driven by a laser at a red or blue mechanical subband, and a probe laser measures the reflection close to the cavity resonance. Under these conditions, we find that the cavity exhibits optomechanically induced reflection (OMIR) or absorption (OMIA) and investigate the optomechanical response in the limit of nonlinear driving of the mechanics. Similar to linear mechanical drive, in an overcoupled cavity the red sideband drive may lead to both OMIA and OMIR depending on the strength of the drive, whereas the blue sideband drive only leads to OMIR. The dynamics of the phase of the mechanical resonator leads to the difference between the shapes of the response of the cavity and the amplitude response of the driven Duffing oscillator, for example, at weak red sideband drive the OMIA dip has no inflection point. We also verify that mechanical nonlinearities beyond Duffing model have little effect on the size of the OMIA dip though they affect the width of the dip.

  14. Responses to low doses of ionizing radiation in biological systems.

    Science.gov (United States)

    Feinendegen, Ludwig E; Pollycove, Myron; Sondhaus, Charles A

    2004-07-01

    1 per day for protracted exposure. The balance between damage and protection favors protection at low cell doses and damage at high cell doses. Bystander effects from high-dosed cells to nonirradiated neighboring cells appear to include both damage and protection.Regarding oncogenesis, a model based on the aforementioned dual response pattern at low doses and dose rates is consistant with the nonlinear reponse data and contradicts the linear no-threshold dose-risk hypothesis for radiation-induced cancer. Indeed, a dose-cancer risk function should include both linear and nonlinear terms.

  15. Nonlinear Response of Strong Nonlinear System Arisen in Polymer Cushion

    Directory of Open Access Journals (Sweden)

    Jun Wang

    2013-01-01

    Full Text Available A dynamic model is proposed for a polymer foam-based nonlinear cushioning system. An accurate analytical solution for the nonlinear free vibration of the system is derived by applying He's variational iteration method, and conditions for resonance are obtained, which should be avoided in the cushioning design.

  16. Dose response biology: the case of resveratrol.

    Science.gov (United States)

    Calabrese, Edward J; Mattson, Mark P; Calabrese, Vittorio

    2010-12-01

    Resveratrol often displays hormesis-like biphasic dose responses. This occurs in a broad range of biological models and for numerous endpoints of biomedical interest and public health concern. Recognition of the widespread occurrence of the hormetic nature of many of the responses of resveratrol is important on multiple levels. It can help optimize study design protocols by investigators, create a dose-response framework for better addressing dose-related biological complexities and assist in the development of public health and medical guidance with respect to considerations for what is an optimal dose not just for an agent such as resveratrol, but also for the plethora of agents that also act via hormetic mechanisms.

  17. Maximum likelihood estimation for cytogenetic dose-response curves

    Energy Technology Data Exchange (ETDEWEB)

    Frome, E.L; DuFrain, R.J.

    1983-10-01

    In vitro dose-response curves are used to describe the relation between the yield of dicentric chromosome aberrations and radiation dose for human lymphocytes. The dicentric yields follow the Poisson distribution, and the expected yield depends on both the magnitude and the temporal distribution of the dose for low LET radiation. A general dose-response model that describes this relation has been obtained by Kellerer and Rossi using the theory of dual radiation action. The yield of elementary lesions is kappa(..gamma..d + g(t, tau)d/sup 2/), where t is the time and d is dose. The coefficient of the d/sup 2/ term is determined by the recovery function and the temporal mode of irradiation. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting models are intrinsically nonlinear in the parameters. A general purpose maximum likelihood estimation procedure is described and illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure.

  18. Prolactin response to low dose sulpiride.

    OpenAIRE

    1987-01-01

    1 Prolactin levels in response to sulpiride were studied in healthy volunteers. 2 Oral doses of 1 mg-50 mg sulpiride or placebo were given. 3 A 3 mg sulpiride dose produced similar levels to those achieved with both 10 mg and 50 mg. 4 Circadian effects were studied showing no significant differences in the prolactin response to sulpiride. 5 Acute or chronic responses showed an attenuation with chronic sulpiride treatment to 50% of the peak levels attained with acute treatment. 6 These results...

  19. Induction of chromosome aberrations is non-linear within the low dose region and depends on dose rate

    Energy Technology Data Exchange (ETDEWEB)

    Oudalova, A.A.; Geras' kin, S.A.; Dikarev, V.G.; Nesterov, Y.B.; Dikareva, N.S

    2002-07-01

    The low dose region was evaluated for meristem cells of spring barley. A study of the cytogenetic damage in the low dose range was carried out to determine the genuine shape of the dose curve. The relationship between the frequency of aberrant cells and the absorbed dose is shown to be non-linear with a site at low doses within which the cytogenetic damage exceeds the control level significantly and does not depend on dose value. Within the tested exposure region, the aberrant cell frequency is found to decrease with increasing dose rate, but the shape of the dose curve remained invariable. The piecewise linear model fits the experimental data much better than the linear one. (author)

  20. [Dose response curve of paclitaxel measured by histoculture drug response assay].

    Science.gov (United States)

    Yoshimasu, Tatsuya; Oura, Shoji; Hirai, Issei; Kokawa, Yozo; Okamura, Yoshitaka; Furukawa, Tomoko

    2005-04-01

    Dose response curves of paclitaxel were measured by histoculture drug response assay (HDRA) in 11 lung cancer patients. Inhibition rates of paclitaxel at several concentrations were measured and fitted to the sigmoid dose response curve, using non-linear least square analysis, with fitting equation y=A (1-1/(1+exp (b (x-log (ED50)). Parameters A, b, and ED50 were 88.3+/-6.0 (80.0-100.0) %, 9.57+/-4.32 (2.25-15.0), and 26.8+/-8.1 (15.0-41.0) microg/ml, respectively. The parameter b was lower in well-differentiated tumors compared with moderately and poorly-differentiated tumors. Dose response curves of paclitaxel could be measured by HDRA in lung cancer. This method provides us more information for drug sensitivity than the usual HDRA method. This may lead to the improved accuracy of HDRA.

  1. Inferring mechanisms from dose-response curves

    OpenAIRE

    Chow, Carson C.; Ong, Karen M.; Dougherty, Edward J.; Simons, S. Stoney

    2011-01-01

    The steady state dose-response curve of ligand-mediated gene induction usually appears to precisely follow a first-order Hill equation (Hill coefficient equal to 1). Additionally, various cofactors/reagents can affect both the potency and the maximum activity of gene induction in a gene-specific manner. Recently, we have developed a general theory for which an unspecified sequence of steps or reactions yields a first-order Hill dose-response curve (FHDC) for plots of the final product vs. ini...

  2. Model identification for dose response signal detection

    OpenAIRE

    Bretz, Frank; Dette, Holger; Titoff, Stefanie; Volgushev, Stanislav

    2012-01-01

    We consider the problem of detecting a dose response signal if several competing regression models are available to describe the dose response relationship. In particular, we re-analyze the MCP-Mod approach from Bretz et al. (2005), which has become a very popular tool for this problem in recent years. We propose an improvement based on likelihood ratio tests and prove that in linear models this approach is always at least as powerful as the MCP-Mod method. This result remains ...

  3. Patient factors that influence warfarin dose response.

    Science.gov (United States)

    White, Pamela J

    2010-06-01

    Warfarin has long been the mainstay of oral anticoagulation therapy for the treatment and prevention of venous and arterial thrombosis. The narrow therapeutic index of warfarin, and the complex number of factors that influence international normalized ratio (INR) response, makes optimization of warfarin therapy challenging. Determination of the appropriate warfarin dose during initiation and maintenance therapy requires an understanding of patient factors that influence dose response: age, body weight, nutritional status, acute and chronic disease states, and changes in concomitant drug therapy and diet. This review will examine specific clinical factors that can affect the pharmacokinetics and pharmacodynamics of warfarin, as well as the role of pharmacogenetics in optimizing warfarin therapy.

  4. Dose-response analysis using R

    DEFF Research Database (Denmark)

    Ritz, Christian; Baty, Florent; Streibig, Jens Carl

    2015-01-01

    Dose-response analysis can be carried out using multi-purpose commercial statistical software, but except for a few special cases the analysis easily becomes cumbersome as relevant, non-standard output requires manual programming. The extension package drc for the statistical environment R provides...

  5. Analysis of nonlinear transient responses of piezoelectric resonators.

    Science.gov (United States)

    Hagiwara, Manabu; Takahashi, Seita; Hoshina, Takuya; Takeda, Hiroaki; Tsurumi, Takaaki

    2011-09-01

    The electric transient response method is an effective technique to evaluate material constants of piezoelectric ceramics under high-power driving. In this study, we tried to incorporate nonlinear piezoelectric behaviors in the analysis of transient responses. As a base for handling the nonlinear piezoelectric responses, we proposed an assumption that the electric displacement is proportional to the strain without phase lag, which could be described by a real and constant piezoelectric e-coefficient. Piezoelectric constitutive equations including nonlinear responses were proposed to calculate transient responses of a piezoelectric resonator. The envelopes and waveforms of current and vibration velocity in transient responses observed in some piezoelectric ceramics could be fitted with the calculation including nonlinear responses. The procedure for calculation of mechanical quality factor Q(m) for piezoelectric resonators with nonlinear behaviors was also proposed.

  6. Insulin dose response analysis of free fatty acid kinetics.

    Science.gov (United States)

    Jensen, Michael D; Nielsen, Søren

    2007-01-01

    Insulin regulation of free fatty acid (FFA) release is an important aspect of metabolic function; however, FFA release is exquisitely sensitive to insulin, which complicates the design and analysis of dose response experiments. We measured FFA ([(3)H]palmitate) and glucose ([(3)H]glucose) kinetics in 7 nonobese men, 7 nonobese women, 7 obese men, and 7 obese women by using a two-step insulin clamp (0.25 and 2.5 mU/kg fat-free mass per minute). Obese men and women were characterized as having a BMI of 28 or greater and body fat of 28% and 40% or greater for men and for women, respectively. Nonobese men and women had 22% and 35% or less body fat, respectively. All volunteers were Caucasian. Glucose disposal increased in a linear fashion with plasma insulin concentrations. The nonlinear suppression of plasma palmitate flux and concentrations could be linearized by logarithmically transforming both the insulin concentration and palmitate axes, except in nonobese men. We repeated the studies in 7 nonobese and 7 obese men, using 1.0 mU/kg fat-free mass per minute as the second insulin dose, which linearized the log-transformed lipolysis measures. The indices of insulin regulation of lipolysis predicted using 2 points (basal and second insulin dose) vs 3 points (basal, low, and high dose) were not different provided the proper second dose was selected. The EC(50) for insulin suppression of lipolysis correlated linearly with plasma triglycerides (r = 0.52, P < .001) and exponentially with insulin sensitivity(glucose) (r = 0.70, P < .001). We conclude that log transformation of insulin dose response data for FFA permits straightforward data analysis and simplifies the estimation of metabolically relevant parameters.

  7. Non-linear stochastic response of a shallow cable

    DEFF Research Database (Denmark)

    Larsen, Jesper Winther; Nielsen, Søren R.K.

    2004-01-01

    The paper considers the stochastic response of geometrical non-linear shallow cables. Large rain-wind induced cable oscillations with non-linear interactions have been observed in many large cable stayed bridges during the last decades. The response of the cable is investigated for a reduced two-degrees-of-freedom...

  8. CALUX measurements: statistical inferences for the dose-response curve.

    Science.gov (United States)

    Elskens, M; Baston, D S; Stumpf, C; Haedrich, J; Keupers, I; Croes, K; Denison, M S; Baeyens, W; Goeyens, L

    2011-09-30

    Chemical Activated LUciferase gene eXpression [CALUX] is a reporter gene mammalian cell bioassay used for detection and semi-quantitative analyses of dioxin-like compounds. CALUX dose-response curves for 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD] are typically smooth and sigmoidal when the dose is portrayed on a logarithmic scale. Non-linear regression models are used to calibrate the CALUX response versus TCDD standards and to convert the sample response into Bioanalytical EQuivalents (BEQs). Several complications may arise in terms of statistical inference, specifically and most important is the uncertainty assessment of the predicted BEQ. This paper presents the use of linear calibration functions based on Box-Cox transformations to overcome the issue of uncertainty assessment. Main issues being addressed are (i) confidence and prediction intervals for the CALUX response, (ii) confidence and prediction intervals for the predicted BEQ-value, and (iii) detection/estimation capabilities for the sigmoid and linearized models. Statistical comparisons between different calculation methods involving inverse prediction, effective concentration ratios (ECR(20-50-80)) and slope ratio were achieved with example datasets in order to provide guidance for optimizing BEQ determinations and expand assay performance with the recombinant mouse hepatoma CALUX cell line H1L6.1c3.

  9. Delocalization of nonlinear optical responses in plasmonic nanoantennas

    CERN Document Server

    Viarbitskaya, Sviatlana; Cluzel, Benoit; Francs, Gérard Colas des; Bouhelier, Alexandre

    2015-01-01

    Remote excitation and emission of two-photon luminescence and second-harmonic generation are observed in micrometer long gold rod optical antennas upon local illumination with a tightly focused near-infrared femtosecond laser beam. We show that the nonlinear radiations can be emitted from the entire antenna and the measured far-field angular patterns bear the information regarding the nature and origins of the respective nonlinear processes. We demonstrate that the nonlinear responses are transported by the propagating surface plasmon at excitation frequency, enabling thereby polariton-mediated tailoring and design of nonlinear responses.

  10. Highly nonlinear stress-relaxation response of articular cartilage in indentation: Importance of collagen nonlinearity.

    Science.gov (United States)

    Mäkelä, J T A; Korhonen, R K

    2016-06-14

    Modern fibril-reinforced computational models of articular cartilage can include inhomogeneous tissue composition and structure, and nonlinear mechanical behavior of collagen, proteoglycans and fluid. These models can capture well experimental single step creep and stress-relaxation tests or measurements under small strains in unconfined and confined compression. Yet, it is known that in indentation, especially at high strain velocities, cartilage can express highly nonlinear response. Different fibril reinforced poroelastic and poroviscoelastic models were used to assess measured highly nonlinear stress-relaxation response of rabbit articular cartilage in indentation. Experimentally measured depth-dependent volume fractions of different tissue constituents and their mechanical nonlinearities were taken into account in the models. In particular, the collagen fibril network was modeled using eight separate models that implemented five different constitutive equations to describe the nonlinearity. These consisted of linear elastic, nonlinear viscoelastic and multiple nonlinear elastic representations. The model incorporating the most nonlinearly increasing Young׳s modulus of collagen fibrils as a function of strain captured best the experimental data. Relative difference between the model and experiment was ~3%. Surprisingly, the difference in the peak forces between the experiment and the model with viscoelastic collagen fibrils was almost 20%. Implementation of the measured volume fractions did not improve the ability of the model to capture the measured mechanical data. These results suggest that a highly nonlinear formulation for collagen fibrils is needed to replicate multi-step stress-relaxation response of rabbit articular cartilage in indentation with high strain rates.

  11. NONLINEAR RESPONSES OF A FLUID-CONVEYING PIPE EMBEDDED IN NONLINEAR ELASTIC FOUNDATIONS

    Institute of Scientific and Technical Information of China (English)

    Qin Qian; Lin Wang; Qiao Ni

    2008-01-01

    The nonlinear responses of planar motions of a fluid-conveying pipe embedded in nonlinear elastic foundations are investigated via the differential quadrature method diseretization (DQMD) of the governing partial differential equation. For the analytical model, the effect of the nonlinear elastic foundation is modeled by a nonlinear restraining force. By using an iterative algorithm, a set of ordinary differential dynamical equations derived from the equation of motion of the system are solved numerically and then the bifurcations are analyzed. The numerical results, in which the existence of chaos is demonstrated, are presented in the form of phase portraits of the oscillations. The intermittency transition to chaos has been found to arise.

  12. Harmonic Phase Response of Nonlinear Radar Targets

    Science.gov (United States)

    2015-10-01

    to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT...of an improvised explosive device (IED). Previous nonlinear radar systems detect targets via transmission of a single frequency ω, stepping...electronically nonlinear components, such as transistors, diodes , and semiconductors. While many circuit devices, such as amplifiers, mixers, and

  13. Dose-response relationships for carcinogens: a review.

    OpenAIRE

    Zeise, L; Wilson, R.; Crouch, E A

    1987-01-01

    We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinea...

  14. Optical nonlinear response of a single nonlinear dielectric layer sandwiched between two linear dielectric structures

    Energy Technology Data Exchange (ETDEWEB)

    Lidorikis, E. [Ames Laboratory--USDOE and Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011 (United States); Busch, K. [Ames Laboratory--USDOE and Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011 (United States)]|[Instituet fuer Theorie der Kondensierten Materie, Universitaet Karlsruhe, D-76128, Karlsruhe (Germany); Li, Q. [Ames Laboratory--USDOE and Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011 (United States); Chan, C.T. [Ames Laboratory--USDOE and Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011 (United States)]|[Department of Physics, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (China); Soukoulis, C.M. [Ames Laboratory--USDOE and Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011 (United States)

    1997-12-01

    We consider the general problem of electromagnetic wave propagation through a one-dimensional system consisting of a nonlinear medium sandwiched between two linear structures. Special emphasis is given to systems where the latter comprise Bragg reflectors. We obtain an exact expression for the nonlinear response of such dielectric superlattices when the nonlinear impurity is very thin, or in the {delta}-function limit. We find that both the switching-up and switching-down intensities of the bistable response can be made very low, when the frequency of the incident wave matches that of the impurity mode of the structure. Numerical results for a nonlinear layer of finite width display qualitatively similar behavior, thus confirming the usefulness of the simpler {delta}-function model. In addition, an analytical solution for the resonance states of an infinitely extended finite-width superlattice with a finite-width nonlinear impurity is presented. {copyright} {ital 1997} {ital The American Physical Society}

  15. Semiclassical mode-coupling factorizations of coherent nonlinear optical response

    NARCIS (Netherlands)

    Jansen, TL; Mukamel, S

    2003-01-01

    The identification of relevant collective coordinates is crucial for the interpretation of coherent nonlinear spectroscopies of complex molecules and liquids. Using an h expansion of Liouville space generating functions, we show how to factorize multitime nonlinear response functions into products o

  16. A Photonic Basis for Deriving Nonlinear Optical Response

    Science.gov (United States)

    Andrews, David L.; Bradshaw, David S.

    2009-01-01

    Nonlinear optics is generally first presented as an extension of conventional optics. Typically the subject is introduced with reference to a classical oscillatory electric polarization, accommodating correction terms that become significant at high intensities. The material parameters that quantify the extent of the nonlinear response are cast as…

  17. [Radiation dose reduction using a non-linear image filter in MDCT].

    Science.gov (United States)

    Nakashima, Junya; Takahashi, Toshiyuki; Takahashi, Yoshimasa; Imai, Yasuhiro; Ishihara, Yotaro; Kato, Kyoichi; Nakazawa, Yasuo

    2010-05-20

    The development of MDCT enabled various high-quality 3D imaging and optimized scan timing with contrast injection in a multi-phase dynamic study. Since radiation dose tends to increase to yield such high-quality images, we have to make an effort to reduce radiation dose. A non-linear image filter (Neuro 3D filter: N3D filter) has been developed in order to improve image noise. The purpose of this study was to evaluate the physical performance and effectiveness of this non-linear image filter using phantoms, and show how we can reduce radiation dose in clinical use of this filter. This N3D filter reduced radiation dose by about 50%, with minimum deterioration of spatial reduction in phantom and clinical studies. This filter shows great potential for clinical application.

  18. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    applications of NEOTRANS2, indicate that nonlinear threshold-type, dose-response relationships for excess stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected after exposure to low linear energy transfer (LET) gamma rays or gamma rays in combination with high-LET alpha radiation. Similar thresholds are expected for low-dose-rate low-LET beta irradiation. We attribute the thresholds to low-dose, low-LET radiation induced protection against spontaneous mutations and neoplastic transformations. The protection is presumed mainly to involve selective elimination of problematic cells via apoptosis. Low-dose, low-LET radiation is presumed to trigger wide-area cell signaling, which in turn leads to problematic bystander cells (e.g., mutants, neoplastically transformed cells) selectively undergoing apoptosis. Thus, this protective bystander effect leads to selective elimination of problematic cells (a tissue cleansing process in vivo). However, this protective bystander effects is a different process from low-dose stimulation of the immune system. Low-dose, low-LET radiation stimulation of the immune system may explain why thresholds for inducing excess cancer appear much larger (possibly more than 100-fold larger) than thresholds for inducing excess mutations and neoplastic transformations, when the dose rate is low. For ionizing radiation, the current risk assessment paradigm is such that the relative risk (RR) is always ¡Ý 1, no matter how small the dose. Our research results indicate that for low-dose or low-dose-rate, low-LET irradiation, RR < 1 may be more the rule than the exception. Directly tied to the current RR paradigm are the billion-dollar cleanup costs for radionuclide-contaminated DOE sites. Our research results suggest that continued use of the current RR paradigm for which RR ¡Ý 1 could cause more harm than benefit to society (e.g., by spreading unwarranted fear about phantom excess risks associated with low-dose low

  19. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    applications of NEOTRANS2, indicate that nonlinear threshold-type, dose-response relationships for excess stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected after exposure to low linear energy transfer (LET) gamma rays or gamma rays in combination with high-LET alpha radiation. Similar thresholds are expected for low-dose-rate low-LET beta irradiation. We attribute the thresholds to low-dose, low-LET radiation induced protection against spontaneous mutations and neoplastic transformations. The protection is presumed mainly to involve selective elimination of problematic cells via apoptosis. Low-dose, low-LET radiation is presumed to trigger wide-area cell signaling, which in turn leads to problematic bystander cells (e.g., mutants, neoplastically transformed cells) selectively undergoing apoptosis. Thus, this protective bystander effect leads to selective elimination of problematic cells (a tissue cleansing process in vivo). However, this protective bystander effects is a different process from low-dose stimulation of the immune system. Low-dose, low-LET radiation stimulation of the immune system may explain why thresholds for inducing excess cancer appear much larger (possibly more than 100-fold larger) than thresholds for inducing excess mutations and neoplastic transformations, when the dose rate is low. For ionizing radiation, the current risk assessment paradigm is such that the relative risk (RR) is always ¡Ý 1, no matter how small the dose. Our research results indicate that for low-dose or low-dose-rate, low-LET irradiation, RR < 1 may be more the rule than the exception. Directly tied to the current RR paradigm are the billion-dollar cleanup costs for radionuclide-contaminated DOE sites. Our research results suggest that continued use of the current RR paradigm for which RR ¡Ý 1 could cause more harm than benefit to society (e.g., by spreading unwarranted fear about phantom excess risks associated with low-dose low

  20. Nonparallel nephrotoxicity dose-response curves of aminoglycosides.

    OpenAIRE

    1981-01-01

    Nephrotoxicity comparisons of aminoglycosides in rats, utilizing large multiples of human doses, have indicated an advantage for netilmicin. However, no nephrotoxicity advantage of netilmicin has been demonstrated at the lower doses used in clinics. Some high-dose studies in rats have also suggested that the slope of the nephrotoxicity dose-response curve of netilmicin was less steep than the slopes of other aminoglycosides. Therefore, the slopes of the nephrotoxicity dose-response curves of ...

  1. Effective nonlinear AC response to composite with spherical particles

    Institute of Scientific and Technical Information of China (English)

    Chen Xiao-Gang; Liang Fang-Chu; Wei En-Bo

    2005-01-01

    An effective nonlinear alternative-current (AC) response to granular nonlinear-composite with spherical inclusions embedded in a host medium under the action of an external AC field is investigated by using a perturbation approach.The local potentials of composite at higher harmonics are derived both in a region of local inclusion particles and in a local host region under the action of a sinusoidal field E1 sinωt + E3sin3ωt. An effective nonlinear-response to composite and the relationship between the effective nonlinear-responses at the fundamental frequency and the third harmonics are also studied for the spherical inclusions in a dilute limit.

  2. Relationships between nonlinear normal modes and response to random inputs

    Science.gov (United States)

    Schoneman, Joseph D.; Allen, Matthew S.; Kuether, Robert J.

    2017-02-01

    The ability to model nonlinear structures subject to random excitation is of key importance in designing hypersonic aircraft and other advanced aerospace vehicles. When a structure is linear, superposition can be used to construct its response to a known spectrum in terms of its linear modes. Superposition does not hold for a nonlinear system, but several works have shown that a system's dynamics can still be understood qualitatively in terms of its nonlinear normal modes (NNMs). This work investigates the connection between a structure's undamped nonlinear normal modes and the spectrum of its response to high amplitude random forcing. Two examples are investigated: a spring-mass system and a clamped-clamped beam modeled within a geometrically nonlinear finite element package. In both cases, an intimate connection is observed between the smeared peaks in the response spectrum and the frequency-energy dependence of the nonlinear normal modes. In order to understand the role of coupling between the underlying linear modes, reduced order models with and without modal coupling terms are used to separate the effect of each NNM's backbone from the nonlinear couplings that give rise to internal resonances. In the cases shown here, uncoupled, single-degree-of-freedom nonlinear models are found to predict major features in the response with reasonable accuracy; a highly inexpensive approximation such as this could be useful in design and optimization studies. More importantly, the results show that a reduced order model can be expected to give accurate results only if it is also capable of accurately predicting the frequency-energy dependence of the nonlinear modes that are excited.

  3. Dose-response relationship in multistage carcinogenesis: promoters.

    OpenAIRE

    Kitchin, K T; Brown, J. L.; Setzer, R.W.

    1994-01-01

    Published dose-response curves of promoters of multistage carcinogenesis were selected that met the combined criteria of long study times, multiple doses, and low doses. In rat liver, 12 dose-response studies of 7 different promoters (phenobarbital, 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], clophen A-50 (a polychlorinated biphenyl), alpha-, beta-, and gamma-hexachlorocyclohexane [HCH], and chloroform) were selected. These promoters were studied for 7-86 weeks and either altered hepatic foci...

  4. Review of dose-response curves for acute antimigraine drugs

    DEFF Research Database (Denmark)

    Hougaard, Anders; Tfelt-Hansen, Peer

    2015-01-01

    INTRODUCTION: Dose-response curves for efficacy and tolerability are the important determinants for the choice of doses of acute migraine drugs. Areas covered: Dose-response curves for the efficacy of seven triptans (5-HT1B/1D receptor agonists), a 5-HT1F receptor agonist (lasmiditan) and four oral...... calcitonin-gene related peptide receptor antagonists (telcagepant, MK-3207, BI 44370 TA and BMS-927711) in placebo-controlled trials were reviewed. In addition, dose-response curves for adverse events (AEs) were reviewed. Expert opinion: For most triptans, the dose-response curve for efficacy is flat......, whereas AEs often increase with increasing doses. The two other groups of drugs also have flat dose-response curves for efficacy. Overall, the triptans still have the most favorable efficacy-tolerability profile. Current acute antimigraine drugs do not fulfill the expectations of the patients, and thus...

  5. Dose response of thin-film dosimeters irradiated with 80-120 keV electrons

    DEFF Research Database (Denmark)

    Helt-Hansen, J.; Miller, A.; Sharpe, P.

    2005-01-01

    Thin-film dosimeters (Riso B3 and alanine films) were irradiated at 10 MeV and 80-120 keV electron accelerators, and it has been shown that the radiation response of the dosimeter materials (the radiation chemical yields) are constant at these irradiation energies. However, dose gradients within...... the dosimeters mean that calibration functions at the lower electron energies will be dependent on both irradiation energy and the required effective point of measurement of the dosimeter. These are general effects that apply to any dosimeters that have non-linear response functions and where dose gradients...

  6. Interpreting 'dose-response' curves using homeodynamic data: with an improved explanation for hormesis.

    Science.gov (United States)

    Stebbing, A R D

    2009-04-15

    A re-interpretation of the 'dose-response' curve is given that accommodates homeostasis. The outcome, or overall effect, of toxicity is the consequence of toxicity that is moderated by homeodynamic responses. Equilibrium is achieved by a balance of opposing forces of toxic inhibition countered by a stimulatory response. A graphical model is given consisting of two linked curves (response vs concentration and effect vs concentration), which provide the basis for a re-interpretation of the 'dose-response' curve. The model indicates that such relationships are non-linear with a threshold, which is due to homeodynamic responses. Subthreshold concentrations in 'dose-response' curves provide the sum of toxic inhibition minus the homeodynamic response; the response itself is unseen in serving its purpose of neutralizing perturbation. This interpretation suggests why the alpha- and beta-curves are non-linear. The beta-curve indicates adaptive overcorrection to toxicity that confers greater resistance to subsequent toxic exposure, with hormesis as an epiphenomenon.

  7. On the dimension of complex responses in nonlinear structural vibrations

    Science.gov (United States)

    Wiebe, R.; Spottswood, S. M.

    2016-07-01

    The ability to accurately model engineering systems under extreme dynamic loads would prove a major breakthrough in many aspects of aerospace, mechanical, and civil engineering. Extreme loads frequently induce both nonlinearities and coupling which increase the complexity of the response and the computational cost of finite element models. Dimension reduction has recently gained traction and promises the ability to distill dynamic responses down to a minimal dimension without sacrificing accuracy. In this context, the dimensionality of a response is related to the number of modes needed in a reduced order model to accurately simulate the response. Thus, an important step is characterizing the dimensionality of complex nonlinear responses of structures. In this work, the dimensionality of the nonlinear response of a post-buckled beam is investigated. Significant detail is dedicated to carefully introducing the experiment, the verification of a finite element model, and the dimensionality estimation algorithm as it is hoped that this system may help serve as a benchmark test case. It is shown that with minor modifications, the method of false nearest neighbors can quantitatively distinguish between the response dimension of various snap-through, non-snap-through, random, and deterministic loads. The state-space dimension of the nonlinear system in question increased from 2-to-10 as the system response moved from simple, low-level harmonic to chaotic snap-through. Beyond the problem studied herein, the techniques developed will serve as a prescriptive guide in developing fast and accurate dimensionally reduced models of nonlinear systems, and eventually as a tool for adaptive dimension-reduction in numerical modeling. The results are especially relevant in the aerospace industry for the design of thin structures such as beams, panels, and shells, which are all capable of spatio-temporally complex dynamic responses that are difficult and computationally expensive to

  8. Mixed-effects Gaussian process functional regression models with application to dose-response curve prediction.

    Science.gov (United States)

    Shi, J Q; Wang, B; Will, E J; West, R M

    2012-11-20

    We propose a new semiparametric model for functional regression analysis, combining a parametric mixed-effects model with a nonparametric Gaussian process regression model, namely a mixed-effects Gaussian process functional regression model. The parametric component can provide explanatory information between the response and the covariates, whereas the nonparametric component can add nonlinearity. We can model the mean and covariance structures simultaneously, combining the information borrowed from other subjects with the information collected from each individual subject. We apply the model to dose-response curves that describe changes in the responses of subjects for differing levels of the dose of a drug or agent and have a wide application in many areas. We illustrate the method for the management of renal anaemia. An individual dose-response curve is improved when more information is included by this mechanism from the subject/patient over time, enabling a patient-specific treatment regime.

  9. Dose-response features of neuroprotective agents: an integrative summary.

    Science.gov (United States)

    Calabrese, Edward J

    2008-01-01

    This article provides an integrative summary of the effects of neuroprotective agents on neuronal survival and neurite outgrowth using primary cell cultures, multiple neuronal cell lines, and astroglial cells. These findings are dealt with in considerable detail in the following three articles (Calabrese, 2008a, 2008b, 2008c) of this series of issues of Critical Reviews in Toxicology. The principal finding is that the overwhelming majority of neuroprotective agents display biphasic dose responses, characterized by modest low-dose enhancement/stimulation and high-dose inhibitory responses. The quantitative features of these dose responses are consistent with the hormetic dose-response model. Mechanisms that account for numerous hormetic dose responses of neuroprotective agents are summarized, as well as the clinical implications of specific experimental findings.

  10. Computation of the effective nonlinear mechanical response of lattice materials considering geometrical nonlinearities

    Science.gov (United States)

    ElNady, Khaled; Goda, Ibrahim; Ganghoffer, Jean-François

    2016-09-01

    The asymptotic homogenization technique is presently developed in the framework of geometrical nonlinearities to derive the large strains effective elastic response of network materials viewed as repetitive beam networks. This works extends the small strains homogenization method developed with special emphasis on textile structures in Goda et al. (J Mech Phys Solids 61(12):2537-2565, 2013). A systematic methodology is established, allowing the prediction of the overall mechanical properties of these structures in the nonlinear regime, reflecting the influence of the geometrical and mechanical micro-parameters of the network structure on the overall response of the chosen equivalent continuum. Internal scale effects of the initially discrete structure are captured by the consideration of a micropolar effective continuum model. Applications to the large strain response of 3D hexagonal lattices and dry textiles exemplify the powerfulness of the proposed method. The effective mechanical responses obtained for different loadings are validated by FE simulations performed over a representative unit cell.

  11. Aspartame tablets-gamma dose response and usability for routine radiation processing dosimetry using spectrophotometry

    Energy Technology Data Exchange (ETDEWEB)

    Shinde, S.H. [Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: shs_barc@yahoo.com; Mukherjee, T. [Radiation Safety Systems Division, Chemistry Group, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2007-02-15

    Aspartame tablets were studied for gamma dose response, using spectrophotometric read-out method. The optimum concentration for ferrous ions was 2x10{sup -4}moldm{sup -3} and xylenol orange with 2.5x10{sup -1}moldm{sup -3} of sulphuric acid for the optimum acidity in FX solution. Wavelength of maximum absorbance is 548nm. Post-irradiation stability is appreciable i.e. for not less than one month. Dose response is non-linear with third order polynomial fit, in the dose range of 1000-10000Gy. This system of aspartame was further used for carrying out relative percentage dose profile measurement in Gamma Cell-220. Results obtained were inter-compared with that of a glutamine dosimeter, which showed that maximum difference between the values of aspartame and glutamine systems is within +/-10%.

  12. Dose-Response Calculator for ArcGIS

    Science.gov (United States)

    Hanser, Steven E.; Aldridge, Cameron L.; Leu, Matthias; Nielsen, Scott E.

    2011-01-01

    The Dose-Response Calculator for ArcGIS is a tool that extends the Environmental Systems Research Institute (ESRI) ArcGIS 10 Desktop application to aid with the visualization of relationships between two raster GIS datasets. A dose-response curve is a line graph commonly used in medical research to examine the effects of different dosage rates of a drug or chemical (for example, carcinogen) on an outcome of interest (for example, cell mutations) (Russell and others, 1982). Dose-response curves have recently been used in ecological studies to examine the influence of an explanatory dose variable (for example, percentage of habitat cover, distance to disturbance) on a predicted response (for example, survival, probability of occurrence, abundance) (Aldridge and others, 2008). These dose curves have been created by calculating the predicted response value from a statistical model at different levels of the explanatory dose variable while holding values of other explanatory variables constant. Curves (plots) developed using the Dose-Response Calculator overcome the need to hold variables constant by using values extracted from the predicted response surface of a spatially explicit statistical model fit in a GIS, which include the variation of all explanatory variables, to visualize the univariate response to the dose variable. Application of the Dose-Response Calculator can be extended beyond the assessment of statistical model predictions and may be used to visualize the relationship between any two raster GIS datasets (see example in tool instructions). This tool generates tabular data for use in further exploration of dose-response relationships and a graph of the dose-response curve.

  13. Computation simulation of the nonlinear response of suspension bridges

    Energy Technology Data Exchange (ETDEWEB)

    McCallen, D.B.; Astaneh-Asl, A.

    1997-10-01

    Accurate computational simulation of the dynamic response of long- span bridges presents one of the greatest challenges facing the earthquake engineering community The size of these structures, in terms of physical dimensions and number of main load bearing members, makes computational simulation of transient response an arduous task. Discretization of a large bridge with general purpose finite element software often results in a computational model of such size that excessive computational effort is required for three dimensional nonlinear analyses. The aim of the current study was the development of efficient, computationally based methodologies for the nonlinear analysis of cable supported bridge systems which would allow accurate characterization of a bridge with a relatively small number of degrees of freedom. This work has lead to the development of a special purpose software program for the nonlinear analysis of cable supported bridges and the methodologies and software are described and illustrated in this paper.

  14. Model Averaging Software for Dichotomous Dose Response Risk Estimation

    Directory of Open Access Journals (Sweden)

    Matthew W. Wheeler

    2008-02-01

    Full Text Available Model averaging has been shown to be a useful method for incorporating model uncertainty in quantitative risk estimation. In certain circumstances this technique is computationally complex, requiring sophisticated software to carry out the computation. We introduce software that implements model averaging for risk assessment based upon dichotomous dose-response data. This software, which we call Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD, fits the quantal response models, which are also used in the US Environmental Protection Agency benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates. The software fulfills a need for risk assessors, allowing them to go beyond one single model in their risk assessments based on quantal data by focusing on a set of models that describes the experimental data.

  15. NONLINEAR RESPONSES OF GAMMA —RAY DOSIMETERS

    Institute of Scientific and Technical Information of China (English)

    罗达玲; 杨健明; 等

    1994-01-01

    Either sublinear or supralinear responses of dosimeters to γ-ray can be described by a response function derived from statistical Poisson distribution.The characteristic parameters of the function determine linearity,sublinearity and supralinearlty in their responses.The experimental data of gamma dose-responses of alanine ESR dosimeters film dosimeters.LiF(Mg,Cu,P) and LiF(Mg,Ti) thermoluminescence dosimeters are used to test the response function.

  16. Cardiac dose-response relationships of oral and intravenous pindolol

    OpenAIRE

    Carruthers, S. George

    1982-01-01

    1 The dose-response curve of pindolol on exercise heart rate has been constructed from observations in healthy male subjects studied 2 h after oral doses of pindolol 0.25 mg, 0.5 mg, 1 mg, 2.5 mg, 5 mg, 10 mg and 20 mg. This dose-response curve has been compared with historical controls who received atenolol, oxprenolol, practolol, propranolol and sotalol.

  17. A Method to Evaluate Hormesis in Nanoparticle Dose-Responses

    OpenAIRE

    Nascarella, Marc A.; Calabrese, Edward J.

    2012-01-01

    The term hormesis describes a dose-response relationship that is characterized by a response that is opposite above and below the toxicological or pharmacological threshold. Previous reports have shown that this relationship is ubiquitous in the response of pharmaceuticals, metals, organic chemicals, radiation, and physical stressor agents. Recent reports have also indicated that certain nanoparticles (NPs) may also exhibit a hormetic dose-response. We describe the application of three previo...

  18. Nonlinear Response of Cantilever Beams to Combination and Subcombination Resonances

    Directory of Open Access Journals (Sweden)

    Ali H. Nayfeh

    1998-01-01

    Full Text Available The nonlinear planar response of cantilever metallic beams to combination parametric and external subcombination resonances is investigated, taking into account the effects of cubic geometric and inertia nonlinearities. The beams considered here are assumed to have large length-to-width aspect ratios and thin rectangular cross sections. Hence, the effects of shear deformations and rotatory inertia are neglected. For the case of combination parametric resonance, a two-mode Galerkin discretization along with Hamilton’s extended principle is used to obtain two second-order nonlinear ordinary-differential equations of motion and associated boundary conditions. Then, the method of multiple scales is applied to obtain a set of four first-order nonlinear ordinary-differential equations governing the modulation of the amplitudes and phases of the two excited modes. For the case of subcombination resonance, the method of multiple scales is applied directly to the Lagrangian and virtual-work term. Then using Hamilton’s extended principle, we obtain a set of four first-order nonlinear ordinary-differential equations governing the amplitudes and phases of the two excited modes. In both cases, the modulation equations are used to generate frequency- and force-response curves. We found that the trivial solution exhibits a jump as it undergoes a subcritical pitchfork bifurcation. Similarly, the nontrivial solutions also exhibit jumps as they undergo saddle-node bifurcations.

  19. Modeling and non-linear responses of MEMS capacitive accelerometer

    Directory of Open Access Journals (Sweden)

    Sri Harsha C.

    2014-01-01

    Full Text Available A theoretical investigation of an electrically actuated beam has been illustrated when the electrostatic-ally actuated micro-cantilever beam is separated from the electrode by a moderately large gap for two distinct types of geometric configurations of MEMS accelerometer. Higher order nonlinear terms have been taken into account for studying the pull in voltage analysis. A nonlinear model of gas film squeezing damping, another source of nonlinearity in MEMS devices is included in obtaining the dynamic responses. Moreover, in the present work, the possible source of nonlinearities while formulating the mathematical model of a MEMS accelerometer and their influences on the dynamic responses have been investigated. The theoretical results obtained by using MATLAB has been verified with the results obtained in FE software and has been found in good agreement. Criterion towards stable micro size accelerometer for each configuration has been investigated. This investigation clearly provides an understanding of nonlinear static and dynamics characteristics of electrostatically micro cantilever based device in MEMS.

  20. Measurement of Localized Nonlinear Microwave Response of Superconductors

    Science.gov (United States)

    Lee, Sheng-Chiang; Palmer, Benjamin; Maiorov, B.

    2005-03-01

    We measure the local harmonic generation from superconducting thin films at microwave frequencies to investigate the intrinsic nonlinear Meissner effect near T/c in zero magnetic field. Both second and third harmonic generation are measured to identify time-reversal symmetry breaking (TRSB) and time-reversal symmetric (TRS) nonlinearities. The microscope can measure the local nonlinear response of a bicrystal grain boundary [Sheng-Chiang Lee and Steven M. Anlage, Physica C 408-410, 324 (2004); cond-mat/0408170]. We also performed a systematic doping-dependent study of the nonlinear response and find that the TRS characteristic nonlinearity current density scale follows the doping dependence of the de-pairing critical current density [cond-mat/0405595]. We extract a spontaneous TRSB characteristic current density scale that onsets at T/c, grows with decreasing temperature, and systematically decreases in magnitude (at fixed T/T/c) with under-doping. The origin of this current scale could be Josephson circulating currents or the spontaneous magnetization associated with a TRSB order parameter.

  1. Pooling Bio-Specimens in the Presence of Measurement Error and Non-Linearity in Dose-Response: Simulation Study in the Context of a Birth Cohort Investigating Risk Factors for Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Karyn Heavner

    2015-11-01

    Full Text Available We sought to determine the potential effects of pooling on power, false positive rate (FPR, and bias of the estimated associations between hypothetical environmental exposures and dichotomous autism spectrum disorders (ASD status. Simulated birth cohorts in which ASD outcome was assumed to have been ascertained with uncertainty were created. We investigated the impact on the power of the analysis (using logistic regression to detect true associations with exposure (X1 and the FPR for a non-causal correlate of exposure (X2, r = 0.7 for a dichotomized ASD measure when the pool size, sample size, degree of measurement error variance in exposure, strength of the true association, and shape of the exposure-response curve varied. We found that there was minimal change (bias in the measures of association for the main effect (X1. There is some loss of power but there is less chance of detecting a false positive result for pooled compared to individual level models. The number of pools had more effect on the power and FPR than the overall sample size. This study supports the use of pooling to reduce laboratory costs while maintaining statistical efficiency in scenarios similar to the simulated prospective risk-enriched ASD cohort.

  2. Stochastic Nonlinear Response of Woven CMCs

    Science.gov (United States)

    Kuang, C. Liu; Arnold, Steven M.

    2013-01-01

    It is well known that failure of a material is a locally driven event. In the case of ceramic matrix composites (CMCs), significant variations in the microstructure of the composite exist and their significance on both deformation and life response need to be assessed. Examples of these variations include changes in the fiber tow shape, tow shifting/nesting and voids within and between tows. In the present work, the influence of scale specific architectural features of woven ceramic composite are examined stochastically at both the macroscale (woven repeating unit cell (RUC)) and structural scale (idealized using multiple RUCs). The recently developed MultiScale Generalized Method of Cells methodology is used to determine the overall deformation response, proportional elastic limit (first matrix cracking), and failure under tensile loading conditions and associated probability distribution functions. Prior results showed that the most critical architectural parameter to account for is weave void shape and content with other parameters being less in severity. Current results show that statistically only the post-elastic limit region (secondary hardening modulus and ultimate tensile strength) is impacted by local uncertainties both at the macro and structural level.

  3. Nonlinear analysis of the forced response of structural elements

    Science.gov (United States)

    Nayfeh, A. H.; Mook, D. T.; Sridhar, S.

    1974-01-01

    A general procedure is presented for the nonlinear analysis of the forced response of structural elements to harmonic excitations. Internal resonances (i.e., modal interactions) are taken into account. All excitations are considered, with special consideration given to resonant excitations. The general procedure is applied to clamped-hinged beams. The results reveal that exciting a higher mode may lead to a larger response in a lower interacting mode, contrary to the results of linear analyses.

  4. Nonlinear microwave switching response of BSCCO single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, T.; Sridhar, S. [Northeastern Univ., Boston, MA (United States). Dept. of Physics; Willemsen, B.A. [Northeastern Univ., Boston, MA (United States). Dept. of Physics]|[Rome Lab., Hanscom AFB, MA (United States); Li, Qiang [Brookhaven National Lab., Upton, NY (United States); Gu, G.D.; Koshizuka, N. [Superconductivity Research Lab., Tokyo (Japan)

    1996-06-01

    Measurements of the surface impedance in Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8+{delta}} single crystal with microwave currents flowing along the {cflx c} axis show clear evidence of a step-like nonlinearity. The surface resistance switches between apparently quantized levels for microwave field strength changes < 1 mG. This nonlinear response can arise from the presence of intrinsic Josephson junctions along the {cflx c} axis of these samples driven by the microwave current.

  5. Investigating quartz optically stimulated luminescence dose-response curves at high doses

    Energy Technology Data Exchange (ETDEWEB)

    Lowick, Sally E., E-mail: lowick@geo.unibe.c [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Preusser, Frank [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Wintle, Ann G. [Institute of Geography and Earth Sciences, Aberystwyth University, AberystwythSY23 3DB (United Kingdom)

    2010-10-15

    Despite the general expectation that optically stimulated luminescence (OSL) growth should be described by a simple saturating exponential function, an additional high dose component is often reported in the dose response of quartz. Although often reported as linear, it appears that this response is the early expression of a second saturating exponential. While some studies using equivalent doses that fall in this high dose region have produced ages that correlate well with independent dating, others report that it results in unreliable age determinations. Two fine grain sedimentary quartz samples that display such a response were used to investigate the origin of this additional high dose component: three experiments were conducted to examine their dose-response up to >1000 Gy. The high dose rates provided by laboratory irradiation were found not to induce a sensitivity change in the response to a subsequent test dose, with the latter not being significantly different from those generated following naturally acquired doses. The relative percentage contributions of the fast and medium OSL components remained fixed throughout the dose-response curve, suggesting that the electron traps that give rise to the initial OSL do not change with dose. An attempt was made to investigate a change in luminescence centre recombination probability by monitoring the depletion of the '325 {sup o}C' thermoluminescence (TL) during the optical stimulation that would result in depletion of the OSL signal. The emissions measured through both the conventional ultraviolet (UV), and a longer wavelength violet/blue (VB) window, displayed similar relative growth with dose, although it was not possible to resolve the origin of the VB emissions. No evidence was found to indicate whether the additional component at high doses occurs naturally or is a product of laboratory treatment. However, it appears that these samples display an increased sensitivity of quartz OSL to high doses

  6. The relationship between terazosin dose and blood pressure response in hypertensive patients.

    Science.gov (United States)

    Achari, R; Hosmane, B; Bonacci, E; O'Dea, R

    2000-10-01

    A double-blind, randomized, placebo-controlled, multicenter study was conducted to describe the dose-response curve for terazosin on blood pressure. A total of 128 patients with mild to moderate essential hypertension (supine diastolic blood pressure, 100 to 114 mmHg) participated in the study. The study consisted of a 4-week single-blind placebo lead-in period and a 14-week double-blind treatment period. Patients were randomized in equal numbers to four parallel treatment groups: terazosin 1, 2, and 5 mg; terazosin 2, 5, and 10 mg; terazosin 20, 40, and 80 mg; and placebo. The 24-hour ambulatory blood pressure measurements were performed at the end of the placebo lead-in period and at the end of each 4-week fixed-dose period. The nonlinear, mixed-effect model computer program was used to analyze the dose-response relationship. There was a strong dose-response relationship between fall in blood pressure and the 1 to 10 mg terazosin dose, as well as a plateauing of response for terazosin doses above 10 mg. The maximum antihypertensive response (Emax) to terazosin was 10.7 mmHg for systolic blood pressure and 8.0 mmHg for diastolic blood pressure. The daily dose of terazosin, which produced 50% of the maximum response (ED50), was 3.0 mg for systolic blood pressure and 1.5 mg for diastolic blood pressure. The results of this study suggest that although some patients may benefit from terazosin doses of greater than 10 mg, doses up to 10 mg will maximize therapeutic benefit for most patients, with acceptable side effects.

  7. Nonlinear THz response of metallic armchair graphene nanoribbon superlattices

    Science.gov (United States)

    Wang, Yichao; Andersen, David R.

    2016-11-01

    We study the third order THz nonlinear response of metallic armchair graphene nanoribbon superlattices in the presence of an elliptically-polarized excitation field using the time dependent perturbation theory. For a one-dimensional Kronig-Penney potential of infinite length, the nonlinear response can be described perturbatively by a low energy \\mathbf{k}\\centerdot \\mathbf{p} N-photon coupling model. Remarkably, as shown by Burset et al the energy dispersion of the metallic band in the direction parallel to the superlattice wavevector is independent of the applied superlattice potential while the energy dispersion in the direction perpendicular to the superlattice wavevector depends strongly on the superlattice parameters. As a result, we predict novel behavior for the nonlinear response of single layer metallic acGNR superlattices to an applied elliptically-polarized electric field. Our work shows that the superlattice potential, periodicity, Fermi level, excitation field polarization state, and temperature all play a significant role in the resulting THz nonlinear conductances.

  8. Structure property relationships for the nonlinear optical response of fullerenes

    Science.gov (United States)

    Rustagi, Kailash C.; Ramaniah, Lavanya M.; Nair, Selvakumar V.

    1994-11-01

    We present a phenomenological theory of nonlinear optical response of fullerenes. An empirical tight-binding model is used in conjunction with a classical electromagnetic picture for the screening. Since in bulk media such a picture of screening corresponds to the self- consistent field approach, the only additional approximation involved in our approach is the neglect of nonlocality. We obtain reliable estimates for the linear and nonlinear susceptibilities of C60, C70, C76 and other pure carbon fullerenes and also substituted fullerenes. The relatively large values of (beta) that we obtain for C76 and substituted fullerenes appear promising for the development of fullerene-based nonlinear optical materials. Our phenomenological picture of screening provides a good understanding of the linear absorption spectra of higher fullerenes and predicts that a comparison of the one-photon and multi-photon spectra will provide an insight into screening effects in these systems.

  9. Dose Effects of Ion Beam Exposure on Deinococcus Radiodurans: Survival and Dose Response

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To explore the survival and dose response of organism for different radiation sources is of great importance in the research of radiobiology. In this study, the survival-dose response of Deinococcus radiodurans (E.coli, as the control) for ultra-violet (UV), γ-rays radiation and ion beam exposure was investigated. The shoulder type of survival curves were found for both UV and γ-ray ionizing radiation, but the saddle type of survival curves were shown for H+ 、 N+( 20keV and 30keV) and Ar+ beam exposure. This dose effect of the survival initially decreased withthe increase in dose and then increased in the high dose range and finally decreased again in thehigher dose range. Our experimental results suggest that D. radiodurans, which is considerablyradio-resistant to UV and x-ray and γ-ray ionizing radiation, do not resist ion beam exposure.

  10. Dose response relationship in local radiotherapy for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2001-06-01

    In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2{+-}7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non

  11. Full Hydrodynamic Model of Nonlinear Electromagnetic Response in Metallic Metamaterials

    CERN Document Server

    Fang, Ming; Sha, Wei E I; Xiong, Xiaoyan Y Z; Wu, Xianliang

    2016-01-01

    Applications of metallic metamaterials have generated significant interest in recent years. Electromagnetic behavior of metamaterials in the optical range is usually characterized by a local-linear response. In this article, we develop a finite-difference time-domain (FDTD) solution of the hydrodynamic model that describes a free electron gas in metals. Extending beyond the local-linear response, the hydrodynamic model enables numerical investigation of nonlocal and nonlinear interactions between electromagnetic waves and metallic metamaterials. By explicitly imposing the current continuity constraint, the proposed model is solved in a self-consistent manner. Charge, energy and angular momentum conservation laws of high-order harmonic generation have been demonstrated for the first time by the Maxwell-hydrodynamic FDTD model. The model yields nonlinear optical responses for complex metallic metamaterials irradiated by a variety of waveforms. Consequently, the multiphysics model opens up unique opportunities f...

  12. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    Energy Technology Data Exchange (ETDEWEB)

    Levy, R.P.

    1991-12-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute {gamma}-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.

  13. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Richard P. [Univ. of California, Berkeley, CA (United States)

    1991-12-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute γ-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.

  14. Effective Dielectric Response of Nonlinear Composites of Coated Metal Inclusions

    Institute of Scientific and Technical Information of China (English)

    CHEN Guo-Qing; WU Ya-Min

    2007-01-01

    The effective dielectric response of the composites in which nondilute coated metal particles are randomly embedded in a linear host is investigated. Two types of coated particles are considered, one is that the core is nonlinear, the other is that the shell is nonlinear. We derive general expressions for the effective linear dielectric function and the effective third-order nonlinear susceptibility, and take one step forward to perform numerical calculations on the coated metal/dielectric composites. Numerical results show that the effective linear and nonlinear dielectric responses can be greatly enhanced near the surface plasmon resonant frequency. Moreover, the resonant peaks are found within a range from 0.46ωp to 0.57ωp for spherical particles and from 0.59ωp to 0.7ωp for cylindrical inclusions. In the frequency region, the resonant peak can achieve the maximum, according to an optimal structural parameter and volume fraction. The resonant frequency exhibits a redshift with the increasing structural parameter k or volume fraction f or dimensionality factor D.

  15. Frequency Response and Gap Tuning for Nonlinear Electrical Oscillator Networks

    Science.gov (United States)

    Bhat, Harish S.; Vaz, Garnet J.

    2013-01-01

    We study nonlinear electrical oscillator networks, the smallest example of which consists of a voltage-dependent capacitor, an inductor, and a resistor driven by a pure tone source. By allowing the network topology to be that of any connected graph, such circuits generalize spatially discrete nonlinear transmission lines/lattices that have proven useful in high-frequency analog devices. For such networks, we develop two algorithms to compute the steady-state response when a subset of nodes are driven at the same fixed frequency. The algorithms we devise are orders of magnitude more accurate and efficient than stepping towards the steady-state using a standard numerical integrator. We seek to enhance a given network's nonlinear behavior by altering the eigenvalues of the graph Laplacian, i.e., the resonances of the linearized system. We develop a Newton-type method that solves for the network inductances such that the graph Laplacian achieves a desired set of eigenvalues; this method enables one to move the eigenvalues while keeping the network topology fixed. Running numerical experiments using three different random graph models, we show that shrinking the gap between the graph Laplacian's first two eigenvalues dramatically improves a network's ability to (i) transfer energy to higher harmonics, and (ii) generate large-amplitude signals. Our results shed light on the relationship between a network's structure, encoded by the graph Laplacian, and its function, defined in this case by the presence of strongly nonlinear effects in the frequency response. PMID:24223751

  16. Nonlinear response from the perspective of energy landscapes and beyond

    Science.gov (United States)

    Heuer, Andreas; Schroer, Carsten F. E.; Diddens, Diddo; Rehwald, Christian; Blank-Burian, Markus

    2017-08-01

    The paper discusses the nonlinear response of disordered systems. In particular we show how the nonlinear response can be interpreted in terms of properties of the potential energy landscape. It is shown why the use of relatively small systems is very helpful for this approach. For a standard model system we check which system sizes are particular suited. In case of the driving of a single particle via an external force the concept of an effective temperature helps to scale the force dependence for different temperature on a single master curve. In all cases the mobility increases with increasing external force. These results are compared with a stochastic process described by a 1d Langevin equation where a similar scaling is observed. Furthermore it is shown that for different classes of disordered systems the mobility can also decrease with increasing force. The results can be related to the properties of the chosen potential energy landscape. Finally, results for the crossover from the linear to the nonlinear conductivity of ionic liquids are presented, inspired by recent experimental results in the Roling group. Apart from a standard imidazolium-based ionic liquid we study a system which is characterized by a low conductivity as compared to other ionic liquids and very small nonlinear effects. We show via a real space structural analysis that for this system a particularly strong pair formation is observed and that the strength of the pair formation is insensitive to the application of strong electric fields. Consequences of this observation are discussed.

  17. Analysis of clinical trials with biologics using dose-time-response models.

    Science.gov (United States)

    Lange, Markus R; Schmidli, Heinz

    2015-09-30

    Biologics such as monoclonal antibodies are increasingly and successfully used for the treatment of many chronic diseases. Unlike conventional small drug molecules, which are commonly given as tablets once daily, biologics are typically injected at much longer time intervals, that is, weeks or months. Hence, both the dose and the time interval have to be optimized during the drug development process for biologics. To identify an adequate regimen for the investigated biologic, the dose-time-response relationship must be well characterized, based on clinical trial data. The proposed approach uses semi-mechanistic nonlinear regression models to describe and predict the time-changing response for complex dosing regimens. Both likelihood-based and Bayesian methods for inference and prediction are discussed. The methodology is illustrated with data from a clinical study in an auto-immune disease.

  18. Diverse dose-response effects of yolk androgens on embryo development and nestling growth in a wild passerine.

    Science.gov (United States)

    Muriel, Jaime; Pérez-Rodríguez, Lorenzo; Puerta, Marisa; Gil, Diego

    2015-07-01

    Avian egg yolks contain various amounts of maternally derived androgens that can modify offspring phenotype and adjust their development to the post-hatching environment. Seemingly adaptive variation in yolk androgen levels with respect to breeding density conditions or male attractiveness has been found in numerous studies. One important consideration that has been overlooked in previous research is the likely non-linear nature of hormone effects. To examine possible complex dose-response effects of maternal androgens on chick development, we experimentally administered three different androgen doses of the naturally occurring mixture of yolk testosterone and androstenedione to spotless starling eggs (Sturnus unicolor). We found that yolk androgens induce a non-linear dose-response pattern in several traits. Androgens had a stimulatory effect on hatchling body mass and nestling skeletal growth, but maximum values were found at intermediate doses, whereas our highest dose resulted in a decrease. However, the opposite U-shaped effect was found on nestling body mass. We also detected linear negative and positive effects on embryonic development period and nestling gape width, respectively. Our results suggest differential tissue responsiveness to yolk androgens, which may result in compromises in maternal allocation to produce adapted phenotypes. Because of the non-linear dose-response pattern, future investigations should carefully consider a wide range of concentrations, as the balance of costs and benefits may strongly differ depending on concentration.

  19. Nonlinear Effects of Nanoparticles: Biological Variability From Hormetic Doses, Small Particle Sizes, and Dynamic Adaptive Interactions

    OpenAIRE

    Bell, Iris R.; Ives, John A.; Wayne B. Jonas

    2013-01-01

    Researchers are increasingly focused on the nanoscale level of organization where biological processes take place in living systems. Nanoparticles (NPs, e.g., 1–100 nm diameter) are small forms of natural or manufactured source material whose properties differ markedly from those of the respective bulk forms of the “same” material. Certain NPs have diagnostic and therapeutic uses; some NPs exhibit low-dose toxicity; other NPs show ability to stimulate low-dose adaptive responses (hormesis). B...

  20. Assembled cross-species perchlorate dose-response data

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data set contains dose-response data for perchlorate exposure in multiple species. These data were assembled from peer-reviewed studies. Species included in...

  1. Dose-Finding when the Target Dose Is on a Plateau of a Dose-Response Curve: Comparison of Fully Sequential Designs

    OpenAIRE

    Ivanova, Anastasia; Xiao, Changfu

    2013-01-01

    Consider the problem of estimating a dose with a certain response rate. Many multistage dose-finding designs for this problem were originally developed for oncology studies where the mean dose-response is strictly increasing in dose. In non-oncology Phase II dose-finding studies the dose-response curve often plateaus in the range of interest and there are several doses with the mean response equal to the target. In this case it is usually of interest to find the lowest of these doses since hi...

  2. The Response of Rats to Cutaneous Dosing with Trichothecene Mycotoxins,

    Science.gov (United States)

    1983-10-01

    trichothecene absorption by human skin is unknown. We have found no synergism between T-2 and DAS, but to test all aspects of synergism and of solvent...AD Al39 548 THE RESPONSE OF RATS TO CUTANEOUS DOSING WITH TRICHOTHECENE MYCOTOXINSIU) MATERIALS RESEARCH LABS ASCOT VALE IAUSTRALIA) H 0 CRONE OCT 83...902 de THE RESPONSE OF RATS TO CUTANEOUS DOSING WITH TRICHOTHECENE MYCOTOXINS 4 H.D. Crone TDTI Approved for Public Rlelease 2 004 Cmmealth of

  3. Updating Dosimetry for Emergency Response Dose Projections.

    Science.gov (United States)

    DeCair, Sara

    2016-02-01

    In 2013, the U.S. Environmental Protection Agency (EPA) proposed an update to the 1992 Protective Action Guides (PAG) Manual. The PAG Manual provides guidance to state and local officials planning for radiological emergencies. EPA requested public comment on the proposed revisions, while making them available for interim use by officials faced with an emergency situation. Developed with interagency partners, EPA's proposal incorporates newer dosimetric methods, identifies tools and guidelines developed since the current document was issued, and extends the scope of the PAGs to all significant radiological incidents, including radiological dispersal devices or improvised nuclear devices. In order to best serve the emergency management community, scientific policy direction had to be set on how to use International Commission on Radiological Protection Publication 60 age groups in dose assessment when implementing emergency guidelines. Certain guidelines that lend themselves to different PAGs for different subpopulations are the PAGs for potassium iodide (KI), food, and water. These guidelines provide age-specific recommendations because of the radiosensitivity of the thyroid and young children with respect to ingestion and inhalation doses in particular. Taking protective actions like using KI, avoiding certain foods or using alternative sources of drinking water can be relatively simple to implement by the parents of young children. Clear public messages can convey which age groups should take which action, unlike how an evacuation or relocation order should apply to entire households or neighborhoods. New in the PAG Manual is planning guidance for the late phase of an incident, after the situation is stabilized and efforts turn toward recovery. Because the late phase can take years to complete, decision makers are faced with managing public exposures in areas not fully remediated. The proposal includes quick-reference operational guidelines to inform re-entry to

  4. Radiation Dose-Response Relationships and Risk Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Strom, Daniel J.

    2005-07-05

    The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is also the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of

  5. Bayesian penalized log-likelihood ratio approach for dose response clinical trial studies.

    Science.gov (United States)

    Tang, Yuanyuan; Cai, Chunyan; Sun, Liangrui; He, Jianghua

    2017-02-13

    In literature, there are a few unified approaches to test proof of concept and estimate a target dose, including the multiple comparison procedure using modeling approach, and the permutation approach proposed by Klingenberg. We discuss and compare the operating characteristics of these unified approaches and further develop an alternative approach in a Bayesian framework based on the posterior distribution of a penalized log-likelihood ratio test statistic. Our Bayesian approach is much more flexible to handle linear or nonlinear dose-response relationships and is more efficient than the permutation approach. The operating characteristics of our Bayesian approach are comparable to and sometimes better than both approaches in a wide range of dose-response relationships. It yields credible intervals as well as predictive distribution for the response rate at a specific dose level for the target dose estimation. Our Bayesian approach can be easily extended to continuous, categorical, and time-to-event responses. We illustrate the performance of our proposed method with extensive simulations and Phase II clinical trial data examples.

  6. Dose-time-response modeling using negative binomial distribution.

    Science.gov (United States)

    Roy, Munmun; Choudhury, Kanak; Islam, M M; Matin, M A

    2013-01-01

    People exposed to certain diseases are required to be treated with a safe and effective dose level of a drug. In epidemiological studies to find out an effective dose level, different dose levels are applied to the exposed and a certain number of cures is observed. Negative binomial distribution is considered to fit overdispersed Poisson count data. This study investigates the time effect on the response at different time points as well as at different dose levels. The point estimation and confidence bands for ED(100p)(t) and LT(100p)(d) are formulated in closed form for the proposed dose-time-response model with the negative binomial distribution. Numerical illustrations are carried out in order to check the performance level of the proposed model.

  7. Nonlinear Dielectric Response of Water Treed XLPE Cable Insulation

    Energy Technology Data Exchange (ETDEWEB)

    Hvidsten, Sverre

    1999-07-01

    Condition assessment of XLPE power cables is becoming increasingly important for the utilities, due to a large number of old cables in service with high probability of failure caused by water tree degradation. The commercial available techniques are generally based upon measurements of the dielectric response, either by time (polarisation/depolarisation current or return voltage) or frequency domain measurements. Recently it has been found that a high number of water trees in XLPE insulated cables causes the dielectric response to increase more than linearly with increasing test voltage. This nonlinear feature of water tree degraded XLPE insulation has been suggested to be of a great importance, both for diagnostic purposes, and for fundamental understanding of the water tree phenomenon itself. The main purpose of this thesis have been to study the nonlinear feature of the dielectric response measured on watertreed XLPE insulation. This has been performed by dielectric response measurements in both time and frequency domain, numerical calculations of losses of simplified water tree models, and fmally water content and water permeation measurements on single water trees. The dielectric response measurements were performed on service aged cable samples and laboratory aged Rogowski type objects. The main reason for performing laboratory ageing was to facilitate diagnostic testing as a function of ageing time of samples containing mainly vented water trees. A new method, based upon inserting NaC1 particles at the interface between the upper semiconductive screen and the insulation, was found to successfully enhance initiation and growth of vented water trees. AC breakdown strength testing show that it is the vented water trees that reduce the breakdown level of both the laboratory aged test objects and service aged cable samples. Vented water treeing was found to cause the dielectric response to become nonlinear at a relatively low voltage level. However, the measured

  8. Using machine learning to model dose-response relationships.

    Science.gov (United States)

    Linden, Ariel; Yarnold, Paul R; Nallamothu, Brahmajee K

    2016-12-01

    Establishing the relationship between various doses of an exposure and a response variable is integral to many studies in health care. Linear parametric models, widely used for estimating dose-response relationships, have several limitations. This paper employs the optimal discriminant analysis (ODA) machine-learning algorithm to determine the degree to which exposure dose can be distinguished based on the distribution of the response variable. By framing the dose-response relationship as a classification problem, machine learning can provide the same functionality as conventional models, but can additionally make individual-level predictions, which may be helpful in practical applications like establishing responsiveness to prescribed drug regimens. Using data from a study measuring the responses of blood flow in the forearm to the intra-arterial administration of isoproterenol (separately for 9 black and 13 white men, and pooled), we compare the results estimated from a generalized estimating equations (GEE) model with those estimated using ODA. Generalized estimating equations and ODA both identified many statistically significant dose-response relationships, separately by race and for pooled data. Post hoc comparisons between doses indicated ODA (based on exact P values) was consistently more conservative than GEE (based on estimated P values). Compared with ODA, GEE produced twice as many instances of paradoxical confounding (findings from analysis of pooled data that are inconsistent with findings from analyses stratified by race). Given its unique advantages and greater analytic flexibility, maximum-accuracy machine-learning methods like ODA should be considered as the primary analytic approach in dose-response applications. © 2016 John Wiley & Sons, Ltd.

  9. Linearization of dose-response curve of the radiochromic film dosimetry system

    Energy Technology Data Exchange (ETDEWEB)

    Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad; DeBlois, Francois; Seuntjens, Jan; Chan, Maria F.; Lewis, Dave [Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Executive Administration for Radiation Protection and Safety Medical Devices Sector, Saudi Food and Drug Authority, Riyadh, Kingdom of Saudi Arabia 13312 (Saudi Arabia); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center Basking Ridge, New Jersey 07920 (United States); Ashland Inc., Wayne, New Jersey 07470 (United States)

    2012-08-15

    Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to test the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also

  10. A FORTRAN program for calculating nonlinear seismic ground response

    Science.gov (United States)

    Joyner, William B.

    1977-01-01

    The program described here was designed for calculating the nonlinear seismic response of a system of horizontal soil layers underlain by a semi-infinite elastic medium representing bedrock. Excitation is a vertically incident shear wave in the underlying medium. The nonlinear hysteretic behavior of the soil is represented by a model consisting of simple linear springs and Coulomb friction elements arranged as shown. A boundary condition is used which takes account of finite rigidity in the elastic substratum. The computations are performed by an explicit finite-difference scheme that proceeds step by step in space and time. A brief program description is provided here with instructions for preparing the input and a source listing. A more detailed discussion of the method is presented elsewhere as is the description of a different program employing implicit integration.

  11. Effects of Particle Shape and Microstructure on Effective Nonlinear Response

    Institute of Scientific and Technical Information of China (English)

    HUANG Ji-Ping; LI Zhen-Ya

    2001-01-01

    We consider a binary granular composite medium, in which two materials have high-order nonlinearities.The effect of particle shape on effective nonlinear response (ENR) is investigated by assuming all the particles to be shaped as uniaxial ellipsoid. We discuss two types of arrangements of particles: 1) parallel axes (Case I); 2) random axes (Case II). During the process of numerical calculation, one component material is assumed to be linear, and two kinds of conductors are assumed to be at high conducting contrast. We find that: 1) the shape effect on ENR is possibly strong; 2) the enhanced ENR can even be obtained by choosing particles of appropriate ellipsoidal shapes; 3) the ENR enhancement predicted by Case I is much stronger than that by Case II.``

  12. Strong nonlinear photonic responses from microbiologically synthesized tellurium nanocomposites

    Science.gov (United States)

    Liao, K.-S.; Wang, Jingyuan; Dias, S.; Dewald, J.; Alley, N.J.; Baesman, S.M.; Oremland, R.S.; Blau, W.J.; Curran, S.A.

    2010-01-01

    A new class of nanomaterials, namely microbiologically-formed nanorods composed of elemental tellurium [Te(0)] that forms unusual nanocomposites when combined with poly(m-phenylenevinylene-co-2,5-dioctoxy-phenylenevinylene) (PmPV) is described. These bio-nanocomposites exhibit excellent broadband optical limiting at 532 and 1064 nm. Nonlinear scattering, originating from the laser induced solvent bubbles and microplasmas, is responsible for this nonlinear behavior. The use of bacterially-formed Te(0) when combined with an organic chemical host (e.g., PmPV) is a new green method of nanoparticle syntheses. This opens the possibilities of using unique, biologically synthesized materials to advance future nanoelectronic and nanophotonic applications. ?? 2009 Elsevier B.V. All rights reserved.

  13. Nonlinear dynamic response of stay cables under axial harmonic excitation

    Institute of Scientific and Technical Information of China (English)

    Xu XIE; He ZHAN; Zhi-cheng ZHANG

    2008-01-01

    This paper proposes a new numerical simulation method for analyzing the parametric vibration of stay cables based on the theory of nonlinear dynamic response of structures under the asynchronous support excitation.The effects of important parameters related to parametric vibration of cables,I.e., characteristics of structure,excitation frequency,excitation amplitude,damping effect of the air and the viscous damping coefficient of the cables,were investigated by using the proposed method for the cables with significant length difference as examples.The analysis results show that nonlinear finite element method is a powerful technique in analyzing the parametric vibration of cables,the behavior of parametric vibration of the two cables with different Irvine parameters has similar properties,the amplitudes of parametric vibration of cables are related to the frequency and amplitude of harmonic support excitations and the effect of distributed viscous damping on parametric vibration of the cables is very small.

  14. Epidemiological methods for assessing dose-response and dose-effect relationships

    DEFF Research Database (Denmark)

    Kjellström, Tord; Grandjean, Philippe

    2007-01-01

    of the Toxic Effects of Metals Aluminum Antimony Arsenic Barium Beryllium Bismuth Cadmium Chromium Cobalt Copper Gallium and Semiconductor Compounds Germanium Indium Iron Lead Manganese Mercury Molybdenum Nickel Palladium Platinum Selenium Silver Tellurium Thallium Tin Titanium Tungsten Uranium Vanadium Zinc...... and their compounds. An entirely new structure and illustrations represent the vast array of advancements made since the last edition. Special emphasis has been placed on the toxic effects in humans with chapters on the diagnosis, treatment and prevention of metal poisoning. This up-to-date reference provides easy...... Selected Molecular Mechanisms of Metal Toxicity and Carcinogenicity General Considerations of Dose-Effect and Dose-Response Relationships Interactions in Metal Toxicology Epidemiological Methods for Assessing Dose-Response and Dose-Effect Relationships Essential Metals: Assessing Risks from Deficiency...

  15. Analytical modelling of regional radiotherapy dose response of lung

    Science.gov (United States)

    Lee, Sangkyu; Stroian, Gabriela; Kopek, Neil; AlBahhar, Mahmood; Seuntjens, Jan; El Naqa, Issam

    2012-06-01

    Knowledge of the dose-response of radiation-induced lung disease (RILD) is necessary for optimization of radiotherapy (RT) treatment plans involving thoracic cavity irradiation. This study models the time-dependent relationship between local radiation dose and post-treatment lung tissue damage measured by computed tomography (CT) imaging. Fifty-eight follow-up diagnostic CT scans from 21 non-small-cell lung cancer patients were examined. The extent of RILD was segmented on the follow-up CT images based on the increase of physical density relative to the pre-treatment CT image. The segmented RILD was locally correlated with dose distribution calculated by analytical anisotropic algorithm and the Monte Carlo method to generate the corresponding dose-response curves. The Lyman-Kutcher-Burman (LKB) model was fit to the dose-response curves at six post-RT time periods, and temporal change in the LKB parameters was recorded. In this study, we observed significant correlation between the probability of lung tissue damage and the local dose for 96% of the follow-up studies. Dose-injury correlation at the first three months after RT was significantly different from later follow-up periods in terms of steepness and threshold dose as estimated from the LKB model. Dependence of dose response on superior-inferior tumour position was also observed. The time-dependent analytical modelling of RILD might provide better understanding of the long-term behaviour of the disease and could potentially be applied to improve inverse treatment planning optimization.

  16. Curious cases: Altered dose-response relationships in addiction genetics.

    Science.gov (United States)

    Uhl, George R; Drgonova, Jana; Hall, F Scott

    2014-03-01

    Dose-response relationships for most addictive substances are "inverted U"-shaped. Addictive substances produce both positive features that include reward, euphoria, anxiolysis, withdrawal-relief, and negative features that include aversion, dysphoria, anxiety and withdrawal symptoms. A simple model differentially associates ascending and descending limbs of dose-response curves with rewarding and aversive influences, respectively. However, Diagnostic and Statistical Manual (DSM) diagnoses of substance dependence fail to incorporate dose-response criteria and don't directly consider balances between euphoric and dysphoric drug effects. Classical genetic studies document substantial heritable influences on DSM substance dependence. Linkage and genome-wide association studies identify modest-sized effects at any locus. Nevertheless, clusters of SNPs within selected genes display 10(-2)>p>10(-8) associations with dependence in many independent samples. For several of these genes, evidence for cis-regulatory, level-of-expression differences supports the validity of mouse models in which levels of expression are also altered. This review documents surprising, recently defined cases in which convergent evidence from humans and mouse models supports central influences of altered dose-response relationships in mediating the impact of relevant genomic variation on addiction phenotypes. For variation at loci for the α5 nicotinic acetylcholine receptor, cadherin 13, receptor type protein tyrosine phosphatase Δ and neuronal cell adhesion molecule genes, changed dose-response relationships conferred by gene knockouts in mice are accompanied by supporting human data. These observations emphasize desirability of carefully elucidating dose-response relationships for both rewarding and aversive features of abused substances wherever possible. They motivate consideration of individual differences in dose-response relationships in addiction nosology and therapeutics.

  17. Slope of the dose-response curve: usefulness in assessing bronchial responses to inhaled histamine.

    OpenAIRE

    Cockcroft, D. W.; Berscheid, B A

    1983-01-01

    The value of determining the slope of the histamine dose-response curve, in addition to the histamine provocation concentration producing a 20% reduction in FEV1 (PC20-FEV1), was assessed by analysis of histamine dose-response curves in 40 patients selected as having a wide range of increased non-specific bronchial responsiveness to inhaled histamine. The histamine dose-response curves were found to be fit the linear curve (dose v response, mean r2 = 0.97) better than the logarithmic curve (l...

  18. Models of the delayed nonlinear Raman response in diatomic gases

    Science.gov (United States)

    Palastro, J. P.; Antonsen, T. M., Jr.; Pearson, A.

    2011-07-01

    We examine the delayed response of a diatomic gas to a polarizing laser field with the goal of obtaining computationally efficient methods for use with laser pulse propagation simulations. We demonstrate that for broadband pulses, heavy molecules such as O2 and N2, and typical atmospheric temperatures, the initial delayed response requires only classical physics. The linear kinetic Green's function is derived from the Boltzmann equation and shown to be in excellent agreement with full density-matrix calculations. A straightforward perturbation approach for the fully nonlinear, kinetic impulse response is also presented. With the kinetic theory a reduced fluid model of the diatomic gas’ orientation is derived. Transport coefficients are introduced to model the kinetic phase mixing of the delayed response. In addition to computational rapidity, the fluid model provides intuition through the use of familiar macroscopic quantities. Both the kinetic and the fluid descriptions predict a nonlinear steady-state alignment after passage of the laser pulse, which in the fluid model is interpreted as an anisotropic temperature of the diatomic fluid with respect to motion about the polarization axis.

  19. Response of cellulose nitrate track detectors to electron doses

    CERN Document Server

    Segovia, N; Moreno, A; Vazquez-Polo, G; Santamaría, T; Aranda, P; Hernández, A

    1999-01-01

    In order to study alternative dose determination methods, the bulk etching velocity and the latent track annealing of LR 115 track detectors was studied during electron irradiation runs from a Pelletron accelerator. For this purpose alpha irradiated and blank detectors were exposed to increasing electron doses from 10.5 to 317.5 kGy. After the irradiation with electrons the detectors were etched under routine conditions, except for the etching time, that was varied for each electron dose in order to reach a fixed residual thickness. The variation of the bulk etching velocity as a function of each one of the electron doses supplied, was interpolated in order to obtain dosimetric response curves. The observed annealing effect on the latent tracks is discussed as a function of the total electron doses supplied and the temperature.

  20. Dose Response of Alanine Detectors Irradiated with Carbon Ion Beams

    DEFF Research Database (Denmark)

    Herrmann, Rochus; Jäkel, Oliver; Palmans, Hugo

    2011-01-01

    Purpose: The dose response of the alanine detector shows a dependence on particle energy and type, when irradiated with ion beams. The purpose of this study is to investigate the response behaviour of the alanine detector in clinical carbon ion beams and compare the results with model predictions....... Methods: Alanine detectors have been irradiated with carbon ions with an energy range of 89-400 MeV/u. The relative effectiveness of alanine has been measured in this regime. Pristine and spread out Bragg peak depth-dose curves have been measured with alanine dosimeters. The track-structure based alanine......-dose curves deviate from predictions in the peak region, most pronounced at the distal edge of the peak. Conclusions: The used model and its implementation show a good overall agreement for quasi mono energetic measurements. Deviations in depth-dose measurements are mainly attributed to uncertainties...

  1. Transient response of an active nonlinear sandwich piezolaminated plate

    Science.gov (United States)

    Oveisi, Atta; Nestorović, Tamara

    2017-04-01

    In this paper, the dynamic modelling and active vibration control of a piezolaminated plate with geometrical nonlinearities are investigated using a semi-analytical approach. For active vibration control purposes, the core orthotropic elastic layer is assumed to be perfectly bonded with two piezo-layers on its top and bottom surfaces which act as sensor and actuator, respectively. In the modelling procedure, the piezo-layers are assumed to be connected via a proportional derivative (PD) feedback control law. Hamilton's principle is employed to acquire the strong form of the dynamic equation in terms of additional higher order strain expressions by means of von Karman strain-displacement correlation. The obtained nonlinear partial differential equation (NPDE) is converted to a system of nonlinear ordinary differential equations (NODEs) by engaging Galerkin method and using the orthogonality of shape functions for the simply supported boundary conditions. Then, the resulting system of NODEs is solved numerically by employing the built-in Mathematica function, "NDSolve". Next, the vibration attenuation performance is evaluated and sensitivity of the closed-loop system is investigated for several control parameters and the external disturbance parameters. The proposed solution in open loop configuration is validated by finite element (FE) package ABAQUS both in the spatial domain and for the time-/frequency-dependent response.

  2. Nonlinear electromechanical response of the ferroelectret ultrasonic transducers

    Science.gov (United States)

    Döring, Joachim; Bovtun, Viktor; Bartusch, Jürgen; Erhard, Anton; Kreutzbruck, Marc; Yakymenko, Yuriy

    2010-08-01

    The ultrasonic transmission between two air-coupled polypropylene (PP) ferroelectret (FE) transducers in dependence on the amplitude of the high-voltage exciting pulse revealed a strongly nonlinear electromechanical response of the FE transmitter. This phenomenon is described by a linear increase of the inverse electromechanical transducer constant t_{33}^{(1)} of the PP FE film with an increase of the exciting electrical pulse amplitude. Enlargement of t_{33}^{(1)} by a factor of 4 was achieved by application of 3500 V exciting pulses. The electrostriction contribution to t_{33}^{(1)} can be attributed to the electrostatic force between electrodes and the Maxwell stress effect. The nonlinear electromechanical properties of the PP FE result in a strong increase of its air-coupled ultrasonic (ACUS) figure of merit ( FOM) under the high-voltage excitation, which exceeds results of the PP FE technological optimization. The FOM increase can be related to the increase of PP FE coupling factor and/or to the decrease of its acoustic impedance. A significant enhancement of the ACUS system transmission (12 dB) and signal-to-noise ratio (32 dB) was demonstrated by the increase of excitation voltage up to 3500 V. The nonlinear electromechanical properties of the PP FEs seem to be very important for their future applications.

  3. Bayesian dose-response analysis for epidemiological studies with complex uncertainty in dose estimation.

    Science.gov (United States)

    Kwon, Deukwoo; Hoffman, F Owen; Moroz, Brian E; Simon, Steven L

    2016-02-10

    Most conventional risk analysis methods rely on a single best estimate of exposure per person, which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the relationship between radiation dose and disease outcomes by accounting for shared and unshared uncertainty in estimated dose. Our Bayesian risk analysis method utilizes multiple realizations of sets (vectors) of doses generated by a two-dimensional Monte Carlo simulation method that properly separates shared and unshared errors in dose estimation. The exposure model used in this work is taken from a study of the risk of thyroid nodules among a cohort of 2376 subjects who were exposed to fallout from nuclear testing in Kazakhstan. We assessed the performance of our method through an extensive series of simulations and comparisons against conventional regression risk analysis methods. When the estimated doses contain relatively small amounts of uncertainty, the Bayesian method using multiple a priori plausible draws of dose vectors gave similar results to the conventional regression-based methods of dose-response analysis. However, when large and complex mixtures of shared and unshared uncertainties are present, the Bayesian method using multiple dose vectors had significantly lower relative bias than conventional regression-based risk analysis methods and better coverage, that is, a markedly increased capability to include the true risk coefficient within the 95% credible interval of the Bayesian-based risk estimate. An evaluation of the dose-response using our method is presented for an epidemiological study of thyroid disease following radiation exposure.

  4. Optimal designs for dose response curves with common parameters

    OpenAIRE

    Feller, Chrystel; Schorning, Kirsten; Dette, Holger; Bermann, Georgina; Bornkamp, Björn

    2016-01-01

    A common problem in Phase II clinical trials is the comparison of dose response curves corresponding to different treatment groups. If the effect of the dose level is described by parametric regression models and the treatments differ in the administration frequency (but not in the sort of drug) a reasonable assumption is that the regression models for the different treatments share common parameters. This paper develops optimal design theory for the comparison of different regression models ...

  5. Linear and nonlinear optical response of spherical anisotropic semiconductor microcrystallites

    Science.gov (United States)

    Ramaniah, Lavanya M.; Nair, Selvakumar V.; Rustagi, Kailash C.

    1989-12-01

    We present a phenomenological theory of the linear and nonlinear optical properties associated with the Fröhlich resonances of an optically anisotropic, spherical semiconductor crystallite. Using the Maxwell-Garnett approach, we calculate the effective dielectric function of a composite medium containing such crystallites. To study the effect of anisotropy, we take CdS and CdSe quantum dots as examples for the inclusions, and use a two-resonance model for the dielectric function. Even for randomly oriented inclusions, the Fröhlich resonances split as a result of anisotropic local-field corrections. At higher laser intensities, absorption saturation leads to bistability or tristability in the optical response of individual crystallites, while the response of the composite medium with randomly oriented inclusions shows multistability, with many intermediate branches. The nonlinear response of such a composite medium also exhibits a new kind of orientation-induced broadening of resonances. We also find that tristability is possible in another kind of inhomogeneous material, viz., a composite medium containing two types of isotropic spherical crystallites.

  6. Response of MDOF strongly nonlinear systems to fractional Gaussian noises

    Science.gov (United States)

    Deng, Mao-Lin; Zhu, Wei-Qiu

    2016-08-01

    In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.

  7. Response of MDOF strongly nonlinear systems to fractional Gaussian noises

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Mao-Lin; Zhu, Wei-Qiu, E-mail: wqzhu@zju.edu.cn [Department of Mechanics, State Key Laboratory of Fluid Power and Mechatronic Systems, Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province, Zhejiang University, Hangzhou 310027 (China)

    2016-08-15

    In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.

  8. Response of MDOF strongly nonlinear systems to fractional Gaussian noises.

    Science.gov (United States)

    Deng, Mao-Lin; Zhu, Wei-Qiu

    2016-08-01

    In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.

  9. Simulations of coherent nonlinear optical response of molecular vibronic dimers

    CERN Document Server

    Perlík, Václav

    2016-01-01

    We have implemented vibronic dynamics for simulations of the third order coherent response of electronic dimers. In the present communication we provide the full and detailed description of the dynamical model, recently used for simulations of chlorophyll-carotenoid dyads, terylene dimers, or hypericin. We allow for explicit vibronic level structure, by including selected vibrational modes into a "system". Bath dynamics include the Landau-Teller vibrational relaxation, electronic dephasing, and nonlinear vibronic (to bath) coupling. Simulations combine effects of transport and dephasing between vibronic levels. Transport is described by master equation within secular approximation, phase is accumulated in cumulants and its calculation follows the transport pathways during waiting time period.

  10. A Theoretical Model for the Hormetic Dose-response Curve for Anticancer Agents.

    Science.gov (United States)

    Yoshimasu, Tatsuya; Ohashi, Takuya; Oura, Shoji; Kokawa, Yozo; Kawago, Mitsumasa; Hirai, Yoshimitsu; Miyasaka, Miwako; Nishiguchi, Haruka; Kawashima, Sayoko; Yata, Yumi; Honda, Mariko; Fujimoto, Takahiro; Okamura, Yoshitaka

    2015-11-01

    In the present article, we quantitatively evaluated the dose-response relationship of hormetic reactions of anticancer agents in vitro. Serial dilutions of gemcitabine, cisplatin, 5-fluorouracil, vinorelbine, and paclitaxel were administered to the A549 non-small-cell lung cancer cell line. The bi-phasic sigmoidal curve with hormetic and cytotoxic effects is given by the formula y=(a-b/(1+exp(c(*)log(x)-d)))/(1+exp(e(*)log(x)-f)), that was used to perform a non-linear least square regression. The dose-responses of the five anticancer agents were fitted to this equation. Gemcitabine and 5-fluorouracil, which had the lowest ED50 for their hormetic reaction, had the most pronounced promotive effects out of the five anticancer agents tested. The hormetic reaction progressed exponentially with culturing time. Our theoretical model will be useful in predicting how hormetic reactions affect patients with malignant tumors.

  11. Pseudomonas aeruginosa dose response and bathing water infection.

    Science.gov (United States)

    Roser, D J; van den Akker, B; Boase, S; Haas, C N; Ashbolt, N J; Rice, S A

    2014-03-01

    Pseudomonas aeruginosa is the opportunistic pathogen mostly implicated in folliculitis and acute otitis externa in pools and hot tubs. Nevertheless, infection risks remain poorly quantified. This paper reviews disease aetiologies and bacterial skin colonization science to advance dose-response theory development. Three model forms are identified for predicting disease likelihood from pathogen density. Two are based on Furumoto & Mickey's exponential 'single-hit' model and predict infection likelihood and severity (lesions/m2), respectively. 'Third-generation', mechanistic, dose-response algorithm development is additionally scoped. The proposed formulation integrates dispersion, epidermal interaction, and follicle invasion. The review also details uncertainties needing consideration which pertain to water quality, outbreaks, exposure time, infection sites, biofilms, cerumen, environmental factors (e.g. skin saturation, hydrodynamics), and whether P. aeruginosa is endogenous or exogenous. The review's findings are used to propose a conceptual infection model and identify research priorities including pool dose-response modelling, epidermis ecology and infection likelihood-based hygiene management.

  12. Methodology for Estimating Ingestion Dose for Emergency Response at SRS

    CERN Document Server

    Simpkins, A A

    2002-01-01

    At the Savannah River Site (SRS), emergency response models estimate dose for inhalation and ground shine pathways. A methodology has been developed to incorporate ingestion doses into the emergency response models. The methodology follows a two-phase approach. The first phase estimates site-specific derived response levels (DRLs) which can be compared with predicted ground-level concentrations to determine if intervention is needed to protect the public. This phase uses accepted methods with little deviation from recommended guidance. The second phase uses site-specific data to estimate a 'best estimate' dose to offsite individuals from ingestion of foodstuffs. While this method deviates from recommended guidance, it is technically defensibly and more realistic. As guidance is updated, these methods also will need to be updated.

  13. Stochastic response of nonlinear system in probability domain

    Indian Academy of Sciences (India)

    Deepak Kumar; T K Datta

    2006-08-01

    A stochastic averaging procedure for obtaining the probability density function (PDF) of the response for a strongly nonlinear single-degree-of-freedom system, subjected to both multiplicative and additive random excitations is presented. The procedure uses random Van Der Pol transformation, Ito’s equation of limiting diffusion process and stochastic averaging technique as outlined by Zhu and others. However, the equations are rederived in generalized form and arranged in such a way that the procedure lends itself to a numerical computational scheme using FFT. The main objective of the modification is to consider highly irregular nonlinear functions which cannot be integrated in closed form and also to solve problems where analytical expressions for probability density function cannot be obtained. The procedure is applied to obtain the PDF of the response of Duffing oscillator subjected to additive and multiplicative random excitations represented by rational power spectral density functions (PSDFs). The results are verified by digital simulation. It is shown that the procedure provides results which compare very well with those obtained from simulation analysis not only for wide-band excitations but also for very narrow-band excitations, which are weak (when normalized with respect to mass of the system).

  14. Dose-response aligned circuits in signaling systems.

    Science.gov (United States)

    Yan, Long; Ouyang, Qi; Wang, Hongli

    2012-01-01

    Cells use biological signal transduction pathways to respond to environmental stimuli and the behavior of many cell types depends on precise sensing and transmission of external information. A notable property of signal transduction that was characterized in the Saccharomyces cerevisiae yeast cell and many mammalian cells is the alignment of dose-response curves. It was found that the dose response of the receptor matches closely the dose responses of the downstream. This dose-response alignment (DoRA) renders equal sensitivities and concordant responses in different parts of signaling system and guarantees a faithful information transmission. The experimental observations raise interesting questions about the nature of the information transmission through DoRA signaling networks and design principles of signaling systems with this function. Here, we performed an exhaustive computational analysis on network architectures that underlie the DoRA function in simple regulatory networks composed of two and three enzymes. The minimal circuits capable of DoRA were examined with Michaelis-Menten kinetics. Several motifs that are essential for the dynamical function of DoRA were identified. Systematic analysis of the topology space of robust DoRA circuits revealed that, rather than fine-tuning the network's parameters, the function is primarily realized by enzymatic regulations on the controlled node that are constrained in limiting regions of saturation or linearity.

  15. Harderian Gland Tumorigenesis: Low-Dose and LET Response

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Polly Y. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cucinotta, Francis A. [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Bjornstad, Kathleen A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Bakke, James [SRI International, Menlo Park, CA (United States). Biosciences Div.; Rosen, Chris J. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Du, Nicholas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Fairchild, David G. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cacao, Eliedonna [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Blakely, Eleanor A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

    2016-04-19

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  16. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    Science.gov (United States)

    Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

    2016-05-01

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ∼70 keV/μm) and 1,000 MeV/u titanium (LET ∼100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  17. The analysis of dose-response curve from bioassays with quantal response: Deterministic or statistical approaches?

    Science.gov (United States)

    Mougabure-Cueto, G; Sfara, V

    2016-04-25

    Dose-response relations can be obtained from systems at any structural level of biological matter, from the molecular to the organismic level. There are two types of approaches for analyzing dose-response curves: a deterministic approach, based on the law of mass action, and a statistical approach, based on the assumed probabilities distribution of phenotypic characters. Models based on the law of mass action have been proposed to analyze dose-response relations across the entire range of biological systems. The purpose of this paper is to discuss the principles that determine the dose-response relations. Dose-response curves of simple systems are the result of chemical interactions between reacting molecules, and therefore are supported by the law of mass action. In consequence, the shape of these curves is perfectly sustained by physicochemical features. However, dose-response curves of bioassays with quantal response are not explained by the simple collision of molecules but by phenotypic variations among individuals and can be interpreted as individual tolerances. The expression of tolerance is the result of many genetic and environmental factors and thus can be considered a random variable. In consequence, the shape of its associated dose-response curve has no physicochemical bearings; instead, they are originated from random biological variations. Due to the randomness of tolerance there is no reason to use deterministic equations for its analysis; on the contrary, statistical models are the appropriate tools for analyzing these dose-response relations.

  18. Dose finding when the target dose is on a plateau of a dose-response curve: comparison of fully sequential designs.

    Science.gov (United States)

    Ivanova, Anastasia; Xiao, Changfu

    2013-01-01

    Consider the problem of estimating a dose with a certain response rate. Many multistage dose-finding designs for this problem were originally developed for oncology studies where the mean dose-response is strictly increasing in dose. In non-oncology phase II dose-finding studies, the dose-response curve often plateaus in the range of interest, and there are several doses with the mean response equal to the target. In this case, it is usually of interest to find the lowest of these doses because higher doses might have higher adverse event rates. It is often desirable to compare the response rate at the estimated target dose with a placebo and/or active control. We investigate which of the several known dose-finding methods developed for oncology phase I trials is the most suitable when the dose-response curve plateaus. Some of the designs tend to spread the allocation among the doses on the plateau. Others, such as the continual reassessment method and the t-statistic design, concentrate allocation at one of the doses with the t-statistic design selecting the lowest dose on the plateau more frequently.

  19. Application of adaptive non-linear 2D and 3D postprocessing filters for reduced dose abdominal CT.

    Science.gov (United States)

    Borgen, Lars; Kalra, Mannudeep K; Laerum, Frode; Hachette, Isabelle W; Fredriksson, Carina H; Sandborg, Michael; Smedby, Orjan

    2012-04-01

    Abdominal computed tomography (CT) is a frequently performed imaging procedure, resulting in considerable radiation doses to the patient population. Postprocessing filters are one of several dose reduction measures that might help to reduce radiation doses without loss of image quality. To assess and compare the effect of two- and three-dimensional (2D, 3D) non-linear adaptive filters on reduced dose abdominal CT images. Two baseline abdominal CT image series with a volume computer tomography dose index (CTDI (vol)) of 12 mGy and 6 mGy were acquired for 12 patients. Reduced dose images were postprocessed with 2D and 3D filters. Six radiologists performed blinded randomized, side-by-side image quality assessments. Objective noise was measured. Data were analyzed using visual grading regression and mixed linear models. All image quality criteria were rated as superior for 3D filtered images compared to reduced dose baseline and 2D filtered images (P 0.05). There were no significant variations of objective noise between standard dose and 2D or 3D filtered images. The quality of 3D filtered reduced dose abdominal CT images is superior compared to reduced dose unfiltered and 2D filtered images. For patients with BMI < 30 kg/m(2), 3D filtered images are comparable to standard dose images.

  20. Predicting nonlinear properties of metamaterials from the linear response.

    Science.gov (United States)

    O'Brien, Kevin; Suchowski, Haim; Rho, Junsuk; Salandrino, Alessandro; Kante, Boubacar; Yin, Xiaobo; Zhang, Xiang

    2015-04-01

    The discovery of optical second harmonic generation in 1961 started modern nonlinear optics. Soon after, R. C. Miller found empirically that the nonlinear susceptibility could be predicted from the linear susceptibilities. This important relation, known as Miller's Rule, allows a rapid determination of nonlinear susceptibilities from linear properties. In recent years, metamaterials, artificial materials that exhibit intriguing linear optical properties not found in natural materials, have shown novel nonlinear properties such as phase-mismatch-free nonlinear generation, new quasi-phase matching capabilities and large nonlinear susceptibilities. However, the understanding of nonlinear metamaterials is still in its infancy, with no general conclusion on the relationship between linear and nonlinear properties. The key question is then whether one can determine the nonlinear behaviour of these artificial materials from their exotic linear behaviour. Here, we show that the nonlinear oscillator model does not apply in general to nonlinear metamaterials. We show, instead, that it is possible to predict the relative nonlinear susceptibility of large classes of metamaterials using a more comprehensive nonlinear scattering theory, which allows efficient design of metamaterials with strong nonlinearity for important applications such as coherent Raman sensing, entangled photon generation and frequency conversion.

  1. Characterization of a developmental toxicity dose-response model.

    OpenAIRE

    Faustman, E M; Wellington, D G; Smith, W P; Kimmel, C A

    1989-01-01

    The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included ...

  2. Patch test dose-response study of p-phenylenediamine

    DEFF Research Database (Denmark)

    Sosted, Heidi; Menné, Torkil; Johansen, Jeanne Duus

    2006-01-01

    The elicitation response in allergic contact dermatitis for the hair dye substance p-phenylenediamine (PPD) is dose dependent, but threshold concentrations have not previously been investigated. 15 PPD-sensitive patients participated in a serial dilution 48-hr patch test with PPD using 8 concentr...

  3. Linearity of dose-response relationships for human carcinogenic exposures

    Energy Technology Data Exchange (ETDEWEB)

    Smith, A.H. (Univ. of California, Berkeley (USA))

    The shape of dose-response relationships is a critical factor in considering cancer risks for the work place and environmental exposure to carcinogens. Markedly different risk estimates result from assumptions of linearity versus sublinear and threshold assumptions. This paper presents evidence that the relationship between the relative risk of development of cancer and the dose rate to carcinogenic exposures is frequently linear with no evidence for thresholds. Dose-response relationships from four studies of asbestos and lung cancer were examined, all of which were consistent with a linear relationship. Analysis of the relationship between the relative risk of lung cancer and exposure to nickel in a smelter study, selected because of relatively good exposure data, demonstrated a close agreement with a linear relationship. The relationship between the level of arsenic in drinking wter and the prevalence of skin cancer also was linear for males in the highest prevalence age group in Taiwan, although there was some evidence of sublinearity for females and younger persons. Also, the relationships between the number of cigarettes smoked per day and the relative risk of lung cancer was very close to linear in many studies. The analysis of these and other studies involving human exposure to carcinogens provides empirical evidence for linearity when the response variable is a rate ratio measure, rather than a risk difference measure. Linearity in dose-response is biologically plausible, without invoking a one-hit model. Except in special circumstances. the epidemiological evidence supports linear extrapolation of cancer relative risks.

  4. Design methods for some dose-response models

    NARCIS (Netherlands)

    Albers, Willem/Wim; Strijbosch, Leo W.G.; Does, Ronald J.M.M.

    1990-01-01

    A recently described design method for one-parameter biomedical models such as limiting or serial dilution assays is generalized to two-parameter models for which the dose-response relationship can be expressed as a linear regression model with parameters α (intercept) and β (slope). Design formulae

  5. Nonlinear dynamic response of an electrically actuated imperfect microbeam resonator

    KAUST Repository

    Ruzziconi, Laura

    2013-08-04

    We present a study of the dynamic behavior of a MEMS device constituted of an imperfect clamped-clamped microbeam subjected to electrostatic and electrodynamic actuation. Our objective is to develop a theoretical analysis, which is able to describe and predict all the main relevant aspects of the experimental response. Extensive experimental investigation is conducted, where the main imperfections coming from microfabrication are detected and the nonlinear dynamics are explored at increasing values of electrodynamic excitation, in a neighborhood of the first symmetric resonance. The nonlinear behavior is highlighted, which includes ranges of multistability, where the non-resonant and the resonant branch coexist, and intervals where superharmonic resonances are clearly visible. Numerical simulations are performed. Initially, two single mode reduced-order models are considered. One is generated via the Galerkin technique, and the other one via the combined use of the Ritz method and the Padé approximation. Both of them are able to provide a satisfactory agreement with the experimental data. This occurs not only at low values of electrodynamic excitation, but also at higher ones. Their computational efficiency is discussed in detail, since this is an essential aspect for systematic local and global simulations. Finally, the theoretical analysis is further improved and a two-degree-of-freedom reduced-order model is developed, which is capable also to capture the measured second symmetric superharmonic resonance. Despite the apparent simplicity, it is shown that all the proposed reduced-order models are able to describe the experimental complex nonlinear dynamics of the device accurately and properly, which validates the proposed theoretical approach. Copyright © 2013 by ASME.

  6. Steepness of the radiation dose-response curve for dose-per-fraction escalation keeping the number of fractions fixed.

    Science.gov (United States)

    Bentzen, Søren M

    2005-01-01

    Clinically, there is growing interest in strategies for intensifying radiation therapy by escalating the dose per fraction. This paper considers the steepness of the dose-response curve in this case. The steepness of a radiation dose-response curve is most conveniently quantified by the normalized dose-response gradient, gamma. Under the assumption of a linear-quadratic dose-effect model, a simple analytical relationship is derived between the gamma-value for a dose-response curve generated by varying the total dose while keeping the number of fractions constant, i.e. escalating the dose per fraction, and the gamma-value for a dose-response curve generated by varying the total dose while keeping the dose per fraction constant. This formulation is compared with clinical dose-response data from the literature and shown to be in good agreement with the observations. Some implications of this formulation for non-uniform dose distributions delivered using 3D conformal radiotherapy or intensity modulated radiotherapy (IMRT) are briefly discussed.

  7. Nonlinear optical response of some Graphene oxide and Graphene fluoride derivatives

    Science.gov (United States)

    Liaros, Nikolaos; Orfanos, Ioannis; Papadakis, Ioannis; Couris, Stelios

    2016-12-01

    The nonlinear optical properties of two graphene derivatives, graphene oxide and graphene fluoride, are investigated by means of the Z-scan technique employing 35 ps and 4 ns, visible (532 nm) laser excitation. Both derivatives were found to exhibit significant third-order nonlinear optical response at both excitation regimes, with the nonlinear absorption being relatively stronger and concealing the presence of nonlinear refraction under ns excitation, while ps excitation reveals the presence of both nonlinear absorption and refraction. Both nonlinear properties are of great interest for several photonics, opto-fluidics, opto-electronics and nanotechnology applications.

  8. Understanding nonlinear responses of the climate system to orbital forcing

    Science.gov (United States)

    Rial, J. A.; Anaclerio, C. A.

    2000-12-01

    We have recently introduced the working hypothesis that frequency modulation (FM) of the orbital eccentricity forcing may be one important source of the nonlinearities observed in δ 18O time series from deep-sea sediment cores (J.H. Rial (1999a) Pacemaking the lce Ages by frequency modulation of Earth's orbital eccentricity. Science 285, 564-568). In this paper we shall discuss further evidence of frequency modulation found in data from the Vostok ice core. Analyses of the 430,000-year long, orbitally untuned, time series of CO 2, deuterium, aerosol and methane, suggest frequency modulation of the 41 kyr (0.0244 kyr -1) obliquity forcing by the 413 kyr-eccentricity signal and its harmonics. Conventional and higher-order spectral analyses show that two distinct spectral peaks at ˜29 kyr (0.034 kyr -1) and ˜69 kyr (0.014 kyr -1) and other, smaller peaks surrounding the 41 kyr obliquity peak are harmonically (nonlinearly) related and likely to be FM-generated sidebands of the obliquity signal. All peaks can be closely matched by the spectrum of an appropriately built theoretical FM signal. A preliminary model, based on the classic logistic growth delay differential equation, reproduces the longer period FM effect and the familiar multiply peaked spectra of the eccentricity band. Since the FM effect appears to be a common feature in climate response, finding out its cause may help understand climate dynamics and global climate change.

  9. Optical and Nonlinear Optical Response of Light Sensor Thin Films

    Directory of Open Access Journals (Sweden)

    S. Z. Weisz

    2005-04-01

    Full Text Available For potential ultrafast optical sensor application, both VO2 thin films andnanocomposite crystal-Si enriched SiO2 thin films grown on fused quartz substrates weresuccessfully prepared using pulsed laser deposition (PLD and RF co-sputteringtechniques. In photoluminescence (PL measurement c-Si/SiO2 film containsnanoparticles of crystal Si exhibits strong red emission with the band maximum rangingfrom 580 to 750 nm. With ultrashort pulsed laser excitation all films show extremelyintense and ultrafast nonlinear optical (NLO response. The recorded holography fromall these thin films in a degenerate-four-wave-mixing configuration shows extremelylarge third-order response. For VO2 thin films, an optically induced semiconductor-tometalphase transition (PT immediately occurred upon laser excitation. it accompanied.It turns out that the fast excited state dynamics was responsible to the induced PT. For c-Si/SiO2 film, its NLO response comes from the contribution of charge carriers created bylaser excitation in conduction band of the c-Si nanoparticles. It was verified byintroducing Eu3+ which is often used as a probe sensing the environment variations. Itturns out that the entire excited state dynamical process associated with the creation,movement and trapping of the charge carriers has a characteristic 500 ps duration.

  10. Dose-response relationship for breast cancer induction at radiotherapy dose

    Directory of Open Access Journals (Sweden)

    Gruber Günther

    2011-06-01

    Full Text Available Abstract Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i the analysis of breast cancer induction after Hodgkin's disease, (ii a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy, (iv the breast cancer induction of the A-bomb survivor data. Results The fitted model parameters for an α/β = 3 Gy were α = 0.067Gy-1 and R = 0.62. The risk for breast cancer is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 20 Gy and drops off only slightly at larger doses. The predicted EAR for breast cancer after radiotherapy of Hodgkin's disease is 11.7/10000PY which can be compared to the findings of several epidemiological studies where EAR for breast cancer varies between 10.5 and 29.4/10000PY. The model was used to predict the impact of the reduction of radiation volume on breast cancer risk. It was estimated that mantle field irradiation is associated with a 3.2-fold increased risk compared with mediastinal irradiation alone, which is in agreement with a published value of 2.7. It was also shown that the modelled age dependency of breast cancer risk is in satisfying agreement with published data. Conclusions The dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients.

  11. Bayesian multimodel inference for dose-response studies

    Science.gov (United States)

    Link, W.A.; Albers, P.H.

    2007-01-01

    Statistical inference in dose?response studies is model-based: The analyst posits a mathematical model of the relation between exposure and response, estimates parameters of the model, and reports conclusions conditional on the model. Such analyses rarely include any accounting for the uncertainties associated with model selection. The Bayesian inferential system provides a convenient framework for model selection and multimodel inference. In this paper we briefly describe the Bayesian paradigm and Bayesian multimodel inference. We then present a family of models for multinomial dose?response data and apply Bayesian multimodel inferential methods to the analysis of data on the reproductive success of American kestrels (Falco sparveriuss) exposed to various sublethal dietary concentrations of methylmercury.

  12. Nonlinear Stochastic Analysis of Subharmonic Response of a Shallow Cable

    DEFF Research Database (Denmark)

    Zhou, Q.; Stærdahl, Jesper Winther; Nielsen, Søren R.K.

    2007-01-01

    The paper deals with the subharmonic response of a shallow cable due to time variations of the chord length of the equilibrium suspension, caused by time varying support point motions. Initially, the capability of a simple nonlinear two-degree-of-freedom model for the prediction of chaotic...... time-consuming for the finite difference model, most of the results are next based on the reduced model. Under harmonical varying support point motions the stable subharmonic motion consists of a harmonically varying component in the equilibrium plane and a large subharmonic out-of-plane component......, producing a trajectory at the mid-point of shape as an infinity sign. However, when the harmonical variation of the chordwise elongation is replaced by a narrow-banded Gaussian excitation with the same standard deviation and a centre frequency equal to the circular frequency of the harmonic excitation...

  13. Crystal growth in fluid flow: Nonlinear response effects

    Science.gov (United States)

    Peng, H. L.; Herlach, D. M.; Voigtmann, Th.

    2017-08-01

    We investigate crystal-growth kinetics in the presence of strong shear flow in the liquid, using molecular-dynamics simulations of a binary-alloy model. Close to the equilibrium melting point, shear flow always suppresses the growth of the crystal-liquid interface. For lower temperatures, we find that the growth velocity of the crystal depends nonmonotonically on the shear rate. Slow enough flow enhances the crystal growth, due to an increased particle mobility in the liquid. Stronger flow causes a growth regime that is nearly temperature-independent, in striking contrast to what one expects from the thermodynamic and equilibrium kinetic properties of the system, which both depend strongly on temperature. We rationalize these effects of flow on crystal growth as resulting from the nonlinear response of the fluid to strong shearing forces.

  14. Application of adaptive non-linear 2D and 3D postprocessing filters for reduced dose abdominal CT

    Energy Technology Data Exchange (ETDEWEB)

    Borgen, Lars (Dept. of Radiology, Drammen Hospital, Drammen and Buskerud Univ. College, Drammen (Norway)), Email: lars.borgen@vestreviken.no; Kalra, Mannudeep K. (Massachusetts General Hospital Imaging, Harvard Medical School, Massachusetts General Hospital, Boston (United States)); Laerum, Frode (Dept. of Radiology, Akershus Univ. Hospital, Loerenskog (Norway)); Hachette, Isabelle W.; Fredriksson, Carina H. (ContextVision AB, Linkoeping (Sweden)); Sandborg, Michael (Dept. of Medical Physics, IMH, Faculty of Health Sciences, Linkoeping Univ., County Council of Oestergoetland, Linkoeping (Sweden); Center for Medical Image Science and Visualization, Linkoeping (Sweden)); Smedby, Oerjan (Center for Medical Image Science and Visualization, Linkoeping (Sweden); Dept. of Radiology, Linkoeping Univ., Linkoeping (Sweden))

    2012-04-15

    Background: Abdominal computed tomography (CT) is a frequently performed imaging procedure, resulting in considerable radiation doses to the patient population. Postprocessing filters are one of several dose reduction measures that might help to reduce radiation doses without loss of image quality. Purpose: To assess and compare the effect of two- and three-dimensional (2D, 3D) non-linear adaptive filters on reduced dose abdominal CT images. Material and Methods: Two baseline abdominal CT image series with a volume computer tomography dose index (CTDI{sub vol}) of 12 mGy and 6 mGy were acquired for 12 patients. Reduced dose images were postprocessed with 2D and 3D filters. Six radiologists performed blinded randomized, side-by-side image quality assessments. Objective noise was measured. Data were analyzed using visual grading regression and mixed linear models. Results: All image quality criteria were rated as superior for 3D filtered images compared to reduced dose baseline and 2D filtered images (P < 0.01). Standard dose images had better image quality than reduced dose 3D filtered images (P < 0.01), but similar image noise. For patients with body mass index (BMI) < 30 kg/m2 however, 3D filtered images were rated significantly better than normal dose images for two image criteria (P < 0.05), while no significant difference was found for the remaining three image criteria (P > 0.05). There were no significant variations of objective noise between standard dose and 2D or 3D filtered images. Conclusion: The quality of 3D filtered reduced dose abdominal CT images is superior compared to reduced dose unfiltered and 2D filtered images. For patients with BMI < 30 kg/m2, 3D filtered images are comparable to standard dose images

  15. Large nonlocal nonlinear optical response of castor oil

    Science.gov (United States)

    Souza, Rogério F.; Alencar, Márcio A. R. C.; Meneghetti, Mario R.; Hickmann, Jandir M.

    2009-09-01

    The nonlocal nonlinearity of castor oil was investigated using the Z-scan technique in the CW regime at 514 nm and in femtosecond regime at 810 nm. Large negative nonlinear refractive indexes of thermal origin, thermo-optical coefficients and degree of nonlocality were obtained for both laser excitation wavelengths. The results indicate that the electronic part of the nonlinear refractive index and nonlinear absorption were negligible. Our results suggest that castor oil is promising candidate as a nonlinear medium for several nonlocal optical applications, such as in spatial soliton propagation, as well as a dispersant agent in the measurement of absorptive properties of nanoparticles.

  16. Biphasic dose response in low level light therapy - an update.

    Science.gov (United States)

    Huang, Ying-Ying; Sharma, Sulbha K; Carroll, James; Hamblin, Michael R

    2011-01-01

    Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments.

  17. Alanine aminotransferase and risk of the metabolic syndrome: a linear dose-response relationship.

    Directory of Open Access Journals (Sweden)

    Setor K Kunutsor

    Full Text Available BACKGROUND: Elevated baseline circulating alanine aminotransferase (ALT level has been demonstrated to be associated with an increased risk of the metabolic syndrome (MetS, but the nature of the dose-response relationship is uncertain. METHODS: We performed a systematic review and meta-analysis of published prospective cohort studies to characterize in detail the nature of the dose-response relationship between baseline ALT level and risk of incident MetS in the general population. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science up to December 2013. Prospective studies in which investigators reported relative risks (RRs of MetS for 3 or more categories of ALT levels were eligible. A potential nonlinear relationship between ALT levels and MetS was examined using restricted cubic splines. RESULTS: Of the 489 studies reviewed, relevant data were available on 29,815 non-overlapping participants comprising 2,125 incident MetS events from five prospective cohort studies. There was evidence of a linear association (P for nonlinearity=0.38 between ALT level and risk of MetS, characterised by a graded increase in MetS risk at ALT levels 6-40 U/L. The risk of MetS increased by 14% for every 5 U/L increment in circulating ALT level (95% CI: 12-17%. Evidence was lacking of heterogeneity and publication bias among the contributing studies. CONCLUSIONS: Baseline ALT level is associated with risk of the MetS in a linear dose-response manner. Studies are needed to determine whether the association represents a causal relationship.

  18. Dose-response curve of a microfluidic magnetic bead-based surface coverage sandwich assay.

    Science.gov (United States)

    Cornaglia, Matteo; Trouillon, Raphaël; Tekin, H Cumhur; Lehnert, Thomas; Gijs, Martin A M

    2015-09-25

    Magnetic micro- and nanoparticles ('magnetic beads') have been used to advantage in many microfluidic devices for sensitive antigen (Ag) detection. Today, assays that use as read-out of the signal the number count of immobilized beads on a surface for quantification of a sample's analyte concentration have been among the most sensitive and have allowed protein detection lower than the fgmL(-1) concentration range. Recently, we have proposed in this category a magnetic bead surface coverage assay (Tekin et al., 2013 [1]), in which 'large' (2.8μm) antibody (Ab)-functionalized magnetic beads captured their Ag from a serum and these Ag-carrying beads were subsequently exposed to a surface pattern of fixed 'small' (1.0μm) Ab-coated magnetic beads. When the system was exposed to a magnetic induction field, the magnet dipole attractive interactions between the two bead types were used as a handle to approach both bead surfaces and assist with Ag-Ab immunocomplex formation, while unspecific binding (in absence of an Ag) of a large bead was reduced by exploiting viscous drag flow. The dose-response curve of this type of assay had two remarkable features: (i) its ability to detect an output signal (i.e. bead number count) for very low Ag concentrations, and (ii) an output signal of the assay that was non-linear with respect to Ag concentration. We explain here the observed dose-response curves and show that the type of interactions and the concept of our assay are in favour of detecting the lowest analyte concentrations (where typically either zero or one Ag is carried per large bead), while higher concentrations are less efficiently detected. We propose a random walk process for the Ag-carrying bead over the magnetic landscape of small beads and this model description explains the enhanced overall capture probability of this assay and its particular non-linear dose response curves.

  19. Nonlinear Allometric Equation for Crop Response to Soil Salinity

    Directory of Open Access Journals (Sweden)

    E. Misle

    2015-06-01

    Full Text Available Crop response to soil salinity has been extensively studied, from empirical works to modelling approach, being described by different equations, first as a piecewise linear model. The equation employed can differ with actual response, causing miscalculation in practical situations, particularly at the higher extremes of the curve. The aim of this work is to propose a new equation, which allows determining the full response to salinity of plant species and to provide a verification using different experimental data sets. A new nonlinear equation is exposed supported by the allometric approach, in which the allometric exponent is salinity-dependent and decreases with the increase in relative salinity. A conversion procedure of parameters of the threshold-slope model is presented; also, a simple procedure for estimating the maximum salinity (zero-yield point when data sets are incomplete is exposed. The equation was tested in a wide range of experimental situations, using data sets from published works, as well as new measurements on seed germination. The statistical indicators of quality (R2, absolute sum of squares and standard deviation of residuals showed that the equation accurately fits the tested empirical results. The new equation for determining crop response to soil salinity is able to follow the response curve of any crop with remarkable accuracy and flexibility. Remarkable characteristics are: a maximum at minimum salinity, a maximum salinity point can be found (zero-yield depending on the data sets, and a meaningful inflection point, as well as the two points at which the slope of the curve equals unity, can be found.

  20. Ozone as U-Shaped Dose Responses Molecules (Hormetins)

    OpenAIRE

    Martínez- Sánchez, G.; Pérez-Davison, G.; Re, L.; Giuliani, A.

    2010-01-01

    Redox environment involves a broad network of pro-oxidant and antioxidant components. Health benefit or damage can be induced as a consequence of an adaptive cellular stress response. A consequence of hormetic amplification is an increase in the homeodynamic space of a living system in terms of an increased defense capacity and a reduced load of damaged macromolecules. Ozone, when used at appropriate doses, promotes the formation of reactive oxygen species and lipid peroxides allows them to b...

  1. Development of a dose-response model for SARS coronavirus.

    Science.gov (United States)

    Watanabe, Toru; Bartrand, Timothy A; Weir, Mark H; Omura, Tatsuo; Haas, Charles N

    2010-07-01

    In order to develop a dose-response model for SARS coronavirus (SARS-CoV), the pooled data sets for infection of transgenic mice susceptible to SARS-CoV and infection of mice with murine hepatitis virus strain 1, which may be a clinically relevant model of SARS, were fit to beta-Poisson and exponential models with the maximum likelihood method. The exponential model (k= 4.1 x l0(2)) could describe the dose-response relationship of the pooled data sets. The beta-Poisson model did not provide a statistically significant improvement in fit. With the exponential model, the infectivity of SARS-CoV was calculated and compared with those of other coronaviruses. The does of SARS-CoV corresponding to 10% and 50% responses (illness) were estimated at 43 and 280 PFU, respectively. Its estimated infectivity was comparable to that of HCoV-229E, known as an agent of human common cold, and also similar to those of some animal coronaviruses belonging to the same genetic group. Moreover, the exponential model was applied to the analysis of the epidemiological data of SARS outbreak that occurred at an apartment complex in Hong Kong in 2003. The estimated dose of SARS-CoV for apartment residents during the outbreak, which was back-calculated from the reported number of cases, ranged from 16 to 160 PFU/person, depending on the floor. The exponential model developed here is the sole dose-response model for SARS-CoV at the present and would enable us to understand the possibility for reemergence of SARS.

  2. Quantitative Dose-Response Curves from Subcellular Lipid Multilayer Microarrays

    Science.gov (United States)

    Kusi-Appiah, A. E.; Lowry, T. W.; Darrow, E. M.; Wilson, K.; Chadwick, B. P.; Davidson, M. W.; Lenhert, S.

    2015-01-01

    The dose-dependent bioactivity of small molecules on cells is a crucial factor in drug discovery and personalized medicine. Although small-molecule microarrays are a promising platform for miniaturized screening, it has been a challenge to use them to obtain quantitative dose-response curves in vitro, especially for lipophilic compounds. Here we establish a small-molecule microarray assay capable of controlling the dosage of small lipophilic molecules delivered to cells by varying the sub-cellular volumes of surface supported lipid micro- and nanostructure arrays fabricated with nanointaglio. Features with sub-cellular lateral dimensions were found necessary to obtain normal cell adhesion with HeLa cells. The volumes of the lipophilic drug-containing nanostructures were determined using a fluorescence microscope calibrated by atomic-force microscopy. We used the surface supported lipid volume information to obtain EC-50 values for the response of HeLa cells to three FDA-approved lipophilic anticancer drugs, docetaxel, imiquimod and triethylenemelamine, which were found to be significantly different from neat lipid controls. No significant toxicity was observed on the control cells surrounding the drug/lipid patterns, indicating lack of interference or leakage from the arrays. Comparison of the microarray data to dose-response curves for the same drugs delivered liposomally from solution revealed quantitative differences in the efficacy values, which we explain in terms of cell-adhesion playing a more important role in the surface-based assay. The assay should be scalable to a density of at least 10,000 dose response curves on the area of a standard microtiter plate. PMID:26167949

  3. Modeling of the nonlinear resonant response in sedimentary rocks

    Energy Technology Data Exchange (ETDEWEB)

    Ten Cate, James A [Los Alamos National Laboratory; Shankland, Thomas J [Los Alamos National Laboratory; Vakhnenko, Vyacheslav O [NON LANL; Vakhnenko, Oleksiy [NON LANL

    2009-04-03

    We suggest a model for describing a wide class of nonlinear and hysteretic effects in sedimentary rocks at longitudinal bar resonance. In particular, we explain: hysteretic behaviour of a resonance curve on both its upward and downward slopes; linear softening of resonant frequency with increase of driving level; gradual (almost logarithmic) recovery of resonant frequency after large dynamical strains; and temporal relaxation of response amplitude at fixed frequency. Starting with a suggested model, we predict the dynamical realization of end-point memory in resonating bar experiments with a cyclic frequency protocol. These theoretical findings were confirmed experimentally at Los Alamos National Laboratory. Sedimentary rocks, particularly sandstones, are distinguished by their grain structure in which each grain is much harder than the intergrain cementation material. The peculiarities of grain and pore structures give rise to a variety of remarkable nonlinear mechanical properties demonstrated by rocks, both at quasistatic and alternating dynamic loading. Thus, the hysteresis earlier established for the stress-strain relation in samples subjected to quasistatic loading-unloading cycles has also been discovered for the relation between acceleration amplitude and driving frequency in bar-shaped samples subjected to an alternating external drive that is frequency-swept through resonance. At strong drive levels there is an unusual, almost linear decrease of resonant frequency with strain amplitude, and there are long-term relaxation phenomena such as nearly logarithmic recovery (increase) of resonant frequency after the large conditioning drive has been removed. In this report we present a short sketch of a model for explaining numerous experimental observations seen in forced longitudinal oscillations of sandstone bars. According to our theory a broad set of experimental data can be understood as various aspects of the same internally consistent pattern. Furthermore

  4. Non-Linearity of dose-effect relationship on the example of cytogenetic effects in plant cells at low level exposure to ionising radiation

    Energy Technology Data Exchange (ETDEWEB)

    Oudalova, Alla; Geras' kin, Stanislav; Dikarev, Vladimir; Dikareva, Nina; Chernonog, Elena [Russian Institute of Agricultural Radiology and Agroecology, RIARAE, 249032 Obninsk (Russian Federation); Copplestone, David [Environment Agency, Millbank Tower, 25th. Floor, 21/24 Millbank, London, SW1P 4XL (United Kingdom); Evseeva, Tatyana [Institute of Biology, Kommunisticheskaya st., 28 Syktyvkar 167610, Komi Republic (Russian Federation)

    2006-07-01

    Over several decades, modelling the effects of ionizing radiation on biological system has relied on the target principle [Timofeeff-Ressovsky et al., 1935], which assumes that cell damage or modification to genes appear as a direct consequence of the exposure of biological macromolecules to charged particles. Furthermore, it is assumed that there is no threshold for the induction of biological damage and that the effects observed are proportional to the energy absorbed. Following this principle, the average number of hits per target should increase linearly with dose, and the yield of mutations per unit of dose is assumed to be the same at both low and high doses (linearity of response). This principle has served as the scientific background for the linear no-threshold (LNT) concept that forms the basis for the radiological protection for the public and the environment [ICRP, 1990]. It follows from the LNT that there is an additional risk for human health from exposure to any radiation level, even below natural background. Since the mid 50's, however, the scientific basis for the LNT concept has been challenged as experimental data have shown that, at low doses, there was a non linear relationship in the dose response. Luchnik and Timofeeff-Ressovsky were the first who showed a non-linear response to a low dose exposure [Luchnik, 1957; Timofeeff-Ressovsky and Luchnik, 1960]. Since then, many data have been accumulated which contradict the LNT model at low doses and dose rates. However, the hit-effect paradigm has become such a strong and indissoluble fact that it has persisted even under the growing pressure of scientific evidence for phenomena at low dose exposure that can not be successfully accounted for by the LNT concept. In recent years, additional information on non-targeted effects of radiation has been accumulated following the first reports of an adaptive response in human lymphocytes [Olivieri et al., 1984] as well as bystander mutagenic effect of

  5. Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

    Energy Technology Data Exchange (ETDEWEB)

    Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Gilbert, Ethel; Curtis, Rochelle; Inskip, Peter; Kleinerman, Ruth; Morton, Lindsay; Rajaraman, Preetha; Little, Mark P. [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2013-06-01

    Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ≥60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques.

  6. Coffee and tea consumption and risk of lung cancer: a dose-response analysis of observational studies.

    Science.gov (United States)

    Wang, Yaopeng; Yu, Xuyi; Wu, Yili; Zhang, Dongfeng

    2012-11-01

    Results from the recent meta-analysis suggested a favorable effect of green tea consumption and risk of lung cancer, while no significant association was found between black tea consumption and risk of lung cancer. Besides, a significantly positive association was found between coffee consumption and risk of lung cancer. However, the relationship of green tea and coffee consumption is unclear. Thus the dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Results suggested that a linear dose-response relationship exists between coffee consumption and risk of lung cancer, while the dose-response relationship is nonlinear between green tea consumption and risk of lung cancer.

  7. Bayesian Dose-Response Modeling in Sparse Data

    Science.gov (United States)

    Kim, Steven B.

    This book discusses Bayesian dose-response modeling in small samples applied to two different settings. The first setting is early phase clinical trials, and the second setting is toxicology studies in cancer risk assessment. In early phase clinical trials, experimental units are humans who are actual patients. Prior to a clinical trial, opinions from multiple subject area experts are generally more informative than the opinion of a single expert, but we may face a dilemma when they have disagreeing prior opinions. In this regard, we consider compromising the disagreement and compare two different approaches for making a decision. In addition to combining multiple opinions, we also address balancing two levels of ethics in early phase clinical trials. The first level is individual-level ethics which reflects the perspective of trial participants. The second level is population-level ethics which reflects the perspective of future patients. We extensively compare two existing statistical methods which focus on each perspective and propose a new method which balances the two conflicting perspectives. In toxicology studies, experimental units are living animals. Here we focus on a potential non-monotonic dose-response relationship which is known as hormesis. Briefly, hormesis is a phenomenon which can be characterized by a beneficial effect at low doses and a harmful effect at high doses. In cancer risk assessments, the estimation of a parameter, which is known as a benchmark dose, can be highly sensitive to a class of assumptions, monotonicity or hormesis. In this regard, we propose a robust approach which considers both monotonicity and hormesis as a possibility. In addition, We discuss statistical hypothesis testing for hormesis and consider various experimental designs for detecting hormesis based on Bayesian decision theory. Past experiments have not been optimally designed for testing for hormesis, and some Bayesian optimal designs may not be optimal under a

  8. Low dose effects and non-monotonic dose responses for endocrine active chemicals: Science to practice workshop: Workshop summary

    DEFF Research Database (Denmark)

    Beausoleil, Claire; Ormsby, Jean-Nicolas; Gies, Andreas

    2013-01-01

    A workshop was held in Berlin September 12–14th 2012 to assess the state of the science of the data supporting low dose effects and non-monotonic dose responses (“low dose hypothesis”) for chemicals with endocrine activity (endocrine disrupting chemicals or EDCs). This workshop consisted...

  9. Simulations of the Ocean Response to a Hurricane: Nonlinear Processes

    KAUST Repository

    Zedler, Sarah E.

    2009-10-01

    Superinertial internal waves generated by a tropical cyclone can propagate vertically and laterally away from their local generation site and break, contributing to turbulent vertical mixing in the deep ocean and maintenance of the stratification of the main thermocline. In this paper, the results of a modeling study are reported to investigate the mechanism by which superinertial fluctuations are generated in the deep ocean. The general properties of the superinertial wave wake were also characterized as a function of storm speed and central latitude. The Massachusetts Institute of Technology (MIT) Ocean General Circulation Model (OGCM) was used to simulate the open ocean response to realistic westward-tracking hurricane-type surface wind stress and heat and net freshwater buoyancy forcing for regions representative of midlatitudes in the Atlantic, the Caribbean, and low latitudes in the eastern Pacific. The model had high horizontal [Δ(x, y) = 1/6°] and vertical (Δz = 5 m in top 100 m) resolution and employed a parameterization for vertical mixing induced by shear instability. In the horizontal momentum equation, the relative size of the nonlinear advection terms, which had a dominant frequency near twice the inertial, was large only in the upper 200 m of water. Below 200 m, the linear momentum equations obeyed a linear balance to 2%. Fluctuations at nearly twice the inertial frequency (2f) were prevalent throughout the depth of the water column, indicating that these nonlinear advection terms in the upper 200 m forced a linear mode below at nearly twice the inertial frequency via vorticity conservation. Maximum variance at 2f in horizontal velocity occurred on the south side of the track. This was in response to vertical advection of northward momentum, which in the north momentum equation is an oscillatory positive definite term that constituted a net force to the south at a frequency near 2f. The ratio of this term to the Coriolis force was larger on the

  10. Tailoring the nonlinear response of MEMS resonators using shape optimization

    DEFF Research Database (Denmark)

    Li, Lily L.; Polunin, Pavel M.; Dou, Suguang

    2017-01-01

    We demonstrate systematic control of mechanical nonlinearities in micro-electromechanical (MEMS) resonators using shape optimization methods. This approach generates beams with non-uniform profiles, which have nonlinearities and frequencies that differ from uniform beams. A set of bridge-type mic......We demonstrate systematic control of mechanical nonlinearities in micro-electromechanical (MEMS) resonators using shape optimization methods. This approach generates beams with non-uniform profiles, which have nonlinearities and frequencies that differ from uniform beams. A set of bridge...

  11. Fesoterodine dose response in subjects with overactive bladder syndrome.

    Science.gov (United States)

    Khullar, Vik; Rovner, Eric S; Dmochowski, Roger; Nitti, Victor; Wang, Joseph; Guan, Zhonghong

    2008-05-01

    To compare the efficacy of fesoterodine 4 mg versus 8 mg in treating subjects with overactive bladder (OAB) syndrome. This is a pooled analysis of data from 2 randomized placebo (PBO)-controlled phase III trials. Eligible subjects with frequency and urgency or urgency urinary incontinence (UUI) were randomized to PBO or fesoterodine 4 or 8 mg for 12 weeks. Subjects assessed efficacy using 3-day bladder diaries recording the time of each void, urgency, and incontinence episode. Endpoints included treatment response (based on a 4-point Treatment Benefit scale) and change from baseline in micturitions, UUI episodes, mean volume voided, urgency episodes, and continent days. We assessed tolerability and safety by evaluating adverse events, residual urine volume, laboratory parameters, and treatment withdrawals. At the end of treatment, both doses of fesoterodine showed statistically significant improvements in all efficacy endpoints versus PBO (P Fesoterodine 8 mg performed significantly better than fesoterodine 4 mg in improving all diary variables (P fesoterodine than with PBO included dry mouth, constipation, and urinary tract infection. Both fesoterodine 4 and 8 mg are effective in improving OAB symptoms. The higher 8-mg dose provides additional benefit compared with the lower dose in improving most bladder diary variables, thus offering the possibility of dose flexibility and titration.

  12. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eugene [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Corbett, James R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Moran, Jean M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Ficaro, Edward C. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Pierce, Lori J., E-mail: ljpierce@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-03-15

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

  13. Modeling and regression analysis of semiochemical dose-response curves of insect antennal reception and behavior.

    Science.gov (United States)

    Byers, John A

    2013-08-01

    Dose-response curves of the effects of semiochemicals on neurophysiology and behavior are reported in many articles in insect chemical ecology. Most curves are shown in figures representing points connected by straight lines, in which the x-axis has order of magnitude increases in dosage vs. responses on the y-axis. The lack of regression curves indicates that the nature of the dose-response relationship is not well understood. Thus, a computer model was developed to simulate a flux of various numbers of pheromone molecules (10(3) to 5 × 10(6)) passing by 10(4) receptors distributed among 10(6) positions along an insect antenna. Each receptor was depolarized by at least one strike by a molecule, and subsequent strikes had no additional effect. The simulations showed that with an increase in pheromone release rate, the antennal response would increase in a convex fashion and not in a logarithmic relation as suggested previously. Non-linear regression showed that a family of kinetic formation functions fit the simulated data nearly perfectly (R(2) >0.999). This is reasonable because olfactory receptors have proteins that bind to the pheromone molecule and are expected to exhibit enzyme kinetics. Over 90 dose-response relationships reported in the literature of electroantennographic and behavioral bioassays in the laboratory and field were analyzed by the logarithmic and kinetic formation functions. This analysis showed that in 95% of the cases, the kinetic functions explained the relationships better than the logarithmic (mean of about 20% better). The kinetic curves become sigmoid when graphed on a log scale on the x-axis. Dose-catch relationships in the field are similar to dose-EAR (effective attraction radius, in which a spherical radius indicates the trapping effect of a lure) and the circular EARc in two dimensions used in mass trapping models. The use of kinetic formation functions for dose-response curves of attractants, and kinetic decay curves for

  14. Nonlinear response of superconductors to alternating fields and currents

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-10-08

    This report discusses the following topics on superconductivity: nonlinearities in hard superconductors such as surface impedance of a type II superconductimg half space and harmonic generation and intermodulation due to alternating transport currents; and nonlinearities in superconducting weak links such as harmonic generation by a long Josephson Junction in a superconducting slab.

  15. Nonlinear dynamic response of beam and its application in nanomechanical resonator

    Institute of Scientific and Technical Information of China (English)

    Yin Zhang; Yun Liu; Kevin D. Murphy

    2012-01-01

    Nonlinear dynamic response of nanomechanical resonator is of very important characteristics in its application.Two categories of the tension-dominant and curvaturedominant nonlinearities are analyzed.The dynamic nonlinearity of four beam structures of nanomechanical resonator is quantitatively studied via a dimensional analysis approach.The dimensional analysis shows that for the nanomechanical resonator of tension-dominant nonlinearity,its dynamic nonlinearity decreases monotonically with increasing axial loading and increases monotonically with the increasing aspect ratio of length to thickness; the dynamic nonlinearity can only result in the hardening effects.However,for the nanomechanical resonator of the curvature-dominant nonlinearity,its dynamic nonlinearity is only dependent on axial loading.Compared with the tension-dominant nonlinearity,the curvature-dominant nonlinearity increases monotonically with increasing axial loading; its dynamic nonlinearity can result in both hardening and softening effects.The analysis on the dynamic nonlinearity can be very helpful to the tuning application of the nanomechanical resonator.

  16. Nonlinear Simulation of Plasma Response to the NSTX Error Field

    Science.gov (United States)

    Breslau, J. A.; Park, J. K.; Boozer, A. H.; Park, W.

    2008-11-01

    In order to better understand the effects of the time-varying error field in NSTX on rotation braking, which impedes RWM stabilization, we model the plasma response to an applied low-n external field perturbation using the resistive MHD model in the M3D code. As an initial benchmark, we apply an m=2, n=1 perturbation to the flux at the boundary of a non-rotating model equilibrium and compare the resulting steady-state island sizes with those predicted by the ideal linear code IPEC. For sufficiently small perturbations, the codes agree; for larger perturbations, the nonlinear correction yields an upper limit on the island width beyond which stochasticity sets in. We also present results of scaling studies showing the effects of finite resistivity on island size in NSTX, and of time-dependent studies of the interaction between these islands and plasma rotation. The M3D-C1 code is also being evaluated as a tool for this analysis; first results will be shown. J.E. Menard, et al., Nucl. Fus. 47, S645 (2007). W. Park, et al., Phys. Plasmas 6, 1796 (1999). J.K. Park, et al., Phys. Plasmas 14, 052110 (2007). S.C. Jardin, et al., J. Comp. Phys. 226, 2146 (2007).

  17. Third-order nonlinear optical response of push-pull azobenzene polymers

    Science.gov (United States)

    Papagiannouli, I.; Iliopoulos, K.; Gindre, D.; Sahraoui, B.; Krupka, O.; Smokal, V.; Kolendo, A.; Couris, S.

    2012-12-01

    The nonlinear optical response of a series of azo-containing side-chain polymers is investigated using Z-scan technique, employing 35 ps and 4 ns laser pulses, at 532 nm. The systems were found to exhibit strong nonlinear optical response, dominated by nonlinear refraction. In all cases, the nonlinear absorption and refraction have been determined and are compared with those of disperse red 1 considered as reference. The corresponding third-order susceptibilities χ(3) were determined to be as large as 10-7 and 10-5 esu under ps and ns laser excitation, respectively. Finally, the results are discussed and compared with other reported data.

  18. Analysis of interlaminar stress and nonlinear dynamic response for composite laminated plates with interfacial damage

    Science.gov (United States)

    Zhu, F. H.; Fu, Y. M.

    2008-12-01

    By considering the effect of interfacial damage and using the variation principle, three-dimensional nonlinear dynamic governing equations of the laminated plates with interfacial damage are derived based on the general six-degrees-of-freedom plate theory towards the accurate stress analysis. The solutions of interlaminar stress and nonlinear dynamic response for a simply supported laminated plate with interfacial damage are obtained by using the finite difference method, and the results are validated by comparison with the solution of nonlinear finite element method. In numerical calculations, the effects of interfacial damage on the stress in the interface and the nonlinear dynamic response of laminated plates are discussed.

  19. Enhanced nonlinear optical response of one-dimensional metal-dielectric photonic crystals.

    Science.gov (United States)

    Lepeshkin, Nick N; Schweinsberg, Aaron; Piredda, Giovanni; Bennink, Ryan S; Boyd, Robert W

    2004-09-17

    We describe a new type of artificial nonlinear optical material composed of a one-dimensional metal-dielectric photonic crystal. Because of the resonant nature of multiple Bragg reflections, the transmission within the transmission band can be quite large, even though the transmission through the same total thickness of bulk metal would be very small. This procedure allows light to penetrate into the highly nonlinear metallic layers, leading to a large nonlinear optical response. We present experimental results for a Cu/SiO(2) crystal which displays a strongly enhanced nonlinear optical response (up to 12X) in transmission.

  20. Harmonic response of a class of finite extensibility nonlinear oscillators

    Science.gov (United States)

    Febbo, M.

    2011-06-01

    Finite extensibility oscillators are widely used to simulate those systems that cannot be extended to infinity. For example, they are used when modelling the bonds between molecules in a polymer or DNA molecule or when simulating filaments of non-Newtonian liquids. In this paper, the dynamic behavior of a harmonically driven finite extensibility oscillator is presented and studied. To this end, the harmonic balance method is applied to determine the amplitude-frequency and amplitude-phase equations. The distinguishable feature in this case is the bending of the amplitude-frequency curve to the frequency axis, making it asymptotically approach the limit of maximum elongation of the oscillator, which physically represents the impossibility of the system reaching this limit. Also, the stability condition that defines stable and unstable steady-state solutions is derived. The study of the effect of the system parameters on the response reveals that a decreasing value of the damping coefficient or an increasing value of the excitation amplitude leads to the appearance of a multi-valued response and to the existence of a jump phenomenon. In this sense, the critical amplitude of the excitation, which means here a certain value of external excitation that results in the occurrence of jump phenomena, is also derived. Numerical experiments to observe the effects of system parameters on the frequency-amplitude response are performed and compared with analytical calculations. At a low value of the damping coefficient or at a high value of excitation amplitude, the agreement is poor for low frequencies but good for high frequencies. It is demonstrated that the disagreement is caused by the neglect of higher-order harmonics in the analytical formulation. These higher-order harmonics, which appear as distinguishable peaks at certain values in the frequency response curves, are possible to calculate considering not the linearized frequency of the oscillator but its actual

  1. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework.

    Science.gov (United States)

    Calabrese, Edward J; Bachmann, Kenneth A; Bailer, A John; Bolger, P Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M George; Chiueh, Chuang C; Clarkson, Thomas W; Cook, Ralph R; Diamond, David M; Doolittle, David J; Dorato, Michael A; Duke, Stephen O; Feinendegen, Ludwig; Gardner, Donald E; Hart, Ronald W; Hastings, Kenneth L; Hayes, A Wallace; Hoffmann, George R; Ives, John A; Jaworowski, Zbigniew; Johnson, Thomas E; Jonas, Wayne B; Kaminski, Norbert E; Keller, John G; Klaunig, James E; Knudsen, Thomas B; Kozumbo, Walter J; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I; Masoro, Edward J; McClellan, Roger O; Mehendale, Harihara M; Mothersill, Carmel; Newlin, David B; Nigg, Herbert N; Oehme, Frederick W; Phalen, Robert F; Philbert, Martin A; Rattan, Suresh I S; Riviere, Jim E; Rodricks, Joseph; Sapolsky, Robert M; Scott, Bobby R; Seymour, Colin; Sinclair, David A; Smith-Sonneborn, Joan; Snow, Elizabeth T; Spear, Linda; Stevenson, Donald E; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M; Mattson, Mark P

    2007-07-01

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

  2. Nonlinear optical response in Kronig-Penney type graphene superlattice in terahertz regime

    Science.gov (United States)

    Jiang, Lijuan; Yuan, Rui-Yang; Zhao, Xin; Lv, Jing; Yan, Hui

    2015-05-01

    The terahertz nonlinear optical response in Kronig-Penney (KP) type graphene superlattice is demonstrated. The single-, triple- and quintuple-frequencies of the fifth-order nonlinear responses are investigated for different frequencies and temperatures with the angle φ along the periodicity of the superlattice toward the external field tuning from 0 to π/2. The results show that the fifth-order nonlinear optical conductance of graphene superlattice is enhanced in the terahertz regime when φ = 0, i.e. an external field is applied along the periodicity of the superlattice. The fifth-order nonlinear optical conductances at φ = 0 for different frequencies and temperatures are calculated. The results show that the nonlinear optical conductance is enhanced in low frequency and low temperature. Our results suggest that KP type graphene superlattices are preferred structures for developing graphene-based nonlinear photonics and optoelectronics devices.

  3. Characterization of the bronchodilatory dose response to indacaterol in patients with chronic obstructive pulmonary disease using model-based approaches.

    Science.gov (United States)

    Renard, Didier; Looby, Michael; Kramer, Benjamin; Lawrence, David; Morris, David; Stanski, Donald R

    2011-04-26

    Indacaterol is a once-daily long-acting inhaled β2-agonist indicated for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD). The large inter-patient and inter-study variability in forced expiratory volume in 1 second (FEV1) with bronchodilators makes determination of optimal doses difficult in conventional dose-ranging studies. We considered alternative methods of analysis. We utilized a novel modelling approach to provide a robust analysis of the bronchodilatory dose response to indacaterol. This involved pooled analysis of study-level data to characterize the bronchodilatory dose response, and nonlinear mixed-effects analysis of patient-level data to characterize the impact of baseline covariates. The study-level analysis pooled summary statistics for each steady-state visit in 11 placebo-controlled studies. These study-level summaries encompassed data from 7476 patients at indacaterol doses of 18.75-600 μg once daily, and showed that doses of 75 μg and above achieved clinically important improvements in predicted trough FEV1 response. Indacaterol 75 μg achieved 74% of the maximum effect on trough FEV1, and exceeded the midpoint of the 100-140 mL range that represents the minimal clinically important difference (MCID; ≥120 mL vs placebo), with a 90% probability that the mean improvement vs placebo exceeded the MCID. Indacaterol 150 μg achieved 85% of the model-predicted maximum effect on trough FEV1 and was numerically superior to all comparators (99.9% probability of exceeding MCID). Indacaterol 300 μg was the lowest dose that achieved the model-predicted maximum trough response.The patient-level analysis included data from 1835 patients from two dose-ranging studies of indacaterol 18.75-600 μg once daily. This analysis provided a characterization of dose response consistent with the study-level analysis, and demonstrated that disease severity, as captured by baseline FEV1, significantly affects the dose response

  4. Characterization of the bronchodilatory dose response to indacaterol in patients with chronic obstructive pulmonary disease using model-based approaches

    Directory of Open Access Journals (Sweden)

    Lawrence David

    2011-04-01

    Full Text Available Abstract Background Indacaterol is a once-daily long-acting inhaled β2-agonist indicated for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD. The large inter-patient and inter-study variability in forced expiratory volume in 1 second (FEV1 with bronchodilators makes determination of optimal doses difficult in conventional dose-ranging studies. We considered alternative methods of analysis. Methods We utilized a novel modelling approach to provide a robust analysis of the bronchodilatory dose response to indacaterol. This involved pooled analysis of study-level data to characterize the bronchodilatory dose response, and nonlinear mixed-effects analysis of patient-level data to characterize the impact of baseline covariates. Results The study-level analysis pooled summary statistics for each steady-state visit in 11 placebo-controlled studies. These study-level summaries encompassed data from 7476 patients at indacaterol doses of 18.75-600 μg once daily, and showed that doses of 75 μg and above achieved clinically important improvements in predicted trough FEV1 response. Indacaterol 75 μg achieved 74% of the maximum effect on trough FEV1, and exceeded the midpoint of the 100-140 mL range that represents the minimal clinically important difference (MCID; ≥120 mL vs placebo, with a 90% probability that the mean improvement vs placebo exceeded the MCID. Indacaterol 150 μg achieved 85% of the model-predicted maximum effect on trough FEV1 and was numerically superior to all comparators (99.9% probability of exceeding MCID. Indacaterol 300 μg was the lowest dose that achieved the model-predicted maximum trough response. The patient-level analysis included data from 1835 patients from two dose-ranging studies of indacaterol 18.75-600 μg once daily. This analysis provided a characterization of dose response consistent with the study-level analysis, and demonstrated that disease severity, as captured by

  5. Classification, Dose-response Modelling and the Evaluation of Biomarkers in a Micro-array Setting

    OpenAIRE

    Lin, Dan

    2008-01-01

    Dose-response microarray experiments consist of monitoring expression levels of thousands of genes with respect to increasing dose of the treatment under investigation. The primary goal of such an experiment is to establish a dose-response relationship, while the secondary goals are to determine the minimum effective dose level and to identify the shape of the dose-response curve. Recently, Lin et al.[1] discussed several testing procedures to test for monotone trend based on isotonic regress...

  6. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

    Science.gov (United States)

    Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-DoseCancer Responses.There has been a concerted effort in the field of radiation biology to better understand cellularresponses that could have an impact on the estin1ation of cancer...

  7. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

    Science.gov (United States)

    Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-DoseCancer Responses.There has been a concerted effort in the field of radiation biology to better understand cellularresponses that could have an impact on the estin1ation of cancer...

  8. Nonlinear response of the quantum Hall system to a strong electromagnetic radiation

    Science.gov (United States)

    Avetissian, H. K.; Mkrtchian, G. F.

    2016-12-01

    We study nonlinear response of a quantum Hall system in semiconductor-hetero-structures via third harmonic generation process and nonlinear Faraday effect. We demonstrate that Faraday rotation angle and third harmonic radiation intensity have a characteristic Hall plateaus feature. These nonlinear effects remain robust against the significant broadening of Landau levels. We predict realization of an experiment through the observation of the third harmonic signal and Faraday rotation angle, which are within the experimental feasibility.

  9. Modeling of nonlinear responses for reciprocal transducers involving polarization switching

    DEFF Research Database (Denmark)

    Willatzen, Morten; Wang, Linxiang

    2007-01-01

    Nonlinearities and hysteresis effects in a reciprocal PZT transducer are examined by use of a dynamical mathematical model on the basis of phase-transition theory. In particular, we consider the perovskite piezoelectric ceramic in which the polarization process in the material can be modeled....... We present numerical results for the reciprocal-transducer system and identify the influence of nonlinearities on the system dynamics at high and low frequency as well as electrical impedance effects due to tuning by a series inductance. It is found that nonlinear effects are not important at high...... by Landau theory for the first-order phase transformation, in which each polarization state is associated with a minimum of the Landau free-energy function. Nonlinear constitutive laws are obtained by using thermodynamical equilibrium conditions, and hysteretic behavior of the material can be modeled...

  10. A dose-response model for refractory ceramic fibers.

    Science.gov (United States)

    Turim, J; Brown, R C

    2003-09-15

    Refractory ceramic fibers (RCFs) are man-made vitreous fibers commonly used in insulation applications above 1000 degrees C. Although they have been subjected to considerable toxicologic evaluation, only the pooled results from two rat inhalation studies provide data that may be suitable for performing a numerical risk assessment. Even in these inhalation studies, good evidence exists that the maximum tolerated dose (MTD) was exceeded and that pulmonary overload occurred, a condition that will cause tumors whatever the dust responsible. Indeed, a significant yield of tumors was only obtained at the highest dose tested. If these results are omitted, there is no statistically significant evidence of carcinogenicity within the RCF results. Although there is little evidence that overload-related tumors are relevant to human risk, we adopted a conservative approach to obtain the estimates of risk regardless of overload, using a biologically based model, the two-stage clonal expansion model, as well as various statistical models, including the benchmark dose model. We argue that the data favor the use of a biologically based model, which gives the best fit when the highest dose RCF exposures are omitted. Continuing with this model, we show that available data from the RCF experiment, less outliers, coupled with results from other experiments with man-made mineral fibers (MMVFs), demonstrate that all MMVFs are potentially carcinogenic, with any risk mediated by the fibers' biopersistence. Application of this "all MMVF data set" model yields a maximum likely estimate for RCF excess unit risk of 4.6 x 10(-5) (95% upper confidence limit = 9.2 x 10(-5) per fiber/ml). This implies that the risk from occupational exposure to RCFs at 1 fiber/ml for a typical working lifetime would not exceed 10(-4).

  11. Parametric characteristic of the random vibration response of nonlinear systems

    Institute of Scientific and Technical Information of China (English)

    Xing-Jian Dong; Zhi-Ke Peng; Wen-Ming Zhang; Guang Meng; Fu-Lei Chu

    2013-01-01

    Volterra series is a powerful mathematical tool for nonlinear system analysis,and there is a wide range of non-linear engineering systems and structures that can be represented by a Volterra series model.In the present study,the random vibration of nonlinear systems is investigated using Volterra series.Analytical expressions were derived for the calculation of the output power spectral density (PSD) and input-output cross-PSD for nonlinear systems subjected to Gaussian excitation.Based on these expressions,it was revealed that both the output PSD and the input-output crossPSD can be expressed as polynomial functions of the nonlinear characteristic parameters or the input intensity.Numerical studies were carried out to verify the theoretical analysis result and to demonstrate the effectiveness of the derived relationship.The results reached in this study are of significance to the analysis and design of the nonlinear engineering systems and structures which can be represented by a Volterra series model.

  12. Effective Response of Nonlinear Composite under External AC and DC Electric Field

    Institute of Scientific and Technical Information of China (English)

    LIU Ye; LIANG Fang-Chu; SHEN Hong-Liang

    2005-01-01

    A perturbation method is used to study effective response of nonlinear Kerr composites, which are subject to the constitutive relation of electric displacement and electric field, Dα = εαE + xα|E|2E. Under the external AC and DC electric field Eapp = Eα(1 + sinwt), the effective nonlinear responses and local potentials are induced by the cubic nonlinearity of Kerr materials at all harmonics. As an example in three dimensions, we have investigated this kind of nonlinear composites with spherical inclusions embedded in a host. At all harmonic frequencies, the potentials in inclusion and host regions are derived. Furthermore, the formulae of the effective linear and nonlinear responses are given in the dilute limit.

  13. Relationship of dose rate and total dose to responses of continuously irradiated beagles

    Energy Technology Data Exchange (ETDEWEB)

    Fritz, T E; Norris, W P; Tolle, D V; Seed, T M; Poole, C M; Lombard, L S; Doyle, D E

    1978-01-01

    Young-adult beagles were exposed continuously (22 hours/day) to /sup 60/Co ..gamma.. rays in a specially constructed facility. The exposure rates were either 5, 10, 17, or 35 R/day, and the exposures were terminated at either 600, 1400, 2000, or 4000 R. A total of 354 dogs were irradiated; 221 are still alive as long-term survivors, some after more than 2000 days. The data on survival of these dogs, coupled with data from similar preliminary experiments, allow an estimate of the LD/sub 50/ for ..gamma..-ray exposures given at a number of exposure rates. They also allow comparison of the relative importance of dose rate and total dose, and the interaction of these two variables, in the early and late effects after protracted irradiation. The LD/sub 50/ for the beagle increases from 258 rad delivered at 15 R/minute to approximately 3000 rad at 10 R/day. Over this entire range, the LD/sub 50/ is dependent upon hematopoietic damage. At 5 R/day and less, no meaningful LD/sub 50/ can be determined; there is nearly normal continued hematopoietic function, survival is prolonged, and the dogs manifest varied individual responses in other organ systems. Although the experiment is not complete, interim data allow several important conclusions. Terminated exposures, while not as effective as radiation continued until death, can produce myelogenous leukemia at the same exposure rate, 10 R/day. More importantly, at the same total accumulated dose, lower exposure rates are more damaging than higher rates on the basis of the rate and degree of hematological recovery that occurs after termination of irradiation. Thus, the rate of hematologic depression, the nadir of the depression, and the rate of recovery are dependent upon exposure rate; the latter is inversely related and the former two are directly related to exposure rate.

  14. Nonlinear response to a click in a time-domain model of the mammalian ear.

    Science.gov (United States)

    Meaud, Julien; Lemons, Charlsie

    2015-07-01

    In this paper, a state-space implementation of a previously developed frequency-domain model of the cochlea is coupled to a lumped parameter model of the middle ear. After validation of the time-domain model by comparison of its steady-state response to results obtained with a frequency-domain formulation, the nonlinear response of the cochlea to clicks is investigated. As observed experimentally, a compressive nonlinearity progressively develops within the first few cycles of the response of the basilar membrane (BM). Furthermore, a time-frequency analysis shows that the instantaneous frequency of the BM response to a click progressively approaches the characteristic frequency. This phenomenon, called glide, is predicted at all stimulus intensities, as in experiments. In typical experiments with sensitive animals, the click response is characterized by a long ringing and the response envelope includes several lobes. In order to achieve similar results, inhomogeneities are introduced in the cochlear model. Simulations demonstrate the strong link between characteristics of the frequency response, such as dispersion and frequency-dependent nonlinearity, and characteristics of the time-domain response, such as the glide and a time-dependent nonlinearity. The progressive buildup of cochlear nonlinearity in response to a click is shown to be a consequence of the glide and of frequency-dependent nonlinearity.

  15. Z-scan for thin media with more than one nonlocal nonlinear response.

    Science.gov (United States)

    Irivas, B A Martinez; Carrasco, M L Arroyo; Otero, M M Mendez; García, R Ramos; Castillo, M D Iturbe

    2016-06-13

    A model to characterize the response of a thin media that can exhibit more than one nonlocal nonlinear response when it is illuminated with a Gaussian beam in a z-scan experiment is proposed. The model considers that these nonlocal contributions can be treated as independent contributions in the refractive or absorptive nonlinear response. Numerical results for two nonlocal nonlinear contributions with different magnitudes between them are presented. Experimental results obtained from a hydrogenated amorphous silicon sample are used to corroborate this model.

  16. INVESTIGATION OF RANDOM RESPONSE OF ROTATIONAL SHELL WHEN CONSIDERING GEOMETRIC NONLINEAR BEHAVIOUR

    Institute of Scientific and Technical Information of China (English)

    GAO Shi-qiao(高世桥); JIN Lei(金磊); H.J.Niemann; LIU Hai-peng(刘海鹏)

    2001-01-01

    An iteration method of statistic linearization (IMSL) is presented. By this method, an equivalent linear term was formed in geometric relation and then an equivalent stiffness matrix for nonlinear term in vibration equation was established. Using the method to solve the statistic linear vibration equations, the effect of geometric nonlinearity on the random response of rotational shell is obtained.

  17. Measurements of dynamical response of non-linear systems. How hard can it be?

    DEFF Research Database (Denmark)

    Darula, Radoslav

    2015-01-01

    Measurements of a dynamical response of linear system are widely used in praxis, they are standardized and well known. On the other hand, for the non-linear systems the principle of superposition can’t be applied and also the non-linear systems can excite the harmonics or undergo jump phenomena...

  18. Artificial Neural Networks for Nonlinear Dynamic Response Simulation in Mechanical Systems

    DEFF Research Database (Denmark)

    Christiansen, Niels Hørbye; Høgsberg, Jan Becker; Winther, Ole

    2011-01-01

    It is shown how artificial neural networks can be trained to predict dynamic response of a simple nonlinear structure. Data generated using a nonlinear finite element model of a simplified wind turbine is used to train a one layer artificial neural network. When trained properly the network is able...

  19. Modeling the toxicity of aromatic compounds to tetrahymena pyriformis: the response surface methodology with nonlinear methods.

    Science.gov (United States)

    Ren, Shijin

    2003-01-01

    Response surface models based on multiple linear regression had previously been developed for the toxicity of aromatic chemicals to Tetrahymena pyriformis. However, a nonlinear relationship between toxicity and one of the molecular descriptors in the response surface model was observed. In this study, response surface models were established using six nonlinear modeling methods to handle the nonlinearity exhibited in the aromatic chemicals data set. All models were validated using the method of cross-validation, and prediction accuracy was tested on an external data set. Results showed that response surface models based on locally weighted regression scatter plot smoothing (LOESS), multivariate adaptive regression splines (MARS), neural networks (NN), and projection pursuit regression (PPR) provided satisfactory power of model fitting and prediction and had similar applicabilities. The response surface models based on nonlinear methods were difficult to interpret and conservative in discriminating toxicity mechanisms.

  20. Breastfeeding Mode and Risk of Breast Cancer: A Dose-Response Meta-Analysis.

    Science.gov (United States)

    Unar-Munguía, Mishel; Torres-Mejía, Gabriela; Colchero, M Arantxa; González de Cosío, Teresita

    2017-05-01

    Breastfeeding reduces women's risk of breast cancer. Since exclusive breastfeeding has a stronger hormonal effect, it could theoretically result in a greater reduction in breast cancer risk than any breastfeeding mode. No meta-analysis has examined breast cancer risk by breastfeeding mode. Research aim: The authors conducted a meta-analysis for breast cancer risk in parous women who breastfed exclusively or in any mode versus parous women who formula fed their infants, and they estimated the summary dose-response association by the accumulated duration of any breastfeeding mode. A systematic review of studies published between 2005 and 2015 analyzing breastfeeding and breast cancer risk in women was conducted in PubMed and EBSCOhost. A meta-analysis ( n = 65 studies) with fixed effects (or random effects, if heterogeneity existed) was carried out stratified by breastfeeding mode and menopausal and parity status. A summary dose-response association was estimated using the generalized least-squares method. The summary relative risk (SRR) for breast cancer in parous women who breastfed exclusively was 0.72, 95% confidence interval (CI) [0.58, 0.90], versus parous women who had never breastfed. For parous women who breastfed in any mode, the SRR was lower in both premenopausal women (0.86, 95% CI [0.80, 0.93]) and postmenopausal women (0.89, 95% CI [0.83, 0.95]). There was no heterogeneity or publication bias. There is weak evidence of a difference between exclusive and any breastfeeding mode ( p = .08). The summary dose-response curve was nonlinear ( p < .001). Exclusive breastfeeding among parous women reduces the risk of breast cancer compared with parous women who do not breastfeed exclusively.

  1. Equivalent circuit simulation of HPEM-induced transient responses at nonlinear loads

    Directory of Open Access Journals (Sweden)

    M. Kotzev

    2017-09-01

    Full Text Available In this paper the equivalent circuit modeling of a nonlinearly loaded loop antenna and its transient responses to HPEM field excitations are investigated. For the circuit modeling the general strategy to characterize the nonlinearly loaded antenna by a linear and a nonlinear circuit part is pursued. The linear circuit part can be determined by standard methods of antenna theory and numerical field computation. The modeling of the nonlinear circuit part requires realistic circuit models of the nonlinear loads that are given by Schottky diodes. Combining both parts, appropriate circuit models are obtained and analyzed by means of a standard SPICE circuit simulator. It is the main result that in this way full-wave simulation results can be reproduced. Furthermore it is clearly seen that the equivalent circuit modeling offers considerable advantages with respect to computation speed and also leads to improved physical insights regarding the coupling between HPEM field excitation and nonlinearly loaded loop antenna.

  2. Non-linear dynamic response of a wind turbine blade

    Science.gov (United States)

    Chopra, I.; Dugundji, J.

    1979-01-01

    The paper outlines the nonlinear dynamic analysis of an isolated three-degree flap-lag-feather wind turbine blade under a gravity field and with shear flow. Lagrangian equations are used to derive the nonlinear equations of motion of blade for arbitrarily large angular deflections. The limit cycle analysis for forced oscillations and the determination of the principal parametric resonance of the blade due to periodic forces from the gravity field and wind shear are performed using the harmonic balance method. Results are obtained first for a two-degree flap-lag blade, then the effect of the third degree of freedom (feather) is studied. The self-excited flutter solutions are obtained for a uniform wind and with gravity forces neglected. The effects of several parameters on the blade stability are examined, including coning angle, structural damping, Lock number, and feather frequency. The limit cycle flutter solution of a typical configuration shows a substantial nonlinear softening spring behavior.

  3. Low blood lead level effects on intelligence: can a dose-response curve be determined from the epidemiological data?

    Science.gov (United States)

    Banner, W; Kahn, C M

    2014-02-01

    CONTEXT. Recent publications have graphically demonstrated a curvilinear relationship between measures of intelligence and blood lead levels at low concentrations (dose-response curves. METHODS. Random data based on varied distributions were constructed to simulate a previous study using a single, randomly generated covariate income (Inc) to demonstrate the impact of normally versus exponentially distributed data on the shape of the graph of intelligence quotient (IQ) versus blood lead. We also used an existing database of US blood lead levels and constructed a similar model of income and IQ using both assumptions of distribution for the intermediate variable income. RESULTS. When both lead and income are exponentially distributed, the graph of lead and IQ will be a curve. CONCLUSION. The apparent shape of a dose-response relationship from simulated epidemiological data is nonlinear when one variable and a covariate are exponentially distributed. A non-linear biological relationship should not be assumed and in fact may be the least likely explanation. The use of observational epidemiological data to discern a dose-response relationship between two variables may be misleading.

  4. Fundamental investigations of natural and laboratory generated SAR dose response curves for quartz OSL in the high dose range

    DEFF Research Database (Denmark)

    Timar-Gabor, Alida; Constantin, Daniela; Buylaert, Jan-Pieter;

    2015-01-01

    SAR-OSL investigations on quartz from Romanian loess resulted in non concordant fine and coarse-grain ages for equivalent doses higher than ~100 Gy. The laboratory dose response for both grain sizes is well represented by a sum of two saturating exponential functions, fine and coarse grains chara...

  5. Nonlinear Optical Response of Conjugated Polymer to Electric Field

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yu-fang; ZHUANG De-xin; CUI Bin

    2005-01-01

    The organic π-conjugated polymers are of major interest materials for the use in electro-optical and nonlinear optical devices. In this work, for a selected polyacetylene chain, the optical absorption spectra in UV/Vis regime as well as the linear polarizabilitiy and nonlinear hyperpolarizability are calculated by using quantum chemical ab initio and semiempirical methods. The relationship of its optical property to electric field is obtained. Some physical mechanism of electric field effect on molecular optical property is discussed by means of electron distribution and intramolecular charge transfer.

  6. Cardiovascular Response Identification Based on Nonlinear Support Vector Regression

    Science.gov (United States)

    Wang, Lu; Su, Steven W.; Chan, Gregory S. H.; Celler, Branko G.; Cheng, Teddy M.; Savkin, Andrey V.

    This study experimentally investigates the relationships between central cardiovascular variables and oxygen uptake based on nonlinear analysis and modeling. Ten healthy subjects were studied using cycle-ergometry exercise tests with constant workloads ranging from 25 Watt to 125 Watt. Breath by breath gas exchange, heart rate, cardiac output, stroke volume and blood pressure were measured at each stage. The modeling results proved that the nonlinear modeling method (Support Vector Regression) outperforms traditional regression method (reducing Estimation Error between 59% and 80%, reducing Testing Error between 53% and 72%) and is the ideal approach in the modeling of physiological data, especially with small training data set.

  7. Nonlinear dynamical model and response of avian cranial kinesis.

    Science.gov (United States)

    Meekangvan, Preeda; A Barhorst, Alan; Burton, Thomas D; Chatterjee, Sankar; Schovanec, Lawrence

    2006-05-01

    All modern birds have kinetic skulls in which the upper bill can move relative to the braincase, but the biomechanics and motion dynamics of cranial kinesis in birds are poorly understood. In this paper, we model the dynamics of avian cranial kinesis, such as prokinesis and proximal rhynchokinesis in which the upper jaw pivots around the nasal-frontal (N-F) hinge. The purpose of this paper is to present to the biological community an approach that demonstrates the application of sophisticated predictive mathematical modeling tools to avian kinesis. The generality of the method, however, is applicable to the advanced study of the biomechanics of other skeletal systems. The paper begins with a review of the relevant biological literature as well as the essential morphology of avian kinesis, especially the mechanical coupling of the upper and lower jaw by the postorbital ligament. A planar model of the described bird jaw morphology is then developed that maintains the closed kinematic topology of the avian jaw mechanism. We then develop the full nonlinear equations of motion with the assumption that the M. protractor pterygoideus and M. depressor mandibulae act on the quadrate as a pure torque, and the nasal frontal hinge is elastic with damping. The mechanism is shown to be a single degree of freedom device due to the holonomic constraints present in the quadrate-jugal bar-upper jaw-braincase-quadrate kinematic chain as well as the quadrate-lower jaw-postorbital ligament-braincase-quadrate kinematic chain. The full equations are verified via simulation and animation using the parameters of a Grey Heron (Ardea cinerea). Next we develop a simplified analytical model of the equations by power series expansion. We demonstrate that this model reproduces the dynamics of the full model to a high degree of fidelity. We proceed to use the harmonic balance technique to develop the frequency response characteristics of the jaw mechanism. It is shown that this avian cranial

  8. Tuning the nonlinear response of (6,5)-enriched single-wall carbon nanotubes dispersions

    Science.gov (United States)

    Aréstegui, O. S.; Silva, E. C. O.; Baggio, A. L.; Gontijo, R. N.; Hickmann, J. M.; Fantini, C.; Alencar, M. A. R. C.; Fonseca, E. J. S.

    2017-04-01

    Ultrafast nonlinear optical properties of (6,5)-enriched single-wall carbon nanotubes (SWCNTs) dispersions are investigated using the thermally managed Z-scan technique. As the (6,5) SWCNTs presented a strong resonance in the range of 895-1048 nm, the nonlinear refractive index (n2) and the absorption coefficients (β) measurements were performed tuning the laser exactly around absorption peak of the (6,5) SWCNTs. It is observed that the nonlinear response is very sensitive to the wavelength and the spectral behavior of n2 is strongly correlated to the tubes one-photon absorption band, presenting also a peak when the laser photon energy is near the tube resonance energy. This result suggests that a suitable selection of nanotubes types may provide optimized nonlinear optical responses in distinct regions of the electromagnetic spectrum. Analysis of the figures of merit indicated that this material is promising for ultrafast nonlinear optical applications under near infrared excitation.

  9. Nonlinear response of metallic acGNR to an elliptically-polarized terahertz excitation field

    CERN Document Server

    Wang, Yichao

    2016-01-01

    We present a theoretical description of the nonlinear response induced by an elliptically-polarized terahertz beam normally-incident on intrinsic and extrinsic metallic armchair graphene nanorib- bons. Our results show that using a straightforward experimental setup, it should be possible to observe novel polarization-dependent nonlinearities at low excitation field strengths of the or- der of 10 4 V/m. At low temperatures the Kerr nonlinearities in extrinsic nanoribbons persist to significantly higher excitation frequencies than they do for linear polarizations, and at room tem- peratures, the third-harmonic nonlinearities are enhanced by 2-3 orders of magnitude. Finally, the Fermi-level and temperature dependence of the nonlinear response is characterized.

  10. Patients who do not respond to the "usual" dose: why Terry fell off the dose-response curve.

    Science.gov (United States)

    Preskorn, Sheldon H

    2009-11-01

    Clinical trials are aimed at determining what happens in the "usual" patient; however, clinicians are interested in what happens in their patients even if they are not usual. The usual dose-response relationship is determined as part of the drug development process required for approval of a new drug. However, clinicians are likely to encounter patients who "fall off" the usual dose-response curve because they are either sensitive or resistant to the beneficial (efficacy) or adverse effects of a drug. This column is the first in a series that will examine why specific patients fall off the usual dose-response curve and how clinicians can manage such patients when they encounter them. This column discusses what a dose-response curve is, how it is determined, and why it is clinically important.

  11. Alcohol and cirrhosis: dose--response or threshold effect?

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Grønbaek, Morten; Tolstrup, Janne;

    2004-01-01

    BACKGROUND/AIMS: General population studies have shown a strong association between alcohol intake and death from alcoholic cirrhosis, but whether this is a dose-response or a threshold effect remains unknown, and the relation among alcohol misusers has not been studied. METHODS: A cohort of 6152...... alcohol misusing men and women aged 15-83 were interviewed about drinking pattern and social issues and followed for 84,257 person-years. Outcome was alcoholic cirrhosis mortality. Data was analyzed by means of Cox-regression models. RESULTS: In this large prospective cohort study of alcohol misusers...... there was a 27 fold increased mortality from alcoholic cirrhosis in men and a 35 fold increased mortality from alcoholic cirrhosis in women compared to the Danish population. Number of drinks per day was not significantly associated with death from alcoholic cirrhosis, since there was no additional risk of death...

  12. Dose-response curve estimation: a semiparametric mixture approach.

    Science.gov (United States)

    Yuan, Ying; Yin, Guosheng

    2011-12-01

    In the estimation of a dose-response curve, parametric models are straightforward and efficient but subject to model misspecifications; nonparametric methods are robust but less efficient. As a compromise, we propose a semiparametric approach that combines the advantages of parametric and nonparametric curve estimates. In a mixture form, our estimator takes a weighted average of the parametric and nonparametric curve estimates, in which a higher weight is assigned to the estimate with a better model fit. When the parametric model assumption holds, the semiparametric curve estimate converges to the parametric estimate and thus achieves high efficiency; when the parametric model is misspecified, the semiparametric estimate converges to the nonparametric estimate and remains consistent. We also consider an adaptive weighting scheme to allow the weight to vary according to the local fit of the models. We conduct extensive simulation studies to investigate the performance of the proposed methods and illustrate them with two real examples.

  13. On the effects of nonlinearities in room impulse response measurements with exponential sweeps

    DEFF Research Database (Denmark)

    Ciric, Dejan; Markovic, Milos; Mijic, Miomir

    2013-01-01

    In room impulse response measurements, there are some common disturbances that affect the measured results. These disturbances include nonlinearity, noise and time variance. In this paper, the effects of nonlinearities in the measurements with exponential sweep-sine signals are analyzed from...... different perspectives. The analysis combines theoretical approach, simulations and measurements. The focus is on distortion artifacts in the causal part of the impulse response and their effects on room acoustical parameters. The results show that the sweep-sine method is vulnerable to a certain extent...... to nonlinearities from a theoretical standpoint, but the consequences of this vulnerability are reduced in the responses measured in practice. However, due to irretrievable contamination of the impulse responses, the nonlinearities (especially strong ones) should be avoided....

  14. A Novel Method for Prediction of Nonlinear Aeroelastic Responses

    Science.gov (United States)

    2010-01-01

    Brian A. Freno Graduate Student, Texas A&M University Publications Journal articles: 1. Gargoloff, J. I. and Cizmas, P. G. A., “Mesh Generation and...papers: 1. Cizmas, P. G. A., Freno , B. A., Brenner, T. A., Worley, G. D., “A High-Fidelity Nonlinear Aeroelastic Model for Aircraft with Large Wing

  15. Comparison of linear and nonlinear programming approaches for "worst case dose" and "minmax" robust optimization of intensity-modulated proton therapy dose distributions.

    Science.gov (United States)

    Zaghian, Maryam; Cao, Wenhua; Liu, Wei; Kardar, Laleh; Randeniya, Sharmalee; Mohan, Radhe; Lim, Gino

    2017-03-01

    Robust optimization of intensity-modulated proton therapy (IMPT) takes uncertainties into account during spot weight optimization and leads to dose distributions that are resilient to uncertainties. Previous studies demonstrated benefits of linear programming (LP) for IMPT in terms of delivery efficiency by considerably reducing the number of spots required for the same quality of plans. However, a reduction in the number of spots may lead to loss of robustness. The purpose of this study was to evaluate and compare the performance in terms of plan quality and robustness of two robust optimization approaches using LP and nonlinear programming (NLP) models. The so-called "worst case dose" and "minmax" robust optimization approaches and conventional planning target volume (PTV)-based optimization approach were applied to designing IMPT plans for five patients: two with prostate cancer, one with skull-based cancer, and two with head and neck cancer. For each approach, both LP and NLP models were used. Thus, for each case, six sets of IMPT plans were generated and assessed: LP-PTV-based, NLP-PTV-based, LP-worst case dose, NLP-worst case dose, LP-minmax, and NLP-minmax. The four robust optimization methods behaved differently from patient to patient, and no method emerged as superior to the others in terms of nominal plan quality and robustness against uncertainties. The plans generated using LP-based robust optimization were more robust regarding patient setup and range uncertainties than were those generated using NLP-based robust optimization for the prostate cancer patients. However, the robustness of plans generated using NLP-based methods was superior for the skull-based and head and neck cancer patients. Overall, LP-based methods were suitable for the less challenging cancer cases in which all uncertainty scenarios were able to satisfy tight dose constraints, while NLP performed better in more difficult cases in which most uncertainty scenarios were hard to meet

  16. Numerical Simulation of Seabed Response and Liquefaction due to Non-linear Waves

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jin-feng; ZHANG Qing-he; HAN Tao; QIN Chong-ren

    2005-01-01

    Based on Biot's consolidation theory, a two-dimensional model for computation of the seabed response to waves is presented with the finite element method. Numerical results for different wave conditions are obtained, and the effects of wave non-linearity on the wave-induced seabed response are examined. Moreover, the wave-induced momentary liquefaction in uniform and inhomogeneous seabeds is investigated. It is shown that the wave non-linearity affects the distribution of the wave-induced pore pressure and effective stresses, while the influence of wave non-linearity on the seabed liquefaction potential is not so significant.

  17. Synthesis, characterization and non-linear optical response of organophilic carbon dots

    KAUST Repository

    Bourlinos, Athanasios B.

    2013-09-01

    For the first time ever we report the nonlinear optical (NLO) properties of carbon dots (C-dots). The C-dots for these experiments were synthesized by mild pyrolysis of lauryl gallate. The resulting C-dots bear lauryl chains and, hence, are highly dispersible in polar organic solvents, like chloroform. Dispersions in CHCl3 show significant NLO response. Specifically, the C-dots show negative nonlinear absorption coefficient and negative nonlinear refraction. Using suspensions with different concentrations these parameters are quantified and compared to those of fullerene a well-known carbon molecule with proven NLO response. © 2013 Elsevier Ltd. All rights reserved.

  18. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

    Science.gov (United States)

    Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

  19. Nonlinear structural joint model updating based on instantaneous characteristics of dynamic responses

    Science.gov (United States)

    Wang, Zuo-Cai; Xin, Yu; Ren, Wei-Xin

    2016-08-01

    This paper proposes a new nonlinear joint model updating method for shear type structures based on the instantaneous characteristics of the decomposed structural dynamic responses. To obtain an accurate representation of a nonlinear system's dynamics, the nonlinear joint model is described as the nonlinear spring element with bilinear stiffness. The instantaneous frequencies and amplitudes of the decomposed mono-component are first extracted by the analytical mode decomposition (AMD) method. Then, an objective function based on the residuals of the instantaneous frequencies and amplitudes between the experimental structure and the nonlinear model is created for the nonlinear joint model updating. The optimal values of the nonlinear joint model parameters are obtained by minimizing the objective function using the simulated annealing global optimization method. To validate the effectiveness of the proposed method, a single-story shear type structure subjected to earthquake and harmonic excitations is simulated as a numerical example. Then, a beam structure with multiple local nonlinear elements subjected to earthquake excitation is also simulated. The nonlinear beam structure is updated based on the global and local model using the proposed method. The results show that the proposed local nonlinear model updating method is more effective for structures with multiple local nonlinear elements. Finally, the proposed method is verified by the shake table test of a real high voltage switch structure. The accuracy of the proposed method is quantified both in numerical and experimental applications using the defined error indices. Both the numerical and experimental results have shown that the proposed method can effectively update the nonlinear joint model.

  20. Bounding the total-dose response of modern bipolar transistors

    Energy Technology Data Exchange (ETDEWEB)

    Kosier, S.L.; Wei, A.; Schrimpf, R.D. [Arizona Univ., Tucson, AZ (United States). Dept. of Electrical and Computer Engineering; Combs, W.E. [Naval Surface Warfare Center-Crane, Crane, IN (United States); Fleetwood, D.M. [Sandia National Labs., Albuquerque, NM (United States); DeLaus, M. [Analog Devices, Inc., Wilmington, MA (United States); Pease, R.L. [RLP Research, Albuquerque, NM (United States)

    1994-03-01

    The base current in modern bipolar transistors saturates at large total doses once a critical oxide charge is reached. The saturated value of base current is dose-rate independent. Testing implications are discussed.

  1. Ozone as u-shaped dose responses molecules (hormetins).

    Science.gov (United States)

    Martínez-Sánchez, G; Pérez-Davison, G; Re, L; Giuliani, A

    2010-05-10

    Redox environment involves a broad network of pro-oxidant and antioxidant components. Health benefit or damage can be induced as a consequence of an adaptive cellular stress response. A consequence of hormetic amplification is an increase in the homeodynamic space of a living system in terms of an increased defense capacity and a reduced load of damaged macromolecules. Ozone, when used at appropriate doses, promotes the formation of reactive oxygen species and lipid peroxides allows them to become late and long-lasting messengers. Healthy aging may be achieved by hormesis through mild and periodic, but not severe or chronic, physical and mental challenges, and by the use of nutritional hormesis incorporating mild stress-inducing molecules called hormetins. The paradoxical concept that ozone eventually induces an antioxidant response capable of reversing a chronic oxidative stress is common in the animal and vegetal kingdom; it is already supported by findings of an increased level of antioxidant enzymes during ozone therapy. Those facts can include ozone as a hormetin. The established scientific foundations of hormesis are ready to pave the way for new and effective approaches in redox-related disease research and intervention; ozone therapy can be a good candidate.

  2. Nonlinear optical response of a two-dimensional atomic crystal.

    Science.gov (United States)

    Merano, Michele

    2016-01-01

    The theory of Bloembergen and Pershan for the light waves at the boundary of nonlinear media is extended to a nonlinear two-dimensional (2D) atomic crystal, i.e., a single planar atomic lattice, placed between linear bulk media. The crystal is treated as a zero-thickness interface, a real 2D system. Harmonic waves emanate from it. Generalization of the laws of reflection and refraction give the direction and the intensity of the harmonic waves. As a particular case that contains all the essential physical features, second-order harmonic generation is considered. The theory, due to its simplicity that stems from the special character of a single planar atomic lattice, is able to elucidate and explain the rich experimental details of harmonic generation from a 2D atomic crystal.

  3. Terahertz-Driven Nonlinear Spin Response of Antiferromagnetic Nickel Oxide

    Science.gov (United States)

    Baierl, S.; Mentink, J. H.; Hohenleutner, M.; Braun, L.; Do, T.-M.; Lange, C.; Sell, A.; Fiebig, M.; Woltersdorf, G.; Kampfrath, T.; Huber, R.

    2016-11-01

    Terahertz magnetic fields with amplitudes of up to 0.4 Tesla drive magnon resonances in nickel oxide while the induced dynamics is recorded by femtosecond magneto-optical probing. We observe distinct spin-mediated optical nonlinearities, including oscillations at the second harmonic of the 1 THz magnon mode. The latter originate from coherent dynamics of the longitudinal component of the antiferromagnetic order parameter, which are probed by magneto-optical effects of second order in the spin deflection. These observations allow us to dynamically disentangle electronic from lattice-related contributions to magnetic linear birefringence and dichroism—information so far only accessible by ultrafast THz spin control. The nonlinearities discussed here foreshadow physics that will become essential in future subcycle spin switching.

  4. Frequency Response of Synthetic Vocal Fold Models with Linear and Nonlinear Material Properties

    Science.gov (United States)

    Shaw, Stephanie M.; Thomson, Scott L.; Dromey, Christopher; Smith, Simeon

    2014-01-01

    Purpose The purpose of this study was to create synthetic vocal fold models with nonlinear stress-strain properties and to investigate the effect of linear versus nonlinear material properties on fundamental frequency during anterior-posterior stretching. Method Three materially linear and three materially nonlinear models were created and stretched up to 10 mm in 1 mm increments. Phonation onset pressure (Pon) and fundamental frequency (F0) at Pon were recorded for each length. Measurements were repeated as the models were relaxed in 1 mm increments back to their resting lengths, and tensile tests were conducted to determine the stress-strain responses of linear versus nonlinear models. Results Nonlinear models demonstrated a more substantial frequency response than did linear models and a more predictable pattern of F0 increase with respect to increasing length (although range was inconsistent across models). Pon generally increased with increasing vocal fold length for nonlinear models, whereas for linear models, Pon decreased with increasing length. Conclusions Nonlinear synthetic models appear to more accurately represent the human vocal folds than linear models, especially with respect to F0 response. PMID:22271874

  5. Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons.

    Science.gov (United States)

    Dionet, Claude; Müller-Barthélémy, Melanie; Marceau, Geoffroy; Denis, Jean-Marc; Averbeck, Dietrich; Gueulette, John; Sapin, Vincent; Pereira, Bruno; Tchirkov, Andrei; Chautard, Emmanuel; Verrelle, Pierre

    2016-09-01

    To analyze the dose rate influence in hyper-radiosensitivity (HRS) of human melanoma cells to very low doses of fast neutrons and to compare to the behaviour of normal human skin fibroblasts. We explored different neutron dose rates as well as possible implication of DNA double-strand breaks (DSB), apoptosis, and energy-provider adenosine-triphosphate (ATP) levels during HRS. HRS in melanoma cells appears only at a very low dose rate (VLDR), while a high dose rate (HDR) induces an initial cell-radioresistance (ICRR). HRS does not seem to be due either to DSB or to apoptosis. Both phenomena (HRS and ICRR) appear to be related to ATP availability for triggering cell repair. Fibroblast survival after neutron irradiation is also dose rate-dependent but without HRS. Melanoma cells or fibroblasts exert their own survival behaviour at very low doses of neutrons, suggesting that in some cases there is a differential between cancer and normal cells radiation responses. Only the survival of fibroblasts at HDR fits the linear no-threshold model. This new insight into human cell responses to very low doses of neutrons, concerns natural radiations, surroundings of accelerators, proton-therapy devices, flights at high altitude. Furthermore, ATP inhibitors could increase HRS during high-linear energy transfer (high-LET) irradiation.

  6. Measurement of nonlinear elastic response in rock by the resonant bar method

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, P.A. [Los Alamos National Lab., NM (United States); Rasolofosaon, P.; Zinszner, B. [Institut Francais du Petrole (IFP), 92 - Rueil-Malmaison (France)

    1993-04-01

    In this work we are studying the behavior of the fundamental (Young`s) mode resonant peak as a function of drive amplitude in rock samples. Our goal from these studies is to obtain nonlinear moduli for many rock types, and to study the nonlinear moduli as a function of water saturation and other changes in physical properties. Measurements were made on seven different room dry rock samples. For one sample measurements were taken at 16 saturation levels between 1 and 98%. All samples display a ``softening`` nonlinearity, that is, the resonant frequency shifts downward with increasing drive amplitude. In extreme cases, the resonant frequency changes by as much as 25% over a strain interval of 10{sup {minus}7} to {approximately}4 {times} 10{sup {minus}5}. Measurements indicate that the nonlinear response is extremely sensitive to saturation. Estimates of a combined cubic and quartic nonlinear parameter {Gamma} range from approximately {minus}300 to {minus}10{sup 9} for the rock samples.

  7. Numerical investigation of amplitude-dependent dynamic response in acoustic metamaterials with nonlinear oscillators.

    Science.gov (United States)

    Manimala, James M; Sun, C T

    2016-06-01

    The amplitude-dependent dynamic response in acoustic metamaterials having nonlinear local oscillator microstructures is studied using numerical simulations on representative discrete mass-spring models. Both cubically nonlinear hardening and softening local oscillator cases are considered. Single frequency, bi-frequency, and wave packet excitations at low and high amplitude levels were used to interrogate the models. The propagation and attenuation characteristics of harmonic waves in a tunable frequency range is found to correspond to the amplitude and nonlinearity-dependent shifts in the local resonance bandgap for such nonlinear acoustic metamaterials. A predominant shift in the propagated wave spectrum towards lower frequencies is observed. Moreover, the feasibility of amplitude and frequency-dependent selective filtering of composite signals consisting of individual frequency components which fall within propagating or attenuating regimes is demonstrated. Further enrichment of these wave manipulation mechanisms in acoustic metamaterials using different combinations of nonlinear microstructures presents device implications for acoustic filters and waveguides.

  8. Dose calculation and in-phantom measurement in BNCT using response matrix method.

    Science.gov (United States)

    Rahmani, Faezeh; Shahriari, Majid

    2011-12-01

    In-phantom measurement of physical dose distribution is very important for Boron Neutron Capture Therapy (BNCT) planning validation. If any changes take place in therapeutic neutron beam due to the beam shaping assembly (BSA) change, the dose will be changed so another group of simulations should be carried out for dose calculation. To avoid this time consuming procedure and speed up the dose calculation to help patients not wait for a long time, response matrix method was used. This procedure was performed for neutron beam of the optimized BSA as a reference beam. These calculations were carried out using the MCNPX, Monte Carlo code. The calculated beam parameters were measured for a SNYDER head phantom placed 10 cm away from beam the exit of the BSA. The head phantom can be assumed as a linear system and neutron beam and dose distribution can be assumed as an input and a response of this system (head phantom), respectively. Neutron spectrum energy was digitized into 27 groups. Dose response of each group was calculated. Summation of these dose responses is equal to a total dose of the whole neutron/gamma spectrum. Response matrix is the double dimension matrix (energy/dose) in which each parameter represents a depth-dose resulted from specific energy. If the spectrum is changed, response of each energy group may be differed. By considering response matrix and energy vector, dose response can be calculated. This method was tested for some BSA, and calculations show statistical errors less than 10%.

  9. Fertility of Tall Girls Treated with High-Dose Estrogen, a Dose-Response Relationship

    NARCIS (Netherlands)

    Hendriks, A. E. J.; Drop, S. L. S.; Laven, J. S. E.; Boot, A. M.

    2012-01-01

    Context: High-dose estrogen treatment to reduce final height of tall girls increases their risk for infertility in later life. Objective: The aim was to study the effect of estrogen dose on fertility outcome of these women. Design/Setting: We conducted a retrospective cohort study of university hosp

  10. Mutations induced in Tradescantia by small doses of X-rays and neutrons - Analysis of dose-response curves.

    Science.gov (United States)

    Sparrow, A. H.; Underbrink, A. G.; Rossi, H. H.

    1972-01-01

    Dose-response curves for pink somatic mutations in Tradescantia stamen hairs were analyzed after neutron and X-ray irradiation with doses ranging from a fraction of a rad to the region of saturation. The dose-effect relation for neutrons indicates a linear dependence from 0.01 to 8 rads; between 0.25 and 5 rads, a linear dependence is indicated for X-rays also. As a consequence the relative biological effectiveness reaches a constant value (about 50) at low doses. The observations are in good agreement with the predictions of the theory of dual radiation action and support its interpretation of the effects of radiation on higher organisms. The doubling dose of X-rays was found to be nearly 1 rad.

  11. Analysis of interlaminar stress and nonlinear dynamic response for composite laminated plates with interfacial damage

    Institute of Scientific and Technical Information of China (English)

    F. H. Zhu; Y. M. Fu

    2008-01-01

    By considering the effect of interfacial damage and using the variation principle, three-dimensional nonli-near dynamic governing equations of the laminated plates with interfacial damage are derived based on the general six-degrees-of-freedom plate theory towards the accurate stress analysis. The solutions of interlaminar stress and nonlinear dynamic response for a simply supported laminated plate with interfacial damage are obtained by using the finite dif-ference method, and the results are validated by compari-son with the solution of nonlinear finite element method. In numerical calculations, the effects of interfacial damage on the stress in the interface and the nonlinear dynamic response of laminated plates are discussed.

  12. Experimental and theoretical studies of spectral alteration in ultrasonic waves resulting from nonlinear elastic response in rock

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, P.A.; McCall, K.R.; Meegan, G.D. Jr.

    1993-01-01

    Experiments in rock show a large nonlinear elastic wave response, far greater than that of gases, liquids and most other solids. The large response is attributed to structural defects in rock including microcracks and grain boundaries. In the earth, a large nonlinear response may be responsible for significant spectral alteration at amplitudes and distances currently considered to be well within the linear elastic regime.

  13. Experimental and theoretical studies of spectral alteration in ultrasonic waves resulting from nonlinear elastic response in rock

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, P.A.; McCall, K.R.; Meegan, G.D. Jr.

    1993-06-01

    Experiments in rock show a large nonlinear elastic wave response, far greater than that of gases, liquids and most other solids. The large response is attributed to structural defects in rock including microcracks and grain boundaries. In the earth, a large nonlinear response may be responsible for significant spectral alteration at amplitudes and distances currently considered to be well within the linear elastic regime.

  14. Experimental and theoretical studies of spectral alteration in ultrasonic waves resulting from nonlinear elastic response in rock

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, P.A.; McCall, K.R.; Meegan, G.D. Jr. [Los Alamos National Lab., NM (United States)

    1993-11-01

    Experiments in rock show a large nonlinear elastic wave response, far greater than that of gases, liquids and most other solids. The large response is attributed to structural defects in rock including microcracks and grain boundaries. In the earth, a large nonlinear response may be responsible for significant spectral alteration at amplitudes and distances currently considered to be well within the linear elastic regime.

  15. Cylindrical PVF2 film based fiber optic phase modulator - Phase shift nonlinearity and frequency response

    Science.gov (United States)

    Sudarshanam, V. S.; Claus, Richard O.

    1993-03-01

    A new cylindrical coil configuration for polyvinylidene flouride (PVF2) film based fiber optic phase modulator is studied for the frequency response and nonlinearity of phase shift at the resonance frequency. This configuration, hitherto unapproached for PVF2 film modulators, offers resonance at well defined, controllable and higher frequencies than possible for the flat-strip configuration. Two versions of this configuration are presented that differ strongly in both the resonance frequency and the phase shift nonlinearity coefficient.

  16. Nonlinear Site Response Due to Large Ground Acceleration: Observation and Computer Simulation

    Science.gov (United States)

    Noguchi, S.; Furumura, T.; Sasatani, T.

    2009-12-01

    We studied nonlinear site response due to large ground acceleration during the 2003 off-Miyagi Earthquake (Mw7.0) in Japan by means of horizontal-to-vertical spectral ratio analysis of S-wave motion. The results were then confirmed by finite-difference method (FDM) simulation of nonlinear seismic wave propagation. A nonlinear site response is often observed at soft sediment sites, and even at hard bedrock sites which are covered by thin soil layers. Nonlinear site response can be induced by strong ground motion whose peak ground acceleration (PGA) exceeds about 100 cm/s/s, and seriously affects the amplification of high frequency ground motion and PGA. Noguchi and Sasatani (2008) developed an efficient technique for quantitative evaluation of nonlinear site response using the horizontal-to-vertical spectral ratio of S-wave (S-H/V) derived from strong ground motion records, based on Wen et al. (2006). We applied this technique to perform a detailed analysis of the properties of nonlinear site response based on a large amount of data recorded at 132 K-NET and KiK-net strong motion stations in Northern Japan during the off-Miyagi Earthquake. We succeeded in demonstrating a relationship between ground motion level, nonlinear site response and surface soil characteristics. For example, the seismic data recorded at KiK-net IWTH26 showed obvious characteristics of nonlinear site response when the PGA exceeded 100 cm/s/s. As the ground motion level increased, the dominant peak of S-H/V shifted to lower frequency, the high frequency level of S-H/V dropped, and PGA amplification decreased. On the other hand, the records at MYGH03 seemed not to be affected by nonlinear site response even for high ground motion levels in which PGA exceeds 800 cm/s/s. The characteristics of such nonlinear site amplification can be modeled by evaluating Murnaghan constants (e.g. McCall, 1994), which are the third-order elastic constants. In order to explain the observed characteristics of

  17. Response bounds for complex systems with a localised and uncertain nonlinearity

    Science.gov (United States)

    Butlin, T.

    2016-12-01

    Predicting the vibration response of complex nonlinear structures is a significant challenge: the response may involve many modes of the structure; nonlinearity precludes the use of efficient techniques developed for linear systems; and there is often uncertainty associated with the nonlinear law, even to the extent that its functional form is not always known. This paper builds on a recently developed method for handling this class of problem in a novel way. The method exploits the fact that nonlinearities are often spatially localised, and seeks the best- and worst-case system response with respect to a chosen metric by regarding the internal nonlinear force as an independent excitation to the underlying linear system. Constraints are used to capture what is thought to be known about the nonlinearity without needing to specify a particular law. This paper focuses on the case of systems with a single point nonlinearity but with arbitrarily complex underlying linear dynamics, driven by a sinusoidal force excitation. Semi-analytic upper and lower bounds are proposed for root-mean-square response metrics subject to constraints which specify that the nonlinearity should be a combination of (A) passive, (B) displacement-limited, and / or (C) force-saturating. The concept of 'equivalent linear bounds' is also introduced for cases where the response metric is thought to be dominated by the same frequency as the input. The bounds corresponding to a passive and displacement-limited nonlinearity are compared with Monte Carlo experimental and numerical results from an impacting beam test rig. The bounds corresponding to a passive and force-saturating nonlinearity are compared with numerical results for a friction-damped beam. The global upper and lower bounds are satisfied for all input frequencies but are generally found to be rather conservative. The 'equivalent linear bounds' show remarkably good agreement for predicting the range of root-mean-square velocity responses

  18. Computational Modelling Strategies for Nonlinear Response Prediction of Corroded Circular RC Bridge Piers

    Directory of Open Access Journals (Sweden)

    Mohammad M. Kashani

    2016-01-01

    Full Text Available A numerical model is presented that enables simulation of the nonlinear flexural response of corroded reinforced concrete (RC components. The model employs a force-based nonlinear fibre beam-column element. A new phenomenological uniaxial material model for corroded reinforcing steel is used. This model accounts for the impact of corrosion on buckling strength, postbuckling behaviour, and low-cycle fatigue degradation of vertical reinforcement under cyclic loading. The basic material model is validated through comparison of simulated and observed responses for uncorroded RC columns. The model is used to explore the impact of corrosion on the inelastic response of corroded RC columns.

  19. Nonlinear magneto-electric response of a giant magnetostrictive/piezoelectric composite cylinder

    Institute of Scientific and Technical Information of China (English)

    Yuan-Wen Gao; Juan-Juan Zhang

    2012-01-01

    In this study,we investigate the nonlinear coupling magneto-electric (ME) effect of a giant magnetostrictive/piezoelectric composite cylinder.The nonlinear constitutive relations of the ME material are taken into account,and the influences of the nonlinear material properties on the ME effect are investigated for the static and dynamic cases,respectively.The influences of different constraint conditions on the ME effect are discussed.In the dynamic case considering nonlinear material properties,the double frequency ME response (The response frequency is twice the applied magnetic frequency) is obtained and discussed,which can be used to explain the experiment phenomenon in which the input signal with frequency f is converted to the output signal with 2f in ME laminated structures.Some calculations on nonlinear ME effect are conducted.The obtained results indicate that the nonlinear material properties affect not only the magnitude of the ME effect in the static case but also the ME response frequency in the dynamic case.

  20. Estradiol valerate and alcohol intake: dose-response assessments

    Science.gov (United States)

    Quirarte, Gina L; Reid, Larry D; de la Teja, I Sofía Ledesma; Reid, Meta L; Sánchez, Marco A; Díaz-Trujillo, Arnulfo; Aguilar-Vazquez, Azucena; Prado-Alcalá, Roberto A

    2007-01-01

    Background An injection of estradiol valerate (EV) provides estradiol for a prolonged period. Recent research indicates that a single 2.0 mg injection of EV modifies a female rat's appetite for alcoholic beverages. This research extends the initial research by assessing 8 doses of EV (from .001 to 2.0 mg/female rat), as well assessing the effects of 2.0 mg EV in females with ovariectomies. Results With the administration of EV, there was a dose-related loss of bodyweight reaching the maximum loss, when it occurred, at about 4 days after injections. Subsequently, rats returned to gaining weight regularly. Of the doses tested, only the 2.0 mg dose produced a consistent increase in intake of ethanol during the time previous research indicated that the rats would show enhanced intakes. There was, however, a dose-related trend for smaller doses to enhance intakes. Rats with ovariectomies showed a similar pattern of effects, to intact rats, with the 2 mg dose. After extensive histories of intake of alcohol, both placebo and EV-treated females had estradiol levels below the average measured in females without a history of alcohol-intake. Conclusion The data support the conclusion that pharmacological doses of estradiol can produce enduring changes that are manifest as an enhanced appetite for alcoholic beverages. The effect can occur among females without ovaries. PMID:17335585

  1. A Grid Algorithm for High Throughput Fitting of Dose-Response Curve Data

    OpenAIRE

    Wang, Yuhong; Jadhav, Ajit; Southal, Noel; Huang, Ruili; Nguyen, Dac-Trung

    2010-01-01

    We describe a novel algorithm, Grid algorithm, and the corresponding computer program for high throughput fitting of dose-response curves that are described by the four-parameter symmetric logistic dose-response model. The Grid algorithm searches through all points in a grid of four dimensions (parameters) and finds the optimum one that corresponds to the best fit. Using simulated dose-response curves, we examined the Grid program’s performance in reproducing the actual values that were used ...

  2. Dimensionality of InGaAs nonlinear optical response

    Energy Technology Data Exchange (ETDEWEB)

    Bolton, S.R. [Univ. of California, Berkeley, CA (United States). Dept. of Physics]|[Lawrence Berkeley National Lab., CA (United States). Materials Sciences Div.

    1995-07-01

    In this thesis the ultrafast optical properties of a series of InGaAs samples ranging from the two to the three dimensional limit are discussed. An optical system producing 150 fs continuum centered at 1.5 microns was built. Using this system, ultrafast pump-probe and four wave mixing experiments were performed. Carrier thermalization measurements reveal that screening of the Coulomb interaction is relatively unaffected by confinement, while Pauli blocking nonlinearities at the band edge are approximately twice as strong in two dimensions as in three. Carrier cooling via phonon emission is influenced by confinement due both to the change in electron distribution function and the reduction in electron phonon coupling. Purely coherent band edge effects, as measured by the AC Stark effect and four wave mixing, are found to be dominated by the changes in excitonic structure which take place with confinement.

  3. Ultrafast third-order nonlinear optical response of pyrene derivatives

    Science.gov (United States)

    Shi, Yufang; Li, Zhongguo; Fang, Yu; Sun, Jinyu; Zhao, Minggen; Song, Yinglin

    2017-05-01

    Two mono-substituted pyrene derivatives with delocalized electron system 1-(pyren-1-yl)-3-(4-Methyl thiophene-2-yl) acrylic ketone (13#) and 1-(pyren-1-yl)-3-(4-bromo thiophene-2-yl) acrylic ketone (15#) were successfully synthesized. The resultant compounds were characterized by nuclear magnetic resonance (NMR), infrared spectroscopy (IR), high resolution mass spectrum (HR-MS), and UV-vis spectra. The third-order nonlinear optical properties of the compounds were investigated using Z-scan technique with femtosecond laser pulses at 500 nm and 700 nm, respectively. Both of the compounds showed a decrease in transmittance about the focus, which are typical of two-photon absorption. It was found that the two-photon absorption behavior of the pyrene derivatives were modified by substituents on thiophene ring. These results indicate that both compounds can be promising candidates for future optoelectronic and bio-imaging applications.

  4. Nonlinear laser pulse response in a crystalline lens.

    Science.gov (United States)

    Sharma, R P; Gupta, Pradeep Kumar; Singh, Ram Kishor; Strickland, D

    2016-04-01

    The propagation characteristics of a spatial Gaussian laser pulse have been studied inside a gradient-index structured crystalline lens with constant-density plasma generated by the laser-tissue interaction. The propagation of the laser pulse is affected by the nonlinearities introduced by the generated plasma inside the crystalline lens. Owing to the movement of plasma species from a higher- to a lower-temperature region, an increase in the refractive index occurs that causes the focusing of the laser pulse. In this study, extended paraxial approximation has been applied to take into account the evolution of the radial profile of the Gaussian laser pulse. To examine the propagation characteristics, variation of the beam width parameter has been observed as a function of the laser power and initial beam radius. The cavitation bubble formation, which plays an important role in the restoration of the elasticity of the crystalline lens, has been investigated.

  5. Chronic periodontitis and smoking Prevalence and dose-response relationship

    Science.gov (United States)

    Khan, Shahrukh; Khalid, Taimur; Awan, Kamran H.

    2016-01-01

    Objectives: To determine the prevalence and dose-response relationship of chronic periodontitis among smokers in Pakistan. Methods: This is a cross-sectional study among participants seeking dental care in Karachi Medical and Dental College, Karachi, Pakistan. A total of 443 participants with a mean age of 44.3 (±6.5) participated in the study from April 2011 to December 2011. Males comprised 64.7%, and females comprised 35.2%. Participants were interviewed on social demographics and oral habits. Participants with shallow pockets (3.5-5.5 mm) and deep pockets (>5.5 mm) were considered suffering from chronic periodontitis. The characteristics of participants were assessed using frequency distribution for categorical variables and mean (standard deviation) for continuous variables. Results: Among 443 participants, smokers were distributed as 55.1% and non-smokers as 44.9%. Smoking was found to be significantly related to young adults (p<0.007), male gender (p<0.001), and lower education level (p<0.01). Overall prevalence of chronic periodontitis among smokers was estimated at 81.6%. Heavy smoking was found to have significantly high prevalence (p<0.001) and severity (p<0.001) of periodontitis as compared with moderate and light smokers. The multivariate unadjusted model depicted 3.5 times higher risk of chronic periodontitis among smokers (p<0.001). Conclusion: Chronic periodontitis had a high prevalence among smokers. Heavy smoking was found to have a higher risk for having periodontitis. PMID:27464867

  6. The cytokinesis-blocked micronucleus assay: dose-response calibration curve, background frequency in the population and dose estimation.

    Science.gov (United States)

    Rastkhah, E; Zakeri, F; Ghoranneviss, M; Rajabpour, M R; Farshidpour, M R; Mianji, F; Bayat, M

    2016-03-01

    An in vitro study of the dose responses of human peripheral blood lymphocytes was conducted with the aim of creating calibrated dose-response curves for biodosimetry measuring up to 4 Gy (0.25-4 Gy) of gamma radiation. The cytokinesis-blocked micronucleus (CBMN) assay was employed to obtain the frequencies of micronuclei (MN) per binucleated cell in blood samples from 16 healthy donors (eight males and eight females) in two age ranges of 20-34 and 35-50 years. The data were used to construct the calibration curves for men and women in two age groups, separately. An increase in micronuclei yield with the dose in a linear-quadratic way was observed in all groups. To verify the applicability of the constructed calibration curve, MN yields were measured in peripheral blood lymphocytes of two real overexposed subjects and three irradiated samples with unknown dose, and the results were compared with dose values obtained from measuring dicentric chromosomes. The comparison of the results obtained by the two techniques indicated a good agreement between dose estimates. The average baseline frequency of MN for the 130 healthy non-exposed donors (77 men and 55 women, 20-60 years old divided into four age groups) ranged from 6 to 21 micronuclei per 1000 binucleated cells. Baseline MN frequencies were higher for women and for the older age group. The results presented in this study point out that the CBMN assay is a reliable, easier and valuable alternative method for biological dosimetry.

  7. Idiorrhythmic dose-rate variability in dietary zinc intake generates a different response pattern of zinc metabolism than conventional dose-response feeding.

    Science.gov (United States)

    Momcilović, B; Reeves, P G; Blake, M J

    1997-07-01

    We compared the effects of idiorrhythmic dose-rate feeding and conventional dose-response on the induction of intestinal metallothionein (iMT), expression of aortal heat-shock protein mRNA (HSP70mRNA) induced by restraint stress, and accumulation of Zn in the femur and incisor of young growing male rats. An idiorrhythmic approach requires that the average dietary Zn concentration (modulo, M) over the whole experiment (epoch, E) is kept constant across different groups. This is done by adjusting the Zn concentration of the supplemented diet supplied to compensate for the reduction in the number of days on which Zn-supplemented diet is fed, the latter being spread evenly over the experiment. Idiorrhythms involve offering the diet with n times the overall Zn concentration (M) only every nth day with Zn-deficient diet offered on other days. Idiorrythmic Zn dose-rate feeding changed Zn accumulation in the femur and incisor in a complex bi-modal fashion, indicating that metabolic efficiency of dietary Zn is not constant but depends on Zn dose-rate. In contrast to feeding Zn in the conventional dose-response scheme, iMT and HSP70mRNA were not affected by idiorrhythmic dose-rate feeding. Idiorrhythmic cycling in dietary Zn load posed no risk of a biochemical overload nor caused the animals to be stressed. Idiorrhythmic dose-rate feeding brings the dimension of time to the conventional dose-response model.

  8. NONLINEAR DYNAMICS RESPONSE OF CASING PIPE UNDER COMBINED WAVE-CURRENT

    Institute of Scientific and Technical Information of China (English)

    TANG You-gang; GU Jia-yang; ZUO Jian-li; MIN Jian-qin

    2005-01-01

    The vortex-induced nonlinear vibration of casing pipes in the deep water was studied considering the loads of current and combined wave-current. The vortex-induced vibration equation of a casing pipe was set up considering the beam mode and Morison's nonlinear fluid loads as well as the vortex-excited loads. The approach of calculating vortex-excited nonlinear vibration by Galerkin's method was proposed. The natural vibration frequencies and modes were obtained, and the response including primary resonance induced by current and the composite resonance under combined wave-current for the 170 m long casing pipe in the 160 m depth of water were investigated. The results show that the dynamics response of casing pipe obviously increases, and the complicated response behaviors of casing pipe are described under combined wave-current.

  9. Regular nonlinear response of the driven Duffing oscillator to chaotic time series

    Institute of Scientific and Technical Information of China (English)

    YuanYe; Li Yue; Danilo P. Mandic; Yang Bao-Jun

    2009-01-01

    Nonlinear response of the driven Duffing oscillator to periodic or quasi-periodic signals has been well studied. In this paper, we investigate the nonlinear response of the driven Duffing oscillator to non-periodic, more specifically, chaotic time series. Through numerical simulations, we find that the driven Duffing oscillator can also show regular nonlinear response to the chaotic time series with different degree of chaos as generated by the same chaotic series generating model, and there exists a relationship between the state of the driven Duffing oscillator and the chaoticity of the input signal of the driven Duffing oscillator. One real-world and two artificial chaotic time series are used to verify the new feature of Duffing oscillator. A potential application of the new feature of Duffing oscillator is also indicated.

  10. RBFNN Model for Predicting Nonlinear Response of Uniformly Loaded Paddle Cantilever

    Directory of Open Access Journals (Sweden)

    Abdullah H. Abdullah

    2009-01-01

    Full Text Available The Radial basis Function neural network (RBFNN model has been developed for the prediction of nonlinear response for paddle Cantilever with built-in edges and different sizes, thickness and uniform loads. Learning data was performed by using a nonlinear finite element program, incremental stages of the nonlinear finite element analysis were generated by using 25 schemes of built paddle Cantilevers with different thickness and uniform distributed loads. The neural network model has 5 input nodes representing the uniform distributed load and paddle size, length, width and thickness, eight nodes at hidden layer and one output node representing the max. deflection response (1500×1 represent the deflection response of load. Regression analysis between finite element results and values predicted by the neural network model shows the least error.

  11. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis.

    Science.gov (United States)

    Crippa, Alessio; Discacciati, Andrea; Larsson, Susanna C; Wolk, Alicja; Orsini, Nicola

    2014-10-15

    Several studies have analyzed the relationship between coffee consumption and mortality, but the shape of the association remains unclear. We conducted a dose-response meta-analysis of prospective studies to examine the dose-response associations between coffee consumption and mortality from all causes, cardiovascular disease (CVD), and all cancers. Pertinent studies, published between 1966 and 2013, were identified by searching PubMed and by reviewing the reference lists of the selected articles. Prospective studies in which investigators reported relative risks of mortality from all causes, CVD, and all cancers for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Twenty-one prospective studies, with 121,915 deaths and 997,464 participants, met the inclusion criteria. There was strong evidence of nonlinear associations between coffee consumption and mortality for all causes and CVD (P for nonlinearity Coffee consumption was not associated with cancer mortality. Findings from this meta-analysis indicate that coffee consumption is inversely associated with all-cause and CVD mortality.

  12. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

    Science.gov (United States)

    Hada, M.; George, Kerry; Cucinotta, Francis A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

  13. Dose-dependent hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to sublethal doses of gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Song, You, E-mail: you.song@niva.no [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway); Salbu, Brit; Teien, Hans-Christian; Heier, Lene Sørlie [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Rosseland, Bjørn Olav [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian University of Life Sciences (NMBU), Department of Ecology and Natural Resource Management, P.O. Box 5003, N-1432 Ås (Norway); Tollefsen, Knut Erik [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway)

    2014-11-15

    Highlights: • First study on early stress responses in salmon exposed to low-dose gamma radiation. • Dramatic dose-dependent transcriptional responses characterized. • Multiple modes of action proposed for gamma radiation. - Abstract: Due to the production of free radicals, gamma radiation may pose a hazard to living organisms. The high-dose radiation effects have been extensively studied, whereas the ecotoxicity data on low-dose gamma radiation is still limited. The present study was therefore performed using Atlantic salmon (Salmo salar) to characterize effects of low-dose (15, 70 and 280 mGy) gamma radiation after short-term (48 h) exposure. Global transcriptional changes were studied using a combination of high-density oligonucleotide microarrays and quantitative real-time reverse transcription polymerase chain reaction (qPCR). Differentially expressed genes (DEGs; in this article the phrase gene expression is taken as a synonym of gene transcription, although it is acknowledged that gene expression can also be regulated, e.g., at protein stability and translational level) were determined and linked to their biological meanings predicted using both Gene Ontology (GO) and mammalian ortholog-based functional analyses. The plasma glucose level was also measured as a general stress biomarker at the organism level. Results from the microarray analysis revealed a dose-dependent pattern of global transcriptional responses, with 222, 495 and 909 DEGs regulated by 15, 70 and 280 mGy gamma radiation, respectively. Among these DEGs, only 34 were commonly regulated by all radiation doses, whereas the majority of differences were dose-specific. No GO functions were identified at low or medium doses, but repression of DEGs associated with GO functions such as DNA replication, cell cycle regulation and response to reactive oxygen species (ROS) were observed after 280 mGy gamma exposure. Ortholog-based toxicity pathway analysis further showed that 15 mGy radiation

  14. Understanding and Ameliorating Non-Linear Phase and Amplitude Responses in AMCW Lidar

    Directory of Open Access Journals (Sweden)

    John P. Godbaz

    2011-12-01

    Full Text Available Amplitude modulated continuous wave (AMCW lidar systems commonly suffer from non-linear phase and amplitude responses due to a number of known factors such as aliasing and multipath inteference. In order to produce useful range and intensity information it is necessary to remove these perturbations from the measurements. We review the known causes of non-linearity, namely aliasing, temporal variation in correlation waveform shape and mixed pixels/multipath inteference. We also introduce other sources of non-linearity, including crosstalk, modulation waveform envelope decay and non-circularly symmetric noise statistics, that have been ignored in the literature. An experimental study is conducted to evaluate techniques for mitigation of non-linearity, and it is found that harmonic cancellation provides a significant improvement in phase and amplitude linearity.

  15. Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations.

    Science.gov (United States)

    Calabrese, Edward J

    2016-08-01

    This article provides the first extensive documentation of the dose response features of pre- and postconditioning. Pre- and postconditioning studies with rigorous study designs, using multiple doses/concentrations along with refined dose/concentration spacing strategies, often display hormetic dose/concentration response relationships with considerable generality across biological model, inducing (i.e., conditioning) agent, challenging dose treatment, endpoint, and mechanism. Pre- and postconditioning hormesis dose/concentration-response relationships are reported for 154 diverse conditioning agents, affecting more than 550 dose/concentration responses, across a broad range of biological models and endpoints. The quantitative features of the pre- and postconditioning-induced protective responses are modest, typically being 30-60% greater than control values at maximum, findings that are consistent with a large body (>10,000) of hormetic dose/concentration responses not related to pre- and postconditioning. Regardless of the biological model, inducing agent, endpoint or mechanism, the quantitative features of hormetic dose/concentration responses are similar, suggesting that the magnitude of response is a measure of biological plasticity. This paper also provides the first documentation that hormetic effects account for preconditioning induced early (1-3h) and delayed (12-72h) windows of protection. These findings indicate that pre- and postconditioning are specific types of hormesis.

  16. Nonlinear biosynthetic gene cluster dose effect on penicillin production by Penicillium chrysogenum.

    Science.gov (United States)

    Nijland, Jeroen G; Ebbendorf, Bjorg; Woszczynska, Marta; Boer, Rémon; Bovenberg, Roel A L; Driessen, Arnold J M

    2010-11-01

    Industrial penicillin production levels by the filamentous fungus Penicillium chrysogenum increased dramatically by classical strain improvement. High-yielding strains contain multiple copies of the penicillin biosynthetic gene cluster that encodes three key enzymes of the β-lactam biosynthetic pathway. We have analyzed the gene cluster dose effect on penicillin production using the high-yielding P. chrysogenum strain DS17690 that was cured from its native clusters. The amount of penicillin V produced increased with the penicillin biosynthetic gene cluster number but was saturated at high copy numbers. Likewise, transcript levels of the biosynthetic genes pcbAB [δ-(l-α-aminoadipyl)-l-cysteinyl-d-valine synthetase], pcbC (isopenicillin N synthase), and penDE (acyltransferase) correlated with the cluster copy number. Remarkably, the protein level of acyltransferase, which localizes to peroxisomes, was saturated already at low cluster copy numbers. At higher copy numbers, intracellular levels of isopenicillin N increased, suggesting that the acyltransferase reaction presents a limiting step at a high gene dose. Since the number and appearance of the peroxisomes did not change significantly with the gene cluster copy number, we conclude that the acyltransferase activity is limiting for penicillin biosynthesis at high biosynthetic gene cluster copy numbers. These results suggest that at a high penicillin production level, productivity is limited by the peroxisomal acyltransferase import activity and/or the availability of coenzyme A (CoA)-activated side chains.

  17. A DoseResponse Study of Magnesium Sulfate in Suppressing Cardiovascular Responses to Laryngoscopy & Endotracheal Intubation

    Directory of Open Access Journals (Sweden)

    K Montazeri

    2005-03-01

    Full Text Available Background: The effects of pretreatment with magnesium on cardiovascular responses associated with intubation have been studied previously. In this study we wanted to find optimal dose of magnesium that causes decreased cardiovascular responses after laryngoscopy & endotracheal intubation. Methods: In a double-blind , randomized, clinical trial ,120 ASA-1 patients with ages between 15-50 years old , who were candidates for elective surgery, were selected and classified in 6 groups (20 patients in each . The pulse rate and arterial blood pressure were measured and recorded at 5 minutes before taking any drug then, according to different groups, patients took magnesium sulfate (10, 20, 30, 40, 50mg/kg and lidocaine (1.5 mg/kg. The induction of anesthesia was same in all groups and the pulse rate and arterial blood pressure were measured and recorded just before intubation and also at 1, 3 , and 5 minutes after intubation (before surgical incision . Statistical analysis was performed by use of ANOVA, Post Hoc test (Duncan, Pearson correlation, and Chi square test. Results: there were no statistically significant differences in blood pressure, pulse rate, Train Of Four (TOF, and complications between groups who received magnesium but the significant differences in these parameters were seen between magnesium and lidocaine groups. Conclusion: We concluded that pretreatment with different doses of magnesium sulfate have a safe decreasing effect on cardiovascular responses that is more effective than pretreatment with lidocaine. Keywords: magnesium sulfate, cardiovascular responses, lidocaine.

  18. Body mass index and risk of renal cell cancer: a dose-response meta-analysis of published cohort studies.

    Science.gov (United States)

    Wang, Furan; Xu, Yinghua

    2014-10-01

    Obesity is accepted as one of the major risk factors for renal cell cancer (RCC). However, conflicting results persist for the pooled risks based on the results from case-control and cohort studies combined, and the exact shape of the dose-response relationship has not been clearly defined yet. To help elucidate the role of obesity, PubMed and Embase databases were searched for published cohort studies on associations between body mass index (BMI) and risk of RCC. Random-effects models and dose-response meta-analyses were used to pool study results. Subgroup analyses were conducted by the available characteristics of studies and participants. Cohort studies (21) with 15,144 cases and 9,080,052 participants were identified. Compared to normal weight, the pooled relative risks and the corresponding 95% confidence intervals of RCC were 1.28(1.24-1.33) for preobesity and 1.77(1.68-1.87) for obesity, respectively. A nonlinear dose-response relationship was also found for RCC risk with BMI (p = 0.000), and the risk increased by 4% for each 1 kg/m(2) increment in BMI. There was no significant between-study heterogeneity among studies (I(2) = 35.6% for preobesity and I(2) = 44.2% for obesity, respectively). Subgroup analysis showed a basically consistent result with the overall analysis. These results suggest that increased BMI are associated with increased risk of RCC both for men and women. © 2014 UICC.

  19. Intake of fruit and vegetables and risk of bladder cancer: a dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Yao, Baodong; Yan, Yujie; Ye, Xianwu; Fang, Hong; Xu, Huilin; Liu, Yinan; Li, Sheran; Zhao, Yanping

    2014-12-01

    Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial. We therefore summarized the evidence from observational studies in categorical, linear, and nonlinear, dose-response meta-analysis. Pertinent studies were identified by searching EMBASE and PubMed from their inception to August 2013. Thirty-one observational studies involving 12,610 cases and 1,121,649 participants were included. The combined rate ratio (RR, 95 % CI) of bladder cancer for the highest versus lowest intake was 0.83 (0.69-0.99) for total fruit and vegetables, 0.81 (0.70-0.93) for total vegetables, 0.77 (0.69-0.87) for total fruit, 0.84 (0.77-0.91) for cruciferous vegetables, 0.79 (0.68-0.91) for citrus fruits, and 0.74 (0.66-0.84) for yellow-orange vegetables. Subgroup analysis showed study design and gender as possible sources of heterogeneity. A nonlinear relationship was found of citrus fruits intake with risk of bladder cancer (P for nonlinearity = 0.018), and the RRs (95 % CI) of bladder cancer were 0.87 (0.78-0.96), 0.80 (0.67-0.94), 0.79 (0.66-0.94), 0.79 (0.65-0.96), and 0.79 (0.64-0.99) for 30, 60, 90, 120, and 150 g/day. A nonlinear relationship was also found of yellow-orange vegetable intake with risk of bladder cancer risk (P for nonlinearity = 0.033). Some evidence of publication bias was observed for fruit, citrus fruits, and yellow-orange vegetables. This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.

  20. Dose-response modeling : Evaluation, application, and development of procedures for benchmark dose analysis in health risk assessment of chemical substances

    OpenAIRE

    Sand, Salomon

    2005-01-01

    In this thesis, dose-response modeling and procedures for benchmark dose (BMD) analysis in health risk assessment of chemical substances have been investigated. The BMD method has been proposed as an alternative to the NOAEL (no-observedadverse- effect-level) approach in health risk assessment of non-genotoxic agents. According to the BMD concept, a dose-response model is fitted to data and the BMD is defined as the dose causing a predetermined change in response. A lowe...

  1. Diagnosing nonlinearities in the local and remote responses to partial Amazon deforestation

    Science.gov (United States)

    Badger, Andrew M.; Dirmeyer, Paul A.

    2016-08-01

    Using a set of fully coupled climate model simulations, the response to partial deforestation over the Amazon due to agricultural expansion has been analyzed. Three variations of 50% deforestation (all of western half, all of eastern half, and half of each grid box) were compared with total deforestation to determine the degree and character of nonlinearity of the climate response to partial deforestation. A metric is developed to quantify the degree and distribution of nonlinearity in the response, applicable to any variable. The metric also quantifies whether the response is saturating or accelerating, meaning significantly either more or less than 50% of the simulated response to total deforestation is attained at 50% deforestation. The spatial structure of the atmospheric response to Amazon deforestation reveals large areas across the tropics that exhibit a significant nonlinear component, particularly for temperature and geopotential height. Over the domain between 45°S and 45°N across all longitudes, 50% deforestation generally provides less than half of the total response to deforestation over oceans, indicating the marine portion of climate system is somewhat resilient to progressive deforestation. However, over continents there are both accelerating and saturating responses to 50% Amazon deforestation, and the response is different depending on whether the eastern or western half of Amazonia is deforested or half of the forest is removed uniformly across the region.

  2. Dose-response regressions for algal growth and similar continuous endpoints: Calculation of effective concentrations

    DEFF Research Database (Denmark)

    Christensen, Erik R.; Kusk, Kresten Ole; Nyholm, Niels

    2009-01-01

    % inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4...

  3. Biphasic and triphasic dose responses in zebrafish embryos to low-dose 150 kV X-rays with different levels of hardness.

    Science.gov (United States)

    Kong, Eva Yi; Cheng, Shuk Han; Yu, Kwan Ngok

    2016-07-01

    The in vivo low-dose responses of zebrafish (Danio rerio) embryos to 150 kV X-rays with different levels of hardness were examined through the number of apoptotic events revealed at 24 h post fertilization by vital dye acridine orange staining. Our results suggested that a triphasic dose response was likely a common phenomenon in living organisms irradiated by X-rays, which comprised an ultra-low-dose inhibition, low-dose stimulation and high-dose inhibition. Our results also suggested that the hormetic zone (or the stimulation zone) was shifted towards lower doses with application of filters. The non-detection of a triphasic dose response in previous experiments could likely be attributed to the use of hard X-rays, which shifted the hormetic zone into an unmonitored ultra-low-dose region. In such cases where the subhormetic zone was missed, a biphasic dose response would be reported instead.

  4. Nonlinear Gust Response Analysis of Free Flexible Aircraft

    Directory of Open Access Journals (Sweden)

    Chen Shilu

    2013-01-01

    Full Text Available Gust response analysis plays a very important role in large aircraft design. This paper presents a methodology for calculating the flight dynamic characteristics and gust response of free flexible aircraft. A multidisciplinary coupled numerical tool is developed to simulate detailed aircraft models undergoing arbitrary free flight motion in the time domain, by Computational Fluid Dynamics (CFD, Computational Structure Dynamics (CSD and Computational Flight Mechanics (CFM coupling. To achieve this objective, a structured, time-accurate flow-solver is coupled with a computational module solving the flight mechanics equations of motion and a structural mechanics code determining the structural deformations. A novel method to determine the trim state of flexible aircraft is also stated. First, the field velocity approach is validated, after the trim state is attained, gust responses for the one-minus-cosine gust profile are analyzed for the longitudinal motion of a slender-wing aircraft configuration with and without the consideration of structural deformation.

  5. Effects on the Floor Response Spectra by the Nonlinear Behavior of a Seismic Base Isolation System

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyungkui; Kim, Jung Han; Choi, Inkil [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    An evaluation of safety being carried out for various risk factors of prevents for nuclear power plant accident. In general, an evaluation of the structural integrity was performed about seismic risk. In recent years, an assessment of integrity of internal equipment being carried out for earthquake loads owing to the possibility of severe accidents caused by the destruction of internal equipment or a blackout. Floor response spectra of the structure should be sought for evaluating of the integrity of internal equipment. The floor response spectra depends on the characteristics of seismic base isolation system such as the natural frequency, damping ratio, and height of the floor of the structure. An evaluation of the structural integrity using the equivalent stiffness of the seismic base isolation system was satisfactory. In this study, the effect of the non-linearity of isolated system in the floor response spectrum of the structure is analyzed. In this study, the floor response spectrum of the seismic base isolation system by the non-linear effect of the rubber isolator was analyzed. As a result, the influence of the non-linear isolated system was increased in hi-frequency domain. In addition, each floor exhibited a more different of responses compared with the equivalent linear model of the isolated structure. The non-linearity of the isolation system of the structure was considered, because of a more reliable assessment of integrity of equipment at each floor of seismic base the isolation system.

  6. Dose response characteristics of a novel CCD camera-based electronic portal imaging device comparison with OCTAVIUS detector.

    Science.gov (United States)

    Anvari, Akbar; Aghamiri, Seyed Mahmoud Reza; Mahdavi, Seyed Rabie; Alaei, Parham

    2015-01-01

    Dosimetric properties of a CCD camera-based Electronic Portal Imaging Device (EPID) for clinical dosimetric application have been evaluated. Characteristics obtained by EPID also compared with commercial 2D array of ion chambers. Portal images acquired in dosimetry mode then exported raw fluence or uncorrected images were investigated. Integration time of image acquisition mode has adjusted on 1 s per frame. As saturation of camera of the EPID, dose response does not have linear behavior. The slight nonlinearity of the camera response can be corrected by a logarithmic expression. A fourth order polynomial regression model with coefficient of determination of 0.998 predicts a response to absolute dose values at less than 50 cGy. A field size dependent response of up to 7% (0.99-1.06) relative OCTAVIUS detector measurement was found. The EPID response can be fitted by a cubic regression for field size changes, yielded coefficient of determination of 0.999. These results indicate that the EPID is well suited for accurate dosimetric purposes, the major limitation currently being due to integration time and dead-time in frame acquisition.

  7. Dose-response relationships and threshold levels in skin and respiratory allergy

    NARCIS (Netherlands)

    Arts, J.H.E.; Mommers, C.; Heer, C.de

    2006-01-01

    A literature study was performed to evaluate dose-response relationships and no-effect levels for sensitization and elicitation in skin- and respiratory allergy. With respect to the skin, dose-response relationships and no-effect levels were found for both intradermal and topical induction, as well

  8. The key events dose-response framework: its potential for application to foodborne pathogenic microorganisms.

    NARCIS (Netherlands)

    Buchanan, R.L.; Havelaar, A.H.; Smith, M.A.; Whiting, R.C.; Julien, E.

    2009-01-01

    The Key Events Dose-Response Framework (KEDRF) is an analytical approach that facilitates the use of currently available data to gain insight regarding dose-response relationships. The use of the KEDRF also helps identify critical knowledge gaps that once filled, will reduce reliance on assumptions.

  9. Health damage of air pollution : an estimate of a dose-response relationship for The Netherlands

    NARCIS (Netherlands)

    Nentjes, A; Schneider, T

    1998-01-01

    This paper estimates the dose-response relationship between air pollution and the number of work loss days for The Netherlands. The study is based on illness data (work loss days) for the Dutch labor population and average year concentrations of air pollution in 29 districts. The dose-response

  10. Statistical strategies for averaging EC50 from multiple dose-response experiments.

    Science.gov (United States)

    Jiang, Xiaoqi; Kopp-Schneider, Annette

    2015-11-01

    In most dose-response studies, repeated experiments are conducted to determine the EC50 value for a chemical, requiring averaging EC50 estimates from a series of experiments. Two statistical strategies, the mixed-effect modeling and the meta-analysis approach, can be applied to estimate average behavior of EC50 values over all experiments by considering the variabilities within and among experiments. We investigated these two strategies in two common cases of multiple dose-response experiments in (a) complete and explicit dose-response relationships are observed in all experiments and in (b) only in a subset of experiments. In case (a), the meta-analysis strategy is a simple and robust method to average EC50 estimates. In case (b), all experimental data sets can be first screened using the dose-response screening plot, which allows visualization and comparison of multiple dose-response experimental results. As long as more than three experiments provide information about complete dose-response relationships, the experiments that cover incomplete relationships can be excluded from the meta-analysis strategy of averaging EC50 estimates. If there are only two experiments containing complete dose-response information, the mixed-effects model approach is suggested. We subsequently provided a web application for non-statisticians to implement the proposed meta-analysis strategy of averaging EC50 estimates from multiple dose-response experiments.

  11. A method to adjust radiation dose-response relationships for clinical risk factors

    DEFF Research Database (Denmark)

    Appelt, Ane Lindegaard; Vogelius, Ivan R

    2012-01-01

    Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients...

  12. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chuan-Yaun

    2009-01-27

    “Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation " was started on 09/01/03 and ended on 08/31/07. The primary objective of the project was to carry out mechanistic studies of the roles of the anti-oxidant SOD genes in mammalian cellular response to low dose ionizing radiation.

  13. Fundamental investigations of natural and laboratory generated SAR dose response curves for quartz OSL in the high dose range

    DEFF Research Database (Denmark)

    Timar-Gabor, Alida; Constantin, Daniela; Buylaert, Jan-Pieter

    2015-01-01

    SAR-OSL investigations on quartz from Romanian loess resulted in non concordant fine and coarse-grain ages for equivalent doses higher than ~100 Gy. The laboratory dose response for both grain sizes is well represented by a sum of two saturating exponential functions, fine and coarse grains chara...... equivalent dose of 2000e2500 Gy were found to be below the saturation level of the laboratory dose response curve for both grain sizes; this also applied to the luminescence signals measured after >5000 Gy given on top of natural doses. © 2015 Elsevier Ltd. All rights reserved....... characterised by D01 and D02 values of ~140 and ~1400 Gy and ~65 and ~650 Gy respectively. Pulsed OSL experiments confirmed that this behaviour is almost certainly inherent to quartz and not caused by contamination with another mineral. Natural doseeresponse curves do not follow the same pattern and enter...... saturation much earlier. Analysis of time resolved spectra indicated similar luminescence lifetimes for both fine and coarse quartz grains, and natural and laboratory generated OSL signals seem to use the same non-dosedependent recombination pathways. The natural signals of a sample with an expected...

  14. Third-order nonlinear optical response of colloidal gold nanoparticles prepared by sputtering deposition

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Hemerson P. S.; Alencar, Márcio A. R. C.; Hickmann, Jandir M. [Optics and Materials Group–OPTMA, Universidade Federal de Alagoas, CAIXA POSTAL 2051, 57061-970 Maceió (Brazil); Wender, Heberton [Brazilian Synchrotron National Laboratory (LNLS), CNPEM, Rua Giuseppe Máximo Scolfaro 10.000, 13083-970 Campinas (Brazil); Department of Physics, Universidade Federal do Mato Grosso do Sul, 79070-900, Campo Grande (Brazil); Teixeira, Sergio R. [Institute of Physics, Universidade Federal do Rio Grande do Sul, 91501-970, Porto Alegre (Brazil); Dupont, Jairton [Laboratory of Molecular Catalysis, Institute of Chemistry, Universidade Federal do Rio Grande do Sul, 91501-970, Porto Alegre (Brazil)

    2013-11-14

    The nonlinear optical responses of gold nanoparticles dispersed in castor oil produced by sputtering deposition were investigated, using the thermally managed Z-scan technique. Particles with spherical shape and 2.6 nm of average diameter were obtained and characterized by transmission electron microscopy and small angle X-ray scattering. This colloid was highly stable, without the presence of chemical impurities, neither stabilizers. It was observed that this system presents a large refractive third-order nonlinear response and a negligible nonlinear absorption. Moreover, the evaluation of the all-optical switching figures of merit demonstrated that the colloidal nanoparticles prepared by sputtering deposition have a good potential for the development of ultrafast photonic devices.

  15. On the Boundary between Nonlinear Jump Phenomenon and Linear Response of Hypoid Gear Dynamics

    Directory of Open Access Journals (Sweden)

    Jun Wang

    2011-01-01

    Full Text Available A nonlinear time-varying (NLTV dynamic model of a hypoid gear pair system with time-dependent mesh point, line-of-action vector, mesh stiffness, mesh damping, and backlash nonlinearity is formulated to analyze the transitional phase between nonlinear jump phenomenon and linear response. It is found that the classical jump discontinuity will occur if the dynamic mesh force exceeds the mean value of tooth mesh force. On the other hand, the propensity for the gear response to jump disappears when the dynamic mesh force is lower than the mean mesh force. Furthermore, the dynamic analysis is able to distinguish the specific tooth impact types from analyzing the behaviors of the dynamic mesh force. The proposed theory is general and also applicable to high-speed spur, helical and spiral bevel gears even though those types of gears are not the primary focus of this paper.

  16. Nonlinear optics response of semiconductor quantum wells under high magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Chemla, D.S.

    1993-07-01

    Recent investigations on the nonlinear optical response of semiconductor quantum wells in a strong perpendicular magnetic field, H, are reviewed. After some introductory material the evolution of the linear optical properties of GaAs QW`s as a function of H is discussed; an examination is made of how the magneto-excitons (MX) extrapolate continuously between quasi-2D QW excitons (X) when H = 0, and pairs of Landau levels (LL) when H {yields} {infinity}. Next, femtosecond time resolved investigations of their nonlinear optical response are presented; the evolution of MX-MX interactions with increasing H is stressed. Finally, how, as the dimensionality is reduced by application of H, the number of scattering channels is limited and relaxation of electron-hole pairs is affected. How nonlinear optical spectroscopy can be exploited to access the relaxation of angular momentum within magneto-excitons is also discussed.

  17. Wind energy conversion. Volume VI. Nonlinear response of wind turbine rotor

    Energy Technology Data Exchange (ETDEWEB)

    Chopra, I.

    1978-09-01

    The nonlinear equations of motor for a rigid rotor restrained by three flexible springs representing, respectively, the flapping, lagging, and feathering motions are derived using Lagrange's equations, for arbitrary angular rotations. These are reduced to a consistent set of nonlinear equations using nonlinear terms up to third order. The complete analysis is divided into three parts, A, B, and C. Part A consists of forced response of two-degree flapping-lagging rotor under the excitation of pure gravitational field (i.e., no aerodynamic forces). In Part B, the effect of aerodynamic forces on the dynamic response of two-degree flapping-lagging rotor is investigated. In Part C, the effect of third degree of motion, feathering, is considered.

  18. Cytogenetic dose-response in vitro for biological dosimetry after exposure to high doses of gamma-rays.

    Science.gov (United States)

    Vinnikov, Volodymyr A; Maznyk, Nataliya A

    2013-04-01

    The dose response for dicentrics plus centric rings and total unstable chromosome-type aberrations was studied in the first mitoses of cultured human peripheral blood lymphocytes irradiated in vitro to doses of ∼2, 4, 6, 8, 10, 16 and 20 Gy of acute (60)Со gamma-rays. A dose-dependent increase of aberration yield was accompanied by a tendency to the underdispersion of dicentrics and centric rings among cells distributions compared with Poisson statistics at doses ≥6 Gy. The formal fitting of the data to a linear-quadratic model resulted in an equation with the linear and quadratic coefficients ranged 0.098-0.129×cell(-1)×Gy(-1) and 0.039-0.034×cell(-1)×Gy(-2), respectively, depending on the fitting method. The actual radiation-induced aberration yield was markedly lower than expected from a calibration curve, generated earlier within a lower dose range. Interlaboratory variations in reported dicentric yields induced by medium-to-high radiation doses in vitro are discussed.

  19. Synchronous and non-synchronous responses of systems with multiple identical nonlinear vibration absorbers

    Science.gov (United States)

    Issa, Jimmy S.; Shaw, Steven W.

    2015-07-01

    In this work we investigate the nonlinear dynamic response of systems composed of a primary inertia to which multiple identical vibration absorbers are attached. This problem is motivated by observations of systems of centrifugal pendulum vibration absorbers that are designed to reduce engine order torsional vibrations in rotating systems, but the results are relevant to translational systems as well. In these systems the total absorber mass is split into multiple equal masses for purposes of distribution and/or balance, and it is generally expected that the absorbers will act in unison, corresponding to a synchronous response. In order to capture nonlinear effects of the responses of the absorbers, specifically, their amplitude-dependent frequency, we consider them to possess nonlinear stiffness. The equations of motion for the system are derived and it is shown how one can uncouple the equations for the absorbers from that for the primary inertia, resulting in a system of identical resonators that are globally coupled. These symmetric equations are scaled for weak nonlinear effects, near resonant forcing, and small damping. The method of averaging is applied, from which steady-state responses and their stability are investigated. The response of systems with two, three, and four absorbers are considered in detail, demonstrating a rich variety of bifurcations of the synchronous response, resulting in responses with various levels of symmetry in which sub-groups of absorbers are mutually synchronous. It is also shown that undamped models with more than two absorbers possess a degenerate response, which is made robust by the addition of damping to the model. Design guidelines are proposed based on the nature of the system response, with the aim of minimizing the acceleration of the primary system. It is shown that the desired absorber parameters are selected so that the system achieves a stable synchronous response which does not undergo jumps via saddle

  20. A strategy to model nonmonotonic dose-response curve and estimate IC50.

    Science.gov (United States)

    Zhang, Hui; Holden-Wiltse, Jeanne; Wang, Jiong; Liang, Hua

    2013-01-01

    The half-maximal inhibitory concentration IC[Formula: see text] is an important pharmacodynamic index of drug effectiveness. To estimate this value, the dose response relationship needs to be established, which is generally achieved by fitting monotonic sigmoidal models. However, recent studies on Human Immunodeficiency Virus (HIV) mutants developing resistance to antiviral drugs show that the dose response curve may not be monotonic. Traditional models can fail for nonmonotonic data and ignore observations that may be of biologic significance. Therefore, we propose a nonparametric model to describe the dose response relationship and fit the curve using local polynomial regression. The nonparametric approach is shown to be promising especially for estimating the IC[Formula: see text] of some HIV inhibitory drugs, in which there is a dose-dependent stimulation of response for mutant strains. This model strategy may be applicable to general pharmacologic, toxicologic, or other biomedical data that exhibits a nonmonotonic dose response relationship for which traditional parametric models fail.

  1. Response of Saturated Porous Nonlinear Materials to Dynamic Loadings

    Science.gov (United States)

    1984-05-31

    the following section a bilinear hysteretic skeleton was modeled, followed by calculations on an actual sand from Enewetak Atoll . In this section...the response of saturated sand from Enewetak Atoll . The skeleton properties are taken from laboratory data reported in the second volunie of this study...with an actual saturated sand from Enewetak Atoll . In Section 2, the theoretical background and numerical code, TPDAP, used in this study are described

  2. Generation of High Frequency Response in a Dynamically Loaded, Nonlinear Soil Column

    Energy Technology Data Exchange (ETDEWEB)

    Spears, Robert Edward [Idaho National Laboratory; Coleman, Justin Leigh [Idaho National Laboratory

    2015-08-01

    Detailed guidance on linear seismic analysis of soil columns is provided in “Seismic Analysis of Safety-Related Nuclear Structures and Commentary (ASCE 4, 1998),” which is currently under revision. A new Appendix in ASCE 4-2014 (draft) is being added to provide guidance for nonlinear time domain analysis which includes evaluation of soil columns. When performing linear analysis, a given soil column is typically evaluated with a linear, viscous damped constitutive model. When submitted to a sine wave motion, this constitutive model produces a smooth hysteresis loop. For nonlinear analysis, the soil column can be modelled with an appropriate nonlinear hysteretic soil model. For the model in this paper, the stiffness and energy absorption result from a defined post yielding shear stress versus shear strain curve. This curve is input with tabular data points. When submitted to a sine wave motion, this constitutive model produces a hysteresis loop that looks similar in shape to the input tabular data points on the sides with discontinuous, pointed ends. This paper compares linear and nonlinear soil column results. The results show that the nonlinear analysis produces additional high frequency response. The paper provides additional study to establish what portion of the high frequency response is due to numerical noise associated with the tabular input curve and what portion is accurately caused by the pointed ends of the hysteresis loop. Finally, the paper shows how the results are changed when a significant structural mass is added to the top of the soil column.

  3. Accuracy of three-dimensional seismic ground response analysis in time domain using nonlinear numerical simulations

    Science.gov (United States)

    Liang, Fayun; Chen, Haibing; Huang, Maosong

    2017-07-01

    To provide appropriate uses of nonlinear ground response analysis for engineering practice, a three-dimensional soil column with a distributed mass system and a time domain numerical analysis were implemented on the OpenSees simulation platform. The standard mesh of a three-dimensional soil column was suggested to be satisfied with the specified maximum frequency. The layered soil column was divided into multiple sub-soils with a different viscous damping matrix according to the shear velocities as the soil properties were significantly different. It was necessary to use a combination of other one-dimensional or three-dimensional nonlinear seismic ground analysis programs to confirm the applicability of nonlinear seismic ground motion response analysis procedures in soft soil or for strong earthquakes. The accuracy of the three-dimensional soil column finite element method was verified by dynamic centrifuge model testing under different peak accelerations of the earthquake. As a result, nonlinear seismic ground motion response analysis procedures were improved in this study. The accuracy and efficiency of the three-dimensional seismic ground response analysis can be adapted to the requirements of engineering practice.

  4. Non-Linear Wave Loads and Ship responses by a time-domain Strip Theory

    DEFF Research Database (Denmark)

    Xia, Jinzhu; Wang, Zhaohui; Jensen, Jørgen Juncher

    1998-01-01

    A non-linear time-domain strip theory for vertical wave loads and ship responses is presented. The theory is generalized from a rigorous linear time-domain strip theory representaton. The hydrodynamic memory effect due to the free surface is approximated by a higher order differential equation...

  5. Scaling of ac susceptibility and the nonlinear response function of high-temperature superconductors

    Institute of Scientific and Technical Information of China (English)

    CHEN; Kaixuan; NING; Zhenhua; XU; Hengyi; QI; Zhi; LU; Guo

    2005-01-01

    The amplitude-dependent ac susceptibility of high-temperature superconductors is shown to obey some empirical scaling relations. We try to analyze this behavior by extending a dc nonlinear response function of mixed state to the ac cases. The derived equations for critical current and ac susceptibility x(T) agree with the scaling relations of experimental data.

  6. Nonlinear optical response in condensed phases : A microscopic theory using the multipolar Hamiltonian

    NARCIS (Netherlands)

    Knoester, Jasper; Mukamel, Shaul

    1990-01-01

    A general scheme is presented for calculating the nonlinear optical response in condensed phases that provides a unified picture of excitons, polaritons, retardation, and local-field effects in crystals and in disordered systems. A fully microscopic starting point is taken by considering the evoluti

  7. Nonlinear optical response of C60 in solvents: picosecond transient grating experiments

    Science.gov (United States)

    Khudyakov, Dmitriy V.; Rubtsov, Igor V.; Lobach, Anatolii S.; Nadtochenko, Victor A.

    1996-05-01

    Time-resolved resonant nonlinear optical response of C60 in a chlorobenzene solution was measured for 528 nm excitation and 1055, 528, and 351 nm probing for zzzz and zzyy configurations. The slow part of the signal (8 +/- 2 ps) was attributed to the orientational motion of C60 excited molecules.

  8. Nonlinear Optical Response of Disordered J Aggregates in the Motional Narrowing Limit

    NARCIS (Netherlands)

    Knoester, Jasper

    1995-01-01

    We discuss the theory of nonlinear optical response of molecular aggregates with frequency disorder. In contrast to the usual modeling, we allow for spatial correlations in the disorder. We show that the joint distribution of all multi-exciton frequencies can be determined analytically to first orde

  9. Dose-Response Association Between Physical Activity and Incident Hypertension: A Systematic Review and Meta-Analysis of Cohort Studies.

    Science.gov (United States)

    Liu, Xuejiao; Zhang, Dongdong; Liu, Yu; Sun, Xizhuo; Han, Chengyi; Wang, Bingyuan; Ren, Yongcheng; Zhou, Junmei; Zhao, Yang; Shi, Yuanyuan; Hu, Dongsheng; Zhang, Ming

    2017-05-01

    Despite the inverse association between physical activity (PA) and incident hypertension, a comprehensive assessment of the quantitative dose-response association between PA and hypertension has not been reported. We performed a meta-analysis, including dose-response analysis, to quantitatively evaluate this association. We searched PubMed and Embase databases for articles published up to November 1, 2016. Random effects generalized least squares regression models were used to assess the quantitative association between PA and hypertension risk across studies. Restricted cubic splines were used to model the dose-response association. We identified 22 articles (29 studies) investigating the risk of hypertension with leisure-time PA or total PA, including 330 222 individuals and 67 698 incident cases of hypertension. The risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92-0.96) with each 10 metabolic equivalent of task h/wk increment of leisure-time PA. We found no evidence of a nonlinear dose-response association of PA and hypertension (Pnonlinearity=0.094 for leisure-time PA and 0.771 for total PA). With the linear cubic spline model, when compared with inactive individuals, for those who met the guidelines recommended minimum level of moderate PA (10 metabolic equivalent of task h/wk), the risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92-0.97). This meta-analysis suggests that additional benefits for hypertension prevention occur as the amount of PA increases. © 2017 American Heart Association, Inc.

  10. Adaptive response and split-dose effect of radiation on the survival of mice

    Indian Academy of Sciences (India)

    Ashu Bhan Tiku; R K Kale

    2004-03-01

    Although the importance of radiation-induced adaptive response has been recognized in human health, risk assessment and clinical application, the phenomenon has not been understood well in terms of survival of animals. To examine this aspect Swiss albino mice were irradiated with different doses (2–10 Gy) at 0.015 Gy/s dose rate and observed on a regular basis for 30 days. Since almost 50% lethality was seen with 8 Gy, it was selected as the challenging dose for further studies. Irradiation of mice with conditioning doses (0.25 or 0.5 Gy) and subsequent exposure to 8 Gy caused significant increase in the survival of mice compared to irradiated control. The splitting of challenging dose did not influence the efficiency of conditioning doses (0.25 Gy and 0.5 Gy) to induce an adaptive response. However conditioning doses given in fractions (0.25 Gy + 0.25 Gy) or (0.5 Gy + 0.5 Gy) were able to modulate the response of challenging dose of 8 Gy. These results clearly showed the occurrence of adaptive response in terms of survival of animals. The conditioning dose given in small fractions seemed to be more effective. The findings have been discussed from a mechanistic point of view. The possible biological implications, potential medical benefits, uncertainties and controversies related to adaptive response have also been addressed.

  11. RESPONSE OF NONLINEAR OSCILLATOR UNDER NARROW-BAND RANDOM EXCITATION

    Institute of Scientific and Technical Information of China (English)

    戎海武; 王向东; 孟光; 徐伟; 方同

    2003-01-01

    The principal resonance of Duffing oscillator to narrow-band random parametricexcitation was investigated. The method of multiple scales was used to determine theequations of modulation of amplitude and phase. The behavior, stability and bifurcation ofsteady state response were studied by means of qualitative analyses. The effects of damping,detuning, bandwidth and magnitudes of deterministic and random excitations wereanalyzed. The theoretical analyses were verified by numerical results. Theoretical analysesand numerical simulations show that when the intensity of the random excitation increases,the nontrivial steady state solution may change from a limit cycle to a diffused limit cycle.Under some conditions the system may have two ,steady state solutions.

  12. Superoperator representation of nonlinear response: unifying quantum field and mode coupling theories.

    Science.gov (United States)

    Mukamel, Shaul

    2003-08-01

    Computing response functions by following the time evolution of superoperators in Liouville space (whose vectors are ordinary Hilbert space operators) offers an attractive alternative to the diagrammatic perturbative expansion of many-body equilibrium and nonequilibrium Green's functions. The bookkeeping of time ordering is naturally maintained in real (physical) time, allowing the formulation of Wick's theorem for superoperators, giving a factorization of higher order response functions in terms of two fundamental Green's functions. Backward propagations and analytic continuations using artificial times (Keldysh loops and Matsubara contours) are avoided. A generating functional for nonlinear response functions unifies quantum field theory and the classical mode coupling formalism of nonlinear hydrodynamics and may be used for semiclassical expansions. Classical response functions are obtained without the explicit computation of stability matrices.

  13. Dose-response assessment using the benchmark dose approach of changes in hepatic EROD activity for individual polychlorinated biphenyl congeners

    Energy Technology Data Exchange (ETDEWEB)

    Fattore, E.; Fanelli, R. [' ' Mario Negri' ' Institute for Pharmacological Research, Milan (Italy); Chu, I. [Safe Environments Programme, Healthy Environments and Consumer Safety Branch, Tunney' s Pasture, Ottawa, ON (Canada); Sand, S.; Haakansson, H. [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Falk-Filippson, A. [Swedish Chemicals Inspectorate, Sundbyberg (Sweden)

    2004-09-15

    The benchmark dose (BMD) approach was proposed as an alternative to the no-observedadverse- effect-level (NOAEL) or the lowest-observed-adverse-effect-level (LOAEL) as point of departure (POD) for extrapolation of data from animal studies to the low dose human exposure situation. In the risk assessment process using the NOAEL/LOAEL parameter, the reference dose (RfD) or the admissible daily intake (ADI) is obtained by dividing the NOAEL/LOAEL value by uncertainty factors. The uncertainty factors are incorporated in order to take into account variability in the sensitivity of different species, inter-individual differences in sensitivity within the human population, and variability in experimental data. In the BMD approach a dose-response curve is fitted to experimental data (Figure 1) and the BMD is calculated from the equation of the curve as the dose corresponding to a predetermined change in the response defined as the benchmark response (BMR). The 95% lower confidence bound of the BMD, usually referred to as BMDL, can be used as the POD in the extrapolation process to get a RfD or an ADI. The advantages of using the BMD approach are many. First, all the experimental data are utilized to construct the doseresponse curve; second, the variability and uncertainty are taken into account by incorporating standard deviations of means; and third, it represents a single methodology for cancer and noncancer endpoints. In this study the BMD methodology was applied to evaluate dose-response data of seven chlorinated biphenyl (CB) congeners (Table 1), some of which are dioxin-like while others are not. The data were obtained from subchronic dietary exposure studies in male and female Sprague Dawley rats. Elevation in ethoxyresorufin-O-deethylase (EROD) activity was selected as biological response because it is known to be an endpoint sensitive to the exposure of dioxin-like PCBs. Since this response is not an adverse effect per se, in this paper we will refer to the no

  14. Equivalent Dynamic Stiffness Mapping technique for identifying nonlinear structural elements from frequency response functions

    Science.gov (United States)

    Wang, X.; Zheng, G. T.

    2016-02-01

    A simple and general Equivalent Dynamic Stiffness Mapping technique is proposed for identifying the parameters or the mathematical model of a nonlinear structural element with steady-state primary harmonic frequency response functions (FRFs). The Equivalent Dynamic Stiffness is defined as the complex ratio between the internal force and the displacement response of unknown element. Obtained with the test data of responses' frequencies and amplitudes, the real and imaginary part of Equivalent Dynamic Stiffness are plotted as discrete points in a three dimensional space over the displacement amplitude and the frequency, which are called the real and the imaginary Equivalent Dynamic Stiffness map, respectively. These points will form a repeatable surface as the Equivalent Dynamic stiffness is only a function of the corresponding data as derived in the paper. The mathematical model of the unknown element can then be obtained by surface-fitting these points with special functions selected by priori knowledge of the nonlinear type or with ordinary polynomials if the type of nonlinearity is not pre-known. An important merit of this technique is its capability of dealing with strong nonlinearities owning complicated frequency response behaviors such as jumps and breaks in resonance curves. In addition, this technique could also greatly simplify the test procedure. Besides there is no need to pre-identify the underlying linear parameters, the method uses the measured data of excitation forces and responses without requiring a strict control of the excitation force during the test. The proposed technique is demonstrated and validated with four classical single-degree-of-freedom (SDOF) numerical examples and one experimental example. An application of this technique for identification of nonlinearity from multiple-degree-of-freedom (MDOF) systems is also illustrated.

  15. Liposomal Amphotericin B and Leishmaniasis: Dose and Response

    OpenAIRE

    Shyam Sundar; Jaya Chakravarty

    2010-01-01

    Liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). It is the treatment of choice for immunocompetent patients in the Mediterranean region and the preferred drug for HIV/VL co-infection. Although there is a regional variation in the susceptibility of the parasite a total dose of 20 mg/kg is effective in immunocompetent patients. Randomized clinical trials of liposomal amphotericin B in the treatment and secondary prophylaxis of HIV-VL coinfec...

  16. Dose dependency and individual variability of the lipopolysaccharide-induced bovine acute phase protein response

    DEFF Research Database (Denmark)

    Jacobsen, S.; Andersen, P.H.; Tølbøll, T.

    2004-01-01

    In order to investigate the dose dependency and the individual variability of the lipopolysaccharide (LPS)-induced acute phase protein response in cattle, 8 nonlactating, nonpregnant Danish Holstein cows were challenged 3 times each by intravenous injection of increasing doses (10, 100, and 1000 ng...... for several days after each LPS injection, and their increase or decrease was significantly related to LPS dose. In addition to dose dependency, the response was also dependent on the individual, as APP concentrations differed significantly among cows. To compare APP production in 2 consecutive challenges...

  17. Nonlinear response studies and corrections for a liquid crystal spatial light modulator

    Indian Academy of Sciences (India)

    Ravinder Kumar Banyal; B Raghavendra Prasad

    2010-06-01

    The nonlinear response of light transmission characteristics of a liquid crystal (LC) spatial light modulator (SLM) is studied. The results show that the device exhibits a wide range of variations with different control parameters and input settings. Experiments were performed to obtain intensity modulation that is best described by either power-law or sigmoidal functions. Based on the inverse transformation, an appropriate pre-processing scheme for electrically addressed input gray-scale images, particularly important in several optical processing and imaging applications, is suggested. Further, the necessity to compensate the SLM image nonlinearities in a volume holographic data storage and retrieval system is demonstrated.

  18. Towards a unifying theory for the first-, second-, and third-order molecular (non)linear optical response

    Science.gov (United States)

    Pérez-Moreno, Javier; Clays, Koen; Kuzyk, Mark G.

    2010-05-01

    We present a procedure for the modeling of the dispersion of the nonlinear optical response of complex molecular structures that is based strictly on the results from experimental characterization. We show how under some general conditions, the use of the Thomas-Kuhn sum-rules leads to a successful modeling of the nonlinear response of complex molecular structures.

  19. Nonlinear biofluvial responses to vegetation change in a semiarid environment

    Science.gov (United States)

    Neave, Mel; Rayburg, Scott

    2007-09-01

    The desertification of grassland communities in the Jornada del Muerto Basin, southern New Mexico, USA, has occurred in association with a series of geomorphic responses that have influenced the system of vegetation change. Rainfall simulation experiments indicate that the volume of runoff generated from basin surfaces and its ability to erode are greatly affected by the distribution of vegetation, which ultimately controls processes such as rainsplash erosion, soil infiltrability and crust development. Animal activities also influence rates of sediment movement from unvegetated surfaces by disrupting soil crusts and making loose sediment available for transportation by overland flow. Shrublands in the Jornada Basin have a patchier vegetation cover than grasslands, with vegetated areas (shrubs) being separated by unvegetated (intershrub) zones. The exposed intershrub surfaces are more vulnerable to erosion than the grass and shrub surfaces. Thus, water and sediment yields, calculated using rainfall simulation experiments, were higher for vegetated (shrub and grass) plots than they were for unvegetated (intershrub) plots. The runoff and erosion model, KINEROS2, predicts that at the base of a 100 m slope, shrubland surfaces shed seven times more runoff and 25 times more sediment than grassland surfaces. Evidence to support the prediction of higher rates of erosion in the shrubland can be found in the form of the extensive rill networks that are common in this community. The contraction of grasslands has been associated with elevated rates of erosion that have altered the morphology of the surface, lowering slopes between shrubs, and increasing the amplitude of the microtopography. Overall, the viability of the exposed soils for recolonization by grasses has been reduced, reinforcing the system of shrubland invasion and lending support to the use of state-and-transition models to describe ecologic responses to change within this environment. Combined, these results

  20. Nonlinear response of summer temperature to Holocene insolation forcing in Alaska.

    Science.gov (United States)

    Clegg, Benjamin F; Kelly, Ryan; Clarke, Gina H; Walker, Ian R; Hu, Feng Sheng

    2011-11-29

    Regional climate responses to large-scale forcings, such as precessional changes in solar irradiation and increases in anthropogenic greenhouse gases, may be nonlinear as a result of complex interactions among earth system components. Such nonlinear behaviors constitute a major source of climate "surprises" with important socioeconomic and ecological implications. Paleorecords are key for elucidating patterns and mechanisms of nonlinear responses to radiative forcing, but their utility has been greatly limited by the paucity of quantitative temperature reconstructions. Here we present Holocene July temperature reconstructions on the basis of midge analysis of sediment cores from three Alaskan lakes. Results show that summer temperatures during 10,000-5,500 calibrated years (cal) B.P. were generally lower than modern and that peak summer temperatures around 5,000 were followed by a decreasing trend toward the present. These patterns stand in stark contrast with the trend of precessional insolation, which decreased by ∼10% from 10,000 y ago to the present. Cool summers before 5,500 cal B.P. coincided with extensive summer ice cover in the western Arctic Ocean, persistence of a positive phase of the Arctic Oscillation, predominantly La Niña-like conditions, and variation in the position of the Alaskan treeline. These results illustrate nonlinear responses of summer temperatures to Holocene insolation radiative forcing in the Alaskan sub-Arctic, possibly because of state changes in the Arctic Oscillation and El Niño-Southern Oscillation and associated land-atmosphere-ocean feedbacks.

  1. RESPONSE ANALYSIS OF RANDOMLY EXCITED NONLINEAR SYSTEMS WITH SYMMETRIC WEIGHTING PREISACH HYSTERESIS

    Institute of Scientific and Technical Information of China (English)

    应祖光

    2003-01-01

    An approximate method for analyzing the response of nonlinear systems with the Preisach hysteresis of the non-local memory under a stationary Gaussian excitation is presented based on the covariance and switching probability analysis. The covariance matrix equation of the Preisach hysteretic system response is derived. The cross correlation function of the Preisach hysteretic force and response in the covariance equation is evaluated by the switching probability analysis and the Gaussian approximation to the response process. Then an explicit expression of the correlation function is given for the case of symmetric Preisach weighting functions. The numerical result obtained is in good agreement with that from the digital simulation.

  2. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses.

    Directory of Open Access Journals (Sweden)

    Hae Mi Joo

    Full Text Available Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6 and LAD2 cells, mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6 and LAD2 cells that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i. The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13, and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro.

  3. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses.

    Science.gov (United States)

    Joo, Hae Mi; Kang, Su Jin; Nam, Seon Young; Yang, Kwang Hee; Kim, Cha Soon; Lee, In Kyung; Kim, Ji Young

    2015-01-01

    Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6) and LAD2 cells), mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6) and LAD2 cells) that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i). The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13), and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro.

  4. Excited-state dynamics and nonlinear optical response of Ge nanocrystals embedded in silica matrix

    Science.gov (United States)

    Razzari, Luca; Gnoli, Andrea; Righini, Marcofabio; Dâna, Aykutlu; Aydinli, Atilla

    2006-05-01

    We use a dedicated Z-scan setup, arranged to account for cumulative effects, to study the nonlinear optical response of Ge nanocrystals embedded in silica matrix. Samples are prepared with plasma-enchanced chemical-vapor deposition and post-thermal annealing. We measure a third-order nonlinear refraction coefficient of γ =1×10-16m2/W. The nonlinear absorption shows an intensity-independent coefficient of β =4×10-10m/W related to fast processes. In addition, we measure a second β component around 10-9m /W with a relaxation time of 300μs that rises linearly with the laser intensity. We associate its origin to the absorption of excited carriers from a surface-defect state with a long depopulation time.

  5. Beyond the effective mass approximation: predictive theory of the nonlinear optical response of conduction electrons

    CERN Document Server

    Yu, Shukai; Talbayev, Diyar

    2016-01-01

    We present an experimental and computational study of the nonlinear optical response of conduction electrons to intense terahertz (THz) electric field. Our observations (saturable absorption and an amplitude-dependent group refractive index) can be understood on the qualitative level as the breakdown of the effective mass approximation. However, a predictive theoretical description of the nonlinearity has been missing. We propose a model based on the semiclassical electron dynamics, a realistic band structure, and the free electron Drude parameters to accurately calculate the experimental observables in InSb. Our results open a path to predictive modeling of the conduction-electron optical nonlinearity in semiconductors, metamaterials, as well as high-field effects in THz plasmonics.

  6. Identifying the nonlinear mechanical behaviour of micro-speakers from their quasi-linear electrical response

    Science.gov (United States)

    Zilletti, Michele; Marker, Arthur; Elliott, Stephen John; Holland, Keith

    2017-05-01

    In this study model identification of the nonlinear dynamics of a micro-speaker is carried out by purely electrical measurements, avoiding any explicit vibration measurements. It is shown that a dynamic model of the micro-speaker, which takes into account the nonlinear damping characteristic of the device, can be identified by measuring the response between the voltage input and the current flowing into the coil. An analytical formulation of the quasi-linear model of the micro-speaker is first derived and an optimisation method is then used to identify a polynomial function which describes the mechanical damping behaviour of the micro-speaker. The analytical results of the quasi-linear model are compared with numerical results. This study potentially opens up the possibility of efficiently implementing nonlinear echo cancellers.

  7. Semiclassical theory of nonlinear magneto-optical responses with applications to topological Dirac/Weyl semimetals

    Science.gov (United States)

    Morimoto, Takahiro; Zhong, Shudan; Orenstein, Joseph; Moore, Joel E.

    2016-12-01

    We study nonlinear magneto-optical responses of metals by a semiclassical Boltzmann equation approach. We derive general formulas for linear and second-order nonlinear optical effects in the presence of magnetic fields that include both the Berry curvature and the orbital magnetic moment. Applied to Weyl fermions, the semiclassical approach (i) captures the directional anisotropy of linear conductivity under a magnetic field as a consequence of an anisotropic B2 contribution, which may explain the low-field regime of recent experiments; and (ii) predicts strong second harmonic generation proportional to B that is enhanced as the Fermi energy approaches the Weyl point, leading to large nonlinear Kerr rotation. Moreover, we show that the semiclassical formula for the circular photogalvanic effect arising from the Berry curvature dipole is reproduced by a full quantum calculation using a Floquet approach.

  8. Nonlinear response speedup in bimodal visual-olfactory object identification

    Directory of Open Access Journals (Sweden)

    Richard eHöchenberger

    2015-09-01

    Full Text Available Multisensory processes are vital in the perception of our environment. In the evaluation of foodstuff, redundant sensory inputs not only assist the identification of edible and nutritious substances, but also help avoiding the ingestion of possibly hazardous substances. While it is known that the non-chemical senses interact already at early processing levels, it remains unclear whether the visual and olfactory senses exhibit comparable interaction effects. To address this question, we tested whether the perception of congruent bimodal visual-olfactory objects is facilitated compared to unimodal stimulation. We measured response times (RT and accuracy during speeded object identification. The onset of the visual and olfactory constituents in bimodal trials was physically aligned in the first and perceptually aligned in the second experiment. We tested whether the data favored coactivation or parallel processing consistent with race models. A redundant-signals effect was observed for perceptually aligned redundant stimuli only, i.e. bimodal stimuli were identified faster than either of the unimodal components. Analysis of the RT distributions and accuracy data revealed that these observations could be explained by a race model. More specifically, visual and olfactory channels appeared to be operating in a parallel, positively dependent manner. While these results suggest the absence of early sensory interactions, future studies are needed to substantiate this interpretation.

  9. A study of non-linearity in rainfall-runoff response using 120 UK catchments

    Science.gov (United States)

    Mathias, Simon A.; McIntyre, Neil; Oughton, Rachel H.

    2016-09-01

    This study presents a catchment characteristic sensitivity analysis concerning the non-linearity of rainfall-runoff response in 120 UK catchments. Two approaches were adopted. The first approach involved, for each catchment, regression of a power-law to flow rate gradient data for recession events only. This approach was referred to as the recession analysis (RA). The second approach involved calibrating a rainfall-runoff model to the full data set (both recession and non-recession events). The rainfall-runoff model was developed by combining a power-law streamflow routing function with a one parameter probability distributed model (PDM) for soil moisture accounting. This approach was referred to as the rainfall-runoff model (RM). Step-wise linear regression was used to derive regionalization equations for the three parameters. An advantage of the RM approach is that it utilizes much more of the observed data. Results from the RM approach suggest that catchments with high base-flow and low annual precipitation tend to exhibit greater non-linearity in rainfall-runoff response. In contrast, the results from the RA approach suggest that non-linearity is linked to low evaporative demand. The difference in results is attributed to the aggregation of storm-flow and base-flow into a single system giving rise to a seemingly more non-linear response when applying the RM approach to catchments that exhibit a strongly dual storm-flow base-flow response. The study also highlights the value and limitations in a regionlization context of aggregating storm-flow and base-flow pathways into a single non-linear routing function.

  10. NOTE: Study of Gafchromic® EBT film response over a large dose range

    Science.gov (United States)

    Martišíková, Mária; Jäkel, Oliver

    2010-05-01

    Presently Gafchromic EBT films are widely used for relative dose verification in standard radiation therapy using high-energy photons, inclusive IMRT. The use of films for dosimetry in medical ion beams is more complicated due to the strongly inhomogeneous dose deposition by ions on microscopic level. Track structure models, presently used to describe dosimeter response as a function of the ion field properties, are based on input information which can be obtained from the film response in photon beams. We therefore studied the performance of Gafchromic EBT films, ancestors of currently available EBT2 films, in 60Co photon beams. The dose-response curve was measured from 7.5 × 10-2 Gy to 3 × 104 Gy. The dynamic range, linearity and dose rate dependence of this calibration curve were studied. A high saturation dose of 3 × 103 Gy, and thus a large dynamic range, was observed. No signs of supralinearity and bleaching due to radiation were found. No dependence of the response on the dose rate at high dose rates and high doses was found. All those properties justify the use of simplified models of the film response to ions. Furthermore, fits of the calibration data by predictions of different models for signal creation mechanism of dosimetric materials were performed. The best description was found for the recently published gamma-distributed single-hit model which takes into account different sizes of the active centres.

  11. Measurement of nonlinear elastic response in rock by the resonant bar method

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, P.A. (Los Alamos National Lab., NM (United States)); Rasolofosaon, P.; Zinszner, B. (Institut Francais du Petrole (IFP), 92 - Rueil-Malmaison (France))

    1993-01-01

    In this work we are studying the behavior of the fundamental (Young's) mode resonant peak as a function of drive amplitude in rock samples. Our goal from these studies is to obtain nonlinear moduli for many rock types, and to study the nonlinear moduli as a function of water saturation and other changes in physical properties. Measurements were made on seven different room dry rock samples. For one sample measurements were taken at 16 saturation levels between 1 and 98%. All samples display a softening'' nonlinearity, that is, the resonant frequency shifts downward with increasing drive amplitude. In extreme cases, the resonant frequency changes by as much as 25% over a strain interval of 10[sup [minus]7] to [approximately]4 [times] 10[sup [minus]5]. Measurements indicate that the nonlinear response is extremely sensitive to saturation. Estimates of a combined cubic and quartic nonlinear parameter [Gamma] range from approximately [minus]300 to [minus]10[sup 9] for the rock samples.

  12. Seismic response analysis of a nuclear reactor structure considering nonlinear soil-structure interaction

    Energy Technology Data Exchange (ETDEWEB)

    Bhaumik, Lopamudra, E-mail: lbhaumi2@illinois.edu [University of Illinois at Urbana-Champaign (United States); Raychowdhury, Prishati, E-mail: prishati@iitk.ac.in [Indian Institute of Technology Kanpur (India)

    2013-12-15

    Highlights: • Seismic response analysis of an internal shearwall of a reactor is done. • Incremental dynamic analysis is performed with 30 recorded ground motions. • Equivalent viscous damping increases up to twice when nonlinear SSI is considered. • Roof drift demand increases up to 25% upon consideration of foundation nonlinearity. • Base shear, base moment and ductility reduce up to 62%, 40%, and 35%, respectively. - Abstract: This study focuses on the seismic response analysis of an internal shearwall of a typical Indian reactor resting on a medium dense sandy silty soil, incorporating the nonlinear behavior of the soil-foundation interface. The modeling is done in an open-source finite element framework, OpenSees, where the soil-structure interaction (SSI) is modeled using a Beam-on-Nonlinear-Winkler-Foundation (BNWF) approach. Static pushover analysis and cyclic analysis are performed followed by an incremental dynamic analysis (IDA) with 30 recorded ground motions. For performing IDA, the spectral acceleration of each motion corresponding to the fundamental period, S{sub a}(T{sub 1})is incremented from 0.1 g to 1.0 g with an increment step of 0.1 g. It is observed from the cyclic analysis that the equivalent viscous damping of the system increases upto twice upon incorporation of inelastic SSI. The IDA results demonstrate that the average peak base shear, base moment and displacement ductility demand reduces as much as 62%, 40%, and 35%, respectively, whereas the roof drift demand increases up to 25% upon consideration of foundation nonlinearity for the highest intensity motion. These observations indicate the need of critical consideration of nonlinear soil-structure interaction as any deficient modeling of the same may lead to an inaccurate estimation of the seismic demands of the structure.

  13. PACAP38 dose-response pilot study in migraine patients

    DEFF Research Database (Denmark)

    Vollesen, Anne Luise Haulund; Guo, Song; Ashina, Messoud

    2017-01-01

    BACKGROUND: Intravenous infusion of 10 pmol/kg/min pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) induces migraine-like attacks in migraine patients without aura (MO). Here, we conducted a pilot study and investigated if lower doses of PACAP38 exert similar migraine......-inducing abilities. METHODS: We randomly allocated six MO patients to receive intravenous infusion of 4, 6, and 8 pmol/kg/min of PACAP38 over 20 minutes in a double-blind, three-way cross-over study. Headache and migraine characteristics were recorded during hospital (0-2 hours) and post-hospital (2-13 hours) phases...

  14. A computer program for predicting nonlinear uniaxial material responses using viscoplastic models

    Science.gov (United States)

    Chang, T. Y.; Thompson, R. L.

    1984-01-01

    A computer program was developed for predicting nonlinear uniaxial material responses using viscoplastic constitutive models. Four specific models, i.e., those due to Miller, Walker, Krieg-Swearengen-Rhode, and Robinson, are included. Any other unified model is easily implemented into the program in the form of subroutines. Analysis features include stress-strain cycling, creep response, stress relaxation, thermomechanical fatigue loop, or any combination of these responses. An outline is given on the theoretical background of uniaxial constitutive models, analysis procedure, and numerical integration methods for solving the nonlinear constitutive equations. In addition, a discussion on the computer program implementation is also given. Finally, seven numerical examples are included to demonstrate the versatility of the computer program developed.

  15. A hybrid method based upon nonlinear Lamb wave response for locating a delamination in composite laminates.

    Science.gov (United States)

    Yelve, Nitesh P; Mitra, Mira; Mujumdar, P M; Ramadas, C

    2016-08-01

    A new hybrid method based upon nonlinear Lamb wave response in time and frequency domains is introduced to locate a delamination in composite laminates. In Lamb wave based nonlinear method, the presence of damage is shown by the appearance of higher harmonics in the Lamb wave response. The proposed method not only uses this spectral information but also the corresponding temporal response data, for locating the delamination. Thus, the method is termed as a hybrid method. The paper includes formulation of the method and its application to locate a Barely Visible Impact Damage (BVID) induced delamination in a Carbon Fiber Reinforced Polymer (CFRP) laminate. The method gives the damage location fairly well. It is a baseline free method, as it does not need data from the pristine specimen.

  16. Nonlinearity and Strain-Rate Dependence in the Deformation Response of Polymer Matrix Composites Modeled

    Science.gov (United States)

    Goldberg, Robert K.

    2000-01-01

    There has been no accurate procedure for modeling the high-speed impact of composite materials, but such an analytical capability will be required in designing reliable lightweight engine-containment systems. The majority of the models in use assume a linear elastic material response that does not vary with strain rate. However, for containment systems, polymer matrix composites incorporating ductile polymers are likely to be used. For such a material, the deformation response is likely to be nonlinear and to vary with strain rate. An analytical model has been developed at the NASA Glenn Research Center at Lewis Field that incorporates both of these features. A set of constitutive equations that was originally developed to analyze the viscoplastic deformation of metals (Ramaswamy-Stouffer equations) was modified to simulate the nonlinear, rate-dependent deformation of polymers. Specifically, the effects of hydrostatic stresses on the inelastic response, which can be significant in polymers, were accounted for by a modification of the definition of the effective stress. The constitutive equations were then incorporated into a composite micromechanics model based on the mechanics of materials theory. This theory predicts the deformation response of a composite material from the properties and behavior of the individual constituents. In this manner, the nonlinear, rate-dependent deformation response of a polymer matrix composite can be predicted.

  17. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.

    Directory of Open Access Journals (Sweden)

    Sara C Johnston

    Full Text Available Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.

  18. Urochloa ruziziensis responses to sources and doses of urea

    Directory of Open Access Journals (Sweden)

    João E. S. Lima

    2016-05-01

    Full Text Available ABSTRACT The use of products that promote reduction of nitrogen (N losses from the urea fertilizer can contribute to increasing its use efficiency in forage grasses. This study aimed to evaluate the effects of N sources and doses on the growth of Urochloa ruziziensis. The experiment was carried out in the growing season of 2007/2008 in Santo Antônio de Goiás-GO, in a Brazilian Oxisol. A completely randomized block was used, with four replicates in a factorial scheme, corresponding to two N sources (conventional urea and urea with urease inhibitor and five N doses (0, 50, 100, 200 and 300 kg ha-1, divided into equal applications in five periods (Nov 14 to Dec 13, Dec 14 to Jan 12, Jan 13 to Feb 11 - rainy season, Mar 24 to Apr 22 and Jul 10 to Aug 08 - dry season. The effects of the treatments were evaluated for: shoot dry matter, tiller density, total N content in the leaves and relative chlorophyll content. N fertilizer sources did not affect the evaluated variables; however, N fertilization allowed linear increases in all variables with higher values during the rainy period. The relative chlorophyll content in U. ruziziensis had positive correlation with its dry matter productivity.

  19. Dielectric Response of Glass-Forming Liquids in the Nonlinear Regime

    Science.gov (United States)

    Samanta, Subarna

    Broadband dielectric spectroscopy is a powerful technique for understanding the dynamics in supercooled liquids. It generates information about the timescale of the orientational motions of molecular dipoles within the liquid. However, dynamics of liquids measured in the non-linear response regime has recently become an area of significant interest, because additional information can be obtained compared with linear response measurements. The first part of this thesis describes nonlinear dielectric relaxation experiments performed on various molecular glass forming-liquids, with an emphasis on the response at high frequencies (excess wing). A significant nonlinear dielectric effect (NDE) was found to persist in these modes, and the magnitude of this NDE traces the temperature dependence of the activation energy. A time resolved measurement technique monitoring the dielectric loss revealed that for the steady state NDE to develop it would take a very large number of high amplitude alternating current (ac) field cycles. High frequency modes were found to be 'slaved' to the average structural relaxation time, contrary to the standard picture of heterogeneity. Nonlinear measurements were also performed on the Johari-Goldstein beta-relaxation process. High ac fields were found to modify the amplitudes of these secondary modes. The nonlinear features of this secondary process are reminiscent of those found for the excess wing regime, suggesting that these two contributions to dynamics have common origins. The second part of this thesis describes the nonlinear effects observed from the application of high direct current (dc) bias fields superposed with a small amplitude sinusoidal ac field. For several molecular glass formers, the application of a dc field was found to slow down the system via reduction in configurational entropy (Adam-Gibbs relation). Time resolved measurements indicated that the rise of the non-linear effect is slower than its decay, as observed in the

  20. Dose-response plasma appearance of coffee chlorogenic and phenolic acids in adults.

    Science.gov (United States)

    Renouf, Mathieu; Marmet, Cynthia; Giuffrida, Francesca; Lepage, Mélissa; Barron, Denis; Beaumont, Maurice; Williamson, Gary; Dionisi, Fabiola

    2014-02-01

    Coffee contains phenolic compounds, mainly chlorogenic acids (CGAs). Even though coffee intake has been associated with some health benefits in epidemiological studies, the bioavailability of coffee phenolics is not fully understood. We performed a dose-response study measuring plasma bioavailability of phenolics after drinking three increasing, but still nutritionally relevant doses of instant pure soluble coffee. The study design was a one treatment (coffee) three-dose randomized cross-over design, with a washout period of 2 wks between visits. CGAs, phenolic acids, and late-appearing metabolites all increased with increasing ingested dose. Hence, the sum of area under the curve was significantly higher for the medium to low dose, and high to medium dose, by 2.23- and 2.38-fold, respectively. CGAs were not well absorbed in their intact form, regardless of the dose. CGA and phenolic acids appeared rapidly in plasma, indicating an early absorption in the gastrointestinal tract. Late-appearing metabolites were the most abundant, regardless of the dose. This study confirmed previous findings about coffee bioavailability but also showed that coffee phenolics appear in a positive dose-response manner in plasma when drank at nutritionally relevant doses. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Global stabilization of high-energy response of a nonlinear wideband electromagnetic energy harvester

    Science.gov (United States)

    Sato, T.; Kato, S.; Masuda, A.

    2016-09-01

    This paper presents a resonance-type vibration energy harvester with a Duffing-type nonlinear oscillator which is designed to perform effectively in a wide frequency band. For the conventional linear vibration energy harvester, the maximum performance of the power generation and its bandwidth are in a relation of trade-off. Introducing a Duffing-type nonlinearity can expand the resonance frequency band and enable the harvester to generate larger electric power in a wider frequency range. However, since such nonlinear oscillator may have coexisting multiple steady-state solutions in the resonance band, it is difficult for the nonlinear harvester to maintain the high performance of the power generation constantly. The principle of self-excitation and entrainment has been utilized to give global stability to the high-energy orbit by destabilizing other unexpected low-energy orbits by introducing a switching circuit of the load resistance between positive and the negative values depending on the response amplitude of the oscillator. In this paper, an improved control law that switches the load resistance according to a frequency-dependent threshold is proposed to ensure the oscillator to respond in the high-energy orbit without ineffective power consumption. Numerical study shows that the steady-state responses of the harvester with the proposed control low are successfully kept on the high-energy orbit without repeating activation of the excitationmode.

  2. Stable response of low-gravity liquid non-linear sloshing in a circle cylindrical tank

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Under pitch excitation, the sloshing of liquid in circular cylindrical tank includes planar motion, rotary motion and rotary motion inside planar motion. The boundaries between stable motion and unstable motion depend on the radius of the tank, the liquid height, the gravitational intension, the surface tensor and the sloshing damping. In this article, the differential equations of nonlinear sloshing are built first.And by variational principle, the Lagrange function of liquid pressure is constructed in volume intergration form. Then the velocity potential function is expanded in series by wave height function at the free surface. The nonlinear equations with kinematics and dynamics free surface boundary conditions through variation are derived. At last, these equations are solved by multiple-scales method. The influence of Bond number on the global stable response of nonlinear liquid sloshing in circular cylinder tank is analyzed in detail. The result indicates that variation of amplitude frequency response characteristics of the system with Bond, jump, lag and other nonlinear phenomena of liquid sloshing are investigated.

  3. Nonlinear optical response of the collagen triple helix and second harmonic microscopy of collagen liquid crystals

    Science.gov (United States)

    Deniset-Besseau, A.; De Sa Peixoto, P.; Duboisset, J.; Loison, C.; Hache, F.; Benichou, E.; Brevet, P.-F.; Mosser, G.; Schanne-Klein, M.-C.

    2010-02-01

    Collagen is characterized by triple helical domains and plays a central role in the formation of fibrillar and microfibrillar networks, basement membranes, as well as other structures of the connective tissue. Remarkably, fibrillar collagen exhibits efficient Second Harmonic Generation (SHG) and SHG microscopy proved to be a sensitive tool to score fibrotic pathologies. However, the nonlinear optical response of fibrillar collagen is not fully characterized yet and quantitative data are required to further process SHG images. We therefore performed Hyper-Rayleigh Scattering (HRS) experiments and measured a second order hyperpolarisability of 1.25 10-27 esu for rat-tail type I collagen. This value is surprisingly large considering that collagen presents no strong harmonophore in its amino-acid sequence. In order to get insight into the physical origin of this nonlinear process, we performed HRS measurements after denaturation of the collagen triple helix and for a collagen-like short model peptide [(Pro-Pro-Gly)10]3. It showed that the collagen large nonlinear response originates in the tight alignment of a large number of weakly efficient harmonophores, presumably the peptide bonds, resulting in a coherent amplification of the nonlinear signal along the triple helix. To illustrate this mechanism, we successfully recorded SHG images in collagen liquid solutions by achieving liquid crystalline ordering of the collagen triple helices.

  4. Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults with ADHD: An Exploratory Study

    Science.gov (United States)

    Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David

    2012-01-01

    Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…

  5. Eosinophils in the bronchial mucosa in relation to methacholine dose-response curves in atopic asthma

    NARCIS (Netherlands)

    G.M. Moller (Trude); S.E. Overbeek (Shelley); C.G. van Helden-Meeuwsen; H.C. Hoogsteden (Henk); J.M. Bogaard (Jan)

    1999-01-01

    textabstractAsthma is characterized by both local infiltration of eosinophils in the bronchial mucosa and bronchial hyperreactivity (BHR). A detailed characterization of BHR implies analysis of a histamine or methacholine dose-response curve yielding not only the dose a

  6. Liposomal amphotericin B and leishmaniasis: Dose and response

    Directory of Open Access Journals (Sweden)

    Shyam Sundar

    2010-01-01

    Full Text Available Liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL. It is the treatment of choice for immunocompetent patients in the Mediterranean region and the preferred drug for HIV/VL co-infection. Although there is a regional variation in the susceptibility of the parasite a total dose of 20 mg/kg is effective in immunocompetent patients. Randomized clinical trials of liposomal amphotericin B in the treatment and secondary prophylaxis of HIV-VL coinfected patients is urgently needed to optimize treatment in this subset. With the availability of Liposomal amphotericin B at a preferential pricing in the endemic areas, short course combination therapy can become a viable alternative.

  7. Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose-volume outcome relationships

    Energy Technology Data Exchange (ETDEWEB)

    Naqa, I El [Washington University, Saint Louis, MO (United States); Suneja, G [Brown Medical School, Providence, RI (United States); Lindsay, P E [Washington University, St. Louis, MO (United States); Hope, A J [Washington University, Saint Louis, MO (United States); Alaly, J R [Washington University, Saint Louis, MO (United States); Vicic, M [Washington University, Saint Louis, MO (United States); Bradley, J D [Washington University, Saint Louis, MO (United States); Apte, A [Washington University, Saint Louis, MO (United States); Deasy, J O [Washington University, Saint Louis, MO (United States)

    2006-11-21

    Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

  8. Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose volume outcome relationships

    Science.gov (United States)

    El Naqa, I.; Suneja, G.; Lindsay, P. E.; Hope, A. J.; Alaly, J. R.; Vicic, M.; Bradley, J. D.; Apte, A.; Deasy, J. O.

    2006-11-01

    Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

  9. Parametric system identification of resonant micro/nanosystems operating in a nonlinear response regime

    Science.gov (United States)

    Sabater, A. B.; Rhoads, J. F.

    2017-02-01

    The parametric system identification of macroscale resonators operating in a nonlinear response regime can be a challenging research problem, but at the micro- and nanoscales, experimental constraints add additional complexities. For example, due to the small and noisy signals micro/nanoresonators produce, a lock-in amplifier is commonly used to characterize the amplitude and phase responses of the systems. While the lock-in enables detection, it also prohibits the use of established time-domain, multi-harmonic, and frequency-domain methods, which rely upon time-domain measurements. As such, the only methods that can be used for parametric system identification are those based on fitting experimental data to an approximate solution, typically derived via perturbation methods and/or Galerkin methods, of a reduced-order model. Thus, one could view the parametric system identification of micro/nanosystems operating in a nonlinear response regime as the amalgamation of four coupled sub-problems: nonparametric system identification, or proper experimental design and data acquisition; the generation of physically consistent reduced-order models; the calculation of accurate approximate responses; and the application of nonlinear least-squares parameter estimation. This work is focused on the theoretical foundations that underpin each of these sub-problems, as the methods used to address one sub-problem can strongly influence the results of another. To provide context, an electromagnetically transduced microresonator is used as an example. This example provides a concrete reference for the presented findings and conclusions.

  10. Response of Nigerian local breed of dog to graded doses of ...

    African Journals Online (AJOL)

    aliyu.jibril

    2017-01-24

    Jan 24, 2017 ... The experiment investigated the response of Nigerian local breed of dog to different doses of Ancylostoma ... Faecal egg count (FEC), red blood cell (RBC) counts, haemoglobin concentrations (HBC), ..... The drop in PCV.

  11. Intravenous low dose clonidine premedication for attenuation of haemodynamic responses to laryngoscopy and endotracheal intubation

    Directory of Open Access Journals (Sweden)

    Chandrashekarappa Kavi

    2015-06-01

    Conclusion: Preoperative administration of a single dose of clonidine blunted the hemodynamic responses more than the placebo during Laryngoscopy and Intubation with reduced anesthetic requirements. [Int J Res Med Sci 2015; 3(6.000: 1457-1461

  12. Toward a unified approach to dose-response modeling in ecotoxicology.

    Science.gov (United States)

    Ritz, Christian

    2010-01-01

    This study reviews dose-response models that are used in ecotoxicology. The focus lies on clarification of differences and similarities between models, and as a side effect, their different guises in ecotoxicology are unravelled. A look at frequently used dose-response models reveals major discrepancies, among other things in naming conventions. Therefore, there is a need for a unified view on dose-response modeling in order to improve the understanding of it and to facilitate communication and comparison of findings across studies, thus realizing its full potential. This study attempts to establish a general framework that encompasses most dose-response models that are of interest to ecotoxicologists in practice. The framework includes commonly used models such as the log-logistic and Weibull models, but also features entire suites of models as found in various guidance documents. An outline on how the proposed framework can be implemented in statistical software systems is also provided.

  13. Nonlinear Response of Unbiased and Biased Bilayer Graphene at Terahertz Frequencies

    Science.gov (United States)

    McGouran, Riley

    The main focus of this thesis is the investigation of the nonlinear response of unbiased and biased bilayer graphene to incident radiation at terahertz frequencies. We present a tight-binding model of biased and unbiased bilayer graphene that is used to calculate the nonlinear terahertz response. Dynamic equations are developed for the electron density matrix within the length gauge. These equations facilitate the calculation of interband and intraband carrier dynamics. We then obtain nonlinear transmitted and reflected terahertz fields using the calculated nonlinear interband and intraband current densities. We examine the nonlinear response of unbiased bilayer graphene as a function of the incident field amplitude. In this case the sample is taken to be undoped. In the reflected field, we find the maximum third harmonic amplitude to be approximately 30% of the fundamental frequency for an incident field of 1.5 kV cm-1, which is greater than that found in undoped monolayer graphene at the same field amplitude. To examine the nonlinear response of biased bilayer graphene, we investigate two different scenarios. In the first scenario, we consider an undoped sample at fixed temperature. We find that when the external bias has a value of 2 meV, the generated third harmonic in the reflected field is approximately 45% of the fundamental for an incident field amplitude of 2 kV cm-1 . When we increase the external bias further to 8 meV, we find the generated third harmonic field is approximately 38% of the fundamental for an incident field amplitude of 1 kV cm-1. For both of these bias values, the generated third harmonic is greater than that found in undoped monolayer graphene. In that system, the generated third harmonic field is approximately 32% of the fundamental for an incident field amplitude of 200 V cm-1. In the second scenario, we consider doped biased bilayer graphene. We fix the carrier density at 2x1012 cm-2, the incident field amplitude at 50 kV cm-1, and

  14. Differential Response and Priming Dose Effect on the Proteome of Human Fibroblast and Stem Cells Induced by Exposure to Low Doses of Ionizing Radiation.

    Science.gov (United States)

    Hauptmann, Monika; Haghdoost, Siamak; Gomolka, Maria; Sarioglu, Hakan; Ueffing, Marius; Dietz, Anne; Kulka, Ulrike; Unger, Kristian; Babini, Gabriele; Harms-Ringdahl, Mats; Ottolenghi, Andrea; Hornhardt, Sabine

    2016-03-01

    It has been suggested that a mechanistic understanding of the cellular responses to low dose and dose rate may be valuable in reducing some of the uncertainties involved in current risk estimates for cancer- and non-cancer-related radiation effects that are inherited in the linear no-threshold hypothesis. In this study, the effects of low-dose radiation on the proteome in both human fibroblasts and stem cells were investigated. Particular emphasis was placed on examining: 1. the dose-response relationships for the differential expression of proteins in the low-dose range (40-140 mGy) of low-linear energy transfer (LET) radiation; and 2. the effect on differential expression of proteins of a priming dose given prior to a challenge dose (adaptive response effects). These studies were performed on cultured human fibroblasts (VH10) and human adipose-derived stem cells (ADSC). The results from the VH10 cell experiments demonstrated that low-doses of low-LET radiation induced unique patterns of differentially expressed proteins for each dose investigated. In addition, a low priming radiation dose significantly changed the protein expression induced by the subsequent challenge exposure. In the ADSC the number of differentially expressed proteins was markedly less compared to VH10 cells, indicating that ADSC differ in their intrinsic response to low doses of radiation. The proteomic results are further discussed in terms of possible pathways influenced by low-dose irradiation.

  15. Parity and All-cause Mortality in Women and Men: A Dose-Response Meta-Analysis of Cohort Studies.

    Science.gov (United States)

    Zeng, Yun; Ni, Ze-min; Liu, Shu-yun; Gu, Xue; Huang, Qin; Liu, Jun-an; Wang, Qi

    2016-01-13

    To quantitatively assess the association between parity and all-cause mortality, we conducted a meta-analysis of cohort studies. Relevant reports were identified from PubMed and Embase databases. Cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) of all-cause mortality in three or more categories of parity were eligible. Eighteen articles with 2,813,418 participants were included. Results showed that participants with no live birth had higher risk of all-cause mortality (RR= 1.19, 95% CI = 1.03-1.38; I(2) = 96.7%, P < 0.001) compared with participants with one or more live births. Nonlinear dose-response association was found between parity and all-cause mortality (P for non-linearity < 0.0001). Our findings suggest that moderate-level parity is inversely associated with all-cause mortality.

  16. Predicting the nonlinear optical response in the resonant region from the linear characterization: a self-consistent theory for the first-, second-, and third-order (non)linear optical response

    Science.gov (United States)

    Pérez-Moreno, Javier; Clays, Koen; Kuzyk, Mark G.

    2010-08-01

    We introduce a self-consistent theory for the description of the optical linear and nonlinear response of molecules that is based strictly on the results of the experimental characterization. We show how the Thomas-Kuhn sum-rules can be used to eliminate the dependence of the nonlinear response on parameters that are not directly measurable. Our approach leads to the successful modeling of the dispersion of the nonlinear response of complex molecular structures with different geometries (dipolar and octupolar), and can be used as a guide towards the modeling in terms of fundamental physical parameters.

  17. DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES TO PENICILLIUM CHRYSOGENUM

    Science.gov (United States)

    ABSTRACT Indoor mold has been associated with development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and its viable conidia can induce allergic responses in a mouse model of allergic penicilliosis. The hypothesis o...

  18. A Strategy to Model Nonmonotonic Dose-Response Curve and Estimate IC50

    OpenAIRE

    Hui Zhang; Jeanne Holden-Wiltse; Jiong Wang; Hua Liang

    2013-01-01

    The half-maximal inhibitory concentration IC[Formula: see text] is an important pharmacodynamic index of drug effectiveness. To estimate this value, the dose response relationship needs to be established, which is generally achieved by fitting monotonic sigmoidal models. However, recent studies on Human Immunodeficiency Virus (HIV) mutants developing resistance to antiviral drugs show that the dose response curve may not be monotonic. Traditional models can fail for nonmonotonic data and igno...

  19. Loss of response and need for adalimumab dose intensification in Crohn's disease: a systematic review.

    Science.gov (United States)

    Billioud, Vincent; Sandborn, William J; Peyrin-Biroulet, Laurent

    2011-04-01

    The objective of this study was to review loss of response and need for adalimumab dose intensification in adult and pediatric patients with Crohn's disease. Studies were identified through the electronic databases of MEDLINE and the annual meetings of Digestive Disease Week, of the United European Gastroenterology Week, and of the American College of Gastroenterology and the European Crohn's and Colitis Organization meetings. Studies evaluating loss of efficacy and/or need for dose intensification were included. Thirty-nine studies were included. The mean percentage of loss of response to adalimumab among primary responders was 18.2% and the annual risk was 20.3% per patient-year. The mean percentage of patients who required dose intensification among primary responders to adalimumab was 37% and the annual risk was 24.8% per patient-year. When considering initial responders and patients with primary non-response, the mean percentage of patients who needed an adalimumab dose escalation was 21.4% and the annual risk was 24.4% per patient-year. Pooled analysis showed that dose escalation permitted response to be regained in 71.4% and remission in 39.9% of patients. Predictors for loss of response or dose escalation were male gender, current/former smoker status, family history of inflammatory bowel disease, isolated colonic disease, extra-intestinal manifestations, 80/40  mg induction therapy, longer disease duration, greater baseline Crohn's Disease Activity Index, concomitant corticosteroid use, no deep remission at week 12, low serum trough concentrations of adalimumab, previous infliximab non-response and being previously treated with an anti-tumor necrosis factor agent. Overall, around one fifth of adult patients require dose intensification and experience a loss of response after initiation of adalimumab therapy. Adalimumab dose escalation permits response to be regained in the majority of patients.

  20. Beyond the perturbative description of the nonlinear optical response of low-index materials.

    Science.gov (United States)

    Reshef, Orad; Giese, Enno; Zahirul Alam, M; De Leon, Israel; Upham, Jeremy; Boyd, Robert W

    2017-08-15

    We show that standard approximations in nonlinear optics are violated for situations involving a small value of the linear refractive index. Consequently, the conventional equation for the intensity-dependent refractive index, n(I)=n0+n2I, becomes inapplicable in epsilon-near-zero and low-index media, even in the presence of only third-order effects. For the particular case of indium tin oxide, we find that the χ((3)), χ((5)), and χ((7)) contributions to refraction eclipse the linear term; thus, the nonlinear response can no longer be interpreted as a perturbation in these materials. Although the response is non-perturbative, we find no evidence that the power series expansion of the material polarization diverges.

  1. The horizontal angular vestibulo-ocular reflex: a nonlinear mechanism for context-dependent responses.

    Science.gov (United States)

    Ranjbaran, Mina; Galiana, Henrietta L

    2013-11-01

    Studies of the vestibulo-ocular reflex (VOR) have revealed that this type of involuntary eye movement is influenced by viewing distance. This paper presents a bilateral model for the horizontal angular VOR in the dark based on realistic physiological mechanisms. It is shown that by assigning proper nonlinear neural computations at the premotor level, the model is capable of replicating target-distance-dependent VOR responses that are in agreement with geometrical requirements. Central premotor responses in the model are also shown to be consistent with experimental observations. Moreover, the model performance after simulated unilateral canal plugging also reproduces experimental observations, an emerging property. Such local nonlinear computations could similarly generate context-dependent behaviors in other more complex motor systems.

  2. RNA splicing is responsive to MBNL1 dose.

    Directory of Open Access Journals (Sweden)

    Sonali P Jog

    Full Text Available Myotonic dystrophy (DM1 is a highly variable, multi-system disorder resulting from the expansion of an untranslated CTG tract in DMPK. In DM1 expanded CUG repeat RNAs form hairpin secondary structures that bind and aberrantly sequester the RNA splice regulator, MBNL1. RNA splice defects resulting as a consequence of MBNL1 depletion have been shown to play a key role in the development of DM1 pathology. In patient populations, both the number and severity of DM1 symptoms increase broadly as a function of CTG tract length. However significant variability in the DM1 phenotype is observed in patients encoding similar CTG repeat numbers. Here we demonstrate that a gradual decrease in MBNL1 levels results both in the expansion of the repertoire of splice defects and an increase in the severity of the splice alterations. Thus, MBNL1 loss does not have an all or none outcome but rather shows a graded effect on the number and severity of the ensuing splice defects. Our results suggest that once a critical threshold is reached, relatively small dose variations of free MBNL1 levels, which may reflect modest changes in the size of the CUG tract or the extent of hairpin secondary structure formation, can significantly alter the number and severity of splice abnormalities and thus contribute to the phenotype variability observed in DM1 patients.

  3. Dose-response of thermoluminescence in natural kaolinite

    Energy Technology Data Exchange (ETDEWEB)

    Correcher, V., E-mail: v.correcher@ciemat.es [CIEMAT, Av. Complutense, 22, Madrid 28040 (Spain); Garcia-Guinea, J.; Crespo-Feo, E. [Museo Nacional de Ciencias Naturales, CSIC, C. Jose Gutierrez Abascal 2, Madrid 28006 (Spain); Rodriguez-Lazcano, Y. [UCM, Dpto. Fisica de Materiales. Fac. CC. Fisicas. Av. Complutense, Madrid 28040 (Spain); Prado-Herrero, P. [MICINN, Albacete 5, Madrid 28027 (Spain)

    2010-05-20

    The thermal effect on the luminescence emission of a well-characterized natural kaolinite has been investigated by means of differential thermal analysis (DTA) and thermoluminescence (TL) to determine, respectively, the modifications of the material due to the thermal treatments up to 1000 {sup o}C and its potential use in the field of dating and retrospective dosimetry. The DTA detects water loss starting at 100-120 {sup o}C, a dehydroxylation process in the range of 400-500 {sup o}C and the transformation of kaolinite into metakaolinite at 570 {sup o}C. The dose dependence of the 400 nm TL intensity of kaolinite exhibits an excellent linearity in the range of 50 mGy to 8 Gy. In addition, the stability of the induced TL signal after six months of storage shows an initial rapid decay (ca. 60%) followed by a mild slope reaching the stability longer than six months. The tests of thermal stability at different temperatures allow us to speculate in a continuum of trap distribution with progressive changes in the glow curve shape, intensity and temperature position of the maximum peak. According to this thermal behavior, some physical parameters have been estimated using the initial rise method.

  4. A grid algorithm for high throughput fitting of dose-response curve data.

    Science.gov (United States)

    Wang, Yuhong; Jadhav, Ajit; Southal, Noel; Huang, Ruili; Nguyen, Dac-Trung

    2010-10-21

    We describe a novel algorithm, Grid algorithm, and the corresponding computer program for high throughput fitting of dose-response curves that are described by the four-parameter symmetric logistic dose-response model. The Grid algorithm searches through all points in a grid of four dimensions (parameters) and finds the optimum one that corresponds to the best fit. Using simulated dose-response curves, we examined the Grid program's performance in reproducing the actual values that were used to generate the simulated data and compared it with the DRC package for the language and environment R and the XLfit add-in for Microsoft Excel. The Grid program was robust and consistently recovered the actual values for both complete and partial curves with or without noise. Both DRC and XLfit performed well on data without noise, but they were sensitive to and their performance degraded rapidly with increasing noise. The Grid program is automated and scalable to millions of dose-response curves, and it is able to process 100,000 dose-response curves from high throughput screening experiment per CPU hour. The Grid program has the potential of greatly increasing the productivity of large-scale dose-response data analysis and early drug discovery processes, and it is also applicable to many other curve fitting problems in chemical, biological, and medical sciences.

  5. An ultra-high dose of electron radiation response of Germanium Flat Fiber and TLD-100

    Science.gov (United States)

    Alawiah, A.; Amin, Y. M.; Abdul-Rashid, H. A.; Abdullah, W. S. Wan; Maah, M. J.; Bradley, D. A.

    2017-01-01

    The thermoluminescence (TL) response of Germanium Flat Fiber (GFF) and TLD-100 irradiated with 2.5 MeV electrons for the doses up to 1 MGy were studied and compared. The aim was to evaluate the TL supralinearity response at an ultra-high dose (UHD) range and to investigate the change in kinetic parameters of the glow peaks, as the doses increases up to 1 MGy. It is found that the critical dose limit (CDL) of GFF is 5 times higher as compared to TLD-100. CDL is determined by the dose at the maximum supralinearity, f(D)max. It is also found that annealing the TLD-100 and GFF with temperature more than 400 °C is required to reset it back to its original condition, following radiation doses up to 1 MGy. It is also noticed the strange behavior of Peak 4 (TLD-100), which tends to be invisible at the lower dose (<10 kGy) and starts to be appeared at the critical dose limit of 10 kGy. This result might be an important clue to understand the behavior of TLD-100 at extremely high dose range. For both samples, it is observed that the TL intensity is not saturated within the UHD range studied.

  6. Low-Dose UVA Radiation-Induced Adaptive Response in Cultured Human Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Zhongrong Liu

    2012-01-01

    Full Text Available Objective. To investigate the mechanism of the adaptive response induced by low-dose ultraviolet A (UVA radiation. Methods. Cultured dermal fibroblasts were irradiated by a lethal dose of UVA (86.4 J/cm2 with preirradiation of single or repetitive low dose of UVA (7.2 J/cm2. Alterations of cellular morphology were observed by light microscope and electron microscope. Cell cycle and cellular apoptosis were assayed by flow cytometer. The extent of DNA damage was determined by single-cell gel electrophoresis (SCGE. Results. The cultured dermal fibroblasts, with pretreatment of single or repetitive irradiation of 7.2 J/cm2 UVA relieved toxic reaction of cellular morphology and arrest of cell cycle, decreased apoptosis ratio, reduced DNA chain breakage, and accelerated DNA repair caused by subsequent 86.4 J/cm2 UVA irradiation. Compared with nonpretreatment groups, all those differences were significant (P<0.01 or P<0.05. Conclusions. The adaptation reaction might depend on the accumulated dose of low-dose UVA irradiation. Low-dose UVA radiation might induce adaptive response that may protect cultured dermal fibroblasts from the subsequent challenged dose of UVA damage. The duration and protective capability of the adaptive reaction might be related to the accumulated dose of low-dose UVA Irradiation.

  7. Dipole Solitons in Nonlinear Media with an Exponential-Decay Nonlocal Response

    Institute of Scientific and Technical Information of China (English)

    YANG Zhen-Jun; MA Xue-Kai; ZHENG Yi-Zhou; GAO Xing-Hui; LU Da-Quan; HU Wei

    2011-01-01

    By applying the variational approach,the analytical expression of dipole solitons is obtained in nonlinear media with an exponential-decay nonlocal response.The relations of the soliton power versus the propagation constant and the soliton width are given.Some numerical simulations are carried out.The results show that the analytical expression is in excellent agreement with the numerical results for the strongly nonlocal case.

  8. Periodic response of nonlinear dynamical system with large number of degrees of freedom

    Indian Academy of Sciences (India)

    B P Patel; S M Ibrahim; Y Nath

    2009-12-01

    In this paper, a methodology based on shooting technique and Newmark's time integration scheme is proposed for predicting the periodic responses of nonlinear systems directly from solution of second order equations of motion without transforming to double first order equations. The proposed methodology is quite suitable for systems with large number of degrees of freedom such as the banded system of equations from finite element discretization.

  9. Nonlinear pulse propagation in a single- and a few-cycle regimes with Raman response

    Indian Academy of Sciences (India)

    Vimlesh Mishra; Ajit Kumar

    2010-09-01

    The propagation equation for a single- and a few-cycle pulses was derived in a cubic nonlinear medium including the Raman response. Using this equation, the propagation characteristics of a single- and a 4-cycle pulse, at 0.8 m wavelength, were studied numerically in one spatial dimension. It was shown that Raman term does influence the propagation characteristics of a single- as well as a few-cycle pulses by counteracting the self-steepening effect.

  10. MULTISTAGE ADAPTIVE HIGHER-ORDER NONLINEAR FINITE IMPULSE RESPONSE FILTERS FOR CHAOTIC TIME SERIES PREDICTIONS

    Institute of Scientific and Technical Information of China (English)

    ZHANG JIA-SHU; XIAO XIAN-CI

    2001-01-01

    A multistage adaptive higher-order nonlinear finite impulse response (MAHONFIR) filter is proposed to predict chaotic time series. Using this approach, we may readily derive the decoupled parallel algorithm for the adaptation of the coefficients of the MAHONFIR filter, to guarantee a more rapid convergence of the adaptive weights to their optimal values. Numerical simulation results show that the MAHONFIR filters proposed here illustrate a very good performance for making an adaptive prediction of chaotic time series.

  11. Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness

    Science.gov (United States)

    Cajochen, C.; Zeitzer, J. M.; Czeisler, C. A.; Dijk, D. J.

    2000-01-01

    Light can elicit both circadian and acute physiological responses in humans. In a dose response protocol men and women were exposed to illuminances ranging from 3 to 9100 lux for 6.5 h during the early biological night after they had been exposed to dose response curve. Half of the maximum alerting response to bright light of 9100 lux was obtained with room light of approximately 100 lux. This sensitivity to light indicates that variations in illuminance within the range of typical, ambient, room light (90-180 lux) can have a significant impact on subjective alertness and its electrophysiologic concomitants in humans during the early biological night.

  12. Historical blunders: how toxicology got the dose-response relationship half right.

    Science.gov (United States)

    Calabrese, E J

    2005-12-14

    Substantial evidence indicates that reliable examples of hormetic dose responses in the toxicological literature are common and generalizable across biological model, endpoint measured and chemical class. Further evaluation revealed that the hormetic dose response model is more common than the threshold dose response model in objective, head-to-head comparisons. Nonetheless, the field of toxicology made a profound error by rejecting the use of the hormetic dose response model in its teaching, research, risk assessment and regulatory activities over nearly the past century. This paper argues that the hormetic dose response model (formerly called the Arndt-Schulz Law) was rejected principally because of its close historical association with the medical practice of homeopathy as a result of the prolonged and bitter feud between traditional medicine and homeopathy. Opponents of the concept of hormesis, making use of strong appeals to authority, were successful in their misrepresentation of the scientific foundations of hormesis and in their unfair association of it with segments of the homeopathic movement with extreme and discreditable views. These misrepresentations became established and integrated within the pharmacology and toxicology communities as a result of their origins in and continuities with traditional medicine and subsequently profoundly impacted a broad range of governmental risk assessment activities further consolidating the rejection of hormesis. This error of judgment was reinforced by toxicological hazard assessment methods using only high and few doses that were unable to assess hormetic responses, statistical modeling processes that were constrained to deny the possibility of hormetic dose response relationships and by the modest nature of the hormetic stimulatory response itself, which required more rigorous study designs to evaluate possible hormetic responses.

  13. Extrinsic contribution and non-linear response in lead-free KNN-modified piezoceramics

    Energy Technology Data Exchange (ETDEWEB)

    Ochoa, D A; Garcia, J E; Perez, R; Gomis, V; Albareda, A [Department of Applied Physics, Universitat Politecnica de Catalunya, 08034 Barcelona (Spain); Rubio-Marcos, F; Fernandez, J F, E-mail: jose@fa.upc.ed [Department of Electroceramics, Instituto de Ceramica y Vidrio, CSIC, 28049 Madrid (Spain)

    2009-01-21

    Finding lead-free ceramics with good piezoelectric properties is nowadays one of the most important challenges in materials science. The (K, Na, Li)(Nb, Ta, Sb)O{sub 3} system is one of the most promising candidates as a lead-free ceramic for transducer applications and is currently the object of important research work. In this paper, (K{sub 0.44}Na{sub 0.52}Li{sub 0.04})(Nb{sub 0.86}Ta{sub 0.10}Sb{sub 0.04})O{sub 3} was prepared by a conventional ceramic processing route. For this composition, orthorhombic-to-tetragonal phase transition was observed at temperatures very close to room temperature. As a consequence, good room temperature electromechanical properties were observed, displaying good thermal stability. We show that the most important contribution to dielectric, piezoelectric and elastic response comes from extrinsic effects, as was observed in other perovskite based materials. Nonlinearities in electromechanical properties induced by high electric field or mechanical stress were studied. Non-linear dielectric response was found to be less important than for soft PZT ceramics and was analysed within the Rayleigh framework. The results reveal that the non-linear response at room temperature in this material is mainly due to the irreversible wall domain movement.

  14. Stationary variational estimates for the effective response and field fluctuations in nonlinear composites

    Science.gov (United States)

    Ponte Castañeda, Pedro

    2016-11-01

    This paper presents a variational method for estimating the effective constitutive response of composite materials with nonlinear constitutive behavior. The method is based on a stationary variational principle for the macroscopic potential in terms of the corresponding potential of a linear comparison composite (LCC) whose properties are the trial fields in the variational principle. When used in combination with estimates for the LCC that are exact to second order in the heterogeneity contrast, the resulting estimates for the nonlinear composite are also guaranteed to be exact to second-order in the contrast. In addition, the new method allows full optimization with respect to the properties of the LCC, leading to estimates that are fully stationary and exhibit no duality gaps. As a result, the effective response and field statistics of the nonlinear composite can be estimated directly from the appropriately optimized linear comparison composite. By way of illustration, the method is applied to a porous, isotropic, power-law material, and the results are found to compare favorably with earlier bounds and estimates. However, the basic ideas of the method are expected to work for broad classes of composites materials, whose effective response can be given appropriate variational representations, including more general elasto-plastic and soft hyperelastic composites and polycrystals.

  15. Inverse solution technique of steady-state responses for local nonlinear structures

    Science.gov (United States)

    Wang, Xing; Guan, Xin; Zheng, Gangtie

    2016-03-01

    An inverse solution technique with the ability of obtaining complete steady-state primary harmonic responses of local nonlinear structures in the frequency domain is proposed in the present paper. In this method, the nonlinear dynamic equations of motion is first condensed from many to only one algebraic amplitude-frequency equation of relative motion. Then this equation is transformed into a polynomial form, and with its frequency as the unknown variable, the polynomial equation is solved by tracing all the solutions of frequency with the increase of amplitude. With this solution technique, some complicated dynamic behaviors such as sharp tuning, anomalous jumps, breaks in responses and detached resonance curves could be obtained. The proposed method is demonstrated and validated through a finite element beam under force excitations and a lumped parameter model with a local nonlinear element under base excitations. The phenomenon of detached resonance curves in the frequency response and its coupling effects with multiple linear modes in the latter example are observed.

  16. Dose-Response Curve of Chromosome Aberrations in Human Lymphocytes Induced by Gamma-Rays

    Directory of Open Access Journals (Sweden)

    Y. Lusiyanti

    2013-12-01

    Full Text Available Chromosome aberration is a biomarker to predict the level of cell damage caused by exposure to ionizing radiation on human body. Dicentric chromosome is a specific chromosome aberration caused by ionizing radiation and is used as a gold standard biodosimetry of individuals over exposed to ionizing radiation. In radiation accident the dicentric assays has been applied as biological dosimetry to estimate radiation absorbed dose and also to confirm the radiation dose received to radiation workers.The purpose of this study was to generate a dose response curve of chromosome aberration (dicentric in human lymphocyte induced by gamma radiation. Peripheral blood samples from three non smoking healthy volunteers aged between 25-48 years old with informed consent were irradiated with dose between 0.1-4.0 Gy and a control using gamma teletherapy source. The culture procedure was conducted following the IAEA standard procedures with slight modifications. Analysis of dose-response curves used was LQ model Y = a + αD + βD2. The result showed that α and β values of the curve obtained were 0.018 ± 0.006 and 0.013 ± 0.002, respectively. Dose response calibration curve for dicentric chromosome aberrations in human lymphocytes induced by gamma-radiation fitted to linear quadratic model. In order to apply the dose response curve of chromosome aberration disentric for biodosimetry, this standar curve still need to be validated.

  17. Bystander responses in low dose irradiated cells treated with plasma from gamma irradiated blood

    Energy Technology Data Exchange (ETDEWEB)

    Acheva, A; Georgieva, R; Rupova, I; Boteva, R [Laboratory Molecular Radiobiology and Epidemiology, National Centre of Radiobiology and Radiation Protection, 132 Kliment Ohridski blvd, Sofia 1756 (Bulgaria); Lyng, F [Radiation and Environmental Science Center, Dublin Institute of Technology, Kevin st, Dublin 8 (Ireland)], E-mail: anjin_a@mail.bg

    2008-02-01

    There are two specific low-dose radiation-induced responses that have been the focus of radiobiologists' interest in recent years. These are the bystander effect in non-irradiated cells and the adaptive response to a challenge dose after prior low dose irradiation. In the present study we have investigated if plasma from irradiated blood can act as a 'challenge dose' on low dose irradiated reporter epithelial cells (HaCaT cell line). The main aim was to evaluate the overall effect of low dose irradiation (0.05 Gy) of reporter cells and the influence of bystander factors in plasma from 0.5 Gy gamma irradiated blood on these cells. The effects were estimated by clonogenic survival of the reporter cells. We also investigated the involvement of reactive oxygen species (ROS) as potential factors involved in the bystander signaling. Calcium fluxes and mitochondrial membrane potential (MMP) depolarization were also examined as a marker for initiation of apoptosis in the reporter cells. The results show that there are large individual differences in the production of bystander effects and adaptive responses between different donors. These may be due to the specific composition of the donor plasma. The observed effects generally could be divided into two groups: adaptive responses and additive effects. ROS appeared to be involved in the responses of the low dose pretreated reporter cells. In all cases there was a significant decrease in MMP which may be an early event in the apoptotic process. Calcium signaling also appeared to be involved in triggering apoptosis in the low dose pretreated reporter cells. The heterogeneity of the bystander responses makes them difficult to be modulated for medical uses. Specific plasma characteristics that cause these large differences in the responses would need to be identified to make them useful for radiotherapy.

  18. Bystander responses in low dose irradiated cells treated with plasma from gamma irradiated blood

    Science.gov (United States)

    Acheva, A.; Georgieva, R.; Rupova, I.; Boteva, R.; Lyng, F.

    2008-02-01

    There are two specific low-dose radiation-induced responses that have been the focus of radiobiologists' interest in recent years. These are the bystander effect in non-irradiated cells and the adaptive response to a challenge dose after prior low dose irradiation. In the present study we have investigated if plasma from irradiated blood can act as a 'challenge dose' on low dose irradiated reporter epithelial cells (HaCaT cell line). The main aim was to evaluate the overall effect of low dose irradiation (0.05 Gy) of reporter cells and the influence of bystander factors in plasma from 0.5 Gy gamma irradiated blood on these cells. The effects were estimated by clonogenic survival of the reporter cells. We also investigated the involvement of reactive oxygen species (ROS) as potential factors involved in the bystander signaling. Calcium fluxes and mitochondrial membrane potential (MMP) depolarization were also examined as a marker for initiation of apoptosis in the reporter cells. The results show that there are large individual differences in the production of bystander effects and adaptive responses between different donors. These may be due to the specific composition of the donor plasma. The observed effects generally could be divided into two groups: adaptive responses and additive effects. ROS appeared to be involved in the responses of the low dose pretreated reporter cells. In all cases there was a significant decrease in MMP which may be an early event in the apoptotic process. Calcium signaling also appeared to be involved in triggering apoptosis in the low dose pretreated reporter cells. The heterogeneity of the bystander responses makes them difficult to be modulated for medical uses. Specific plasma characteristics that cause these large differences in the responses would need to be identified to make them useful for radiotherapy.

  19. Environmental standards for ionizing radiation: theoretical basis for dose-response curves.

    Science.gov (United States)

    Upton, A C

    1983-10-01

    The types of injury attributable to ionizing radiation are subdivided, for purposes of risk assessment and radiological protection, into two broad categories: stochastic effects and nonstochastic effects. Stochastic effects are viewed as probablistic phenomena, varying in frequency but not severity as a function of the dose, without any threshold; nonstochastic effects are viewed as deterministic phenomena, varying in both frequency and severity as a function of the dose, with clinical thresholds. Included among stochastic effects are heritable effects (mutations and chromosome aberrations) and carcinogenic effects. Both types of effects are envisioned as unicellular phenomena which can result from nonlethal injury of individual cells, without the necessity of damage to other cells. For the induction of mutations and chromosome aberrations in the low-to-intermediate dose range, the dose-response curve with high-linear energy transfer (LET) radiation generally conforms to a linear nonthreshold relationship and varies relatively little with the dose rate. In contrast, the curve with low-LET radiation generally conforms to a linear-quadratic relationship, rising less steeply than the curve with high-LET radiation and increasing in slope with increasing dose and dose rate. The dose-response curve for carcinogenic effects varies widely from one type of neoplasm to another in the intermediate-to-high dose range, in part because of differences in the way large doses of radiation can affect the promotion and progression of different neoplasms. Information about dose-response relations for low-level irradiation is fragmentary but consistent, in general, with the hypothesis that the neoplastic transformation may result from mutation, chromosome aberration or genetic recombination in a single susceptible cell.

  20. On nonlinear oscillation response of a negatively dissipated oscillator and its analogy to long Josephson junction

    Energy Technology Data Exchange (ETDEWEB)

    Lim, C.W. [Department of Building and Construction, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong (China)], E-mail: bccwlim@cityu.edu.hk; Lai, S.K. [Department of Building and Construction, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong (China)

    2007-08-20

    This Letter deals with a research subject in nonlinear mechanics and applied mathematics. It develops (i) accurate higher-order approximate analytical nonlinear oscillator system with negative dissipation, and (ii) analogy to long Josephson junction. Particular emphasis has been placed on the weakly damped nonlinear oscillating system with negative dissipation with respect to a transformed temporal variable derived from the weak link of the simplified Josephson junction model. Nevertheless, the system response is shown to be stable with positive dissipation with respect to the physical time at a specific location. The analysis forms an innovative extension of the harmonic balancing method commonly used in nonlinear oscillation and vibration systems such as the Duffing oscillator and van der Pol oscillator. Besides introducing coupling of linearized governing equation and harmonic balancing method, the method of averaging is also employed to obtain accurate higher-order analytical approximate solutions. Unlike the classical harmonic balance method without analytical solution, the approach not only considers energy dissipation but also presents simple linear algebraic approximate solutions. In addition, general approximate analytical expressions for the dispersion relations are also established. The presence of a small perturbed parameter is not required.

  1. NONLINEAR TRANSIENT RESPONSE OF STAY CABLE WITH VISCOELASTICITY DAMPER IN CABLE-STAYED BRIDGE

    Institute of Scientific and Technical Information of China (English)

    陈水生; 孙炳楠; 冯义卿

    2004-01-01

    Taking the bending stiffness,static sag,and geometric non-linearity into consideration,the space nonlinear vibration partial differential equations were derived.The partical differential equations were discretized in space by finite center difference approximation,then the nonlinear ordinal differential equations were obtained.A hybrid method involving the combination of the Newmark method and the pseudo-force strategy was proposed to analyze the nonlinear transient response of the inclined cable-dampers system subjected to arbitrary dynamic loading.As an example,two typical stay cables were calculated by the present method.The results reveal both the validity and the deficiency of the viscoelasticity damper for vibration control of stay cables.The efficiency and accuracy of the proposed method is also verified by comparing the results with those obtained by using Runge-Kutta direct integration technique.A new time history analysis method is provided for the research on the stay cable vibration control.

  2. Use of nonlinear programming to optimize performance response to energy density in broiler feed formulation.

    Science.gov (United States)

    Guevara, V R

    2004-02-01

    A nonlinear programming optimization model was developed to maximize margin over feed cost in broiler feed formulation and is described in this paper. The model identifies the optimal feed mix that maximizes profit margin. Optimum metabolizable energy level and performance were found by using Excel Solver nonlinear programming. Data from an energy density study with broilers were fitted to quadratic equations to express weight gain, feed consumption, and the objective function income over feed cost in terms of energy density. Nutrient:energy ratio constraints were transformed into equivalent linear constraints. National Research Council nutrient requirements and feeding program were used for examining changes in variables. The nonlinear programming feed formulation method was used to illustrate the effects of changes in different variables on the optimum energy density, performance, and profitability and was compared with conventional linear programming. To demonstrate the capabilities of the model, I determined the impact of variation in prices. Prices for broiler, corn, fish meal, and soybean meal were increased and decreased by 25%. Formulations were identical in all other respects. Energy density, margin, and diet cost changed compared with conventional linear programming formulation. This study suggests that nonlinear programming can be more useful than conventional linear programming to optimize performance response to energy density in broiler feed formulation because an energy level does not need to be set.

  3. UNBALANCE RESPONSE AND TOUCH-RUBBING THRESHOLD SPEED OF ROTOR SUBJECTED TO NONLINEAR MAGNETIC FORCES

    Institute of Scientific and Technical Information of China (English)

    JING Minqing; LI Zixin; LUO Min; YU Lie

    2008-01-01

    Because of the effect of unbalance excitation and nonlinear magnetic force, the large vibration of the rotor supported by active magnetic bearing(AMB) will go beyond the radial gap of the bearing, even causing mechanical touch-rubbing when the system works at an operational speed closer to the critical speed. In order to investigate this problem, the linear model and nonlinear model of the single mass symmetric rigid rotor system supported by AMB are established respectively and the corresponding transfer functions of close-loop system are given. To pass through the numerical calculation by using MATLAB/Simulink, the effect of both the unbalance response and threshold speed of touch-rubbing of the system subjected to nonlinear magnetic forces and nonlinear output current of power amplifier are studied. Furthermore, threshold speed of touch-rubbing of the rotor-bearing system is defined and the results of numerical simulation are presented. Finally, based on above studies, two methods of increasing the touch-rubbing threshold speed are discussed.

  4. Coffee, tea, caffeine and risk of depression: A systematic review and dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Grosso, Giuseppe; Micek, Agnieszka; Castellano, Sabrina; Pajak, Andzrej; Galvano, Fabio

    2016-01-01

    The aim of the study was to systematically review and analyze results from observational studies on coffee, caffeine, and tea consumption and association or risk of depression. Embase and PubMed databases were searched from inception to June 2015 for observational studies reporting the odds ratios or relative risks (RRs) and 95% confidence intervals (CI) of depression by coffee/tea/caffeine consumption. Random effects models, subgroup analyses, and dose-response analyses were performed. Twelve studies with 23 datasets were included in the meta-analysis, accounting for a total of 346 913 individuals and 8146 cases of depression. Compared to individuals with lower coffee consumption, those with higher intakes had pooled RR of depression of 0.76 (95% CI: 0.64, 0.91). Dose-response effect suggests a nonlinear J-shaped relation between coffee consumption and risk of depression with a peak of protective effect for 400 mL/day. A borderline nonsignificant association between tea consumption and risk of depression was found (RR 0.70, 95% CI: 0.48, 1.01), while significant results were found only for analysis of prospective studies regarding caffeine consumption (RR = 0.84, 95% CI: 0.75, 0.93). This study suggests a protective effect of coffee and, partially, of tea and caffeine on risk of depression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Nonlinear system stochastic response determination via fractional equivalent linearization and Karhunen-Loève expansion

    Science.gov (United States)

    Dai, Hongzhe; Zheng, Zhibao; Wang, Wei

    2017-08-01

    In this paper, a novel fractional equivalent linearization (EL) approach is developed by incorporating a fractional derivative term into the classical linearization equation. Due to the introduction of the fractional derivative term, the accuracy of the new linearization is improved, illustrated by a Duffing oscillator that is subjected to a harmonic excitation. Furthermore, a new method for solving stochastic response of nonlinear SDOF system is developed by combining Karhunen-Loève (K-L) expansion and fractional EL. The method firstly decomposes the stochastic excitation in terms of a set of random variables and deterministic sub-excitations using K-L expansion, and then construct sub-fractional equivalent linear system according to each sub-excitation by fractional EL, the response of the original nonlinear system is finally approximated as the weighed summation of the deterministic response of each sub-system multiplied by the corresponding random variable. The random nature of the final response comes from the set of random variables that is obtained in K-L expansion. In this way, the stochastic response computation is converted to a set of deterministic response analysis problems. The effectiveness of the developed method is demonstrated by a Duffing oscillator that is subjected to stochastic excitation modeled by Winner process. The results are compared with the numerical method and Monte Carlo simulation (MCS).

  6. Dose-response investigation into glucose facilitation of memory performance and mood in healthy young adults.

    Science.gov (United States)

    Sünram-Lea, Sandra I; Owen, Lauren; Finnegan, Yvonne; Hu, Henglong

    2011-08-01

    It has been suggested that the memory enhancing effect of glucose follows an inverted U-shaped curve, with 25 g resulting in optimal facilitation in healthy young adults. The aim of this study was to further investigate the dose dependency of the glucose facilitation effect in this population across different memory domains and to assess moderation by interindividual differences in glucose regulation and weight. Following a double-blind, repeated measures design, 30 participants were administered drinks containing five different doses of glucose (0 g, 15 g, 25 g, 50 g, and 60 g) and were tested across a range of memory tasks. Glycaemic response and changes in mood state were assessed following drink administration. Analysis of the data showed that glucose administration did not affect mood, but significant glucose facilitation of several memory tasks was observed. However, dose-response curves differed depending on the memory task with only performance on the long-term memory tasks adhering largely to the previously observed inverted U-shaped dose-response curve. Moderation of the response profiles by interindividual differences in glucose regulation and weight was observed. The current data suggest that dose-response function and optimal dose might depend on cognitive domain and are moderated by interindividual differences in glucose regulation and weight.

  7. The response of various neutron dose meters considering the application at a high energy particle accelerator

    CERN Document Server

    Gutermuth, F; Fehrenbacher, G; Festag, J G

    2003-01-01

    The applicability of several neutron detectors for dose measurements at a neutron field typical for high energy particle accelerators is investigated. The response of four commercially available active neutron dose meters and two passive detectors to neutrons from a sup 2 sup 4 sup 1 Am-Be(alpha,n) source and to neutrons at the CERN EU high energy reference field was determined experimentally and simulated using the Monte-Carlo code FLUKA. Fluence response functions and dose responses for the different detectors were calculated in the energy range between 1 keV and 10 GeV. The results show that the dose response to the high energy neutron field at CERN of the conventional rem-counters is lower by a factor of 2 to 2.5 if compared to the dose response to a sup 2 sup 4 sup 1 Am-Be(alpha,n) neutron source. The rem-counters exhibiting an additional layer of lead inside the moderating structure showed dose readings which differ only up to 25%. A thermoluminescent based neutron detector was tested for comparison. Th...

  8. Dose-response and concentration-response relation of rocuronium infusion during propofol nitrous oxide and isoflurane nitrous oxide anaesthesia

    NARCIS (Netherlands)

    Kansanaho, M; Olkkola, KT; Wierda, JMKH

    1997-01-01

    The dose-response and concentration-response relation of rocuronium infusion was studied in 20 adult surgical patients during proporfol-nitrous oxide and isoflurane (1 MAC) -nitrous oxide anaesthesia. Neuromuscular block was kept constant, initially at 90% and then at 50% with a closed-loop feedback

  9. Microscopic investigations of the terahertz and the extreme nonlinear optical response of semiconductors

    Energy Technology Data Exchange (ETDEWEB)

    Golde, Daniel

    2010-06-22

    In the major part of this Thesis, we discuss the linear THz response of semiconductor nanostructures based on a microscopic theory. Here, two different problems are investigated: intersubband transitions in optically excited quantum wells and the THz plasma response of two-dimensional systems. In the latter case, we analyze the response of correlated electron and electron-hole plasmas. Extracting the plasma frequency from the linear response, we find significant deviations from the commonly accepted two-dimensional plasma frequency. Besides analyzing the pure plasma response, we also consider an intermediate regime where the response of the electron-hole plasma consists of a mixture of plasma contributions and excitonic transitions. A quantitative experiment-theory comparison provides novel insights into the behavior of the system at the transition from one regime to the other. The discussion of the intersubband transitions mainly focuses on the coherent superposition of the responses from true THz transitions and the ponderomotively accelerated carriers. We present a simple method to directly identify ponderomotive effects in the linear THz response. Apart from that, the excitonic contributions to intersubband transitions are investigated. The last part of the present Thesis deals with a completely different regime. Here, the extreme nonlinear optical response of low-dimensional semiconductor structures is discussed. Formally, extreme nonlinear optics describes the regime of light-matter interaction where the exciting field is strong enough such that the Rabi frequency is comparable to or larger than the characteristic transition frequency of the investigated system. Here, the Rabi frequency is given by the product of the electrical field strength and the dipole-matrix element of the respective transition. Theoretical investigations have predicted a large number of novel nonlinear effects arising for such strong excitations. Some of them have been observed in

  10. Scaling Laws for the Response of Nonlinear Elastic Media with Implications for Cell Mechanics

    Science.gov (United States)

    Shokef, Yair; Safran, Samuel A.

    2012-04-01

    We show how strain stiffening affects the elastic response to internal forces, caused either by material defects and inhomogeneities or by active forces that molecular motors generate in living cells. For a spherical force dipole in a material with a strongly nonlinear strain energy density, strains change sign with distance, indicating that, even around a contractile inclusion or molecular motor, there is radial compression; it is only at a long distance that one recovers the linear response in which the medium is radially stretched. Scaling laws with irrational exponents relate the far-field renormalized strain to the near-field strain applied by the inclusion or active force.

  11. Dietary fiber intake and risk of type 2 diabetes: a dose-response analysis of prospective studies.

    Science.gov (United States)

    Yao, Baodong; Fang, Hong; Xu, Wanghong; Yan, Yujie; Xu, Huilin; Liu, Yinan; Mo, Miao; Zhang, Hua; Zhao, Yanping

    2014-02-01

    Observational studies suggest an association between dietary fiber intake and risk of type 2 diabetes, but the results are inconclusive. We conducted a meta-analysis of prospective studies evaluating the associations of dietary fiber intake and risk of type 2 diabetes. Relevant studies were identified by searching EMBASE (from 1974 to April 2013) and PubMed (from 1966 to April 2013). The fixed or random-effect model was selected based on the homogeneity test among studies. In addition, a 2-stage random-effects dose-response meta-analysis was performed. We identified 17 prospective cohort studies of dietary fiber intake and risk of type 2 diabetes involving 19,033 cases and 488,293 participants. The combined RR (95 % CI) of type 2 diabetes for intake of total dietary fiber, cereal fiber, fruit fiber and insoluble fiber was 0.81 (0.73-0.90), 0.77 (0.69-0.85), 0.94 (0.88-0.99) and 0.75 (0.63-0.89), respectively. A nonlinear relationship was found of total dietary fiber intake with risk of type 2 diabetes (P for nonlinearity fiber intake. Findings from this meta-analysis indicate that the intakes of dietary fiber may be inversely associated with risk of type 2 diabetes.

  12. Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children

    Directory of Open Access Journals (Sweden)

    Decker Ralph

    2012-11-01

    Full Text Available Abstract Background In addition to stimulating linear growth in children, growth hormone (GH influences metabolism and body composition. These effects should be considered when individualizing GH treatment as dose-dependent changes in metabolic markers have been reported. Hypothesis: There are different dose-dependent thresholds for metabolic effects in response to GH treatment. Method A randomized, prospective, multicentre trial TRN 98-0198-003 was performed for a 2-year catch-up growth period, with two treatment regimens (a individualized GH dose including six different dose groups ranging from 17–100 μg/kg/day (n=87 and (b fixed GH dose of 43 μg/kg/day (n=41. The individualized GH dose group was used for finding dose–response effects, where the effective GH dose (ED 50% required to achieve 50% Δ effect was calculated with piecewise linear regressions. Results Different thresholds for the GH dose were found for the metabolic effects. The GH dose to achieve half of a given effect (ED 50%, with 90% confidence interval was calculated as 33(±24.4 μg/kg/day for Δ left ventricular diastolic diameter (cm, 39(±24.5 μg/kg/day for Δ alkaline phosphatase (μkat/L, 47(±43.5 μg/kg/day for Δ lean soft tissue (SDS, 48(±35.7 μg/kg/day for Δ insulin (mU/L, 51(±47.6 μg/kg/day for Δ height (SDS, and 57(±52.7 μg/kg/day for Δ insulin-like growth factor I (IGF-I SDS. Even though lipolysis was seen in all subjects, there was no dose–response effect for Δ fat mass (SDS or Δ leptin ng/ml in the dose range studied. None of the metabolic effects presented here were related to the dose selection procedure in the trial. Conclusions Dose-dependent thresholds were observed for different GH effects, with cardiac tissue being the most responsive and level of IGF-I the least responsive. The level of insulin was more responsive than that of IGF-I, with the threshold effect for height in the interval between.

  13. Coupled large earthquakes in the Baikal rift system: Response to bifurcations in nonlinear resonance hysteresis

    Directory of Open Access Journals (Sweden)

    Anatoly V. Klyuchevskii

    2013-11-01

    Full Text Available The current lithospheric geodynamics and tectonophysics in the Baikal rift are discussed in terms of a nonlinear oscillator with dissipation. The nonlinear oscillator model is applicable to the area because stress change shows up as quasi-periodic inharmonic oscillations at rifting attractor structures (RAS. The model is consistent with the space-time patterns of regional seismicity in which coupled large earthquakes, proximal in time but distant in space, may be a response to bifurcations in nonlinear resonance hysteresis in a system of three oscillators corresponding to the rifting attractors. The space-time distribution of coupled MLH > 5.5 events has been stable for the period of instrumental seismicity, with the largest events occurring in pairs, one shortly after another, on two ends of the rift system and with couples of smaller events in the central part of the rift. The event couples appear as peaks of earthquake ‘migration’ rate with an approximately decadal periodicity. Thus the energy accumulated at RAS is released in coupled large events by the mechanism of nonlinear oscillators with dissipation. The new knowledge, with special focus on space-time rifting attractors and bifurcations in a system of nonlinear resonance hysteresis, may be of theoretical and practical value for earthquake prediction issues. Extrapolation of the results into the nearest future indicates the probability of such a bifurcation in the region, i.e., there is growing risk of a pending M ≈ 7 coupled event to happen within a few years.

  14. The importance of ENSO nonlinearities in tropical pacific response to external forcing

    Science.gov (United States)

    Karamperidou, Christina; Jin, Fei-Fei; Conroy, Jessica L.

    2016-12-01

    Tropical Pacific climate varies at interannual, decadal and centennial time scales, and exerts a significant influence on global climate. Climate model projections exhibit a large spread in the magnitude and pattern of tropical Pacific warming in response to greenhouse-gas forcing. Here, we show that part of this spread can be explained by model biases in the simulation of interannual variability, namely the El Niño/Southern Oscillation (ENSO) phenomenon. We show that models that exhibit strong ENSO nonlinearities simulate a more accurate balance of ENSO feedbacks, and their projected tropical Pacific sea surface temperature warming pattern is closely linked to their projected ENSO response. Within this group, models with ENSO nonlinearity close to observed project stronger warming of the cold tongue, whereas models with stronger than observed ENSO nonlinearity project a more uniform warming of the tropical Pacific. These differences are also manifest in the projected changes of precipitation patterns, thereby highlighting that ENSO simulation biases may lead to potentially biased projections in long-term precipitation trends, with great significance for regional climate adaptation strategies.

  15. $v_4$, $v_5$, $v_6$, $v_7$: nonlinear hydrodynamic response versus LHC data

    CERN Document Server

    Yan, Li

    2015-01-01

    Higher harmonics of anisotropic flow ($v_n$ with $n\\ge 4$) in heavy-ion collisions can be measured either with respect to their own plane, or with respect to a plane constructed using lower-order harmonics. We explain how such measurements are related to event-plane correlations. We show that CMS data on $v_4$ and $v_6$ are compatible with ATLAS data on event-plane correlations. If one assumes that higher harmonics are the superposition of non-linear and linear responses, then the linear and non-linear parts can be isolated under fairly general assumptions. By combining analyses of higher harmonics with analyses of $v_2$ and $v_3$, one can eliminate the uncertainty from initial conditions and define quantities that only involve nonlinear hydrodynamic response coefficients. Experimental data on $v_4$, $v_5$ and $v_6$ are in good agreement with hydrodynamic calculations. We argue that $v_7$ can be measured with respect to elliptic and triangular flow. We present predictions for $v_7$ versus centrality in Pb-Pb ...

  16. Analysis on nonlinear wind-induced dynamic response of membrane roofs with aerodynamic effects

    Institute of Scientific and Technical Information of China (English)

    LI Qing-xiang; SUN Bing-nan

    2008-01-01

    Based on the characteristics of membrane structures and the air influence factors, this paper presen-ted a method to simulate the air aerodynamic force effects including the added air mass, the acoustic radiation damping and the pneumatic stiffness. The infinite air was modeled using the acoustic fluid element of commer-cial FE software and the finite element membrane roof models were coupled with fluid models. A comparison be-tween the results obtained by IrE computation and those obtained by the vibration experiment for a cable-mem-brane verified the validity of the method. Furthermore, applying the method to a flat membrane roof structure and using its wind tunnel test results, the analysis of nonlinear wind-induced dynamic responses for such geo-metrically nonlinear roofs, including the roof-air coupled model was performed. The result shows that the air has large influence on vibrating membrane roofs according to results of comparing the nodal time-history displace-ments, accelerations and stress of the two different cases. Meantime, numerical studies show that the method developed can successfully solve the nonlinear wind-induced dynamic response of the membrane roof with aero-dynamic effects.

  17. Can we detect a nonlinear response to temperature in European plant phenology?

    Science.gov (United States)

    Jochner, Susanne; Sparks, Tim H.; Laube, Julia; Menzel, Annette

    2016-10-01

    Over a large temperature range, the statistical association between spring phenology and temperature is often regarded and treated as a linear function. There are suggestions that a sigmoidal relationship with definite upper and lower limits to leaf unfolding and flowering onset dates might be more realistic. We utilised European plant phenological records provided by the European phenology database PEP725 and gridded monthly mean temperature data for 1951-2012 calculated from the ENSEMBLES data set E-OBS (version 7.0). We analysed 568,456 observations of ten spring flowering or leafing phenophases derived from 3657 stations in 22 European countries in order to detect possible nonlinear responses to temperature. Linear response rates averaged for all stations ranged between -7.7 (flowering of hazel) and -2.7 days °C-1 (leaf unfolding of beech and oak). A lower sensitivity at the cooler end of the temperature range was detected for most phenophases. However, a similar lower sensitivity at the warmer end was not that evident. For only ˜14 % of the station time series (where a comparison between linear and nonlinear model was possible), nonlinear models described the relationship significantly better than linear models. Although in most cases simple linear models might be still sufficient to predict future changes, this linear relationship between phenology and temperature might not be appropriate when incorporating phenological data of very cold (and possibly very warm) environments. For these cases, extrapolations on the basis of linear models would introduce uncertainty in expected ecosystem changes.

  18. Order reduction and efficient implementation of nonlinear nonlocal cochlear response models.

    Science.gov (United States)

    Filo, Maurice; Karameh, Fadi; Awad, Mariette

    2016-12-01

    The cochlea is an indispensable preliminary processing stage in auditory perception that employs mechanical frequency-tuning and electrical transduction of incoming sound waves. Cochlear mechanical responses are shown to exhibit active nonlinear spatiotemporal response dynamics (e.g., otoacoustic emission). To model such phenomena, it is often necessary to incorporate cochlear fluid-membrane interactions. This results in both excessively high-order model formulations and computationally intensive solutions that limit their practical use in simulating the model and analyzing its response even for simple single-tone inputs. In order to address these limitations, the current work employs a control-theoretic framework to reformulate a nonlinear two-dimensional cochlear model into discrete state space models that are of considerably lower order (factor of 8) and are computationally much simpler (factor of 25). It is shown that the reformulated models enjoy sparse matrix structures which permit efficient numerical manipulations. Furthermore, the spatially discretized models are linearized and simplified using balanced transformation techniques to result in lower-order (nonlinear) realizations derived from the dominant Hankel singular values of the system dynamics. Accuracy and efficiency of the reduced-order reformulations are demonstrated under the response to two fixed tones, sweeping tones and, more generally, a brief speech signal. The corresponding responses are compared to those produced by the original model in both frequency and spatiotemporal domains. Although carried out on a specific instance of cochlear models, the introduced framework of control-theoretic model reduction could be applied to a wide class of models that address the micro- and macro-mechanical properties of the cochlea.

  19. Comparisons of linear and nonlinear plasma response models for non-axisymmetric perturbations

    Energy Technology Data Exchange (ETDEWEB)

    Turnbull, A. D.; Ferraro, N. M.; Lao, L. L.; Lanctot, M. J. [General Atomics, P.O. Box 85608, San Diego, California 92186-5608 (United States); Izzo, V. A. [University of California-San Diego, 9500 Gilman Dr., La Jolla, California 92093-0417 (United States); Lazarus, E. A.; Hirshman, S. P. [Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, Tennessee 37831 (United States); Park, J.-K.; Lazerson, S.; Reiman, A. [Princeton Plasma Physics Laboratory, P.O. Box 451, Princeton, New Jersey 08543-0451 (United States); Cooper, W. A. [Association Euratom-Confederation Suisse, Centre de Recherches en Physique des Plasmas, Ecole Polytechnique Federale de Lausanne, Lausanne (Switzerland); Liu, Y. Q. [Culham Centre for Fusion Energy, Culham Science Centre, Abingdon, Oxfordshire, OX14 3DB (United Kingdom); Turco, F. [Columbia University, 116th St and Broadway, New York, New York 10027 (United States)

    2013-05-15

    With the installation of non-axisymmetric coil systems on major tokamaks for the purpose of studying the prospects of ELM-free operation, understanding the plasma response to the applied fields is a crucial issue. Application of different response models, using standard tools, to DIII-D discharges with applied non-axisymmetric fields from internal coils, is shown to yield qualitatively different results. The plasma response can be treated as an initial value problem, following the system dynamically from an initial unperturbed state, or from a nearby perturbed equilibrium approach, and using both linear and nonlinear models [A. D. Turnbull, Nucl. Fusion 52, 054016 (2012)]. Criteria are discussed under which each of the approaches can yield a valid response. In the DIII-D cases studied, these criteria show a breakdown in the linear theory despite the small 10{sup −3} relative magnitude of the applied magnetic field perturbations in this case. For nonlinear dynamical evolution simulations to reach a saturated nonlinear steady state, appropriate damping mechanisms need to be provided for each normal mode comprising the response. Other issues arise in the technical construction of perturbed flux surfaces from a displacement and from the presence of near nullspace normal modes. For the nearby equilibrium approach, in the absence of a full 3D equilibrium reconstruction with a controlled comparison, constraints relating the 2D system profiles to the final profiles in the 3D system also need to be imposed to assure accessibility. The magnetic helicity profile has been proposed as an appropriate input to a 3D equilibrium calculation and tests of this show the anticipated qualitative behavior.

  20. CCL2 mediates the circadian response to low dose endotoxin.

    Science.gov (United States)

    Duhart, José M; Brocardo, Lucila; Mul Fedele, Malena L; Guglielmotti, Angelo; Golombek, Diego A

    2016-09-01

    The mammalian circadian system is mainly originated in a master oscillator located in the suprachiasmatic nuclei (SCN) in the hypothalamus. Previous reports from our and other groups have shown that the SCN are sensitive to systemic immune activation during the early night, through a mechanism that relies on the action of proinflammatory factors within this structure. Chemokine (C-C motif) ligand 2 (CCL2) is induced in the brain upon peripheral immune activation, and it has been shown to modulate neuronal physiology. In the present work we tested whether CCL2 might be involved in the response of the circadian clock to peripheral endotoxin administration. The CCL2 receptor, C-C chemokine receptor type 2 (CCR2), was detected in the SCN of mice, with higher levels of expression during the early night, when the clock is sensitive to immune activation. Ccl2 was induced in the SCN upon intraperitoneal lipopolysaccharide (LPS) administration. Furthermore, mice receiving an intracerebroventricular (Icv) administration of a CCL2 synthesis inhibitor (Bindarit), showed a reduction LPS-induced circadian phase changes and Icv delivery of CCL2 led to phase delays in the circadian clock. In addition, we tested the possibility that CCL2 might also be involved in the photic regulation of the clock. Icv administration of Bindarit did not modify the effects of light pulses on the circadian clock. In summary, we found that CCL2, acting at the SCN level is important for the circadian effects of immune activation.

  1. Transcriptional profiling of the dose response: a more powerful approach for characterizing drug activities.

    Directory of Open Access Journals (Sweden)

    Rui-Ru Ji

    2009-09-01

    Full Text Available The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901 across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data.

  2. Estimating the predictive quality of dose-response after model selection.

    Science.gov (United States)

    Hu, Chuanpu; Dong, Yingwen

    2007-07-20

    Prediction of dose-response is important in dose selection in drug development. As the true dose-response shape is generally unknown, model selection is frequently used, and predictions based on the final selected model. Correctly assessing the quality of the predictions requires accounting for the uncertainties caused by the model selection process, which has been difficult. Recently, a new approach called data perturbation has emerged. It allows important predictive characteristics be computed while taking model selection into consideration. We study, through simulation, the performance of data perturbation in estimating standard error of parameter estimates and prediction errors. Data perturbation was found to give excellent prediction error estimates, although at times large Monte Carlo sizes were needed to obtain good standard error estimates. Overall, it is a useful tool to characterize uncertainties in dose-response predictions, with the potential of allowing more accurate dose selection in drug development. We also look at the influence of model selection on estimation bias. This leads to insights into candidate model choices that enable good dose-response prediction.

  3. Combining in silico evolution and nonlinear dimensionality reduction to redesign responses of signaling networks

    Science.gov (United States)

    Prescott, Aaron M.; Abel, Steven M.

    2016-12-01

    The rational design of network behavior is a central goal of synthetic biology. Here, we combine in silico evolution with nonlinear dimensionality reduction to redesign the responses of fixed-topology signaling networks and to characterize sets of kinetic parameters that underlie various input-output relations. We first consider the earliest part of the T cell receptor (TCR) signaling network and demonstrate that it can produce a variety of input-output relations (quantified as the level of TCR phosphorylation as a function of the characteristic TCR binding time). We utilize an evolutionary algorithm (EA) to identify sets of kinetic parameters that give rise to: (i) sigmoidal responses with the activation threshold varied over 6 orders of magnitude, (ii) a graded response, and (iii) an inverted response in which short TCR binding times lead to activation. We also consider a network with both positive and negative feedback and use the EA to evolve oscillatory responses with different periods in response to a change in input. For each targeted input-output relation, we conduct many independent runs of the EA and use nonlinear dimensionality reduction to embed the resulting data for each network in two dimensions. We then partition the results into groups and characterize constraints placed on the parameters by the different targeted response curves. Our approach provides a way (i) to guide the design of kinetic parameters of fixed-topology networks to generate novel input-output relations and (ii) to constrain ranges of biological parameters using experimental data. In the cases considered, the network topologies exhibit significant flexibility in generating alternative responses, with distinct patterns of kinetic rates emerging for different targeted responses.

  4. Pharmacogenetic Predictors of Methylphenidate Dose-Response in Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Froehlich, Tanya E.; Epstein, Jeffery N.; Nick, Todd G.; Melguizo Castro, Maria S.; Stein, Mark A.; Brinkman, William B.; Graham, Amanda J.; Langberg, Joshua M.; Kahn, Robert S.

    2011-01-01

    Objective: Because of significant individual variability in attention-deficit/hyperactivity disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examined the role of four catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. Method:…

  5. Dose-dependent pheromone responses of mountain pine beetle in stands of lodgepole pine

    Science.gov (United States)

    Daniel R. Miller; B. Staffan Lindgren; John H. Borden

    2005-01-01

    We conducted seven behavioral choice tests with Lindgren multiple-funnel traps in stands of mature lodgepole pine in British Columbia, from 1988 to 1994, to determine the dosedependent responses of the mountain pine beetle, Dendroctonus ponderosae Hopkins, to its pheromones. Amultifunctional dose-dependent response was exhibited by D. ...

  6. Modeling and regression analysis of semiochemical dose-response curves of insect antennal reception and behavior

    Science.gov (United States)

    Dose-response curves with semiochemicals are reported in many articles in insect chemical ecology regarding neurophysiology and behavioral bioassays. Most such curves are shown in figures where the x-axis has order of magnitude increases in dosages versus responses on the y-axis represented by point...

  7. Pharmacogenetic Predictors of Methylphenidate Dose-Response in Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Froehlich, Tanya E.; Epstein, Jeffery N.; Nick, Todd G.; Melguizo Castro, Maria S.; Stein, Mark A.; Brinkman, William B.; Graham, Amanda J.; Langberg, Joshua M.; Kahn, Robert S.

    2011-01-01

    Objective: Because of significant individual variability in attention-deficit/hyperactivity disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examined the role of four catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. Method:…

  8. AN EXTRACT OF PENICILLIUM CHRYSOGENUM INDUCES DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES IN MICE

    Science.gov (United States)

    Rationale: Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of P. chrysogenum (PCE) can dose-dependently induce responses typ...

  9. Dose-Response Modeling Under Simple Order Restrictions Using Bayesian Variable Selection Methods

    OpenAIRE

    Otava, Martin; Shkedy, Ziv; Lin, Dan; Goehlmann, Hinrich W. H.; Bijnens, Luc; Talloen, Willem; Kasim, Adetayo

    2014-01-01

    Bayesian modeling of dose–response data offers the possibility to establish the relationship between a clinical or a genomic response and increasing doses of a therapeutic compound and to determine the nature of the relationship wherever it exists. In this article, we focus on an order-restricted one-way ANOVA model which can be used to test the null hypothesis of no dose effect against an ordered alternative. Within the framework of the dose–response modeling, a model uncertainty can be addr...

  10. Nonlinear static and dynamic responses of an electrically actuated viscoelastic microbeam

    Institute of Scientific and Technical Information of China (English)

    Y. M. Fu; J. Zhang

    2009-01-01

    On the basis of the Euler-Bernoulli hypothesis,nonlinear static and dynamic responses of a viscoelastic microbeam under two kinds of electric forces [a purely direct current (DC) and a combined current composed of a DC and an alternating current] are studied. By using Taylor series expansion, a governing equation of nonlinear integro-differential type is derived, and numerical analyses are performed.When a purely DC is applied, there exist an instantaneous pull-in voltage and a durable pull-in voltage of which the physical meanings are also given, whereas under an applied combined current, the effect of the element relaxation coefficient on the dynamic pull-in phenomenon is observed where the largest Lyapunov exponent is taken as a criterion for the dynamic pull-in instability of viscoelastic microbeams.

  11. Measurement of the frequency response of the electrostrictive nonlinearity in optical fibers.

    Science.gov (United States)

    Buckland, E L; Boyd, R W

    1997-05-15

    The electrostrictive contribution to the nonlinear refractive index is investigated by use of frequency-dependent cross-phase modulation with a weak unpolarized cw probe wave and a harmonically modulated pump copropagating in optical fibers. Self-delayed homodyne detection is used to measure the amplitude of the sidebands imposed upon the probe wave as a function of pump intensity for pump modulation frequencies from 10 MHz to 1 GHz. The ratio of the electrostrictive nonlinear coefficient to the cross-phase-modulation Kerr coefficient for unpolarized light is measured to be 1.58:1 for a standard step-index single-mode fiber and 0.41:1 for dispersion-shifted fibers, indicating a larger electrostrictive response in silica fibers than previously expected.

  12. STEADY-STATE RESPONSES AND THEIR STABILITY OF NONLINEAR VIBRATION OF AN AXIALLY ACCELERATING STRING

    Institute of Scientific and Technical Information of China (English)

    吴俊; 陈立群

    2004-01-01

    The steady-state transverse vibration of an axially moving string with geometric nonlinearity was investigated. The transport speed was assumed to be a constant mean speed with small harmonic variations. The nonlinear partial-differential equation that governs the transverse vibration of the string was derived by use of the Hamilton principle. The method of multiple scales was applied directly to the equation. The solvability condition of eliminating the secular terms was established. Closed form solutions for the amplitude and the existence conditions of nontrivial steady-state response of the two-to-one parametric resonance were obtained. Some numerical examples showing effects of the mean transport speed, the amplitude and the frequency of speed variation were presented. The Liapunov linearized stability theory was employed to derive the instability conditions of the trivial solution and the nontrivial solutions for the two-to-one parametric resonance. Some numerical examples highlighting influences of the related parameters on the instability conditions were presented.

  13. Non-Linear Relationships between Aflatoxin B1 Levels and the Biological Response of Monkey Kidney Vero Cells

    Directory of Open Access Journals (Sweden)

    Mendel Friedman

    2013-08-01

    Full Text Available Aflatoxin-producing fungi contaminate food and feed during pre-harvest, storage and processing periods. Once consumed, aflatoxins (AFs accumulate in tissues, causing illnesses in animals and humans. Most human exposure to AF seems to be a result of consumption of contaminated plant and animal products. The policy of blending and dilution of grain containing higher levels of aflatoxins with uncontaminated grains for use in animal feed implicitly assumes that the deleterious effects of low levels of the toxins are linearly correlated to concentration. This assumption may not be justified, since it involves extrapolation of these nontoxic levels in feed, which are not of further concern. To develop a better understanding of the significance of low dose effects, in the present study, we developed quantitative methods for the detection of biologically active aflatoxin B1 (AFB1 in Vero cells by two independent assays: the green fluorescent protein (GFP assay, as a measure of protein synthesis by the cells, and the microculture tetrazolium (MTT assay, as a measure of cell viability. The results demonstrate a non-linear dose-response relationship at the cellular level. AFB1 at low concentrations has an opposite biological effect to higher doses that inhibit protein synthesis. Additional studies showed that heat does not affect the stability of AFB1 in milk and that the Vero cell model can be used to determine the presence of bioactive AFB1 in spiked beef, lamb and turkey meat. The implication of the results for the cumulative effects of low amounts of AFB1 in numerous foods is discussed.

  14. Permanence of Periodic Predator-Prey System with General Nonlinear Functional Response and Stage Structure for Both Predator and Prey

    Directory of Open Access Journals (Sweden)

    Xuming Huang

    2009-01-01

    Full Text Available We study the permanence of periodic predator-prey system with general nonlinear functional responses and stage structure for both predator and prey and obtain that the predator and the prey species are permanent.

  15. A randomized trial of vitamin D₃ supplementation in children: dose-response effects on vitamin D metabolites and calcium absorption.

    Science.gov (United States)

    Lewis, R D; Laing, E M; Hill Gallant, K M; Hall, D B; McCabe, G P; Hausman, D B; Martin, B R; Warden, S J; Peacock, M; Weaver, C M

    2013-12-01

    Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D₃ in healthy children are unknown. Our objective was to examine the dose-response effects of supplemental vitamin D₃ on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes. Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D₃ (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)₂D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope ⁴⁴Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption. The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from -10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P pill compliance, race, sex, or baseline 25(OH)D. Large increases in serum 25(OH)D with vitamin D₃ supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children.

  16. Experimental damage detection of cracked beams by using nonlinear characteristics of forced response

    Science.gov (United States)

    Andreaus, U.; Baragatti, P.

    2012-08-01

    Experimental evaluation of the flexural forced vibrations of a steel cantilever beam having a transverse surface crack extending uniformly along the width of the beam was performed, where an actual fatigue crack was introduced instead - as usual - of a narrow slot. The nonlinear aspects of the dynamic response of the beam under harmonic excitation were considered and the relevant quantitative parameters were evaluated, in order to relate the nonlinear resonances to the presence and size of the crack. To this end, the existence of sub- and super-harmonic components in the Fourier spectra of the acceleration signals was evidenced, and their amplitudes were quantified. In particular, the acceleration signals were measured in different positions along the beam axis and under different forcing levels at the beam tip. The remarkable relevance of the above mentioned nonlinear characteristics, and their substantial independence on force magnitude and measurement point were worthily noted in comparison with the behavior of the intact beam. Thus, a reliable method of damage detection was proposed which was based on simple tests requiring only harmonically forcing and acceleration measuring in any point non-necessarily near the crack. Then, the time-history of the acceleration recorded at the beam tip was numerically processed in order to obtain the time-histories of velocity and displacement. The nonlinear features of the forced response were described and given a physical interpretation in order to define parameters suitable for damage detection. The efficiency of such parameters was discussed with respect to the their capability of detecting damage and a procedure for damage detection was proposed which was able to detect even small cracks by using simple instruments. A finite element model of the cantilever beam was finally assembled and tuned in order to numerically simulate the results of the experimental tests.

  17. Effect of -OH functionalization, C2 methylation, and high radiation fields on the non-linear optical response of imidazolium ionic liquids

    Science.gov (United States)

    Namboodiri, Vinu V.; Guleria, Apurav; Singh, Ajay K.

    2017-04-01

    Considering the impending applications of room temperature ionic liquids (RTILs) in various areas involving high optical and radiation fields, it is pertinent to probe the structure-property correlation of these solvents exposed to such conditions. Herein, femtosecond Z-scan technique (at high pulse repetition rate, 80 MHz) was employed to investigate the non-linear optical response of imidazolium RTILs in 3 scenarios: (1) -OH functionalization, (2) C2 methylation, and (3) influence of high radiation fields. Large negative non-linear refractive values ( n 2) were observed in all the RTIL samples and have been attributed predominantly due to the thermal effects. In order to isolate and determine the contribution of electronic Kerr effect, the Z-scan experiments were also carried out at low pulse repetition rate (i.e. 500 Hz) by means of a mechanical chopper. The closed aperture transmittance profile showed the valley-peak pattern, which signifies positive non-linearity. Nonetheless, the variation in the n2 values of the RTILs follows the same trend in low pulse repetition rate as was observed in case of high pulse repetition rate. The trend in the n 2 values clearly showed the decrease in the non-linearity in the first two cases and has been attributed to the weakening of the ion-pair formation, which adversely affects the charge transfer between the ionic moieties via C2 position. However, an increase in the n 2 values was observed in case of ILs irradiated to high radiation doses. This enhancement in the non-linearity has been assigned to the formation of double bond order radiolytic products. These results clearly indicate a strong correlation between the non-linearity and the strength of cation-anion interaction amongst them. Therefore, such information about these solvents may significantly contribute to the fundamental understanding of their structure-property relationships.

  18. MCz diode response as a high-dose gamma radiation dosimeter

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, F. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Goncalves, J.A.C. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Depto. de Fisica, Pontificia Universidade Catolica de Sao Paulo-PUC/SP, Rua Marques de Paranagua no 111-01303 050 Sao Paulo/SP (Brazil); Khoury, H.J. [Nuclear Energy Department, Universidade Federal de Pernambuco-UFPE, Av. Prof. Luiz Freire no 1000-50740 540 Recife/PE (Brazil); Napolitano, C.M. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Haerkoenen, J. [Helsinki Institute of Physics-HIP, University of Helsinki, 00014 Helsinki (Finland); Bueno, C.C. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Depto. de Fisica, Pontificia Universidade Catolica de Sao Paulo-PUC/SP, Rua Marques de Paranagua no 111-01303 050 Sao Paulo/SP (Brazil)], E-mail: ccbueno@ipen.br

    2008-02-15

    This work presents the preliminary results obtained with a high-resistivity magnetic Czochralski (MCz) silicon diode processed at the Helsinki Institute of Physics as a high-dose gamma dosimeter in radiation processing. The irradiation was performed using a {sup 60}Co source (Gammacell 220, MDS Nordion) within total doses from 100 Gy up to 3 kGy at a dose rate of 3 kGy/h. In this interval, the dosimetric response of the diode is linear with a correlation coefficient (r{sup 2}) higher than 0.993. However, without any irradiation procedure, the device showed a small sensitivity dependence on the accumulated dose. For total dose of 3 kGy, the observed decrease was about 2%. To clarify the origin of this possible radiation damage effect, some studies are under way.

  19. Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease.

    Science.gov (United States)

    Qi, Hui; Li, Shixue

    2014-04-01

    A dose-response meta-analysis was carried out between Parkinson's disease (PD) risk, and coffee, tea and caffeine consumption. A comprehensive search was carried out to identify eligible studies. The fixed or random effect model was used based on heterogeneity test. The dose-response relationship was assessed by restricted cubic spline. A total of 13 articles involving 901 764 participants for coffee, eight articles involving 344 895 participants for tea and seven articles involving 492 724 participants for caffeine were included. A non-linear relationship was found between coffee consumption and PD risk overall, and the strength of protection reached the maximum at approximately 3 cups/day (smoking-adjusted relative risk: 0.72, 95% confidence interval 0.65-0.81). A linear relationship was found between tea and caffeine consumption, and PD risk overall, and the smoking-adjusted risk of PD decreased by 26% and 17% for every two cups/day and 200 mg/day increments, respectively. The association of coffee and tea consumption with PD risk was stronger for men than that for women, and the association of caffeine consumption with PD risk was stronger for ever users of hormones than that for never users of hormones among postmenopausal women. The aforementioned associations were weaker for USA relative to Europe or Asia. A linear dose-relationship for decreased PD risk with tea and caffeine consumption was found, whereas the strength of protection reached a maximum at approximately 3 cups/day for coffee consumption overall. Further studies are required to confirm the findings. © 2013 Japan Geriatrics Society.

  20. The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, T., E-mail: schmito@uni-mainz.de [Institute for nuclear chemistry, Johannes Gutenberg-University, Mainz D-55128 (Germany); Bassler, N. [Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, Aarhus C, Aarhus 8000 (Denmark); Blaickner, M. [AIT Austrian Institute of Technology GmbH, Vienna A-1220 (Austria); Ziegner, M. [AIT Austrian Institute of Technology GmbH, Vienna A-1220, Austria and TU Wien, Vienna University of Technology, Vienna A-1020 (Austria); Hsiao, M. C. [Insitute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Liu, Y. H. [Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Koivunoro, H. [Department of Physics, University of Helsinki, POB 64, FI-00014, Finland and HUS Medical Imaging Center, Helsinki University Central Hospital, FI-00029 HUS (Finland); Auterinen, I.; Serén, T.; Kotiluoto, P. [VTT Technical Research Centre of Finland, Espoo (Finland); Palmans, H. [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW, United Kingdom and Medical Physics Group, EBG MedAustron GmbH, Wiener Neustadt A-2700 (Austria); Sharpe, P. [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW (United Kingdom); Langguth, P. [Department of Pharmacy and Toxicology, University of Mainz, Mainz D-55128 (Germany); Hampel, G. [Institut für Kernchemie, Johannes Gutenberg-Universität, Mainz D-55128 (Germany)

    2015-01-15

    Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a {sup 60}Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes FLUKA and MCNP. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen and Olsen alanine response model. Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields. Conclusions: The

  1. The nonlinear North Atlantic-Arctic ocean response to CO2 forcing

    Science.gov (United States)

    van der Linden, Eveline C.; Bintanja, Richard; Hazeleger, Wilco

    2017-04-01

    Most climate models project an increase in oceanic energy transport towards high northern latitudes in future climate projections, but the physical mechanisms are not yet fully understood. To obtain a more fundamental understanding of the processes that cause the ocean heat transport to increase, we carried out a set of sensitivity experiments using a coupled atmosphere-ocean general circulation model. Within these experiments, atmospheric CO2 levels are instantaneously set to one-fourth to four times current values. These model integrations, each with a length of 550 years, result in five considerably different quasi-equilibrium climate states. Our simulations show that poleward ocean heat transport in the Atlantic sector of the Arctic at 70°N increases from 0.03 PW in the coldest climate state to 0.2 PW in the warmest climate state. This increase is caused primarily by changes in sea ice cover, in horizontal ocean currents owing to anomalous winds in response to sea ice changes, and in ocean advection of thermal anomalies. Surprisingly, at subpolar latitudes, the subpolar gyre is found to weaken toward both the warmer and colder climates, relative to the current climate. This nonlinear response is caused by a complex interplay between seasonal sea ice melt, the near-surface wind response to sea ice changes, and changes in the density-driven circulation. The Atlantic Meridional Overturning Circulation (AMOC) and its associated heat transport even oppose the total ocean heat transport towards the Arctic in the warmest climate. Going from warm to cold climates, or from high to low CO2 concentrations, the strength of the AMOC initially increases, but then declines towards the coldest climate, implying a nonlinear AMOC-response to CO2-induced climate change. Evidently, the North Atlantic-Arctic ocean heat transport depends on an interplay between various (remote) coupled ocean-atmosphere-sea ice mechanisms that respond in a nonlinear way to climate change.

  2. Immune response to 1 and 2 dose regimens of measles vaccine in Pakistani children.

    Science.gov (United States)

    Hussain, Hamidah; Akram, Dure Samin; Chandir, Subhash; Khan, Aamir J; Memon, Ashraf; Halsey, Neal A

    2013-12-01

    Measles is a significant problem in Pakistan despite vaccine coverage rates reported at 80%. The purpose of this study was to determine the serologic response in children after one dose of measles vaccine at 9 mo versus two doses at 9 and 15 mo of age. From March through December 2006, children were enrolled from immunization clinics and squatter settlements in Karachi. Blood samples were taken from children in Group A at 9-10 mo of age prior to measles vaccine and 8 to 11 weeks later; from children in Group B at 16-17 mo of age after receiving 2 doses of measles vaccine; and from children in Group C who had received at least one dose of measles vaccine by 5 y of age. After the first dose of measles vaccine, 107/147 (73%) of children in Group A were seropositive, 157/180 (87%) of children in Group B were seropositive after two doses and 126/200 (63%) of children in Group C were seropositive at 5 y of age. The post-vaccination geometric mean antibody concentrations were higher in females than males in groups A (irrespective of pre-vaccination antibody levels) and B. The serologic response to one and two doses of measles vaccine was lower in children in Karachi than has been reported in many other countries. Two doses of vaccine were significantly better than one dose. An in-depth investigation is needed to determine the reason for the lower-than-expected protection rates. Differences in immunogenicity between genders need to be further studied. Recent introduction of supplemental measles vaccine doses should help control measles in Pakistan.

  3. Higher harmonic nonlocal polymerization driven diffusion model: generalized nonlinearities and nonlocal responses

    Science.gov (United States)

    Kelly, John V.; O'Brien, Jeff; O'Neill, Feidhlim T.; Gleeson, Michael R.; Sheridan, John T.

    2004-10-01

    Non-local and non-linear models of photopolymer materials, which include diffusion effects, have recently received much attention in the literature. The material response is non-local as it is assumed that monomers are polymerised to form polymer chains and that these chains grow away from a point of initiation. The non-locality is defined in terms of a spatial non-local material response function. The numerical method of solution typically involves retaining either two or four harmonics of the Fourier series of monomer concentration in the calculation. In this paper a general set of equations is derived which allows inclusion of higher number of harmonics for any response function. The numerical convergence for varying number of harmonics retained is investigated with special care being taken to note the effect of the; non-local material variance s, the power law degree k, and the rates of diffusion, D, and polymerisation F0. General non-linear material responses are also included.

  4. Analysis of Dose Response for Circulatory Disease After Radiotherapy for Benign Disease

    Energy Technology Data Exchange (ETDEWEB)

    Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mabuchi, Kiyohiko [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States)

    2012-12-01

    Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy{sup -1} of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy{sup -1} of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  5. Dose response of hydrazine - Deproteinated tooth enamel under blue light stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Yuece, Ulkue Rabia, E-mail: ulkuyuce@hotmail.co [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Meric, Niyazi, E-mail: meric@ankara.edu.t [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Atakol, Orhan, E-mail: atakol@science.ankara.edu.t [Ankara University, Science Faculty, Department of Chemistry, 06100, Tandogan - Ankara (Turkey); Yasar, Fusun, E-mail: ab121310@adalet.gov.t [Council of Forensic Medicine, Ankara Branch, Ankara (Turkey)

    2010-08-15

    The beta dose response and Optically Stimulated Luminescence (OSL) signal stability characteristics of human tooth enamel deproteinated by hydrazine reagent under blue photon stimulation are reported. Removal of the protein organic component of tooth enamel resulted in a higher OSL sensitivity and slower fading of OSL signals. The effect of chemical sample preparation on the enamel sample sensitivity is discussed and further steps to make this deproteinization treatment suitable for in vitro dose reconstruction studies are suggested.

  6. Testing the Capacity of the National Biological Dose Response Plan (NBDRP) EX40801

    Science.gov (United States)

    2009-11-01

    providing radiation biological dose estimates using the dicentric chromosome assay (DCA). As indicated in the CRTI-06-0146RD charter, the existing...laboratories of the National Biological Dose Response Plan plus two US laboratories. Samples were scored for the dicentric chromosome assay and the CBMN...Wilkins, R.C. QuickScan dicentric chromosome analysis for radiation biodosimetry , Health Physics Journal, In Press (2009). 2. McNamee, J.P., Flegal

  7. The Influence of Human Interindividual Variability on the Low-Dose Region of Dose-Response Curve Induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Primary B Cells.

    Science.gov (United States)

    Dornbos, Peter; Crawford, Robert B; Kaminski, Norbert E; Hession, Sarah L; LaPres, John J

    2016-10-01

    The influence of interindividual variability is not typically assessed in traditional toxicological studies. Given that chemical exposures occur in heterogeneous populations, this knowledge gap has the potential to cause undue harm within the realms of public health and industrial and municipal finances. A recent report from the National Research Council (NRC) suggests that when accounting for interindividual variation in responses, traditionally assumed nonlinear dose-response relationships (DRRs) for noncancer-causing endpoints would better be explained with a linear relationship within the low-dose region. To address this knowledge gap and directly test the NRC's assumption, this study focused on assessing the DRR between 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) exposure and immune suppression in a cohort of unique human donors. Human B cells were isolated from 51 individual donors and treated with logarithmically increasing concentrations of TCDD (0-30 nM TCDD). Two endpoints sensitive to TCDD were assessed: (1) number of IgM-secreting B cells and (2) quantity of IgM secreted. The results show that TCDD significantly suppressed both the number of IgM-secreting B cells and the quantity of IgM secreted (P < .05). Statistical model comparisons indicate that the low-dose region of the two DRRs is best explained with a nonlinear relationship. Rather than assuming low-dose linearity for all noncancer-causing DRRs, our study suggests the need to consider the specific mode of action of toxicants and pharmaceuticals during risk-management decision making. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Dose-response of EBT3 radiochromic films to proton and carbon ion clinical beams

    Science.gov (United States)

    Castriconi, Roberta; Ciocca, Mario; Mirandola, Alfredo; Sini, Carla; Broggi, Sara; Schwarz, Marco; Fracchiolla, Francesco; Martišíková, Mária; Aricò, Giulia; Mettivier, Giovanni; Russo, Paolo

    2017-01-01

    We investigated the dose-response of the external beam therapy 3 (EBT3) films for proton and carbon ion clinical beams, in comparison with conventional radiotherapy beams; we also measured the film response along the energy deposition-curve in water. We performed measurements at three hadrontherapy centres by delivering monoenergetic pencil beams (protons: 63-230 MeV; carbon ions: 115-400 MeV/u), at 0.4-20 Gy dose to water, in the plateau of the depth-dose curve. We also irradiated the films to clinical MV-photon and electron beams. We placed the EBT3 films in water along the whole depth-dose curve for 148.8 MeV protons and 398.9 MeV/u carbon ions, in comparison with measurements provided by a plane-parallel ionization chamber. For protons, the response of EBT3 in the plateau of the depth-dose curve is not different from that of photons, within experimental uncertainties. For carbon ions, we observed an energy dependent under-response of EBT3 film, from 16% to 29% with respect to photon beams. Moreover, we observed an under-response in the Bragg peak region of about 10% for 148.8 MeV protons and of about 42% for 398.9 MeV/u carbon ions. For proton and carbon ion clinical beams, an under-response occurs at the Bragg peak. For carbon ions, we also observed an under-response of the EBT3 in the plateau of the depth-dose curve. This effect is the highest at the lowest initial energy of the clinical beams, a phenomenon related to the corresponding higher LET in the film sensitive layer. This behavior should be properly modeled when using EBT3 films for accurate 3D dosimetry.

  9. Quantitative structure-activity relationships of selected phenols with non-monotonic dose-response curves

    Institute of Scientific and Technical Information of China (English)

    GAO ChangAn; ZHANG AiQian; LIN Yuan; YIN DaQiang; WANG LianSheng

    2009-01-01

    Particular non-monotonic dose-response curves of many endocrine disrupting chemicals (EDCs) suggest the existence of diverse toxicity mechanisms at different dose levels. As a result, the biologi-cal activities of EDCs cannot be simply exhibited by unique EC/LD<,50. values, and the quantitative structure-activity relationship (QSAR) analysis for non-monotonic dose-response relationship be-comes an unknown field in the environmental science. In this paper, nine phenols with inverted U-shaped dose-response curves in lymphocyte proliferation test of Carassius auratus were selected. The binding interactions between the phenols and several typical EDCs-related receptors were then explored in a molecular simulation study. The estrogen receptor (ER), androgen receptor (AR), thyroid hormone receptor (TR), bacterial O2 sensing FixL protein (FixL), aryl hydrocarbon receptor (AhR), and the peroxisome proliferator-activated receptor (PPAR) were the target receptors in the study. Linear regression QSAR models for the low and high exposure levels of the compounds were developed separately. The results indicated that the lymphocyte proliferation in the low-dose range might involve ER-mediated process, while the proliferation inhibition in the high dose range was dominated by the acute toxicity of phenols due to receptor occupancy and cell damage.

  10. The Hemochron Response RxDx heparin and protamine dosing system.

    Science.gov (United States)

    Jaryno, Stacy A; Zucker, Marcia L; LaDuca, Frank M

    2004-09-01

    The use of dosing assays to calculate heparin and protamine dose requirements during cardiac surgery has been shown to significantly improve overall postoperative patient outcome. When patients are managed with an individualized dosing system, intraoperative and postoperative transfusion requirements and bleeding are reduced. The Hemochron RxDx system is widely used as a complement to traditional activated clotting time testing to optimize anticoagulation management. The system consists of the heparin response test, the protamine response test, and the protamine dose assay. All are modifications of the activated clotting time using either Celite (Celite Corporation, Santa Barbara, CA) or kaolin as the activator. Dosing is calculated manually using earlier version Hemochron instruments (model 801) or automatically with the Hemochron 8000 or with the early versions of the Hemochron Response and the personal digital assistant (PDA) RxDx calculator. Missing from available user options is an automated RxDx system for the Response. A study was conducted at four clinical sites to compare recently developed Response RxDx software, which eliminates the need for the PDA RxDx calculator, to the existing Hemochron 8000 RxDx and to the Response-PDA RxDx systems. Similar to the current system, the operator inputs the patient's height, weight, and gender, and the software automatically calculates the blood volume. Using the clotting times determined on the Response, bolus heparin and protamine doses and any additional heparin and protamine requirements are calculated automatically. Data were collected from 76 patients, of which, 64 patients were on pump, 11 patients were off pump, and 1 patient was converted from off to on pump. The Response estimated blood volume calculations showed a correlation coefficient of 0.989 when compared with available systems. A good correlation was also observed for the bolus heparin (r = 0.925) and protamine doses (r = 0.900) with equivalence

  11. Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies

    Directory of Open Access Journals (Sweden)

    Xin Fang

    2016-11-01

    Full Text Available The epidemiological evidence for a dose-response relationship between magnesium intake and risk of type 2 diabetes mellitus (T2D is sparse. The aim of the study was to summarize the evidence for the association of dietary magnesium intake with risk of T2D and evaluate the dose-response relationship. We conducted a systematic review and meta-analysis of prospective cohort studies that reported dietary magnesium intake and risk of incident T2D. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to February 2016. We included cohort studies that provided risk ratios, i.e., relative risks (RRs, odds ratios (ORs or hazard ratios (HRs, for T2D. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. A total of 25 studies met the eligibility criteria. These studies comprised 637,922 individuals including 26,828 with a T2D diagnosis. Compared with the lowest magnesium consumption group in the population, the risk of T2D was reduced by 17% across all the studies; 19% in women and 16% in men. A statistically significant linear dose-response relationship was found between incremental magnesium intake and T2D risk. After adjusting for age and body mass index, the risk of T2D incidence was reduced by 8%–13% for per 100 mg/day increment in dietary magnesium intake. There was no evidence to support a nonlinear dose-response relationship between dietary magnesium intake and T2D risk. The combined data supports a role for magnesium in reducing risk of T2D, with a statistically significant linear dose-response pattern within the reference dose range of dietary intake among Asian and US populations. The evidence from Europe and black people is limited and more prospective studies are needed for the two subgroups.

  12. Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation.

    Science.gov (United States)

    Kim, Rae-Kwon; Kim, Min-Jung; Seong, Ki Moon; Kaushik, Neha; Suh, Yongjoon; Yoo, Ki-Chun; Cui, Yan-Hong; Jin, Young Woo; Nam, Seon Young; Lee, Su-Jae

    2015-10-30

    Recently low dose irradiation has gained attention in the field of radiotherapy. For lack of understanding of the molecular consequences of low dose irradiation, there is much doubt concerning its risks on human beings. In this article, we report that low dose irradiation is capable of blocking the oncogenic KRAS-induced malignant transformation. To address this hypothesis, we showed that low dose irradiation, at doses of 0.1 Gray (Gy); predominantly provide defensive response against oncogenic KRAS -induced malignant transformation in human cells through the induction of antioxidants without causing cell death and acts as a critical regulator for the attenuation of reactive oxygen species (ROS). Importantly, we elucidated that knockdown of antioxidants significantly enhanced ROS generation, invasive and migratory properties and abnormal acini formation in KRAS transformed normal as well as cancer cells. Taken together, this study demonstrates that low dose irradiation reduces the KRAS induced malignant cellular transformation through diminution of ROS. This interesting phenomenon illuminates the beneficial effects of low dose irradiation, suggesting one of contributory mechanisms for reducing the oncogene induced carcinogenesis that intensify the potential use of low dose irradiation as a standard regimen.

  13. Dose responses for Colletotrichum lindemuthianum elicitor-mediated enzyme induction in French bean cell suspension cultures.

    Science.gov (United States)

    Dixon, R A; Dey, P M; Murphy, D L; Whitehead, I M

    1981-03-01

    The induction of L-phenylalanine ammonialyase (PAL, EC 4.3.1.5) and flavanone synthase in French bean cell suspension cultures in response to heat-released elicitor from cell walls of the phytopathogenic fungus Colletotrichum lindemuthianum is highly dependent upon elicitor concentration. The elicitor dose-response curve for PAL induction shows two maxima at around 17.5 and 50 μg elicitor carbohydrate per ml culture, whereas the flavanone synthase response shows one maximum at around 100 μg ml(-1). The PAL response is independent of the elicitor concentration present during the lag phase of enzyme induction; if the initial elicitor concentration is increased after 2 h by addition of extra elicitor, or decreased by dilution of the cultures, the dose response curves obtained reflect the concentration of elicitor present at the time of harvest. PAL induction is not prevented by addition of methyl sugar derivatives to the cultures; α-methyl-D-glucoside, itself a weak elicitor of PAL activity, elicits a multiphasic PAL response when increasing concentrations are added in the presence of Colletotrichum elicitor. Eight fractions with different monosaccharide compositions, obtained from the crude elicitor by gel-filtration, each elicit different dose-responses for PAL induction; the response to unfractionated elicitor is not the sum of the response to the isolated fractions. There is no correlation between the ability of the fractions to induce PAL in the cultures and their ability to act as elicitors of isoflavonoid phytoalexin accumulation in bean hypocotyls.

  14. Radiation dose response estimation with emphasis on low dose range using restricted cubic splines: application to all solid cancer mortality data, 1950-2003, in atomic bomb survivors.

    Science.gov (United States)

    Nakashima, Eiji

    2015-07-01

    Using the all solid cancer mortality data set of the Life Span Study (LSS) cohort from 1950 to 2003 (LSS Report 14) data among atomic bomb survivors, excess relative risk (ERR) statistical analyses were performed using the second degree polynomial and the threshold and restricted cubic spline (RCS) dose response models. For the RCS models with 3 to 7 knots of equally spaced percentiles with margins in the dose range greater than 50 mGy, the dose response was assumed to be linear at less than 70 to 90 mGy. Due to the skewed dose distribution of atomic bomb survivors, the current knot system for the RCS analysis results in a detailed depiction of the dose response as less than approximately 0.5 Gy. The 6 knot RCS models for the all-solid cancer mortality dose response of the whole dose or less than 2 Gy were selected with the AIC model selection criterion and fit significantly better (p < 0.05) than the linear (L) model. The usual RCS includes the L-global model but not the quadratic (Q) nor linear-quadratic (LQ) global models. The authors extended the RCS to include L or LQ global models by putting L or LQ constraints on the cubic spline in the lower and upper tails, and the best RCS model selected with AIC criterion was the usual RCS with L-constraints in both the lower and upper tails. The selected RCS had a linear dose-response model in the lower dose range (i.e., < 0.2-0.3 Gy) and was compatible with the linear no-threshold (LNT) model in this dose range. The proposed method is also useful in describing the dose response of a specific cancer or non-cancer disease incidence/mortality.

  15. Nonlinear radiation response of n-doped indium antimonide and indium arsenide in intense terahertz field

    Science.gov (United States)

    Gong, Jiao-Li; Liu, Jin-Song; Chu, Zheng; Yang, Zhen-Gang; Wang, Ke-Jia; Yao, Jian-Quan

    2016-10-01

    The nonlinear radiation responses of two different n-doped bulk semiconductors: indium antimonide (InSb) and indium arsenide (InAs) in an intense terahertz (THz) field are studied by using the method of ensemble Monte Carlo (EMC) at room temperature. The results show that the radiations of two materials generate about 2-THz periodic regular spectrum distributions under a high field of 100 kV/cm at 1-THz center frequency. The center frequencies are enhanced to about 7 THz in InSb, and only 5 THz in InAs, respectively. The electron valley occupancy and the percentage of new electrons excited by impact ionization are also calculated. We find that the band nonparabolicity and impact ionization promote the generation of nonlinear high frequency radiation, while intervalley scattering has the opposite effect. Moreover, the impact ionization dominates in InSb, while impact ionization and intervalley scattering work together in InAs. These characteristics have potential applications in up-convension of THz wave and THz nonlinear frequency multiplication field. Project supported by the National Natural Science Foundation of China (Grant Nos. 11574105 and 61177095), the Natural Science Foundation of Hubei Province, China (Grant Nos. 2012FFA074 and 2013BAA002), the Wuhan Municipal Applied Basic Research Project, China (Grant No. 20140101010009), and the Fundamental Research Funds for the Central Universities, China (Grant Nos. 2013KXYQ004 and 2014ZZGH021).

  16. Nonlinear Local Bending Response and Bulging Factors for Longitudinal and Circumferential Cracks in Pressurized Cylindrical Shells

    Science.gov (United States)

    Young, Richard D.; Rose, Cheryl A.; Starnes, James H., Jr.

    2000-01-01

    Results of a geometrically nonlinear finite element parametric study to determine curvature correction factors or bulging factors that account for increased stresses due to curvature for longitudinal and circumferential cracks in unstiffened pressurized cylindrical shells are presented. Geometric parameters varied in the study include the shell radius, the shell wall thickness, and the crack length. The major results are presented in the form of contour plots of the bulging factor as a function of two nondimensional parameters: the shell curvature parameter, lambda, which is a function of the shell geometry, Poisson's ratio, and the crack length; and a loading parameter, eta, which is a function of the shell geometry, material properties, and the applied internal pressure. These plots identify the ranges of the shell curvature and loading parameters for which the effects of geometric nonlinearity are significant. Simple empirical expressions for the bulging factor are then derived from the numerical results and shown to predict accurately the nonlinear response of shells with longitudinal and circumferential cracks. The numerical results are also compared with analytical solutions based on linear shallow shell theory for thin shells, and with some other semi-empirical solutions from the literature, and limitations on the use of these other expressions are suggested.

  17. Cooperative enhancement of the nonlinear optical response in conjugated energetic materials: A TD-DFT study.

    Science.gov (United States)

    Sifain, Andrew E; Tadesse, Loza F; Bjorgaard, Josiah A; Chavez, David E; Prezhdo, Oleg V; Scharff, R Jason; Tretiak, Sergei

    2017-03-21

    Conjugated energetic molecules (CEMs) are a class of explosives with high nitrogen content that posses both enhanced safety and energetic performance properties and are ideal for direct optical initiation. As isolated molecules, they absorb within the range of conventional lasers. Crystalline CEMs are used in practice, however, and their properties can differ due to intermolecular interaction. Herein, time-dependent density functional theory was used to investigate one-photon absorption (OPA) and two-photon absorption (TPA) of monomers and dimers obtained from experimentally determined crystal structures of CEMs. OPA scales linearly with the number of chromophore units, while TPA scales nonlinearly, where a more than 3-fold enhancement in peak intensity, per chromophore unit, is calculated. Cooperative enhancement depends on electronic delocalization spanning both chromophore units. An increase in sensitivity to nonlinear laser initiation makes these materials suitable for practical use. This is the first study predicting a cooperative enhancement of the nonlinear optical response in energetic materials composed of relatively small molecules. The proposed model quantum chemistry is validated by comparison to crystal structure geometries and the optical absorption of these materials dissolved in solution.

  18. Investigation of local nonlinear electrodynamic response of surface states in cuprate superconductors at low temperatures

    Science.gov (United States)

    Mircea, Dragos I.; Anlage, Steven M.

    2004-03-01

    Traditionally, the Andreev Bound States (ABS) have been studied by means of tunneling experiments and global electromagnetic resonant techniques. The zero bias conductance peak and the strong upturn in the penetration depth at low temperature are considered strong evidence for the existence of ABS. The nonlinear inductance arising from the current-dependent penetration depth leads to a nonlinear electrodynamic response that can be probed with our non-resonant near-field microwave microscope [S. C. Lee and S. M. Anlage, Appl. Phys. Lett. 82, 1893 (2003)]. In the experiment, microwave currents have been applied locally along different directions on the surface of YBCO films exposing the (110) surface in order to investigate the angular dependence of the second and third order harmonics generated by the sample. The temperature and the angular dependence measured for different levels of the applied microwave power, will be presented and compared with the theoretical predictions. This low-temperature anisotropic nonlinear behavior is relevant for the study of ABS as well as for identifying the existence of local pairing states with symmetry different from that of the bulk order parameter.

  19. Lack-of-fit tests for assessing mean structures for continuous dose-response data

    DEFF Research Database (Denmark)

    Martinussen, Torben

    2011-01-01

    We review a range of lack-of-fit tests suitable for assessing the appropriateness of the mean function in dose-response models. The review encompasses both well-known tests and new tests based on recent developments in statistics, which we have extended to the dose-response case. We argue...... that the classical methods are inadequate in certain situations, where the new tests may be applied. Power comparisons are carried out by means of extensive simulation studies, covering both designs with and without replicates at small and large sample sizes. Three datasets from dose-response applications illustrate...... differences and similarities between the tests. The results suggest that the new tests perform better and exhibit a wider applicability....

  20. A novel single-dose dengue subunit vaccine induces memory immune responses.

    Directory of Open Access Journals (Sweden)

    Chen-Yi Chiang

    Full Text Available To protect against dengue viral infection, a novel lipidated dengue subunit vaccine was rationally designed to contain the consensus amino acid sequences derived from four serotypes of dengue viruses. We found that the lipidated consensus dengue virus envelope protein domain III (LcED III is capable of activating antigen-presenting cells and enhancing cellular and humoral immune responses. A single-dose of LcED III immunization in mice without extra adjuvant formulation is sufficient to elicit neutralizing antibodies against all four serotypes of dengue viruses. In addition, strong memory responses were elicited in mice immunized with a single-dose of LcED III. Quick, anamnestic neutralizing antibody responses to a live dengue virus challenge were elicited at week 28 post-immunization. These results demonstrate the promising possibility of a future successful tetravalent vaccine against dengue viral infections that utilizes one-dose vaccination with LcED III.

  1. Assessment of The Dose-Response Relationship of Radiation-Induced Bystander Effect in Two Cell Lines Exposed to High Doses of Ionizing Radiation (6 and 8 Gy).

    Science.gov (United States)

    Bahreyni Toossi, Mohammad Taghi; Khademi, Sara; Azimian, Hosein; Mohebbi, Shokoufeh; Soleymanifard, Shokouhozaman

    2017-10-01

    The dose-response relationship of radiation-induced bystander effect (RIBE) is controversial at high dose levels. The aim of the present study is to assess RIBE at high dose levels by examination of different endpoints. This experimental study used the medium transfer technique to induce RIBE. The cells were divided into two main groups: QU-DB cells which received medium from autologous irradiated cells and MRC5 cells which received medium from irradiated QU-DB cells. Colony, MTT, and micronucleus assays were performed to quantify bystander responses. The medium was diluted and transferred to bystander cells to investigate whether medium dilution could revive the RIBE response that disappeared at a high dose. The RIBE level in QU-DB bystander cells increased in the dose range of 0.5 to 4 Gy, but decreased at 6 and 8 Gy. The Micronucleated cells per 1000 binucleated cells (MNBN) frequency of QU-DB bystander cells which received the most diluted medium from 6 and 8 Gy QU-DB irradiated cells reached the maximum level compared to the MNBN frequency of the cells that received complete medium (Pbystander cells. This finding confirmed that a negative feedback mechanism was responsible for the decrease in RIBE response at high doses. Decrease of RIBE at high doses might be used to predict that in radiosurgery, brachytherapy and grid therapy, in which high dose per fraction is applied, normal tissue damage owing to RIBE may decrease.

  2. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  3. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.

    Science.gov (United States)

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-03-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.

  4. Guidelines for Use of the Approximate Beta-Poisson Dose-Response Model.

    Science.gov (United States)

    Xie, Gang; Roiko, Anne; Stratton, Helen; Lemckert, Charles; Dunn, Peter K; Mengersen, Kerrie

    2016-10-05

    For dose-response analysis in quantitative microbial risk assessment (QMRA), the exact beta-Poisson model is a two-parameter mechanistic dose-response model with parameters α>0 and β>0, which involves the Kummer confluent hypergeometric function. Evaluation of a hypergeometric function is a computational challenge. Denoting PI(d) as the probability of infection at a given mean dose d, the widely used dose-response model PI(d)=1-(1+dβ)-α is an approximate formula for the exact beta-Poisson model. Notwithstanding the required conditions α1, issues related to the validity and approximation accuracy of this approximate formula have remained largely ignored in practice, partly because these conditions are too general to provide clear guidance. Consequently, this study proposes a probability measure Pr(0 (22α̂)0.50 for 0.020.99) . This validity measure and rule of thumb were validated by application to all the completed beta-Poisson models (related to 85 data sets) from the QMRA community portal (QMRA Wiki). The results showed that the higher the probability Pr(0 dose-response curve.

  5. Nonlinear ionospheric responses to large-amplitude infrasonic-acoustic waves generated by undersea earthquakes

    Science.gov (United States)

    Zettergren, M. D.; Snively, J. B.; Komjathy, A.; Verkhoglyadova, O. P.

    2017-02-01

    Numerical models of ionospheric coupling with the neutral atmosphere are used to investigate perturbations of plasma density, vertically integrated total electron content (TEC), neutral velocity, and neutral temperature associated with large-amplitude acoustic waves generated by the initial ocean surface displacements from strong undersea earthquakes. A simplified source model for the 2011 Tohoku earthquake is constructed from estimates of initial ocean surface responses to approximate the vertical motions over realistic spatial and temporal scales. Resulting TEC perturbations from modeling case studies appear consistent with observational data, reproducing pronounced TEC depletions which are shown to be a consequence of the impacts of nonlinear, dissipating acoustic waves. Thermospheric acoustic compressional velocities are ˜±250-300 m/s, superposed with downward flows of similar amplitudes, and temperature perturbations are ˜300 K, while the dominant wave periodicity in the thermosphere is ˜3-4 min. Results capture acoustic wave processes including reflection, onset of resonance, and nonlinear steepening and dissipation—ultimately leading to the formation of ionospheric TEC depletions "holes"—that are consistent with reported observations. Three additional simulations illustrate the dependence of atmospheric acoustic wave and subsequent ionospheric responses on the surface displacement amplitude, which is varied from the Tohoku case study by factors of 1/100, 1/10, and 2. Collectively, results suggest that TEC depletions may only accompany very-large amplitude thermospheric acoustic waves necessary to induce a nonlinear response, here with saturated compressional velocities ˜200-250 m/s generated by sea surface displacements exceeding ˜1 m occurring over a 3 min time period.

  6. Orthogonal expansion of ground motion and PDEM-based seismic response analysis of nonlinear structures

    Institute of Scientific and Technical Information of China (English)

    Li Jie; Liu Zhangjun; Chen Jianbing

    2009-01-01

    This paper introduces an orthogonal expansion method for general stochastic processes. In the method, a normalized orthogonal function of time variable t is first introduced to carry out the decomposition of a stochastic process and then a correlated matrix decomposition technique, which transforms a correlated random vector into a vector of standard uncorrelated random variables, is used to complete a double orthogonal decomposition of the stochastic processes. Considering the relationship between the Hartley transform and Fourier transform of a real-valued function, it is suggested that the first orthogonal expansion in the above process is carried out using the Hartley basis function instead of the trigonometric basis function in practical applications. The seismic ground motion is investigated using the above method. In order to capture the main probabilistic characteristics of the seismic ground motion, it is proposed to directly carry out the orthogonal expansion of the seismic displacements. The case study shows that the proposed method is feasible to represent the seismic ground motion with only a few random variables. In the second part of the paper, the probability density evolution method (PDEM) is employed to study the stochastic response of nonlinear structures subjected to earthquake excitations. In the PDEM, a completely uncoupled one-dimensional partial differential equation, the generalized density evolution equation, plays a central role in governing the stochastic seismic responses of the nonlinear structure. The solution to this equation will yield the instantaneous probability density function of the responses. Computational algorithms to solve the probability density evolution equation are described, An example, which deals with a nonlinear frame structure subjected to stochastic ground motions, is illustrated to validate the above approach.

  7. Stochastic response and bifurcation of periodically driven nonlinear oscillators by the generalized cell mapping method

    Science.gov (United States)

    Han, Qun; Xu, Wei; Sun, Jian-Qiao

    2016-09-01

    The stochastic response of nonlinear oscillators under periodic and Gaussian white noise excitations is studied with the generalized cell mapping based on short-time Gaussian approximation (GCM/STGA) method. The solutions of the transition probability density functions over a small fraction of the period are constructed by the STGA scheme in order to construct the GCM over one complete period. Both the transient and steady-state probability density functions (PDFs) of a smooth and discontinuous (SD) oscillator are computed to illustrate the application of the method. The accuracy of the results is verified by direct Monte Carlo simulations. The transient responses show the evolution of the PDFs from being Gaussian to non-Gaussian. The effect of a chaotic saddle on the stochastic response is also studied. The stochastic P-bifurcation in terms of the steady-state PDFs occurs with the decrease of the smoothness parameter, which corresponds to the deterministic pitchfork bifurcation.

  8. Probiotics reduce symptoms of antibiotic use in a hospital setting: a randomized dose response study.

    Science.gov (United States)

    Ouwehand, Arthur C; DongLian, Cai; Weijian, Xu; Stewart, Morgan; Ni, Jiayi; Stewart, Tad; Miller, Larry E

    2014-01-16

    Probiotics are known to reduce antibiotic associated diarrhea (AAD) and Clostridium difficile associated diarrhea (CDAD) risk in a strain-specific manner. The aim of this study was to determine the dose-response effect of a four strain probiotic combination (HOWARU(®) Restore) on the incidence of AAD and CDAD and severity of gastrointestinal symptoms in adult in-patients requiring antibiotic therapy. Patients (n=503) were randomized among three study groups: HOWARU(®) Restore probiotic 1.70×10(10) CFU (high-dose, n=168), HOWARU(®) Restore probiotic 4.17×10(9) CFU (low-dose, n=168), or placebo (n=167). Subjects were stratified by gender, age, and duration of antibiotic treatment. Study products were administered daily up to 7 days after the final antibiotic dose. The primary endpoint of the study was the incidence of AAD. Secondary endpoints included incidence of CDAD, diarrhea duration, stools per day, bloody stools, fever, abdominal cramping, and bloating. A significant dose-response effect on AAD was observed with incidences of 12.5, 19.6, and 24.6% with high-dose, low-dose, and placebo, respectively (p=0.02). CDAD was the same in both probiotic groups (1.8%) but different from the placebo group (4.8%; p=0.04). Incidences of fever, abdominal pain, and bloating were lower with increasing probiotic dose. The number of daily liquid stools and average duration of diarrhea decreased with higher probiotic dosage. The tested four strain probiotic combination appears to lower the risk of AAD, CDAD, and gastrointestinal symptoms in a dose-dependent manner in adult in-patients.

  9. An alternate method for estimating the dose-response relationships of neuromuscular blocking drugs.

    Science.gov (United States)

    Kopman, A F; Klewicka, M M; Neuman, G G

    2000-05-01

    Slopes of the dose-response relationships for all available neuromuscular blocking drugs appear to be essentially parallel and to approximate a log-dose/logit value of 4.75. We tested the possibility of estimating both 50% effective dose (ED(50)) and 95% effective dose (ED(95)) values from a single dose-response data point when that slope is postulated. We compared the ED(50) and ED(95) values of rocuronium and succinylcholine calculated by using traditional log-dose/logit regression analysis with the same values obtained by averaging individual estimates of potency as determined by using the Hill equation. After the induction of anesthesia (propofol/alfentanil), tracheal intubation was accomplished without the administration of neuromuscular blocking drugs. Anesthesia was maintained with nitrous oxide and propofol. The evoked electromyographic response to 0.10-Hz single stimuli was continuously recorded. After baseline stabilization, a single IV bolus of succinylcholine (0.08-0.26 mg/kg, n = 50) or rocuronium (0. 13-0.30 mg/kg, n = 40) was administered and the peak effect noted. By using log-dose/logit regression analysis, we calculated ED(50) and ED(95) values for rocuronium of 0.17 and 0.33 mg/kg and 0.14 and 0.27 mg/kg for succinylcholine. When potency was calculated from the Hill equation, the resultant ED(50) and ED(95) values did not differ by more than +/-4% from those obtained by using regression analysis. Averaging of single-dose estimates of neuromuscular potency provides a useful adjunct and reasonable alternative to conventional regression analysis.

  10. Cellular response to low dose radiation: Role of phosphatidylinositol-3 kinase like kinases

    Energy Technology Data Exchange (ETDEWEB)

    Balajee, A.S.; Meador, J.A.; Su, Y.

    2011-03-24

    It is increasingly realized that human exposure either to an acute low dose or multiple chronic low doses of low LET radiation has the potential to cause different types of cancer. Therefore, the central theme of research for DOE and NASA is focused on understanding the molecular mechanisms and pathways responsible for the cellular response to low dose radiation which would not only improve the accuracy of estimating health risks but also help in the development of predictive assays for low dose radiation risks associated with tissue degeneration and cancer. The working hypothesis for this proposal is that the cellular mechanisms in terms of DNA damage signaling, repair and cell cycle checkpoint regulation are different for low and high doses of low LET radiation and that the mode of action of phosphatidylinositol-3 kinase like kinases (PIKK: ATM, ATR and DNA-PK) determines the dose dependent cellular responses. The hypothesis will be tested at two levels: (I) Evaluation of the role of ATM, ATR and DNA-PK in cellular response to low and high doses of low LET radiation in simple in vitro human cell systems and (II) Determination of radiation responses in complex cell microenvironments such as human EpiDerm tissue constructs. Cellular responses to low and high doses of low LET radiation will be assessed from the view points of DNA damage signaling, DNA double strand break repair and cell cycle checkpoint regulation by analyzing the activities (i.e. post-translational modifications and kinetics of protein-protein interactions) of the key target proteins for PI-3 kinase like kinases both at the intra-cellular and molecular levels. The proteins chosen for this proposal are placed under three categories: (I) sensors/initiators include ATM ser1981, ATR, 53BP1, gamma-H2AX, MDC1, MRE11, Rad50 and Nbs1; (II) signal transducers include Chk1, Chk2, FANCD2 and SMC1; and (III) effectors include p53, CDC25A and CDC25C. The primary goal of this proposal is to elucidate the

  11. Model of nonlinear coupled thermo-hydro-elastodyanamics response for a saturated poroelastic medium

    Institute of Scientific and Technical Information of China (English)

    LIU GanBin; XIE KangHe; ZHENG RongYue

    2009-01-01

    Based on the Blot's wave equation and theory of thermodynamic,Darcy law of fluid and the modified Fourier law of heat conduction,a nonlinear fully coupled thermo-hydro-elastodynamic response model(THMD)for saturated porous medium is derived.The compressibility of the medium,the influence of fluid flux on the heat flux,and the influence of change of temperature on the fluid flux are considered in this model.With some simplification,the coupled nonlinear thermo-hydro-elastodynamic response model can be reduced to the thermo-elastodynamic(TMD)model based on the traditional Fourier law and,further more,to the Blot's wave equation without considering the heat phase.At last,the problem of one dimensional cylindrical cavity subjected to a time-dependent thermal/mechanical shock is analyzed by using the Laplace technique,the numerical results are used to discuss the influence of Blot's modulus M and coefficient of thermo-osmosis on displacement and to compare with the results of thermo-elastodynamic response to ascertain the validity of this model.

  12. Model of nonlinear coupled thermo-hydro-elastodynamics response for a saturated poroelastic medium

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Based on the Biot’s wave equation and theory of thermodynamic, Darcy law of fluid and the modified Fourier law of heat conduction, a nonlinear fully coupled thermo-hydro-elastodynamic response model (THMD) for saturated porous medium is derived. The compressibility of the medium, the influence of fluid flux on the heat flux, and the influence of change of temperature on the fluid flux are considered in this model. With some simplification, the coupled nonlinear thermo-hydro-elastodynamic response model can be reduced to the thermo-elastodynamic (TMD) model based on the traditional Fourier law and, further more, to the Biot’s wave equation without considering the heat phase. At last, the problem of one dimensional cylindrical cavity subjected to a time-dependent thermal/mechanical shock is analyzed by using the Laplace technique, the numerical results are used to discuss the influence of Biot’s modulus M and coefficient of thermoos-mosis on displacement and to compare with the results of thermo-elastodynamic response to ascertain the validity of this model.

  13. A fast continuation scheme for accurate tracing of nonlinear oscillator frequency response functions

    Science.gov (United States)

    Chen, Guoqiang; Dunne, J. F.

    2016-12-01

    A new algorithm is proposed to combine the split-frequency harmonic balance method (SF-HBM) with arc-length continuation (ALC) for accurate tracing of the frequency response of oscillators with non-expansible nonlinearities. ALC is incorporated into the SF-HBM in a two-stage procedure: Stage I involves finding a reasonably accurate response frequency and solution using a relatively large number of low-frequency harmonics. This step is achieved using the SF-HBM in conjunction with ALC. Stage II uses the SF-HBM to obtain a very accurate solution at the frequency obtained in Stage I. To guarantee rapid path tracing, the frequency axis is appropriately subdivided. This gives high chance of success in finding a globally optimum set of harmonic coefficients. When approaching a turning point however, arc-lengths are adaptively reduced to obtain a very accurate solution. The combined procedure is tested on three hardening stiffness examples: a Duffing model; an oscillator with non-expansible stiffness and single harmonic forcing; and an oscillator with non-expansible stiffness and multiple-harmonic forcing. The results show that for non-expansible nonlinearities and multiple-harmonic forcing, the proposed algorithm is capable of tracing-out frequency response functions with high accuracy and efficiency.

  14. The response of nonlinear controlled system under an external excitation via time delay state feedback

    Directory of Open Access Journals (Sweden)

    A.M. Elnaggar

    2016-01-01

    Full Text Available An analysis of primary, superharmonic of order five, and subharmonic of order one-three resonances for non-linear s.d.o.f. system with two distinct time-delays under an external excitation is investigated. The method of multiple scales is used to determine two first order ordinary differential equations which describe the modulation of the amplitudes and the phases. Steady-state solutions and their stabilities in each resonance are studied. Numerical results are obtained by using the Software of Mathematica, which presented in a group of figures. The effect of the feedback gains and time-delays on the non-linear response of the system is discussed and it is found that: an appropriate feedback can enhance the control performance. A suitable choice of the feedback gains and time-delays can enlarge the critical force amplitude, and reduce the peak amplitude of the response (or peak amplitude of the free oscillation term for the case of primary resonance (superharmonic resonance. Furthermore, a proper feedback can eliminate saddle-node bifurcation, thereby eliminating jump and hysteresis phenomena taking place in the corresponding uncontrolled system. For subharmonic resonance, an adequate feedback can reduce the regions of subharmonic resonance response.

  15. A Space-Time Finite Element Model for Design and Control Optimization of Nonlinear Dynamic Response

    Directory of Open Access Journals (Sweden)

    P.P. Moita

    2008-01-01

    Full Text Available A design and control sensitivity analysis and multicriteria optimization formulation is derived for flexible mechanical systems. This formulation is implemented in an optimum design code and it is applied to the nonlinear dynamic response. By extending the spatial domain to the space-time domain and treating the design variables as control variables that do not change with time, the design space is included in the control space. Thus, one can unify in one single formulation the problems of optimum design and optimal control. Structural dimensions as well as lumped damping and stiffness parameters plus control driven forces, are considered as decision variables. The dynamic response and its sensitivity with respect to the design and control variables are discretized via space-time finite elements, and are integrated at-once, as it is traditionally used for static response. The adjoint system approach is used to determine the design sensitivities. Design optimization numerical examples are performed. Nonlinear programming and optimality criteria may be used for the optimization process. A normalized weighted bound formulation is used to handle multicriteria problems.

  16. Studying Climate Response to Forcing by the Nonlinear Dynamical Mode Decomposition

    Science.gov (United States)

    Mukhin, Dmitry; Gavrilov, Andrey; Loskutov, Evgeny; Feigin, Alexander

    2017-04-01

    An analysis of global climate response to external forcing, both anthropogenic (mainly, CO2 and aerosol) and natural (solar and volcanic), is needed for adequate predictions of global climate change. Being complex dynamical system, the climate reacts to external perturbations exciting feedbacks (both positive and negative) making the response non-trivial and poorly predictable. Thus an extraction of internal modes of climate system, investigation of their interaction with external forcings and further modeling and forecast of their dynamics, are all the problems providing the success of climate modeling. In the report the new method for principal mode extraction from climate data is presented. The method is based on the Nonlinear Dynamical Mode (NDM) expansion [1,2], but takes into account a number of external forcings applied to the system. Each NDM is represented by hidden time series governing the observed variability, which, together with external forcing time series, are mapped onto data space. While forcing time series are considered to be known, the hidden unknown signals underlying the internal climate dynamics are extracted from observed data by the suggested method. In particular, it gives us an opportunity to study the evolution of principal system's mode structure in changing external conditions and separate the internal climate variability from trends forced by external perturbations. Furthermore, the modes so obtained can be extrapolated beyond the observational time series, and long-term prognosis of modes' structure including characteristics of interconnections and responses to external perturbations, can be carried out. In this work the method is used for reconstructing and studying the principal modes of climate variability on inter-annual and decadal time scales accounting the external forcings such as anthropogenic emissions, variations of the solar activity and volcanic activity. The structure of the obtained modes as well as their response to

  17. GLOBAL ASYMPTOTICAL PROPERTIES FOR A DIFFUSED HBV INFECTION MODEL WITH CTL IMMUNE RESPONSE AND NONLINEAR INCIDENCE

    Institute of Scientific and Technical Information of China (English)

    Wang Shaoli; Feng Xinlong; He Yinnian

    2011-01-01

    This article proposes a diffused hepatitis B virus (HBV) model with CTLimmune response and nonlinear incidence for the control of viral infections.By means of different Lyapunov functions,the global asymptotical properties of the viral-free equilibrium and immune-free equilibrium of the model are obtained.Global stability of the positive equilibrium of the model is also considered.The results show that the free diffusion of the virus has no effect on the global stability of such HBV infection problem with Neumann homogeneous boundary conditions.

  18. Optimization of coherent optical OFDM transmitter using DP-IQ modulator with nonlinear response

    Science.gov (United States)

    Chang, Sun Hyok; Kang, Hun-Sik; Moon, Sang-Rok; Lee, Joon Ki

    2016-07-01

    In this paper, we investigate the performance of dual polarization orthogonal frequency division multiplexing (DP-OFDM) signal generation when the signal is generated by a DP-IQ optical modulator. The DP-IQ optical modulator is made of four parallel Mach-Zehnder modulators (MZMs) which have nonlinear responses and limited extinction ratios. We analyze the effects of the MZM in the DP-OFDM signal generation by numerical simulation. The operating conditions of the DP-IQ modulator are optimized to have the best performance of the DP-OFDM signal.

  19. Insulation of nonlinear and random vibrations in the mining industry. [elastodynamic response of rubber insulator

    Science.gov (United States)

    Zeveleanu, C.

    1974-01-01

    The insulation of nonlinear and random vibrations is considered for some ore preparing and sorting implements: rotary crushers, resonance screens, hammer mills, etc. The appearance of subharmonic vibrations is analyzed, and the conditions for their appearance are determined. A method is given for calculating the insulation of these vibrations by means of elastic elements made of rubber. The insulation of the random vibrations produced by Symons crushers is calculated by determining the transmissability and deformation of the insulation system for a narrow band random response.

  20. Phase disruption as a new design paradigm for optimizing the nonlinear-optical response

    CERN Document Server

    Lytel, Rick; Kuzyk, Mark G

    2015-01-01

    The intrinsic optical nonlinearities of quasi-one dimensional structures, including conjugated chain polymers and nanowires, are shown to be dramatically enhanced by the judicious placement of a side group or wire of sufficiently short length to create a large phase disruption in the dominant eigenfunctions along the main path of probability current. Phase disruption is proposed as a new general principle for the design of molecules, nanowires and any quasi-1D quantum system with large intrinsic response and does not require charge donors-acceptors at the ends.

  1. Modeling of nonlinear optic and ESR response of CDW MX materials

    Energy Technology Data Exchange (ETDEWEB)

    Saxena, A.; Gammel, J.T.; Bishop, A.R. [Los Alamos National Lab., NM (United States); Shuai, Z.; Bredas, J.L. [Center de Recherche en Electronique et Photonique Moleculaires, Universite de Mons-Hainaut (Belgium); Batistic, I. [Zagreb Univ. (Croatia). Dept. of Physics; Alouani, M. [Ohio State Univ., Columbus, OH (United States). Dept. of Physics

    1994-09-01

    We report results on the nonlinear optic and ESR response of the PtX MX chain materials calculated using a discrete, 3/4-filled, two-band, tight-binding Peierls-Hubbard model. We calculated electroabsorption (EA) spectra for the three PtX (X=Cl, Br, 1) charge-density-wave (CDW) materials and find good agreement with the experimental data. We also obtain EA spectra for localized defects in PtBr. In addition, the field orientation dependence of the electron spin resonance spectra associated with the spin carrying defects is calculated for PtX materials and compared with ESR data on photoinduced defects.

  2. POD/MAC-Based Modal Basis Selection for a Reduced Order Nonlinear Response Analysis

    Science.gov (United States)

    Rizzi, Stephen A.; Przekop, Adam

    2007-01-01

    A feasibility study was conducted to explore the applicability of a POD/MAC basis selection technique to a nonlinear structural response analysis. For the case studied the application of the POD/MAC technique resulted in a substantial improvement of the reduced order simulation when compared to a classic approach utilizing only low frequency modes present in the excitation bandwidth. Further studies are aimed to expand application of the presented technique to more complex structures including non-planar and two-dimensional configurations. For non-planar structures the separation of different displacement components may not be necessary or desirable.

  3. Non-linear wave loads and ship responses by a time-domain strip theory

    DEFF Research Database (Denmark)

    Xia, Jinzhu; Wang, Zhaohui; Jensen, Jørgen Juncher

    1998-01-01

    A non-linear time-domain strip theory for vertical wave loads and ship responses is presented. The theory is generalized from a rigorous linear time-domain strip theory representation. The hydrodynamic memory effect due to the free surface is approximated by a higher order differential equation. ...... and are systematically compared with the experimental results given by Watanabe et al. (1989, J. Soc. Naval Architects Japan, 166) and O’Dea et al. (1992, Proc. 19th Symp. on Naval Hydrodynamics). The agreement between the present predictions and the experiments is very encouraging....

  4. Prediction analysis of dose equivalent responses of neutron dosemeters used at a MOX fuel facility.

    Science.gov (United States)

    Tsujimura, N; Yoshida, T; Takada, C

    2011-07-01

    To predict how accurately neutron dosemeters can measure the neutron dose equivalent (rate) in MOX fuel fabrication facility work environments, the dose equivalent responses of neutron dosemeters were calculated by the spectral folding method. The dosemeters selected included two types of personal dosemeter, namely a thermoluminescent albedo neutron dosemeter and an electronic neutron dosemeter, three moderator-based neutron survey meters, and one special instrument called an H(p)(10) monitor. The calculations revealed the energy dependences of the responses expected within the entire range of neutron spectral variations observed in neutron fields at workplaces.

  5. Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens.

    Science.gov (United States)

    Fukushima, Shoji; Gi, Min; Kakehashi, Anna; Wanibuchi, Hideki; Matsumoto, Michiharu

    2016-05-01

    Qualitative and quantitative approaches are important issues in field of carcinogenic risk assessment of the genotoxic carcinogens. Herein, we provide quantitative data on low-dose hepatocarcinogenicity studies for three genotoxic hepatocarcinogens: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and N-nitrosodiethylamine (DEN). Hepatocarcinogenicity was examined by quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci, which are the preneoplastic lesions in rat hepatocarcinogenesis and the endpoint carcinogenic marker in the rat liver medium-term carcinogenicity bioassay. We also examined DNA damage and gene mutations which occurred through the initiation stage of carcinogenesis. For the establishment of points of departure (PoD) from which the cancer-related risk can be estimated, we analyzed the above events by quantitative no-observed-effect level and benchmark dose approaches. MeIQx at low doses induced formation of DNA-MeIQx adducts; somewhat higher doses caused elevation of 8-hydroxy-2'-deoxyquanosine levels; at still higher doses gene mutations occurred; and the highest dose induced formation of GST-P positive foci. These data indicate that early genotoxic events in the pathway to carcinogenesis showed the expected trend of lower PoDs for earlier events in the carcinogenic process. Similarly, only the highest dose of IQ caused an increase in the number of GST-P positive foci in the liver, while IQ-DNA adduct formation was observed with low doses. Moreover, treatment with DEN at low doses had no effect on development of GST-P positive foci in the liver. These data on PoDs for the markers contribute to understand whether genotoxic carcinogens have a threshold for their carcinogenicity. The most appropriate approach to use in low dose-response assessment must be approved on the basis of scientific judgment.

  6. Dose-response curve to salbutamol during acute and chronic treatment with formoterol in COPD

    Directory of Open Access Journals (Sweden)

    La Piana GE

    2011-07-01

    Full Text Available Giuseppe Emanuele La Piana¹, Luciano Corda², Enrica Bertella¹, Luigi Taranto Montemurro¹, Laura Pini¹, Claudio Tantucci¹¹Cattedra di Malattie dell'Apparato Respiratorio, Università di Brescia, ²Prima Divisione di Medicina Interna, Spedali Civili, Brescia, ItalyBackground: Use of short-acting ß2-agonists in chronic obstructive pulmonary disease (COPD during treatment with long-acting ß2-agonists is recommended as needed, but its effectiveness is unclear. The purpose of this study was to assess the additional bronchodilating effect of increasing doses of salbutamol during acute and chronic treatment with formoterol in patients with COPD.Methods: Ten patients with COPD underwent a dose-response curve to salbutamol (until 800 µg of cumulative dose after a 1-week washout (baseline, 8 hours after the first administration of formoterol 12 µg (day 1, and after a 12-week and 24-week period of treatment with formoterol (12 µg twice daily by dry powder inhaler. Peak expiratory flow, forced expiratory volume in one second (FEV1, forced vital capacity, and inspiratory capacity were measured at the different periods of treatment and at different steps of the dose-response curve.Results: Despite acute or chronic administration of formoterol, maximal values of peak expiratory flow, FEV1, and forced vital capacity after 800 µg of salbutamol were unchanged compared with baseline. The baseline FEV1 dose-response curve was steeper than that at day 1, week 12, or week 24 (P < 0.0001. Within each dose-response curve, FEV1 was different only at baseline and at day 1 (P < 0.001, when FEV1 was still greater at 800 µg than at 0 µg (P < 0.02. In contrast, the forced vital capacity dose-response curves were similar at the different periods, while within each dose-response curve, forced vital capacity was different in all instances (P < 0.001, always being higher at 800 µg than at 0 µg (P < 0.05.Conclusion: In patients with stable COPD, the maximal effect

  7. The response of mouse embryonic stem cells to low doses of γ-radiation: evidence for an adaptive response.

    Science.gov (United States)

    Kalantari, Hamid; Motamed, Nasrin; Mohseni Meybodi, Anahita; Jabbari Arfaie, Ali; Baharvand, Hossein; Gourabi, Hamid

    2014-02-01

    Low doses of ionizing radiation may induce an adaptive mechanism which protects embryonic stem cells against higher doses, a phenomenon which was reported previously for somatic cells. In this study, a possible adaptive response (AR) was evaluated by measuring cell survival (MTT assay) and chromosomal aberrations (micronucleus assay). Thymidine-synchronized mouse embryonic stem cells (mESCs) were exposed to 2.5, 3.7, or 5cGy (60)Co γ-rays and, after 5h challenged by a dose of 150cGy. mESCs pre-irradiated at 2.5cGy showed an adaptive response. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Construction of a cytogenetic dose-response curve for low-dose range gamma-irradiation in human peripheral blood lymphocytes using three-color FISH.

    Science.gov (United States)

    Suto, Yumiko; Akiyama, Miho; Noda, Takashi; Hirai, Momoki

    2015-12-01

    In order to estimate biological doses after low-dose ionizing radiation exposure, fluorescence in situ hybridization (FISH) using three differentially colored chromosome painting probes was employed to detect exchange-type chromosome aberrations. A reference dose response curve was constructed using blood samples from a female donor whose lymphocytes consistently exhibited a low frequency of cells at the second mitosis under routine culture conditions. Aberration yields were studied for a total of about 155 thousand metaphases obtained from seven dose-points of gamma irradiations (0, 50, 100, 150, 200, 250 and 300mGy). In situ hybridization was performed using commercially available painting probes for chromosomes 1, 2 and 4. With the aid of an automated image-capturing method, exchange-type aberrations involving painted chromosomes were detected with considerable accuracy and speed. The results on the exchange-type aberrations (dicentrics plus translocations) at the seven dose-points showed a good fit to the linear-quadratic model (y=0.0023+0.0015x+0.0819x(2), P=0.83). A blind test proved the reproducibility of the reference dose-response relationship. In the control experiments using blood samples from another donor, the estimated doses calculated on the basis of the present reference curve were proved to be in good agreement with the actual physical doses applied. The present dose-response curve may serve as a means to assess the individual differences in cytogenetical radio-sensitivities.

  9. Robust nonlinear regression in applications

    OpenAIRE

    Lim, Changwon; Sen, Pranab K.; Peddada, Shyamal D.

    2013-01-01

    Robust statistical methods, such as M-estimators, are needed for nonlinear regression models because of the presence of outliers/influential observations and heteroscedasticity. Outliers and influential observations are commonly observed in many applications, especially in toxicology and agricultural experiments. For example, dose response studies, which are routinely conducted in toxicology and agriculture, sometimes result in potential outliers, especially in the high dose gr...

  10. Acidobacteria Community Responses to Nitrogen Dose and Form in Chinese Fir Plantations in Southern China.

    Science.gov (United States)

    Liu, Caixia; Dong, Yuhong; Hou, Lingyu; Deng, Nan; Jiao, Ruzhen

    2017-03-01

    Acidobacteria is a new bacterial group, identified by molecular research, which is widely distributed and has specific ecological functions in forest soil. In this study, we investigated Acidobacteria response to N input, and the effects were related to N form and dose. The experimental design included two N forms (NH4(+)-N and NO3(-)-N) and five levels of N deposition (0, 20, 40, 60, 80 kg N ha(-1)) for 2 years. Research into the Acidobacteria community was conducted using 16Sr RNA gene-based high-throughput pyrosequencing methods. Acidobacteria OTUs and N had a negative relationship in 0-60 kg ha(-1) year(-1); however, at N doses beyond a certain size, nitrogen might promote an increase in Acidobacteria OTUs. The Acidobacteria relative abundance under NH4(+)-N treatment was higher than under NO3(-)-N treatment. Acidobacteria relative abundance decreased with increasing of NH4(+)-N dose, but increased with increasing NO3(-)-N dose. Overall, 13 different Acidobacteria subgroups were identified, with Gp1, Gp2, and Gp3 being dominant. Significant differences in Acidobacteria distribution were primarily caused by N input and pH value. The environmental factors of N were all negatively related to Acidobacteria distribution in low N dose treatments (0-20 kg ha(-1) year(-1)), but were positively related in response to N dose treatments (40-80 kg ha(-1) year(-1)).

  11. Effects of low-dose radiation on adaptive response in colon cancer stem cells.

    Science.gov (United States)

    Zhao, X; Cui, J-W; Hu, J-H; Gao, S-J; Liu, X-L

    2017-07-01

    Biological effects of low-dose radiation (LDR) are distinguishable from those of high-dose radiation. Adaptive response is an important biological effect following low-dose radiation. Cancer stem cells (CSCs) have self-renewal and multidirectional differentiation potency which results in relapse and metastasis of cancer. In this study, we aimed to examine whether adaptive response could be induced in CSCs by LDR. Parental cells of three colon cancer cell lines (HRT18, HT29, and HCT116) and CSCs of these three cell lines were irradiated with LDR (i.e., D1) and then high-dose radiation (HDR) of X-rays (i.e., D1 + D2) or only HDR (D2 alone), followed by examination of adaptive response. Adaptive response was not observed either in the three tumor parental cells lines or in three CSCs lines following LDR, due to the lack of resistance to subsequent D2-induced cell growth inhibition. These results suggested that LDR may not induce adaptive response in colon cancer cells or colon CSCs under in vitro conditions. Our study provided experimental and clinical foundations for the application of LDR in the treatment of colon cancers.

  12. Perception and annoyance due to wind turbine noise--a dose-response relationship.

    Science.gov (United States)

    Pedersen, Eja; Waye, Kerstin Persson

    2004-12-01

    Installed global wind power increased by 26% during 2003, with U.S and Europe accounting for 90% of the cumulative capacity. Little is known about wind turbines' impact on people living in their vicinity. The aims of this study were to evaluate the prevalence of annoyance due to wind turbine noise and to study dose-response relationships. Interrelationships between noise annoyance and sound characteristics, as well as the influence of subjective variables such as attitude and noise sensitivity, were also assessed. A cross-sectional study was performed in Sweden in 2000. Responses were obtained through questionnaires (n = 351; response rate 68.4%), and doses were calculated as A-weighted sound pressure levels for each respondent. A statistically significant dose-response relationship was found, showing higher proportion of people reporting perception and annoyance than expected from the present dose-response relationships for transportation noise. The unexpected high proportion of annoyance could be due to visual interference, influencing noise annoyance, as well as the presence of intrusive sound characteristics. The respondents' attitude to the visual impact of wind turbines on the landscape scenery was found to influence noise annoyance.

  13. Continuous Dose-Response Response Relationship of the LDL-Cholesterol-Lowering Effect of Phytosterol Intake 1,2

    NARCIS (Netherlands)

    Demonty, I.; Ras, R.T.; Knaap, van der H.C.M.; Duchateau, G.S.M.J.E.; Meijer, L.; Zock, P.L.; Geleijnse, J.M.; Trautwein, E.A.

    2009-01-01

    Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)¿lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C¿lowering efficacy of different

  14. Intraspecies variability in the dose-response relationship for Salmonella Enteritidis associated with genetic differences in cellular immune response.

    NARCIS (Netherlands)

    Havelaar, A.H.; Garssen, J.; Takumi, K.; Koedam, M.I.; Ritmeester, W.; Fonteyne, L. de la; Bousema, T.; Vos, J.

    2004-01-01

    To evaluate the effects of differences in host cellular immunity, we studied the dose-response relationship for infection with Salmonella enterica serovar Enteritidis (SE) in two different rat strains, skewed towards T helper 1 (Th1, Lewis rats) or T helper 2 (Th2, Brown Norway rats) immunoregulatio

  15. Cytogenetics dosimetry: dose-response curve for low doses of X-ray; Dosimetria citogenetica: curva dosis-respuesta para bajas dosis de rayos-X

    Energy Technology Data Exchange (ETDEWEB)

    Lara, Virginia E. Noval; Pineda Bolivar, William R.; Riano, Victor M. Pabon, E-mail: venovall.15@hotmail.com, E-mail: wrpineda@misena.edu.co, E-mail: vmpabonr@udistrital.edu.co [Universidad Distrital Francisco Jose de Caldas (UD), Bogota (Colombia). Grupo de Investigacion en Ciencia y Tecnologia Nuclear; Ureana, Cecilia Crane, E-mail: cecicrane@yahoo.com [Instituto Nacional de Salud (INS), Bogota (Colombia). Laboratorio de Genetica

    2013-07-01

    The purpose of this study was to conduct a preliminary study for the standardization in the future, the dose-response curve for low doses of X-rays, through the analysis of in vitro cultures of peripheral blood samples of 3 men and 3 women occupationally not exposed to artificial sources of ionizing radiation, age 18-40 years, where possible nonsmokers.

  16. Prescribing patterns, adherence and LDL-cholesterol response of type 2 diabetes patients initiating statin on low-dose versus standard-dose treatment : a descriptive study

    NARCIS (Netherlands)

    de Vries, F M; Voorham, J; Hak, E; Denig, P

    2016-01-01

    AIMS: The aim of this study was to describe and compare treatment modifications and discontinuation, adherence levels and response to treatment in patients with type 2 diabetes initiating on low-dose vs. standard-dose statin treatment. METHODS: A 2-year follow-up cohort study was performed using dat

  17. Bayesian dose selection design for a binary outcome using restricted response adaptive randomization.

    Science.gov (United States)

    Meinzer, Caitlyn; Martin, Renee; Suarez, Jose I

    2017-09-08

    In phase II trials, the most efficacious dose is usually not known. Moreover, given limited resources, it is difficult to robustly identify a dose while also testing for a signal of efficacy that would support a phase III trial. Recent designs have sought to be more efficient by exploring multiple doses through the use of adaptive strategies. However, the added flexibility may potentially increase the risk of making incorrect assumptions and reduce the total amount of information available across the dose range as a function of imbalanced sample size. To balance these challenges, a novel placebo-controlled design is presented in which a restricted Bayesian response adaptive randomization (RAR) is used to allocate a majority of subjects to the optimal dose of active drug, defined as the dose with the lowest probability of poor outcome. However, the allocation between subjects who receive active drug or placebo is held constant to retain the maximum possible power for a hypothesis test of overall efficacy comparing the optimal dose to placebo. The design properties and optimization of the design are presented in the context of a phase II trial for subarachnoid hemorrhage. For a fixed total sample size, a trade-off exists between the ability to select the optimal dose and the probability of rejecting the null hypothesis. This relationship is modified by the allocation ratio between active and control subjects, the choice of RAR algorithm, and the number of subjects allocated to an initial fixed allocation period. While a responsive RAR algorithm improves the ability to select the correct dose, there is an increased risk of assigning more subjects to a worse arm as a function of ephemeral trends in the data. A subarachnoid treatment trial is used to illustrate how this design can be customized for specific objectives and available data. Bayesian adaptive designs are a flexible approach to addressing multiple questions surrounding the optimal dose for treatment efficacy

  18. INFLUENCE OF DOSE RATE ON THE CELLULAR RESPONSE TO LOW- AND HIGH-LET RADIATIONS

    Directory of Open Access Journals (Sweden)

    Anne-Sophie eWozny

    2016-03-01

    Full Text Available Nowadays, head and neck squamous cell carcinoma (HNSCC treatment failure is mostly explained by loco-regional progression or intrinsic radioresistance. Radiotherapy has recently evolved with the emergence of heavy ion radiations or new fractionation schemes of photon therapy which modify the dose-rate of treatment delivery. The aim of the present study was then to evaluate the in vitro influence of a dose rate variation during conventional radiotherapy or carbon ion hadrontherapy treatment in order to improve the therapeutic care of patient. In this regard, two HNSCC cell lines were irradiated with photons or 72MeV/n carbon ions at a dose rate of 0.5, 2 or 10Gy/min.For both radiosensitive and radioresistant cells, the change in dose rate significantly affected cell survival in response to photon exposure, this variation of radiosensitivity was associated to the number of initial and residual DNA double-strand breaks. By contrast, the dose rate change did not affect neither cell survival nor the residual DNA double-strand breaks after carbon ion irradiation. As a result, the Relative Biological Efficiency at 10% survival increased when the dose rate decreased.In conclusion, in the radiotherapy treatment of HNSCC, it is advised to remain very careful when modifying the classical schemes towards altered-fractionation. At the opposite, as the dose rate does not seem to have any effects after carbon ion exposure, there is less need to adapt hadrontherapy treatment planning during active system irradiation

  19. Influence of Dose Rate on the Cellular Response to Low- and High-LET Radiations.

    Science.gov (United States)

    Wozny, Anne-Sophie; Alphonse, Gersende; Battiston-Montagne, Priscillia; Simonet, Stéphanie; Poncet, Delphine; Testa, Etienne; Guy, Jean-Baptiste; Rancoule, Chloé; Magné, Nicolas; Beuve, Michael; Rodriguez-Lafrasse, Claire

    2016-01-01

    Nowadays, head and neck squamous cell carcinoma (HNSCC) treatment failure is mostly explained by locoregional progression or intrinsic radioresistance. Radiotherapy (RT) has recently evolved with the emergence of heavy ion radiations or new fractionation schemes of photon therapy, which modify the dose rate of treatment delivery. The aim of the present study was then to evaluate the in vitro influence of a dose rate variation during conventional RT or carbon ion hadrontherapy treatment in order to improve the therapeutic care of patient. In this regard, two HNSCC cell lines were irradiated with photons or 72 MeV/n carbon ions at a dose rate of 0.5, 2, or 10 Gy/min. For both radiosensitive and radioresistant cells, the change in dose rate significantly affected cell survival in response to photon exposure. This variation of radiosensitivity was associated with the number of initial and residual DNA double-strand breaks (DSBs). By contrast, the dose rate change did not affect neither cell survival nor the residual DNA DSBs after carbon ion irradiation. As a result, the relative biological efficiency at 10% survival increased when the dose rate decreased. In conclusion, in the RT treatment of HNSCC, it is advised to remain very careful when modifying the classical schemes toward altered fractionation. At the opposite, as the dose rate does not seem to have any effects after carbon ion exposure, there is less need to adapt hadrontherapy treatment planning during active system irradiation.

  20. Dose-rate dependence of epitaxial diodes response for gamma dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, J.A.C.; Santos, T.C. dos; Barbosa, R.F.; Pascoalino, K.C.S.; Bueno, C.C. [Instituto de Pesquisas Energeticas e Nucleares (CTR/IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Tecnologia das Radiacoes

    2011-07-01

    Full text: In this work, we present the preliminary results about the evaluation of dose-rate influence on the response of rad-hard epitaxial (EPI) diodes for on-line gamma-ray dosimetry using Co-60 irradiators. The diodes used were processed at University of Hamburg on n-type 75 micrometer thick epitaxial silicon layer (nominal resistivity of 69 Ohm.cm) grown on a highly doped n-type 300 micrometer thick Czochralski (Cz) silicon substrate. Two samples of EPI diodes were investigated: EPI-08 and EPI-10 - both non-irradiated previously. These devices, with 5mm x 5mm active area, were housed in a PMMA probe and connected, in a photovoltaic mode, to a Keithley 617 electrometer. The EPI-10 device irradiation was performed in the Radiation Technology Center at IPEN-CNEN/SP using a Co-60 irradiator (Gammacell 220 - Nordion) which delivers a dose rate of 2.16 kGy/h, while the EPI-08 device irradiation was performed in Nuclear Energy Department at UFPE/PE using the same model Co-60 irradiator, but with a dose-rate of 7.47 kGy/h. During the irradiation, the devices photocurrents were monitored as a function of the exposure time. The diodes were irradiated at room temperature. The dose-response curves of the EPI diodes were achieved through the integration of the current signals as a function of the exposure time. The normalized current signals as a function of the dose evidenced a decrease of about 60 percent from the initial current for the first 100 kGy dose received. After 500 kGy of exposure, the current signals stabilize (ou maintain stable). The dose-response curves behave as a second order polynomial fit, with correlation coefficients of about 0.99991 and 0.99995, respectively to EPI-10 and EPI-08 diodes. The preliminary results obtained evinced that the EPI diodes response are not dose-rate dependent within the range of 2.16 kGy/h up to 7.47 kGy/h. On the other hand, the devices studied are tolerant to radiation damages for total absorbed doses of approximately 550

  1. Dose response of xylitol and sorbitol for EPR retrospective dosimetry with applications to chewing gum.

    Science.gov (United States)

    Israelsson, A; Gustafsson, H; Lund, E

    2013-04-01

    The purpose of this investigation was to study the radiation-induced electron paramagnetic resonance signal in sweeteners xylitol and sorbitol for use in retrospective dosimetry. For both sweeteners and chewing gum, the signal changed at an interval of 1-84 d after irradiation with minimal changes after 4-8 d. A dependence on storage conditions was noticed and the exposure of the samples to light and humidity was therefore minimised. Both the xylitol and sorbitol signals showed linearity with dose in the measured dose interval, 0-20 Gy. The dose-response measurements for the chewing gum resulted in a decision threshold of 0.38 Gy and a detection limit of 0.78 Gy. A blind test illustrated the possibility of using chewing gums as a retrospective dosemeter with an uncertainty in the dose determination of 0.17 Gy (1 SD).

  2. Effect of increased CRM₁₉₇ carrier protein dose on meningococcal C bactericidal antibody response.

    Science.gov (United States)

    Lee, Lucia H; Blake, Milan S

    2012-04-01

    New multivalent CRM(197)-based conjugate vaccines are available for childhood immunization. Clinical studies were reviewed to assess meningococcal group C (MenC) antibody responses following MenC-CRM(197) coadministration with CRM(197)-based pneumococcal or Haemophilus influenzae type b conjugate vaccines. Infants receiving a total CRM(197) carrier protein dose of ∼50 μg and concomitant diphtheria-tetanus-acellular pertussis (DTaP)-containing vaccine tended to have lower MenC geometric mean antibody titers and continued to have low titers after the toddler dose. Nevertheless, at least 95% of children in the reported studies achieved a MenC serum bactericidal antibody (SBA) titer of ≥ 1:8 after the last infant or toddler dose. SBA was measured using an assay with a baby rabbit or human complement source. Additional studies are needed to assess long-term antibody persistence and MenC CRM(197) conjugate vaccine immunogenicity using alternative dosing schedules.

  3. Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships

    Directory of Open Access Journals (Sweden)

    Jeffrey B. Blumberg

    2015-12-01

    Full Text Available Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship of fruit juice flavonoids to these outcomes. Utilizing the results of clinical trials testing single doses, we have analyzed data from studies of 100% Concord grape juice by placing its flavonoid content in the context of results from randomized clinical trials of other polyphenol-rich foods and beverages describing the same outcomes but covering a broader range of intake. We selected established biomarkers determined by similar methods for measuring flow-mediated vasodilation (FMD, blood pressure, platelet aggregation, and the resistance of low density lipoprotein cholesterol (LDL to oxidation. Despite differences among the clinical trials in the treatment, subjects, and duration, correlations were observed between the dose and FMD. Inverse dose-response relationships, albeit with lower correlation coefficients, were also noted for the other outcomes. These results suggest a clear relationship between consumption of even modest serving sizes of Concord grape juice, flavonoid intake, and effects on risk factors for cardiovascular disease. This approach to dose-response relationships may prove useful for testing other individual foods and beverages.

  4. Effect of nonlinearity of restrainer and supports on the elasto-plastic seismic response of continuous girder bridge

    Directory of Open Access Journals (Sweden)

    Wang Changfeng

    2014-10-01

    Full Text Available During an earthquake, the nonlinearity of the bridge structure mainly occurs at the supports, bridge piers and restrainers. When entering nonlinear stage, members of the bridge structure affect the elasto-plastic seismic response of the whole structure to a certain extent; for multi-span continuous bridges, longitudinal restrainers can be installed on the movable piers to optimise the distribution of seismic force and enable the movable piers to bear a certain amount of seismic effect. In order to evaluate the effect of nonlinearity of restrainer and supports on the elasto-plastic seismic response of continuous girder bridge, analytical models of continuous girder bridge structure considering the nonlinearity of movable supports, restrainers and bridge piers were built and the nonlinear time history analysis was conducted to evaluate the effect of nonlinearity of restraining devices and supports on the elasto-plastic seismic response of continuous girder bridge. Relevant structural measures and recommendation were made to reduce the seismic response of the fixed piers of the continuous girder bridge.

  5. Fluid-structure interaction for nonlinear response of shells conveying pulsatile flow

    Science.gov (United States)

    Tubaldi, Eleonora; Amabili, Marco; Païdoussis, Michael P.

    2016-06-01

    Circular cylindrical shells with flexible boundary conditions conveying pulsatile flow and subjected to pulsatile pressure are investigated. The equations of motion are obtained based on the nonlinear Novozhilov shell theory via Lagrangian approach. The flow is set in motion by a pulsatile pressure gradient. The fluid is modeled as a Newtonian pulsatile flow and it is formulated using a hybrid model that contains the unsteady effects obtained from the linear potential flow theory and the pulsatile viscous effects obtained from the unsteady time-averaged Navier-Stokes equations. A numerical bifurcation analysis employs a refined reduced order model to investigate the dynamic behavior. The case of shells containing quiescent fluid subjected to the action of a pulsatile transmural pressure is also addressed. Geometrically nonlinear vibration response to pulsatile flow and transmural pressure are here presented via frequency-response curves and time histories. The vibrations involving both a driven mode and a companion mode, which appear due to the axial symmetry, are also investigated. This theoretical framework represents a pioneering study that could be of great interest for biomedical applications. In particular, in the future, a more refined model of the one here presented will possibly be applied to reproduce the dynamic behavior of vascular prostheses used for repairing and replacing damaged and diseased thoracic aorta in cases of aneurysm, dissection or coarctation. For this purpose, a pulsatile time-dependent blood flow model is here considered by applying physiological waveforms of velocity and pressure during the heart beating period. This study provides, for the first time in literature, a fully coupled fluid-structure interaction model with deep insights in the nonlinear vibrations of circular cylindrical shells subjected to pulsatile pressure and pulsatile flow.

  6. Non-linear response of soil carbon gas (CO2, CH4) flux to oxygen availability

    Science.gov (United States)

    Mcnicol, G.; Silver, W. L.

    2013-12-01

    Soil oxygen (O2) concentration can impact soil carbon (C) fluxes of carbon dioxide (CO2) and methane (CH4), and is an important chemical gradient across the terrestrial-aquatic interface that drives large differences in ecosystem C storage. Few studies have established quantitative relationships between gas-phase O2 concentration and soil C fluxes in controlled settings. Though standard Michaelis-Menten enzyme kinetics would predict a highly non-linear relationship between O2 concentration and microbial consumption, existing studies have imposed coarse changes in O2 concentration that necessarily prevent detection of non-linearity. We report on the results of laboratory incubations designed to explore the short-term sensitivity of soil C emissions to a wide range of gas-phase O2 concentrations. Organic-rich soil was collected from a drained peatland and subjected to seven O2 concentration treatments ranging from 0.03 % - 20 % O2. We compared the fit of the observed C flux response to O2 concentration to linear, log-linear, and Michaelis-Menten functions using MSE and residual fits as performance metrics. We found that both CO2 and CH4 emissions were highly sensitive to O2 concentration, with emission rates increasing and decreasing, respectively, at higher O2. Net CH4 emission rates were attenuated at higher O2 concentrations most likely due to stimulation of gross CH4 consumption. A log-linear or Michaelis-Menten model better fit data than a linear model by both performance metrics, demonstrating, empirically, a non-linear relationship between O2 concentration and soil CO2 and CH4 fluxes. Our results suggest high O2 sensitivity of C-rich soils at the terrestrial-aquatic interface and show that the microbial response to soil redox chemistry must be measured over a biophysically meaningful range of conditions to derive relationships that accurately predict soil C fluxes.

  7. 'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

    Energy Technology Data Exchange (ETDEWEB)

    Jetten, Marlon J.A.; Gaj, Stan [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Ruiz-Aracama, Ainhoa [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Kok, Theo M. de [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Delft, Joost H.M. van, E-mail: j.vandelft@maastrichtuniversity.nl [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Lommen, Arjen [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Someren, Eugene P. van [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Jennen, Danyel G.J.; Claessen, Sandra M. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Peijnenburg, Ad A.C.M. [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Stierum, Rob H. [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Kleinjans, Jos C.S. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands)

    2012-03-15

    Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has already occurred. Furthermore, these tests do not provide mechanistic information. Here, 'omics techniques (global analysis of metabolomic/gene-expression responses) may provide additional insight. To better understand acetaminophen-induced responses at low doses, we evaluated the effects of (sub-)therapeutic acetaminophen doses on metabolite formation and global gene-expression changes (including, for the first time, full-genome human miRNA expression changes) in blood/urine samples from healthy human volunteers. Many known and several new acetaminophen-metabolites were detected, in particular in relation to hepatotoxicity-linked, oxidative metabolism of acetaminophen. Transcriptomic changes indicated immune-modulating effects (2 g dose) and oxidative stress responses (4 g dose). For the first time, effects of acetaminophen on full-genome human miRNA expression have been considered and confirmed the findings on mRNA level. 'Omics techniques outperformed clinical chemistry tests and revealed novel response pathways to acetaminophen in humans. Although no definitive conclusion about potential immunotoxic effects of acetaminophen can be drawn from this study, there are clear indications that the immune system is triggered even after intake of low doses of acetaminophen. Also, oxidative stress-related gene responses, similar to those seen after high dose acetaminophen exposure, suggest the occurrence of possible pre-toxic effects of therapeutic acetaminophen doses. Possibly, these effects are related to dose-dependent increases in levels of hepatotoxicity-related metabolites. -- Highlights: ► 'Omics techniques

  8. Ultra Low-Dose Radiation: Stress Responses and Impacts Using Rice as a Grass Model

    Directory of Open Access Journals (Sweden)

    Junko Shibato

    2009-03-01

    Full Text Available We report molecular changes in leaves of rice plants (Oryza sativa L. - reference crop plant and grass model exposed to ultra low-dose ionizing radiation, first using contaminated soil from the exclusion zone around Chernobyl reactor site. Results revealed induction of stress-related marker genes (Northern blot and secondary metabolites (LC-MS/MS in irradiated leaf segments over appropriate control. Second, employing the same in vitro model system, we replicated results of the first experiment using in-house fabricated sources of ultra low-dose gamma (g rays and selected marker genes by RT-PCR. Results suggest the usefulness of the rice model in studying ultra low-dose radiation response/s.

  9. Salmonella fecal shedding and immune responses are dose- and serotype- dependent in pigs.

    Directory of Open Access Journals (Sweden)

    Renata Ivanek

    Full Text Available Despite the public health importance of Salmonella infection in pigs, little is known about the associated dynamics of fecal shedding and immunity. In this study, we investigated the transitions of pigs through the states of Salmonella fecal shedding and immune response post-Salmonella inoculation as affected by the challenge dose and serotype. Continuous-time multistate Markov models were developed using published experimental data. The model for shedding had four transient states, of which two were shedding (continuous and intermittent shedding and two non-shedding (latency and intermittent non-shedding, and one absorbing state representing permanent cessation of shedding. The immune response model had two transient states representing responses below and above the seroconversion level. The effects of two doses [low (0.65×10(6 CFU/pig and high (0.65×10(9 CFU/pig] and four serotypes (Salmonella Yoruba, Salmonella Cubana, Salmonella Typhimurium, and Salmonella Derby on the models' transition intensities were evaluated using a proportional intensities model. Results indicated statistically significant effects of the challenge dose and serotype on the dynamics of shedding and immune response. The time spent in the specific states was also estimated. Continuous shedding was on average 10-26 days longer, while intermittent non-shedding was 2-4 days shorter, in pigs challenged with the high compared to low dose. Interestingly, among pigs challenged with the high dose, the continuous and intermittent shedding states were on average up to 10-17 and 3-4 days longer, respectively, in pigs infected with S. Cubana compared to the other three serotypes. Pigs challenged with the high dose of S. Typhimurium or S. Derby seroconverted on average up to 8-11 days faster compared to the low dose. These findings highlight that Salmonella fecal shedding and immune response following Salmonella challenge are dose- and serotype-dependent and that the detection of

  10. West Nile virus infection in American Robins: new insights on dose response.

    Directory of Open Access Journals (Sweden)

    Kaci K VanDalen

    Full Text Available West Nile virus (WNV is a vector-borne pathogen that was first detected in the United States in 1999. The natural transmission cycle of WNV involves mosquito vectors and avian hosts, which vary in their competency to transmit the virus. American robins are an abundant backyard species in the United States and appear to have an important role in the amplification and dissemination of WNV. In this study we examine the response of American robins to infection with various WNV doses within the range of those administered by some natural mosquito vectors. Thirty American robins were assigned a WNV dosage treatment and needle inoculated with 10(0.95 PFU, 10(1.26 PFU, 10(2.15 PFU, or 10(3.15 PFU. Serum samples were tested for the presence of infectious WNV and/or antibodies, while oral swabs were tested for the presence of WNV RNA. Five of the 30 (17% robins had neutralizing antibodies to WNV prior to the experiment and none developed viremia or shed WNV RNA. The proportion of WNV-seronegative birds that became viremic after WNV inoculation increased in a dose dependent manner. At the lowest dose, only 40% (2/5 of the inoculated birds developed productive infections while at the highest dose, 100% (7/7 of the birds became viremic. Oral shedding of WNV RNA followed a similar trend where robins inoculated with the lower two doses were less likely to shed viral RNA (25% than robins inoculated with one of the higher doses (92%. Viremia titers and morbidity did not increase in a dose dependent manner; only two birds succumbed to infection and, interestingly, both were inoculated with the lowest dose of WNV. It is clear that the disease ecology of WNV is a complex interplay of hosts, vectors, and viral dose delivered.

  11. West Nile virus infection in American Robins: new insights on dose response.

    Science.gov (United States)

    VanDalen, Kaci K; Hall, Jeffrey S; Clark, Larry; McLean, Robert G; Smeraski, Cynthia

    2013-01-01

    West Nile virus (WNV) is a vector-borne pathogen that was first detected in the United States in 1999. The natural transmission cycle of WNV involves mosquito vectors and avian hosts, which vary in their competency to transmit the virus. American robins are an abundant backyard species in the United States and appear to have an important role in the amplification and dissemination of WNV. In this study we examine the response of American robins to infection with various WNV doses within the range of those administered by some natural mosquito vectors. Thirty American robins were assigned a WNV dosage treatment and needle inoculated with 10(0.95) PFU, 10(1.26) PFU, 10(2.15) PFU, or 10(3.15) PFU. Serum samples were tested for the presence of infectious WNV and/or antibodies, while oral swabs were tested for the presence of WNV RNA. Five of the 30 (17%) robins had neutralizing antibodies to WNV prior to the experiment and none developed viremia or shed WNV RNA. The proportion of WNV-seronegative birds that became viremic after WNV inoculation increased in a dose dependent manner. At the lowest dose, only 40% (2/5) of the inoculated birds developed productive infections while at the highest dose, 100% (7/7) of the birds became viremic. Oral shedding of WNV RNA followed a similar trend where robins inoculated with the lower two doses were less likely to shed viral RNA (25%) than robins inoculated with one of the higher doses (92%). Viremia titers and morbidity did not increase in a dose dependent manner; only two birds succumbed to infection and, interestingly, both were inoculated with the lowest dose of WNV. It is clear that the disease ecology of WNV is a complex interplay of hosts, vectors, and viral dose delivered.

  12. Non-linear modeling of the plasma response to RMPs in ASDEX Upgrade

    CERN Document Server

    Orain, F; Viezzer, E; Dunne, M; Becoulet, M; Cahyna, P; Huijsmans, G T A; Morales, J; Willensdorfer, M; Suttrop, W; Kirk, A; Pamela, S; Strumberger, E; Guenter, S; Lessig, A

    2016-01-01

    The plasma response to Resonant Magnetic Perturbations (RMPs) in ASDEX Upgrade is modeled with the non-linear resistive MHD code JOREK, using input profiles that match those of the experiments as closely as possible. The RMP configuration for which Edge Localized Modes are best mitigated in experiments is related to the largest edge kink response observed near the X-point in modeling. On the edge resonant surfaces q = m=n, the coupling between the m + 2 kink component and the m resonant component is found to induce the amplification of the resonant magnetic perturbation. The ergodicity and the 3D-displacement near the X-point induced by the resonant ampli?cation can only partly explain the density pumpout observed in experiments.

  13. Response Regimes in Equivalent Mechanical Model of Strongly Nonlinear Liquid Sloshing

    CERN Document Server

    Farid, M

    2016-01-01

    We consider equivalent mechanical model of liquid sloshing in partially-filled cylindrical vessel; the model treats both the regime of linear sloshing, and strongly nonlinear sloshing regime. The latter is related to hydraulic impacts applied to the vessel walls. These hydraulic impacts are commonly simulated with the help of high-power potential and dissipation functions. For the sake of analytic exploration, we substitute this traditional approach by treatment of an idealized vibro-impact system with velocity-dependent restitution coefficient. The obtained reduced model is similar to recently explored system of linear primary oscillator with attached vibro-impact energy sink. The ratio of modal mass of the first sloshing mode to the total mass of the liquid and the tank serves as a natural small parameter for multiple-scale analysis. In the case of external ground forcing, steady-state responses and chaotic strongly modulated responses are revealed. All analytical predictions of the reduced vibro-impact mod...

  14. Response of harmonically and stochastically excited strongly nonlinear oscillators with delayed feedback bang-bang control

    Institute of Scientific and Technical Information of China (English)

    Chang-shui FENG; Wei-qiu ZHU

    2009-01-01

    We studied the response of harmonically and stochastically excited strongly nonlinear oscillators with delayed feedback bang-bang control using the stochastic averaging method. First, the time-delayed feedback bang-bang control force is expressed approximately in terms of the system state variables without time delay. Then the averaged Ito stochastic differential equations for the system are derived using the stochastic averaging method. Finally, the response of the system is obtained by solving the Fokker-Plank-Kolmogorov (FPK) equation associated with the averaged Ito equations. A Duffing oscillator with time-delayed feedback bang-bang control under combined harmonic and white noise excitations is taken as an example to illus-trate the proposed method. The analytical results are confirmed by digital simulation. We found that the time delay in feedback bang-bang control will deteriorate the control effectiveness and cause bifurcation of stochastic jump of Duffing oscillator.

  15. Nonlinear response and dynamical transitions in a phase-field crystal model for adsorbed overlayers

    Energy Technology Data Exchange (ETDEWEB)

    Ramos, J A P [Departamento de Ciencias Exatas, Universidade Estadual do Sudoeste da Bahia, 45000-000 Vitoria da Conquista, BA (Brazil); Granato, E [Laboratorio Associado de Sensores e Materiais, Instituto Nacional de Pesquisas Espaciais, 12245-970 Sao Jose dos Campos, SP (Brazil); Ying, S C; Ala-Nissila, T [Department of Physics, PO Box 1843, Brown University, Providence, RI 02912-1843 (United States); Achim, C V [Department of Applied Physics, Aalto University School of Science and Technology, PO Box 11000, FI-00076 Aalto, Espoo (Finland); Elder, K R, E-mail: Jorge@las.inpe.b [Department of Physics, Oakland University, Rochester, Michigan 48309-4487 (United States)

    2010-09-01

    The nonlinear response and sliding friction behavior of a phase-field crystal model for driven adsorbed atomic layers is determined numerically. The model describes the layer as a continuous density field coupled to the pinning potential of the substrate and under an external driving force. Dynamical equations which take into account both thermal fluctuations and inertial effects are used for numerical simulations of commensurate and incommensurate layers. At low temperatures, the velocity response of an initially commensurate layer shows hysteresis with dynamical melting and freezing transitions at different critical forces. The main features of the sliding friction behavior are similar to the results obtained previously from molecular dynamics simulations of particle models. However, the dynamical transitions correspond to nucleations of stripes rather than closed domains.

  16. Non-linear intensification of Sahel rainfall as a possible dynamic response to future warming

    Directory of Open Access Journals (Sweden)

    J. Schewe

    2017-07-01

    Full Text Available Projections of the response of Sahel rainfall to future global warming diverge significantly. Meanwhile, paleoclimatic records suggest that Sahel rainfall is capable of abrupt transitions in response to gradual forcing. Here we present climate modeling evidence for the possibility of an abrupt intensification of Sahel rainfall under future climate change. Analyzing 30 coupled global climate model simulations, we identify seven models where central Sahel rainfall increases by 40 to 300 % over the 21st century, owing to a northward expansion of the West African monsoon domain. Rainfall in these models is non-linearly related to sea surface temperature (SST in the tropical Atlantic and Mediterranean moisture source regions, intensifying abruptly beyond a certain SST warming level. We argue that this behavior is consistent with a self-amplifying dynamic–thermodynamical feedback, implying that the gradual increase in oceanic moisture availability under warming could trigger a sudden intensification of monsoon rainfall far inland of today's core monsoon region.

  17. Non-linear intensification of Sahel rainfall as a possible dynamic response to future warming

    Science.gov (United States)

    Schewe, Jacob; Levermann, Anders

    2017-07-01

    Projections of the response of Sahel rainfall to future global warming diverge significantly. Meanwhile, paleoclimatic records suggest that Sahel rainfall is capable of abrupt transitions in response to gradual forcing. Here we present climate modeling evidence for the possibility of an abrupt intensification of Sahel rainfall under future climate change. Analyzing 30 coupled global climate model simulations, we identify seven models where central Sahel rainfall increases by 40 to 300 % over the 21st century, owing to a northward expansion of the West African monsoon domain. Rainfall in these models is non-linearly related to sea surface temperature (SST) in the tropical Atlantic and Mediterranean moisture source regions, intensifying abruptly beyond a certain SST warming level. We argue that this behavior is consistent with a self-amplifying dynamic-thermodynamical feedback, implying that the gradual increase in oceanic moisture availability under warming could trigger a sudden intensification of monsoon rainfall far inland of today's core monsoon region.

  18. Nonlinear functional response parameter estimation in a stochastic predator-prey model.

    Science.gov (United States)

    Gilioli, Gianni; Pasquali, Sara; Ruggeri, Fabrizio

    2012-01-01

    Parameter estimation for the functional response of predator-prey systems is a critical methodological problem in population ecology. In this paper we consider a stochastic predator-prey system with non-linear Ivlev functional response and propose a method for model parameter estimation based on time series of field data. We tackle the problem of parameter estimation using a Bayesian approach relying on a Markov Chain Monte Carlo algorithm. The efficiency of the method is tested on a set of simulated data. Then, the method is applied to a predator-prey system of importance for Integrated Pest Management and biological control, the pest mite Tetranychus urticae and the predatory mite Phytoseiulus persimilis. The model is estimated on a dataset obtained from a field survey. Finally, the estimated model is used to forecast predator-prey dynamics in similar fields, with slightly different initial conditions.

  19. Non-linear modeling of the plasma response to RMPs in ASDEX Upgrade

    Science.gov (United States)

    Orain, F.; Hölzl, M.; Viezzer, E.; Dunne, M.; Bécoulet, M.; Cahyna, P.; Huijsmans, G. T. A.; Morales, J.; Willensdorfer, M.; Suttrop, W.; Kirk, A.; Pamela, S.; Günter, S.; Lackner, K.; Strumberger, E.; Lessig, A.; the ASDEX Upgrade Team; the EUROfusion MST1 Team

    2017-02-01

    The plasma response to resonant magnetic perturbations (RMPs) in ASDEX Upgrade is modeled with the non-linear resistive MHD code JOREK, using input profiles that match those of the experiments as closely as possible. The RMP configuration for which edge localized modes are best mitigated in experiments is related to the largest edge kink response observed near the X-point in modeling. On the edge resonant surfaces q  =  m/n, the coupling between the kink component (m  >  nq) and the m resonant component is found to induce the amplification of the resonant magnetic perturbation. The ergodicity and the 3D-displacement near the X-point induced by the resonant amplification can only partly explain the density pumpout observed in experiments.

  20. Nonlinear Response of High Arch Dams to Nonuniform Seismic Excitation Considering Joint Effects

    Directory of Open Access Journals (Sweden)

    Masoomeh Akbari

    2013-01-01

    Full Text Available Nonuniform excitation due to spatially varying ground motions on nonlinear responses of concrete arch dams is investigated. A high arch dam was selected as numerical example, reservoir was modelled as incompressible material, foundation was assumed as mass-less medium, and all contraction and peripheral joints were modelled considering the ability of opening/closing. This study used Monte-Carlo simulation approach for generating spatially nonuniform ground motion. In this approach, random seismic characteristics due to incoherence and wave passage effects were investigated and finally their effects on structural response were compared with uniform excitation at design base level earthquake. Based on the results, nonuniform input leads to some differences than uniform input. Moreover using nonuniform excitation increase, stresses on dam body.

  1. Electrical nonlinear response of a photomixer for applications in ultrafast measurements

    Science.gov (United States)

    Constantin, Florin L.

    2014-05-01

    Electrical nonlinear response of a low-temperature-grown GaAs photomixer is exploited for THz-wave modulation, detection and waveform sampling. Current-voltage response at low bias field is modelled by electron drift velocity saturation. THz-wave rectification is discussed in a small-signal approximation and experimentally addressed in connection with the curvature of IV plot. The optical heterodyne signal from two lasers down-converted with the photomixer is modulated by applying an alternative bias field. Conversely, heterodyne detection of a continuous-wave THz source is demonstrated with the photomixer using the optical beat between the lasers as local oscillator. Alternatively, THz-waves with tunable carrier and pulse repetition rate are generated with a THz frequency multiplier driven by a pulsed microwave synthesizer. Asynchronous optical sampling with a pulsed optical beat is demonstrated with the heterodyne detection scheme.

  2. Mathematical Modeling of Allelopathy. III. A Model for Curve-Fitting Allelochemical Dose Responses

    OpenAIRE

    Liu, Li; An, Min; Johnson, Ian R.; Lovett, John V.

    2003-01-01

    Bioassay techniques are often used to study the effects of allelochemicals on plant processes, and it is generally observed that the processes are stimulated at low allelochemical concentrations and inhibited as the concentrations increase. A simple empirical model is presented to analyze this type of response. The stimulation-inhibition properties of allelochemical-dose responses can be described by the parameters in the model. The indices, p% reductions, are calculated to assess the alleloc...

  3. Dose response of subcutaneous GLP-1 infusion in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Torekov, Signe Sørensen; Kipnes, M S; Harley, R E;

    2011-01-01

    To evaluate the dose-response relationship of the recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes, with respect to reductions in fasting, postprandial and 11-h serum glucose profiles....

  4. Concord grape juice polyphenols and cardiovascular risk factors: dose-response relationships

    Science.gov (United States)

    Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship ...

  5. Empirical Evaluation of Meta-Analytic Approaches for Nutrient and Health Outcome Dose-Response Data

    Science.gov (United States)

    Yu, Winifred W.; Schmid, Christopher H.; Lichtenstein, Alice H.; Lau, Joseph; Trikalinos, Thomas A.

    2013-01-01

    The objective of this study is to empirically compare alternative meta-analytic methods for combining dose-response data from epidemiological studies. We identified meta-analyses of epidemiological studies that analyzed the association between a single nutrient and a dichotomous outcome. For each topic, we performed meta-analyses of odds ratios…

  6. Dose response association of pregnancy cigarette smoke exposure, childhood stature, overweight and obesity

    NARCIS (Netherlands)

    G. Koshy; A. Delpisheh; B.J. Brabin

    2011-01-01

    The combined dose response effects of pregnancy cigarette smoke exposure on childhood overweight, obesity and short stature have not been reported. A community based cross-sectional survey of 3038 children aged 5-11 years from 15 primary schools in Merseyside, UK. Self-completed parental questionnai

  7. Dose-response characteristics of ketamine effect on locomotion, cognitive function and central neuronal activity

    NARCIS (Netherlands)

    Imre, G; Fokkema, DS; Den Boer, JA; Ter Horst, GJ

    2006-01-01

    The present dose-response study sought to determine the effects of subanesthetic dosages (4-16 mg/kg) of ketamine on locomotion, sensorimotor gating (PP1), working memory, as well as c-fos expression in various limbic regions implicated in the pathogenesis of schizophrenia. In addition, we examined

  8. Differential immunomodulatory responses to nine polycyclic aromatic hydrocarbons applied by passive dosing

    DEFF Research Database (Denmark)

    Oostingh, Gertie J.; Smith, Kilian E. C.; Tischler, Ulrike

    2015-01-01

    (a)antracene and benzo(a)pyrene. Cytokine promoter expression was then studied in dose response experiments with acenaphthene, phenanthrene and benzo(a)anthracene. The strongest induction was observed for benzo(a)anthracene. Cell viability analysis was performed and showed that none of the PAHs induced cytotoxicity...

  9. Dose response of a new phytse on dry matter, calcium, and phosphorus digestibility in weaned piglets

    NARCIS (Netherlands)

    Bento, M.H.L.; Pedersen, C.; Plumstead, P.W.; Salmon, L.; Nyachoti, C.M.; Bikker, P.

    2012-01-01

    The present study evaluated the dose response of Buttiauxella phytase on apparent total tract digestibility (ATTD) of DM, Ca, and P in weaned pigs at 2 locations. Experimental diets fed to weaned pigs were a positive control (PC), a negative control (NC), and NC supplemented with increasing levels o

  10. Time course and dose response of alpha tocopherol on oxidative stress in haemodialysis patients

    Directory of Open Access Journals (Sweden)

    Coombes Jeff S

    2009-10-01

    Full Text Available Abstract Background Oxidative stress is associated with increased cardiovascular morbidity and mortality particularly in patients with end stage kidney disease. Although observational data from the general population has shown dietary antioxidant intake is associated with reduced cardiovascular morbidity and mortality, most clinical intervention trials have failed to support this relationship. This may be a consequence of not using an effective antioxidant dose and/or not investigating patients with elevated oxidative stress. The SPACE study, conducted in haemodialysis patients, reported that 800 IU/day of alpha tocopherol significantly reduced cardiovascular disease endpoints. A recent time course and dose response study conducted in hypercholesterolaemic patients that found 1600 IU/day of alpha tocopherol was an optimal dose. There is no such dose response data available for haemodialysis patients. Therefore the aim of this study is to investigate the effect of different doses of oral alpha tocopherol on oxidative stress in haemodialysis patients with elevated oxidative stress and the time taken to achieve this effect. Methods The study will consist of a time-course followed by a dose response study. In the time course study 20 haemodialysis patients with elevated oxidative stress will take either 1600 IU/day natural (RRR alpha tocopherol for 20 weeks or placebo. Blood will be collected every two weeks and analysed for a marker of oxidative stress (plasma F2-isoprostanes and alpha tocopherol. The optimum time period to significantly decrease plasma F2-isoprostanes will be determined from this study. In the dose response study 60 patients will be randomised to receive either placebo, 100, 200, 400, 800 or 1600 IU/day of natural (RRR alpha tocopherol for a time period determined from the time course study. Blood will be collected at baseline and every two weeks and analysed for plasma F2-isoprostanes and alpha tocopherol. It is hypothesised that

  11. Multiscale numerical study on ferroelectric nonlinear response of PZT thin films (Conference Presentation)

    Science.gov (United States)

    Wakabayashi, Hiroki; Uetsuji, Yasutomo; Tsuchiya, Kazuyoshi

    2017-06-01

    PZT thin films have excellent performance in deformation precision and response speed, so it is used widely for actuators and sensors of Micro Electro Mechanical System (MEMS). Although PZT thin films outputs large piezoelectricity at morphotropic phase bounfary (MPB), it shows a complicated hysteresis behavior caused by domain switching and structural phase transition between tetragonal and rhombohedral. In general, PZT thin films have some characteristic crystal morphologies. Additionally mechanical strains occur by lattice mismatch with substrate. Therefore it is important for fabrication and performance improvement of PZT thin films to understand the relation between macroscopic hysteresis response and microstructural changes. In this study, a multiscale nonlinear finite element simulation was proposed for PZT thin films at morphotropic phase boundary (MPB) on the substrate. The homogenization theory was employed for scale-bridging between macrostructure and microstructure. Figure 1 shows the proposed multiscale nonlinear simulation [1-3] based on the homogenization theory. Macrostructure is a homogeneous structure to catch the whole behaviors of actuators and sensors. And microstructure is a periodic inhomogeneous structure consisting of domains and grains. Macrostructure and microstructure are connected perfectly by homogenization theory and are analyzed by finite element method. We utilized an incremental form of fundamental constitutive law in consideration with physical property change caused by domain switching and structural phase transition. The developed multiscale finite element method was applied to PZT thin films with lattice mismatch strain on the substrate, and the relation between the macroscopic hysteresis response and microscopic domain switching and structural phase transition were investigated. Especially, we discuss about the effect of crystal morphologies and lattice mismatch strain on hysteresis response.

  12. Physical activity and cancer risk: dose-response and cancer, all sites and site-specific.

    Science.gov (United States)

    Thune, I; Furberg, A S

    2001-06-01

    The association between physical activity and overall and site-specific cancer risk is elaborated in relation to whether any observed dose-response association between physical activity and cancer can be interpreted in terms of how much physical activity (type, intensity, duration, frequency) is needed to influence site- and gender-specific cancer risk. Observational studies were reviewed that have examined the independent effect of the volume of occupational physical activity (OPA) and/or leisure time physical activity (LPA) on overall and site-specific cancer risk. The evidence of cohort and case-control studies suggests that both leisure time and occupational physical activity protect against overall cancer risk, with a graded dose-response association suggested in both sexes. Confounding effects such as diet, body weight, and parity are often included as a covariate in the analyses, with little influence on the observed associations. A crude graded inverse dose-response association was observed between physical activity and colon cancer in 48 studies including 40,674 colon/colorectal cancer cases for both sexes. A dose-response effect of physical activity on colon cancer risk was especially observed, when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed as MET-hours per week. An observed inverse association with a dose-response relationship between physical activity and breast cancer was also identified in the majority of the 41 studies including 108,031 breast cancer cases. The dose-response relationship was in particular observed in case-control studies and supported by observations in cohort studies when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed by MET-hours per week. This association between physical activity and breast cancer risk is possibly dependent on age at exposure, age at diagnosis, menopausal status and other effect

  13. Study of Magnetic Domain Dynamics Using Nonlinear Magnetic Responses: Magnetic Diagnostics of the Itinerant Magnet MnP

    Science.gov (United States)

    Mito, Masaki; Matsui, Hideaki; Tsuruta, Kazuki; Deguchi, Hiroyuki; Kishine, Jun-ichiro; Inoue, Katsuya; Kousaka, Yusuke; Yano, Shin-ichiro; Nakao, Yuya; Akimitsu, Jun

    2015-10-01

    The nonlinear and linear magnetic responses to an ac magnetic field H are useful for the study of the magnetic dynamics of both magnetic domains and their constituent spins. In particular, the third-harmonic magnetic response M3ω reflects the dynamics of magnetic domains. Furthermore, by considering the ac magnetic response as a function of H, we can evaluate the degree of magnetic nonlinearity, which is closely related to M3ω. In this study, a series of approaches was used to examine the itinerant magnet MnP, in which both ferromagnetic and helical phases are present. On the basis of this investigation, we systematize the diagnostic approach to evaluating nonlinearity in magnetic responses.

  14. A non-linear association between self-reported negative emotional response to stress and subsequent allostatic load

    DEFF Research Database (Denmark)

    Dich, Nadya; Doan, Stacey N; Kivimäki, Mika

    2014-01-01

    Previous research suggests that high levels of negative emotions may affect health. However, it is likely that the absence of an emotional response following stressful events may also be problematic. Accordingly, we investigated whether a non-linear association exists between negative emotional...... cardiovascular, metabolic and immune function biomarkers at three clinical follow-up examinations. A non-linear association between negative emotional response and allostatic load was observed: being at either extreme end of the distribution of negative emotional response increased the risk of physiological...

  15. Effects of measurement strategy and statistical analysis on dose-response relations between physical workload and low back pain

    OpenAIRE

    Jansen, Justin; Burdorf, Alex

    2003-01-01

    textabstractBACKGROUND: In epidemiological studies on physical workloads and back complaints, among the important features in modelling dose-response relations are the measurement strategy of the exposure and the nature of the dose-response relation that is assumed. AIM: To evaluate the effect of these two features on the strength of the dose-response relation between physical load and severe low back pain. METHODS: The study population consisted of 769 workers in nursing homes and homes for ...

  16. Systems Cancer Biology and the Controlling Mechanisms for the J-Shaped Cancer Dose Response: Towards Relaxing the LNT Hypothesis

    OpenAIRE

    Lou, In Chio; Zhao, Yuchao; Wu, YingJie; Ricci, Paolo F

    2012-01-01

    The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transforma...

  17. Evaluation of energy responses for neutron dose-equivalent meters made in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Saegusa, J. E-mail: saegusa@popsvr.tokai.jaeri.go.jp; Yoshizawa, M.; Tanimura, Y.; Yoshida, M.; Yamano, T.; Nakaoka, H

    2004-01-01

    Energy responses of three types of Japanese neutron dose-equivalent (DE) meters were evaluated by Monte Carlo simulations and measurements. The energy responses were evaluated for thermal neutrons, monoenergetic neutrons with energies up to 15.2 MeV, and also for neutrons from such radionuclide sources as {sup 252}Cf and {sup 241}Am-Be. The calculated results were corroborated with the measured ones. The angular dependence of the response and the DE response were also evaluated. As a result, reliable energy responses were obtained by careful simulations of the proportional counter, moderator and absorber of the DE meters. Furthermore, the relationship between pressure of counting gas and response of the DE meter was discussed. By using the obtained responses, relations between predicted readings of the DE meters and true DE values were studied for various workplace spectra.

  18. INFLUENCE OF SUCCINYLCHOLINE ON THE DOSE-RESPONSE RELATIONSHIP OF SUBSEQUENTLY ADMINISTERED ROCURONIUN

    Institute of Scientific and Technical Information of China (English)

    陈锡明; 闻大翔; 杭燕南; 孙大金

    2005-01-01

    Objective To investigate the effect of succinylcholine on the dose-response relationship of subsequently administered rocuronium in healthy patients. Methods Forty-eight ASA physical status Ⅰ-Ⅱ patients,aged 17 -65 years, scheduled for elective general surgery, were randomly assigned to either the rocuronium treatment group (R) or succinylcholine-rocuronium treatment group (SR). General anesthesia was induced with thiopental 4 to 6mg/kg and fentanyl 2 to 5μg/kg intravenously and maintained with 60% nitrous oxide in oxygen. Additional doses of thiopental or fentanyl were administered as required. The dose-response relationship of rocuronium was determined by the single dose-response technique. In R group ( n =24) , rocuronium was given after induction of anesthesia. In SR group (n =24 ) , patients were intubated after 1.5mg/kg of succinylcholine and rocuronium was given after the complete recovery of neuromuscular blockade from succinylcholine. Patients were further randomly divided into 4 subgroups receiving 150, 200, 250 or 300μg/kg of rocuronium respectively in both groups. Neuromuscular function was assessed accelographically with train-of-four (TOF) stimulation at the wrist every 12s (using the TOF Guard(R) accelerometer). The relationship between probit-tranformed percentage depression of first twitch height (Th) of train-of-four stimulation and logarithm dose of rocuronium was analyzed using linear regression.Results The dose-response curve of rocuronium after succinylcholine was shifted to the left in a parallel fashion compared with that of rocuronium given alone. ED50 and ED95 of rocuronium were 193 ±69 and 367 ± 73μg/kg respectively in R group, and 158 ± 35 and 317 ± 80μg/kg respectively in SR group ( P < 0. 05 ). Conclusion Succinylcholine shifts the dose-response curve of rocuronium to the left and potentiates the effects of the neuromuscular blockade by about 15% of subsequently administered rocuronium. Lower doses of rocuronium are

  19. Dairy products consumption and risk of type 2 diabetes: systematic review and dose-response meta-analysis.

    Directory of Open Access Journals (Sweden)

    Dengfeng Gao

    Full Text Available BACKGROUND: The consumption of dairy products may influence the risk of type 2 diabetes mellitus (T2DM, but inconsistent findings have been reported. Moreover, large variation in the types of dairy intake has not yet been fully explored. METHODS AND RESULTS: We conducted a systematic review and meta-analysis to clarify the dose-response association of dairy products intake and T2DM risk. We searched PubMed, EMBASE and Scopus for studies of dairy products intake and T2DM risk published up to the end of October 2012. Random-effects models were used to estimate summary relative risk (RR statistics. Dose-response relations were evaluated using data from different dairy products in each study. We included 14 articles of cohort studies that reported RR estimates and 95% confidence intervals (95% CIs of T2DM with dairy products intake. We found an inverse linear association of consumption of total dairy products (13 studies, low-fat dairy products (8 studies, cheese (7 studies and yogurt (7 studies and risk of T2DM. The pooled RRs were 0.94 (95% CI 0.91-0.97 and 0.88 (0.84-0.93 for 200 g/day total and low-fat dairy consumption, respectively. The pooled RRs were 0.80 (0.69-0.93 and 0.91 (0.82-1.00 for 30 g/d cheese and 50 g/d yogurt consumption, respectively. We also found a nonlinear association of total and low-fat dairy intake and T2DM risk, and the inverse association appeared to be strongest within 200 g/d intake. CONCLUSION: A modest increase in daily intake of dairy products such as low fat dairy, cheese and yogurt may contribute to the prevention of T2DM, which needs confirmation in randomized controlled trials.

  20. Diethylene glycol-induced toxicities show marked threshold dose response in rats

    Energy Technology Data Exchange (ETDEWEB)

    Landry, Greg M., E-mail: Landry.Greg@mayo.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Dunning, Cody L., E-mail: cdunni@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu [Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Latimer, Brian, E-mail: blatim@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Orchard, Elysse, E-mail: eorcha@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Division of Animal Resources, Louisiana State University Health Sciences Center, Shreveport, LA (United States); McMartin, Kenneth E., E-mail: kmcmar@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

    2015-02-01

    Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (