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Sample records for model results reveal

  1. A novel mouse model reveals that polycystin-1 deficiency in ependyma and choroid plexus results in dysfunctional cilia and hydrocephalus.

    Directory of Open Access Journals (Sweden)

    Claas Wodarczyk

    2009-09-01

    Full Text Available Polycystin-1 (PC-1, the product of the PKD1 gene, mutated in the majority of cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD, is a very large (approximately 520 kDa plasma membrane receptor localized in several subcellular compartments including cell-cell/matrix junctions as well as cilia. While heterologous over-expression systems have allowed identification of several of the potential biological roles of this receptor, its precise function remains largely elusive. Studying PC-1 in vivo has been a challenging task due to its complexity and low expression levels. To overcome these limitations and facilitate the study of endogenous PC-1, we have inserted HA- or Myc-tag sequences into the Pkd1 locus by homologous recombination. Here, we show that our approach was successful in generating a fully functional and easily detectable endogenous PC-1. Characterization of PC-1 distribution in vivo showed that it is expressed ubiquitously and is developmentally-regulated in most tissues. Furthermore, our novel tool allowed us to investigate the role of PC-1 in brain, where the protein is abundantly expressed. Subcellular localization of PC-1 revealed strong and specific staining in ciliated ependymal and choroid plexus cells. Consistent with this distribution, we observed hydrocephalus formation both in the ubiquitous knock-out embryos and in newborn mice with conditional inactivation of the Pkd1 gene in the brain. Both choroid plexus and ependymal cilia were morphologically normal in these mice, suggesting a role for PC-1 in ciliary function or signalling in this compartment, rather than in ciliogenesis. We propose that the role of PC-1 in the brain cilia might be to prevent hydrocephalus, a previously unrecognized role for this receptor and one that might have important implications for other genetic or sporadic diseases.

  2. Atmospheric Deposition Modeling Results

    Data.gov (United States)

    U.S. Environmental Protection Agency — This asset provides data on model results for dry and total deposition of sulfur, nitrogen and base cation species. Components include deposition velocities, dry...

  3. Assessing Asset Pricing Models Using Revealed Preference

    OpenAIRE

    Jonathan B. Berk; Jules H. van Binsbergen

    2014-01-01

    We propose a new method of testing asset pricing models that relies on using quantities rather than prices or returns. We use the capital flows into and out of mutual funds to infer which risk model investors use. We derive a simple test statistic that allows us to infer, from a set of candidate models, the model that is closest to the model that investors use in making their capital allocation decisions. Using this methodology, we find that of the models most commonly used in the literature,...

  4. Integrative modelling reveals mechanisms linking productivity and plant species richness.

    Science.gov (United States)

    Grace, James B; Anderson, T Michael; Seabloom, Eric W; Borer, Elizabeth T; Adler, Peter B; Harpole, W Stanley; Hautier, Yann; Hillebrand, Helmut; Lind, Eric M; Pärtel, Meelis; Bakker, Jonathan D; Buckley, Yvonne M; Crawley, Michael J; Damschen, Ellen I; Davies, Kendi F; Fay, Philip A; Firn, Jennifer; Gruner, Daniel S; Hector, Andy; Knops, Johannes M H; MacDougall, Andrew S; Melbourne, Brett A; Morgan, John W; Orrock, John L; Prober, Suzanne M; Smith, Melinda D

    2016-01-21

    How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology. Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns. Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models. These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis, is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems.

  5. Gaussian graphical modeling reveals specific lipid correlations in glioblastoma cells

    Science.gov (United States)

    Mueller, Nikola S.; Krumsiek, Jan; Theis, Fabian J.; Böhm, Christian; Meyer-Bäse, Anke

    2011-06-01

    Advances in high-throughput measurements of biological specimens necessitate the development of biologically driven computational techniques. To understand the molecular level of many human diseases, such as cancer, lipid quantifications have been shown to offer an excellent opportunity to reveal disease-specific regulations. The data analysis of the cell lipidome, however, remains a challenging task and cannot be accomplished solely based on intuitive reasoning. We have developed a method to identify a lipid correlation network which is entirely disease-specific. A powerful method to correlate experimentally measured lipid levels across the various samples is a Gaussian Graphical Model (GGM), which is based on partial correlation coefficients. In contrast to regular Pearson correlations, partial correlations aim to identify only direct correlations while eliminating indirect associations. Conventional GGM calculations on the entire dataset can, however, not provide information on whether a correlation is truly disease-specific with respect to the disease samples and not a correlation of control samples. Thus, we implemented a novel differential GGM approach unraveling only the disease-specific correlations, and applied it to the lipidome of immortal Glioblastoma tumor cells. A large set of lipid species were measured by mass spectrometry in order to evaluate lipid remodeling as a result to a combination of perturbation of cells inducing programmed cell death, while the other perturbations served solely as biological controls. With the differential GGM, we were able to reveal Glioblastoma-specific lipid correlations to advance biomedical research on novel gene therapies.

  6. Engineering model cryocooler test results

    International Nuclear Information System (INIS)

    Skimko, M.A.; Stacy, W.D.; McCormick, J.A.

    1992-01-01

    This paper reports that recent testing of diaphragm-defined, Stirling-cycle machines and components has demonstrated cooling performance potential, validated the design code, and confirmed several critical operating characteristics. A breadboard cryocooler was rebuilt and tested from cryogenic to near-ambient cold end temperatures. There was a significant increase in capacity at cryogenic temperatures and the performance results compared will with code predictions at all temperatures. Further testing on a breadboard diaphragm compressor validated the calculated requirement for a minimum axial clearance between diaphragms and mating heads

  7. Results of the naive quark model

    International Nuclear Information System (INIS)

    Gignoux, C.

    1987-10-01

    The hypotheses and limits of the naive quark model are recalled and results on nucleon-nucleon scattering and possible multiquark states are presented. Results show that with this model, ropers do not come. For hadron-hadron interactions, the model predicts Van der Waals forces that the resonance group method does not allow. Known many-body forces are not found in the model. The lack of mesons shows up in the absence of a far reaching force. However, the model does have strengths. It is free from spuriousness of center of mass, and allows a democratic handling of flavor. It has few parameters, and its predictions are very good [fr

  8. Modelling reveals kinetic advantages of co-transcriptional splicing.

    Directory of Open Access Journals (Sweden)

    Stuart Aitken

    2011-10-01

    Full Text Available Messenger RNA splicing is an essential and complex process for the removal of intron sequences. Whereas the composition of the splicing machinery is mostly known, the kinetics of splicing, the catalytic activity of splicing factors and the interdependency of transcription, splicing and mRNA 3' end formation are less well understood. We propose a stochastic model of splicing kinetics that explains data obtained from high-resolution kinetic analyses of transcription, splicing and 3' end formation during induction of an intron-containing reporter gene in budding yeast. Modelling reveals co-transcriptional splicing to be the most probable and most efficient splicing pathway for the reporter transcripts, due in part to a positive feedback mechanism for co-transcriptional second step splicing. Model comparison is used to assess the alternative representations of reactions. Modelling also indicates the functional coupling of transcription and splicing, because both the rate of initiation of transcription and the probability that step one of splicing occurs co-transcriptionally are reduced, when the second step of splicing is abolished in a mutant reporter.

  9. Modelling reveals kinetic advantages of co-transcriptional splicing.

    Science.gov (United States)

    Aitken, Stuart; Alexander, Ross D; Beggs, Jean D

    2011-10-01

    Messenger RNA splicing is an essential and complex process for the removal of intron sequences. Whereas the composition of the splicing machinery is mostly known, the kinetics of splicing, the catalytic activity of splicing factors and the interdependency of transcription, splicing and mRNA 3' end formation are less well understood. We propose a stochastic model of splicing kinetics that explains data obtained from high-resolution kinetic analyses of transcription, splicing and 3' end formation during induction of an intron-containing reporter gene in budding yeast. Modelling reveals co-transcriptional splicing to be the most probable and most efficient splicing pathway for the reporter transcripts, due in part to a positive feedback mechanism for co-transcriptional second step splicing. Model comparison is used to assess the alternative representations of reactions. Modelling also indicates the functional coupling of transcription and splicing, because both the rate of initiation of transcription and the probability that step one of splicing occurs co-transcriptionally are reduced, when the second step of splicing is abolished in a mutant reporter.

  10. Interpreting Results from the Multinomial Logit Model

    DEFF Research Database (Denmark)

    Wulff, Jesper

    2015-01-01

    This article provides guidelines and illustrates practical steps necessary for an analysis of results from the multinomial logit model (MLM). The MLM is a popular model in the strategy literature because it allows researchers to examine strategic choices with multiple outcomes. However, there see...... suitable for both interpretation and communication of results. The pratical steps are illustrated through an application of the MLM to the choice of foreign market entry mode.......This article provides guidelines and illustrates practical steps necessary for an analysis of results from the multinomial logit model (MLM). The MLM is a popular model in the strategy literature because it allows researchers to examine strategic choices with multiple outcomes. However, there seem...... to be systematic issues with regard to how researchers interpret their results when using the MLM. In this study, I present a set of guidelines critical to analyzing and interpreting results from the MLM. The procedure involves intuitive graphical representations of predicted probabilities and marginal effects...

  11. Pedestrian Walking Behavior Revealed through a Random Walk Model

    Directory of Open Access Journals (Sweden)

    Hui Xiong

    2012-01-01

    Full Text Available This paper applies method of continuous-time random walks for pedestrian flow simulation. In the model, pedestrians can walk forward or backward and turn left or right if there is no block. Velocities of pedestrian flow moving forward or diffusing are dominated by coefficients. The waiting time preceding each jump is assumed to follow an exponential distribution. To solve the model, a second-order two-dimensional partial differential equation, a high-order compact scheme with the alternating direction implicit method, is employed. In the numerical experiments, the walking domain of the first one is two-dimensional with two entrances and one exit, and that of the second one is two-dimensional with one entrance and one exit. The flows in both scenarios are one way. Numerical results show that the model can be used for pedestrian flow simulation.

  12. Results of steel containment vessel model test

    International Nuclear Information System (INIS)

    Luk, V.K.; Ludwigsen, J.S.; Hessheimer, M.F.; Komine, Kuniaki; Matsumoto, Tomoyuki; Costello, J.F.

    1998-05-01

    A series of static overpressurization tests of scale models of nuclear containment structures is being conducted by Sandia National Laboratories for the Nuclear Power Engineering Corporation of Japan and the US Nuclear Regulatory Commission. Two tests are being conducted: (1) a test of a model of a steel containment vessel (SCV) and (2) a test of a model of a prestressed concrete containment vessel (PCCV). This paper summarizes the conduct of the high pressure pneumatic test of the SCV model and the results of that test. Results of this test are summarized and are compared with pretest predictions performed by the sponsoring organizations and others who participated in a blind pretest prediction effort. Questions raised by this comparison are identified and plans for posttest analysis are discussed

  13. The EURAD model: Design and first results

    International Nuclear Information System (INIS)

    1989-01-01

    The contributions are abridged versions of lectures delivered on the occasion of the presentation meeting of the EURAD project on the 20th and 21st of February 1989 in Cologne. EURAD stands for European Acid Deposition Model. The project takes one of the possible and necessary ways to search for scientific answers to the questions which the modifications of the atmosphere caused by anthropogenic influence raise. One of the objectives is to develop a realistic numeric model of long-distance transport of harmful substances in the troposphere over Europe and to use this model for the investigation of pollutant distribution but also for the support of their experimental study. The EURAD Model consists of two parts: a meteorologic mesoscale model and a chemical transport model. In the first part of the presentation, these parts are introduced and questions concerning the implementation of the entire model on the computer system CRAY X-MP/22 discussed. Afterwards it is reported upon the results of the test calculations for the cases 'Chernobyl' and 'Alpex'. Thereafter selected problems concerning the treatments of meteorological and air-chemistry processes as well as the parametrization of subscale processes within the model are discussed. The conclusion is made by two lectures upon emission evaluations and emission scenarios. (orig./KW) [de

  14. A physiological production model for cacao : results of model simulations

    NARCIS (Netherlands)

    Zuidema, P.A.; Leffelaar, P.A.

    2002-01-01

    CASE2 is a physiological model for cocoa (Theobroma cacao L.) growth and yield. This report introduces the CAcao Simulation Engine for water-limited production in a non-technical way and presents simulation results obtained with the model.

  15. Modelling rainfall erosion resulting from climate change

    Science.gov (United States)

    Kinnell, Peter

    2016-04-01

    It is well known that soil erosion leads to agricultural productivity decline and contributes to water quality decline. The current widely used models for determining soil erosion for management purposes in agriculture focus on long term (~20 years) average annual soil loss and are not well suited to determining variations that occur over short timespans and as a result of climate change. Soil loss resulting from rainfall erosion is directly dependent on the product of runoff and sediment concentration both of which are likely to be influenced by climate change. This presentation demonstrates the capacity of models like the USLE, USLE-M and WEPP to predict variations in runoff and erosion associated with rainfall events eroding bare fallow plots in the USA with a view to modelling rainfall erosion in areas subject to climate change.

  16. INTRAVAL test case 1b - modelling results

    International Nuclear Information System (INIS)

    Jakob, A.; Hadermann, J.

    1991-07-01

    This report presents results obtained within Phase I of the INTRAVAL study. Six different models are fitted to the results of four infiltration experiments with 233 U tracer on small samples of crystalline bore cores originating from deep drillings in Northern Switzerland. Four of these are dual porosity media models taking into account advection and dispersion in water conducting zones (either tubelike veins or planar fractures), matrix diffusion out of these into pores of the solid phase, and either non-linear or linear sorption of the tracer onto inner surfaces. The remaining two are equivalent porous media models (excluding matrix diffusion) including either non-linear sorption onto surfaces of a single fissure family or linear sorption onto surfaces of several different fissure families. The fits to the experimental data have been carried out by Marquardt-Levenberg procedure yielding error estimates of the parameters, correlation coefficients and also, as a measure for the goodness of the fits, the minimum values of the χ 2 merit function. The effects of different upstream boundary conditions are demonstrated and the penetration depth for matrix diffusion is discussed briefly for both alternative flow path scenarios. The calculations show that the dual porosity media models are significantly more appropriate to the experimental data than the single porosity media concepts. Moreover, it is matrix diffusion rather than the non-linearity of the sorption isotherm which is responsible for the tailing part of the break-through curves. The extracted parameter values for some models for both the linear and non-linear (Freundlich) sorption isotherms are consistent with the results of independent static batch sorption experiments. From the fits, it is generally not possible to discriminate between the two alternative flow path geometries. On the basis of the modelling results, some proposals for further experiments are presented. (author) 15 refs., 23 figs., 7 tabs

  17. Discussion of gas trade model (GTM) results

    International Nuclear Information System (INIS)

    Manne, A.

    1989-01-01

    This is in response to your invitation to comment on the structure of GTM and also upon the differences between its results and those of other models participating in EMF9. First a word upon the structure. GTM was originally designed to provide both regional and sectoral detail within the North American market for natural gas at a single point in time, e.g. the year 2000. It is a spatial equilibrium model in which a solution is obtained by maximizing a nonlinear function, the sum of consumers and producers surplus. Since transport costs are included in producers cost, this formulation automatically ensures that geographical price differentials will not differ by more than transport costs. For purposes of EMF9, GTM was modified to allow for resource development and depletion over time

  18. Comparative analyses reveal discrepancies among results of commonly used methods for Anopheles gambiaemolecular form identification

    Directory of Open Access Journals (Sweden)

    Pinto João

    2011-08-01

    Full Text Available Abstract Background Anopheles gambiae M and S molecular forms, the major malaria vectors in the Afro-tropical region, are ongoing a process of ecological diversification and adaptive lineage splitting, which is affecting malaria transmission and vector control strategies in West Africa. These two incipient species are defined on the basis of single nucleotide differences in the IGS and ITS regions of multicopy rDNA located on the X-chromosome. A number of PCR and PCR-RFLP approaches based on form-specific SNPs in the IGS region are used for M and S identification. Moreover, a PCR-method to detect the M-specific insertion of a short interspersed transposable element (SINE200 has recently been introduced as an alternative identification approach. However, a large-scale comparative analysis of four widely used PCR or PCR-RFLP genotyping methods for M and S identification was never carried out to evaluate whether they could be used interchangeably, as commonly assumed. Results The genotyping of more than 400 A. gambiae specimens from nine African countries, and the sequencing of the IGS-amplicon of 115 of them, highlighted discrepancies among results obtained by the different approaches due to different kinds of biases, which may result in an overestimation of MS putative hybrids, as follows: i incorrect match of M and S specific primers used in the allele specific-PCR approach; ii presence of polymorphisms in the recognition sequence of restriction enzymes used in the PCR-RFLP approaches; iii incomplete cleavage during the restriction reactions; iv presence of different copy numbers of M and S-specific IGS-arrays in single individuals in areas of secondary contact between the two forms. Conclusions The results reveal that the PCR and PCR-RFLP approaches most commonly utilized to identify A. gambiae M and S forms are not fully interchangeable as usually assumed, and highlight limits of the actual definition of the two molecular forms, which might

  19. The Danish national passenger modelModel specification and results

    DEFF Research Database (Denmark)

    Rich, Jeppe; Hansen, Christian Overgaard

    2016-01-01

    The paper describes the structure of the new Danish National Passenger model and provides on this basis a general discussion of large-scale model design, cost-damping and model validation. The paper aims at providing three main contributions to the existing literature. Firstly, at the general level......, the paper provides a description of a large-scale forecast model with a discussion of the linkage between population synthesis, demand and assignment. Secondly, the paper gives specific attention to model specification and in particular choice of functional form and cost-damping. Specifically we suggest...... a family of logarithmic spline functions and illustrate how it is applied in the model. Thirdly and finally, we evaluate model sensitivity and performance by evaluating the distance distribution and elasticities. In the paper we present results where the spline-function is compared with more traditional...

  20. Superconducting solenoid model magnet test results

    Energy Technology Data Exchange (ETDEWEB)

    Carcagno, R.; Dimarco, J.; Feher, S.; Ginsburg, C.M.; Hess, C.; Kashikhin, V.V.; Orris, D.F.; Pischalnikov, Y.; Sylvester, C.; Tartaglia, M.A.; Terechkine, I.; /Fermilab

    2006-08-01

    Superconducting solenoid magnets suitable for the room temperature front end of the Fermilab High Intensity Neutrino Source (formerly known as Proton Driver), an 8 GeV superconducting H- linac, have been designed and fabricated at Fermilab, and tested in the Fermilab Magnet Test Facility. We report here results of studies on the first model magnets in this program, including the mechanical properties during fabrication and testing in liquid helium at 4.2 K, quench performance, and magnetic field measurements. We also describe new test facility systems and instrumentation that have been developed to accomplish these tests.

  1. Superconducting solenoid model magnet test results

    International Nuclear Information System (INIS)

    Carcagno, R.; Dimarco, J.; Feher, S.; Ginsburg, C.M.; Hess, C.; Kashikhin, V.V.; Orris, D.F.; Pischalnikov, Y.; Sylvester, C.; Tartaglia, M.A.; Terechkine, I.; Tompkins, J.C.; Wokas, T.; Fermilab

    2006-01-01

    Superconducting solenoid magnets suitable for the room temperature front end of the Fermilab High Intensity Neutrino Source (formerly known as Proton Driver), an 8 GeV superconducting H- linac, have been designed and fabricated at Fermilab, and tested in the Fermilab Magnet Test Facility. We report here results of studies on the first model magnets in this program, including the mechanical properties during fabrication and testing in liquid helium at 4.2 K, quench performance, and magnetic field measurements. We also describe new test facility systems and instrumentation that have been developed to accomplish these tests

  2. Barcoded pyrosequencing reveals that consumption of galactooligosaccharides results in a highly specific bifidogenic response in humans.

    Directory of Open Access Journals (Sweden)

    Lauren M G Davis

    Full Text Available Prebiotics are selectively fermented ingredients that allow specific changes in the gastrointestinal microbiota that confer health benefits to the host. However, the effects of prebiotics on the human gut microbiota are incomplete as most studies have relied on methods that fail to cover the breadth of the bacterial community. The goal of this research was to use high throughput multiplex community sequencing of 16S rDNA tags to gain a community wide perspective of the impact of prebiotic galactooligosaccharide (GOS on the fecal microbiota of healthy human subjects. Fecal samples from eighteen healthy adults were previously obtained during a feeding trial in which each subject consumed a GOS-containing product for twelve weeks, with four increasing dosages (0, 2.5, 5, and 10 gram of GOS. Multiplex sequencing of the 16S rDNA tags revealed that GOS induced significant compositional alterations in the fecal microbiota, principally by increasing the abundance of organisms within the Actinobacteria. Specifically, several distinct lineages of Bifidobacterium were enriched. Consumption of GOS led to five- to ten-fold increases in bifidobacteria in half of the subjects. Increases in Firmicutes were also observed, however, these changes were detectable in only a few individuals. The enrichment of bifidobacteria was generally at the expense of one group of bacteria, the Bacteroides. The responses to GOS and the magnitude of the response varied between individuals, were reversible, and were in accordance with dosage. The bifidobacteria were the only bacteria that were consistently and significantly enriched by GOS, although this substrate supported the growth of diverse colonic bacteria in mono-culture experiments. These results suggest that GOS can be used to enrich bifidobacteria in the human gastrointestinal tract with remarkable specificity, and that the bifidogenic properties of GOS that occur in vivo are caused by selective fermentation as well as by

  3. Scale Model Thruster Acoustic Measurement Results

    Science.gov (United States)

    Vargas, Magda; Kenny, R. Jeremy

    2013-01-01

    The Space Launch System (SLS) Scale Model Acoustic Test (SMAT) is a 5% scale representation of the SLS vehicle, mobile launcher, tower, and launch pad trench. The SLS launch propulsion system will be comprised of the Rocket Assisted Take-Off (RATO) motors representing the solid boosters and 4 Gas Hydrogen (GH2) thrusters representing the core engines. The GH2 thrusters were tested in a horizontal configuration in order to characterize their performance. In Phase 1, a single thruster was fired to determine the engine performance parameters necessary for scaling a single engine. A cluster configuration, consisting of the 4 thrusters, was tested in Phase 2 to integrate the system and determine their combined performance. Acoustic and overpressure data was collected during both test phases in order to characterize the system's acoustic performance. The results from the single thruster and 4- thuster system are discussed and compared.

  4. CMS standard model Higgs boson results

    Directory of Open Access Journals (Sweden)

    Garcia-Abia Pablo

    2013-11-01

    Full Text Available In July 2012 CMS announced the discovery of a new boson with properties resembling those of the long-sought Higgs boson. The analysis of the proton-proton collision data recorded by the CMS detector at the LHC, corresponding to integrated luminosities of 5.1 fb−1 at √s = 7 TeV and 19.6 fb−1 at √s = 8 TeV, confirm the Higgs-like nature of the new boson, with a signal strength associated with vector bosons and fermions consistent with the expectations for a standard model (SM Higgs boson, and spin-parity clearly favouring the scalar nature of the new boson. In this note I review the updated results of the CMS experiment.

  5. Modelling Extortion Racket Systems: Preliminary Results

    Science.gov (United States)

    Nardin, Luis G.; Andrighetto, Giulia; Székely, Áron; Conte, Rosaria

    Mafias are highly powerful and deeply entrenched organised criminal groups that cause both economic and social damage. Overcoming, or at least limiting, their harmful effects is a societally beneficial objective, which renders its dynamics understanding an objective of both scientific and political interests. We propose an agent-based simulation model aimed at understanding how independent and combined effects of legal and social norm-based processes help to counter mafias. Our results show that legal processes are effective in directly countering mafias by reducing their activities and changing the behaviour of the rest of population, yet they are not able to change people's mind-set that renders the change fragile. When combined with social norm-based processes, however, people's mind-set shifts towards a culture of legality rendering the observed behaviour resilient to change.

  6. New results in the Dual Parton Model

    International Nuclear Information System (INIS)

    Van, J.T.T.; Capella, A.

    1984-01-01

    In this paper, the similarity between the x distribution for particle production and the fragmentation functions are observed in e+e- collisions and in deep inelastic scattering are presented. Based on the observation, the authors develop a complete approach to multiparticle production which incorporates the most important features and concepts learned about high energy collisions. 1. Topological expansion : the dominant diagram at high energy corresponds to the simplest topology. 2. Unitarity : diagrams of various topology contribute to the cross sections in a way that unitary is preserved. 3. Regge behaviour and Duality. 4. Partonic structure of hadrons. These general theoretical ideas, result from many joint experimental and theoretical efforts on the study of soft hadron physics. The dual parton model is able to explain all the experimental features from FNAL to SPS collider energies. It has all the properties of an S-matrix theory and provides a unified description of hadron-hadron, hadron-nucleus and nucleus-nucleus collisions

  7. Mechanistic species distribution modeling reveals a niche shift during invasion.

    Science.gov (United States)

    Chapman, Daniel S; Scalone, Romain; Štefanić, Edita; Bullock, James M

    2017-06-01

    Niche shifts of nonnative plants can occur when they colonize novel climatic conditions. However, the mechanistic basis for niche shifts during invasion is poorly understood and has rarely been captured within species distribution models. We quantified the consequence of between-population variation in phenology for invasion of common ragweed (Ambrosia artemisiifolia L.) across Europe. Ragweed is of serious concern because of its harmful effects as a crop weed and because of its impact on public health as a major aeroallergen. We developed a forward mechanistic species distribution model based on responses of ragweed development rates to temperature and photoperiod. The model was parameterized and validated from the literature and by reanalyzing data from a reciprocal common garden experiment in which native and invasive populations were grown within and beyond the current invaded range. It could therefore accommodate between-population variation in the physiological requirements for flowering, and predict the potentially invaded ranges of individual populations. Northern-origin populations that were established outside the generally accepted climate envelope of the species had lower thermal requirements for bud development, suggesting local adaptation of phenology had occurred during the invasion. The model predicts that this will extend the potentially invaded range northward and increase the average suitability across Europe by 90% in the current climate and 20% in the future climate. Therefore, trait variation observed at the population scale can trigger a climatic niche shift at the biogeographic scale. For ragweed, earlier flowering phenology in established northern populations could allow the species to spread beyond its current invasive range, substantially increasing its risk to agriculture and public health. Mechanistic species distribution models offer the possibility to represent niche shifts by varying the traits and niche responses of individual

  8. Finiteness results for Abelian tree models

    NARCIS (Netherlands)

    Draisma, J.; Eggermont, R.H.

    2015-01-01

    Equivariant tree models are statistical models used in the reconstruction of phylogenetic trees from genetic data. Here equivariant refers to a symmetry group imposed on the root distribution and on the transition matrices in the model. We prove that if that symmetry group is Abelian, then the

  9. Finiteness results for Abelian tree models

    NARCIS (Netherlands)

    Draisma, J.; Eggermont, R.H.

    2012-01-01

    Equivariant tree models are statistical models used in the reconstruction of phylogenetic trees from genetic data. Here equivariant refers to a symmetry group imposed on the root distribution and on the transition matrices in the model. We prove that if that symmetry group is Abelian, then the

  10. Finiteness results for Abelian tree models

    NARCIS (Netherlands)

    Draisma, J.; Eggermont, R.H.

    2015-01-01

    Equivariant tree models are statistical models used in the reconstruction of phylogenetic trees from genetic data. Here equivariant§ refers to a symmetry group imposed on the root distribution and on the transition matrices in the model. We prove that if that symmetry group is Abelian, then the

  11. Immersive visualization of dynamic CFD model results

    International Nuclear Information System (INIS)

    Comparato, J.R.; Ringel, K.L.; Heath, D.J.

    2004-01-01

    With immersive visualization the engineer has the means for vividly understanding problem causes and discovering opportunities to improve design. Software can generate an interactive world in which collaborators experience the results of complex mathematical simulations such as computational fluid dynamic (CFD) modeling. Such software, while providing unique benefits over traditional visualization techniques, presents special development challenges. The visualization of large quantities of data interactively requires both significant computational power and shrewd data management. On the computational front, commodity hardware is outperforming large workstations in graphical quality and frame rates. Also, 64-bit commodity computing shows promise in enabling interactive visualization of large datasets. Initial interactive transient visualization methods and examples are presented, as well as development trends in commodity hardware and clustering. Interactive, immersive visualization relies on relevant data being stored in active memory for fast response to user requests. For large or transient datasets, data management becomes a key issue. Techniques for dynamic data loading and data reduction are presented as means to increase visualization performance. (author)

  12. Linkage of PRA models. Phase 1, Results

    Energy Technology Data Exchange (ETDEWEB)

    Smith, C.L.; Knudsen, J.K.; Kelly, D.L.

    1995-12-01

    The goal of the Phase I work of the ``Linkage of PRA Models`` project was to postulate methods of providing guidance for US Nuclear Regulator Commission (NRC) personnel on the selection and usage of probabilistic risk assessment (PRA) models that are best suited to the analysis they are performing. In particular, methods and associated features are provided for (a) the selection of an appropriate PRA model for a particular analysis, (b) complementary evaluation tools for the analysis, and (c) a PRA model cross-referencing method. As part of this work, three areas adjoining ``linking`` analyses to PRA models were investigated: (a) the PRA models that are currently available, (b) the various types of analyses that are performed within the NRC, and (c) the difficulty in trying to provide a ``generic`` classification scheme to groups plants based upon a particular plant attribute.

  13. Linkage of PRA models. Phase 1, Results

    International Nuclear Information System (INIS)

    Smith, C.L.; Knudsen, J.K.; Kelly, D.L.

    1995-12-01

    The goal of the Phase I work of the ''Linkage of PRA Models'' project was to postulate methods of providing guidance for US Nuclear Regulator Commission (NRC) personnel on the selection and usage of probabilistic risk assessment (PRA) models that are best suited to the analysis they are performing. In particular, methods and associated features are provided for (a) the selection of an appropriate PRA model for a particular analysis, (b) complementary evaluation tools for the analysis, and (c) a PRA model cross-referencing method. As part of this work, three areas adjoining ''linking'' analyses to PRA models were investigated: (a) the PRA models that are currently available, (b) the various types of analyses that are performed within the NRC, and (c) the difficulty in trying to provide a ''generic'' classification scheme to groups plants based upon a particular plant attribute

  14. Engineering Glass Passivation Layers -Model Results

    Energy Technology Data Exchange (ETDEWEB)

    Skorski, Daniel C.; Ryan, Joseph V.; Strachan, Denis M.; Lepry, William C.

    2011-08-08

    The immobilization of radioactive waste into glass waste forms is a baseline process of nuclear waste management not only in the United States, but worldwide. The rate of radionuclide release from these glasses is a critical measure of the quality of the waste form. Over long-term tests and using extrapolations of ancient analogues, it has been shown that well designed glasses exhibit a dissolution rate that quickly decreases to a slow residual rate for the lifetime of the glass. The mechanistic cause of this decreased corrosion rate is a subject of debate, with one of the major theories suggesting that the decrease is caused by the formation of corrosion products in such a manner as to present a diffusion barrier on the surface of the glass. Although there is much evidence of this type of mechanism, there has been no attempt to engineer the effect to maximize the passivating qualities of the corrosion products. This study represents the first attempt to engineer the creation of passivating phases on the surface of glasses. Our approach utilizes interactions between the dissolving glass and elements from the disposal environment to create impermeable capping layers. By drawing from other corrosion studies in areas where passivation layers have been successfully engineered to protect the bulk material, we present here a report on mineral phases that are likely have a morphological tendency to encrust the surface of the glass. Our modeling has focused on using the AFCI glass system in a carbonate, sulfate, and phosphate rich environment. We evaluate the minerals predicted to form to determine the likelihood of the formation of a protective layer on the surface of the glass. We have also modeled individual ions in solutions vs. pH and the addition of aluminum and silicon. These results allow us to understand the pH and ion concentration dependence of mineral formation. We have determined that iron minerals are likely to form a complete incrustation layer and we plan

  15. CIEMAT model results for Esthwaite Water

    International Nuclear Information System (INIS)

    Aguero, A.; Garcia-Olivares, A.

    2000-01-01

    This study used the transfer model PRYMA-LO, developed by CIEMAT-IMA, Madrid, Spain, to simulate the transfer of Cs-137 in watershed scenarios. The main processes considered by the model include: transfer of the fallout to the ground, incorporation of the fallout radioisotopes into the water flow, and their removal from the system. The model was tested against observation data obtained in water and sediments of Esthwaite Water, Lake District, UK. This comparison made it possible to calibrate the parameters of the model to the specific scenario

  16. Topic Modeling Reveals Distinct Interests within an Online Conspiracy Forum

    Directory of Open Access Journals (Sweden)

    Colin Klein

    2018-02-01

    Full Text Available Conspiracy theories play a troubling role in political discourse. Online forums provide a valuable window into everyday conspiracy theorizing, and can give a clue to the motivations and interests of those who post in such forums. Yet this online activity can be difficult to quantify and study. We describe a unique approach to studying online conspiracy theorists which used non-negative matrix factorization to create a topic model of authors' contributions to the main conspiracy forum on Reddit.com. This subreddit provides a large corpus of comments which spans many years and numerous authors. We show that within the forum, there are multiple sub-populations distinguishable by their loadings on different topics in the model. Further, we argue, these differences are interpretable as differences in background beliefs and motivations. The diversity of the distinct subgroups places constraints on theories of what generates conspiracy theorizing. We argue that traditional “monological” believers are only the tip of an iceberg of commenters. Neither simple irrationality nor common preoccupations can account for the observed diversity. Instead, we suggest, those who endorse conspiracies seem to be primarily brought together by epistemological concerns, and that these central concerns link an otherwise heterogenous group of individuals.

  17. Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis

    DEFF Research Database (Denmark)

    Huang, Sijia; Chong, Nicole; Lewis, Nathan

    2016-01-01

    diagnosis. We applied this method to predict breast cancer occurrence, in combination with correlation feature selection (CFS) and classification methods. Results: The resulting all-stage and early-stage diagnosis models are highly accurate in two sets of testing blood samples, with average AUCs (Area Under.......993. Moreover, important metabolic pathways, such as taurine and hypotaurine metabolism and the alanine, aspartate, and glutamate pathway, are revealed as critical biological pathways for early diagnosis of breast cancer. Conclusions: We have successfully developed a new type of pathway-based model to study...... metabolomics data for disease diagnosis. Applying this method to blood-based breast cancer metabolomics data, we have discovered crucial metabolic pathway signatures for breast cancer diagnosis, especially early diagnosis. Further, this modeling approach may be generalized to other omics data types for disease...

  18. Flying Training Capacity Model: Initial Results

    National Research Council Canada - National Science Library

    Lynch, Susan

    2005-01-01

    OBJECTIVE: (1) Determine the flying training capacity for 6 bases: * Sheppard AFB * Randolph AFB * Moody AFB * Columbus AFB * Laughlin AFB * Vance AFB * (2) Develop versatile flying training capacity simulation model for AETC...

  19. Probabilistic Inference: Task Dependency and Individual Differences of Probability Weighting Revealed by Hierarchical Bayesian Modeling.

    Science.gov (United States)

    Boos, Moritz; Seer, Caroline; Lange, Florian; Kopp, Bruno

    2016-01-01

    Cognitive determinants of probabilistic inference were examined using hierarchical Bayesian modeling techniques. A classic urn-ball paradigm served as experimental strategy, involving a factorial two (prior probabilities) by two (likelihoods) design. Five computational models of cognitive processes were compared with the observed behavior. Parameter-free Bayesian posterior probabilities and parameter-free base rate neglect provided inadequate models of probabilistic inference. The introduction of distorted subjective probabilities yielded more robust and generalizable results. A general class of (inverted) S-shaped probability weighting functions had been proposed; however, the possibility of large differences in probability distortions not only across experimental conditions, but also across individuals, seems critical for the model's success. It also seems advantageous to consider individual differences in parameters of probability weighting as being sampled from weakly informative prior distributions of individual parameter values. Thus, the results from hierarchical Bayesian modeling converge with previous results in revealing that probability weighting parameters show considerable task dependency and individual differences. Methodologically, this work exemplifies the usefulness of hierarchical Bayesian modeling techniques for cognitive psychology. Theoretically, human probabilistic inference might be best described as the application of individualized strategic policies for Bayesian belief revision.

  20. Graphical interpretation of numerical model results

    International Nuclear Information System (INIS)

    Drewes, D.R.

    1979-01-01

    Computer software has been developed to produce high quality graphical displays of data from a numerical grid model. The code uses an existing graphical display package (DISSPLA) and overcomes some of the problems of both line-printer output and traditional graphics. The software has been designed to be flexible enough to handle arbitrarily placed computation grids and a variety of display requirements

  1. Ignalina NPP Safety Analysis: Models and Results

    International Nuclear Information System (INIS)

    Uspuras, E.

    1999-01-01

    Research directions, linked to safety assessment of the Ignalina NPP, of the scientific safety analysis group are presented: Thermal-hydraulic analysis of accidents and operational transients; Thermal-hydraulic assessment of Ignalina NPP Accident Localization System and other compartments; Structural analysis of plant components, piping and other parts of Main Circulation Circuit; Assessment of RBMK-1500 reactor core and other. Models and main works carried out last year are described. (author)

  2. Probabilistic inference: Task dependency and individual differences of probability weighting revealed by hierarchical Bayesian modelling

    Directory of Open Access Journals (Sweden)

    Moritz eBoos

    2016-05-01

    Full Text Available Cognitive determinants of probabilistic inference were examined using hierarchical Bayesian modelling techniques. A classic urn-ball paradigm served as experimental strategy, involving a factorial two (prior probabilities by two (likelihoods design. Five computational models of cognitive processes were compared with the observed behaviour. Parameter-free Bayesian posterior probabilities and parameter-free base rate neglect provided inadequate models of probabilistic inference. The introduction of distorted subjective probabilities yielded more robust and generalizable results. A general class of (inverted S-shaped probability weighting functions had been proposed; however, the possibility of large differences in probability distortions not only across experimental conditions, but also across individuals, seems critical for the model’s success. It also seems advantageous to consider individual differences in parameters of probability weighting as being sampled from weakly informative prior distributions of individual parameter values. Thus, the results from hierarchical Bayesian modelling converge with previous results in revealing that probability weighting parameters show considerable task dependency and individual differences. Methodologically, this work exemplifies the usefulness of hierarchical Bayesian modelling techniques for cognitive psychology. Theoretically, human probabilistic inference might be best described as the application of individualized strategic policies for Bayesian belief revision.

  3. A Simple Exercise Reveals the Way Students Think about Scientific Modeling

    Science.gov (United States)

    Ruebush, Laura; Sulikowski, Michelle; North, Simon

    2009-01-01

    Scientific modeling is an integral part of contemporary science, yet many students have little understanding of how models are developed, validated, and used to predict and explain phenomena. A simple modeling exercise led to significant gains in understanding key attributes of scientific modeling while revealing some stubborn misconceptions.…

  4. Microplasticity of MMC. Experimental results and modelling

    International Nuclear Information System (INIS)

    Maire, E.; Lormand, G.; Gobin, P.F.; Fougeres, R.

    1993-01-01

    The microplastic behavior of several MMC is investigated by means of tension and compression tests. This behavior is assymetric : the proportional limit is higher in tension than in compression but the work hardening rate is higher in compression. These differences are analysed in terms of maxium of the Tresca's shear stress at the interface (proportional limit) and of the emission of dislocation loops during the cooling (work hardening rate). On another hand, a model is proposed to calculate the value of the yield stress, describing the composite as a material composed of three phases : inclusion, unaffected matrix and matrix surrounding the inclusion having a gradient in the density of the thermally induced dilocations. (orig.)

  5. Microplasticity of MMC. Experimental results and modelling

    Energy Technology Data Exchange (ETDEWEB)

    Maire, E. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Lormand, G. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Gobin, P.F. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Fougeres, R. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France))

    1993-11-01

    The microplastic behavior of several MMC is investigated by means of tension and compression tests. This behavior is assymetric : the proportional limit is higher in tension than in compression but the work hardening rate is higher in compression. These differences are analysed in terms of maxium of the Tresca's shear stress at the interface (proportional limit) and of the emission of dislocation loops during the cooling (work hardening rate). On another hand, a model is proposed to calculate the value of the yield stress, describing the composite as a material composed of three phases : inclusion, unaffected matrix and matrix surrounding the inclusion having a gradient in the density of the thermally induced dilocations. (orig.).

  6. Introduction of e-learning in dental radiology reveals significantly improved results in final examination.

    Science.gov (United States)

    Meckfessel, Sandra; Stühmer, Constantin; Bormann, Kai-Hendrik; Kupka, Thomas; Behrends, Marianne; Matthies, Herbert; Vaske, Bernhard; Stiesch, Meike; Gellrich, Nils-Claudius; Rücker, Martin

    2011-01-01

    Because a traditionally instructed dental radiology lecture course is very time-consuming and labour-intensive, online courseware, including an interactive-learning module, was implemented to support the lectures. The purpose of this study was to evaluate the perceptions of students who have worked with web-based courseware as well as the effect on their results in final examinations. Users (n(3+4)=138) had access to the e-program from any networked computer at any time. Two groups (n(3)=71, n(4)=67) had to pass a final exam after using the e-course. Results were compared with two groups (n(1)=42, n(2)=48) who had studied the same content by attending traditional lectures. In addition a survey of the students was statistically evaluated. Most of the respondents reported a positive attitude towards e-learning and would have appreciated more access to computer-assisted instruction. Two years after initiating the e-course the failure rate in the final examination dropped significantly, from 40% to less than 2%. The very positive response to the e-program and improved test scores demonstrated the effectiveness of our e-course as a learning aid. Interactive modules in step with clinical practice provided learning that is not achieved by traditional teaching methods alone. To what extent staff savings are possible is part of a further study. Copyright © 2010 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  7. A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis.

    Directory of Open Access Journals (Sweden)

    Guillem Casanovas

    2014-01-01

    Full Text Available Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.

  8. Revealing the equivalence of two clonal survival models by principal component analysis

    International Nuclear Information System (INIS)

    Lachet, Bernard; Dufour, Jacques

    1976-01-01

    The principal component analysis of 21 chlorella cell survival curves, adjusted by one-hit and two-hit target models, lead to quite similar projections on the principal plan: the homologous parameters of these models are linearly correlated; the reason for the statistical equivalence of these two models, in the present state of experimental inaccuracy, is revealed [fr

  9. Representing Microbial Dormancy in Soil Decomposition Models Improves Model Performance and Reveals Key Ecosystem Controls on Microbial Activity

    Science.gov (United States)

    He, Y.; Yang, J.; Zhuang, Q.; Wang, G.; Liu, Y.

    2014-12-01

    Climate feedbacks from soils can result from environmental change and subsequent responses of plant and microbial communities and nutrient cycling. Explicit consideration of microbial life history traits and strategy may be necessary to predict climate feedbacks due to microbial physiology and community changes and their associated effect on carbon cycling. In this study, we developed an explicit microbial-enzyme decomposition model and examined model performance with and without representation of dormancy at six temperate forest sites with observed soil efflux ranged from 4 to 10 years across different forest types. We then extrapolated the model to all temperate forests in the Northern Hemisphere (25-50°N) to investigate spatial controls on microbial and soil C dynamics. Both models captured the observed soil heterotrophic respiration (RH), yet no-dormancy model consistently exhibited large seasonal amplitude and overestimation in microbial biomass. Spatially, the total RH from temperate forests based on dormancy model amounts to 6.88PgC/yr, and 7.99PgC/yr based on no-dormancy model. However, no-dormancy model notably overestimated the ratio of microbial biomass to SOC. Spatial correlation analysis revealed key controls of soil C:N ratio on the active proportion of microbial biomass, whereas local dormancy is primarily controlled by soil moisture and temperature, indicating scale-dependent environmental and biotic controls on microbial and SOC dynamics. These developments should provide essential support to modeling future soil carbon dynamics and enhance the avenue for collaboration between empirical soil experiment and modeling in the sense that more microbial physiological measurements are needed to better constrain and evaluate the models.

  10. Degrees of Cooperation in Household Consumption Models : A Revealed Preference Analysis

    NARCIS (Netherlands)

    Cherchye, L.J.H.; Demuynck, T.; de Rock, B.

    2009-01-01

    We develop a revealed preference approach to analyze non-unitary con- sumption models with intrahousehold allocations deviating from the cooper- ative (or Pareto e¢ cient) solution. At a theoretical level, we establish re- vealed preference conditions of household consumption models with varying

  11. Choice experiments versus revealed choice models : a before-after study of consumer spatial shopping behavior

    NARCIS (Netherlands)

    Timmermans, H.J.P.; Borgers, A.W.J.; Waerden, van der P.J.H.J.

    1992-01-01

    The purpose of this article is to compare a set of multinomial logit models derived from revealed choice data and a decompositional choice model derived from experimental data in terms of predictive success in the context of consumer spatial shopping behavior. Data on consumer shopping choice

  12. Diverse binding site structures revealed in homology models of polyreactive immunoglobulins

    Science.gov (United States)

    Ramsland, Paul A.; Guddat, Luke W.; Edmundson, Allen B.; Raison, Robert L.

    1997-09-01

    We describe here computer-assisted homology models of the combiningsite structure of three polyreactive immunoglobulins. Template-based modelsof Fv (VL-VH) fragments were derived forthe surface IgM expressed by the malignant CD5 positive B cells from threepatients with chronic lymphocytic leukaemia (CLL). The conserved frameworkregions were constructed using crystal coordinates taken from highlyhomologous human variable domain structures (Pot and Hil). Complementaritydetermining regions (CDRs) were predicted by grafting loops, taken fromknown immunoglobulin structures, onto the Fv framework models. The CDRtemplates were chosen, where possible, to be of the same length and of highresidue identity or similarity. LCDR1, 2 and 3 as well as HCDR1 and 2 forthe Fv were constructed using this strategy. For HCDR3 prediction, adatabase containing the Cartesian coordinates of 30 of these loops wascompiled from unliganded antibody X-ray crystallographic structures and anHCDR3 of the same length as that of the B CLL Fv was selected as a template.In one case (Yar), the resulting HCDR3 model gave unfavourable interactionswhen incorporated into the Fv model. This HCDR3 was therefore modelled usingan alternative strategy of construction of the loop stems, using apreviously described HCDR3 conformation (Pot), followed by chain closurewith a β-turn. The template models were subjected to positionalrefinement using energy minimisation and molecular dynamics simulations(X-PLOR). An electrostatic surface description (GRASP) did not reveal acommon structural feature within the binding sites of the three polyreactiveFv. Thus, polyreactive immunoglobulins may recognise similar and multipleantigens through a diverse array of binding site structures.

  13. Floodplain forest succession reveals fluvial processes: A hydrogeomorphic model for temperate riparian woodlands.

    Science.gov (United States)

    Egger, Gregory; Politti, Emilio; Lautsch, Erwin; Benjankar, Rohan; Gill, Karen M; Rood, Stewart B

    2015-09-15

    River valley floodplains are physically-dynamic environments where fluvial processes determine habitat gradients for riparian vegetation. These zones support trees and shrubs whose life stages are adapted to specific habitat types and consequently forest composition and successional stage reflect the underlying hydrogeomorphic processes and history. In this study we investigated woodland vegetation composition, successional stage and habitat properties, and compared these with physically-based indicators of hydraulic processes. We thus sought to develop a hydrogeomorphic model to evaluate riparian woodland condition based on the spatial mosaic of successional phases of the floodplain forest. The study investigated free-flowing and dam-impacted reaches of the Kootenai and Flathead Rivers, in Idaho and Montana, USA and British Columbia, Canada. The analyses revealed strong correspondence between vegetation assessments and metrics of fluvial processes indicating morphodynamics (erosion and shear stress), inundation and depth to groundwater. The results indicated that common successional stages generally occupied similar hydraulic environments along the different river segments. Comparison of the spatial patterns between the free-flowing and regulated reaches revealed greater deviation from the natural condition for the braided channel segment than for the meandering segment. This demonstrates the utility of the hydrogeomorphic approach and suggests that riparian woodlands along braided channels could have lower resilience than those along meandering channels and might be more vulnerable to influences such as from river damming or climate change. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Landscape effects on demersal fish revealed by field observations and predictive seabed modelling.

    Science.gov (United States)

    Elliott, Sophie A M; Sabatino, Alessandro D; Heath, Michael R; Turrell, William R; Bailey, David M

    2017-01-01

    Nature conservation and fisheries management often focus on particular seabed features that are considered vulnerable or important to commercial species. As a result, individual seabed types are protected in isolation, without any understanding of what effect the mixture of seabed types within the landscape has on ecosystem functions. Here we undertook predictive seabed modelling within a coastal marine protected area using observations from underwater stereo-video camera deployments and environmental information (depth, wave fetch, maximum tidal speeds, distance from coast and underlying geology). The effect of the predicted substratum type, extent and heterogeneity or the diversity of substrata, within a radius of 1500 m around each camera deployment of juvenile gadoid relative abundance was analysed. The predicted substratum model performed well with wave fetch and depth being the most influential predictor variables. Gadus morhua (Atlantic cod) were associated with relatively more rugose substrata (Algal-gravel-pebble and seagrass) and heterogeneous landscapes, than Melanogrammus aeglefinus (haddock) or Merlangius merlangus (whiting) (sand and mud). An increase in M. merlangus relative abundance was observed with increasing substratum extent. These results reveal that landscape effects should be considered when protecting the seabed for fish and not just individual seabed types. The landscape approach used in this study therefore has important implications for marine protected area, fisheries management and monitoring advice concerning demersal fish populations.

  15. Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia

    Science.gov (United States)

    Yang, Quan‐Jun; Zhao, Jiang‐Rong; Hao, Juan; Li, Bin; Huo, Yan; Han, Yong‐Long; Wan, Li‐Li; Li, Jie; Huang, Jinlu; Lu, Jin

    2017-01-01

    Abstract Background Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance‐based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model. Methods Eighty‐four cancer cachexia patients, 33 pre‐cachectic patients, 105 weight‐stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model. Results Forty‐six cancer cachexia patients, 22 pre‐cachectic patients, 68 weight‐stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre‐cachectic patients, 37 weight‐stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age‐matched and sex‐matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = −400.53 – 481.88

  16. Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma.

    Science.gov (United States)

    Lescarbeau, Rebecca S; Lei, Liang; Bakken, Katrina K; Sims, Peter A; Sarkaria, Jann N; Canoll, Peter; White, Forest M

    2016-06-01

    Glioblastoma (GBM) is the most common malignant primary brain cancer. With a median survival of about a year, new approaches to treating this disease are necessary. To identify signaling molecules regulating GBM progression in a genetically engineered murine model of proneural GBM, we quantified phosphotyrosine-mediated signaling using mass spectrometry. Oncogenic signals, including phosphorylated ERK MAPK, PI3K, and PDGFR, were found to be increased in the murine tumors relative to brain. Phosphorylation of CDK1 pY15, associated with the G2 arrest checkpoint, was identified as the most differentially phosphorylated site, with a 14-fold increase in phosphorylation in the tumors. To assess the role of this checkpoint as a potential therapeutic target, syngeneic primary cell lines derived from these tumors were treated with MK-1775, an inhibitor of Wee1, the kinase responsible for CDK1 Y15 phosphorylation. MK-1775 treatment led to mitotic catastrophe, as defined by increased DNA damage and cell death by apoptosis. To assess the extensibility of targeting Wee1/CDK1 in GBM, patient-derived xenograft (PDX) cell lines were also treated with MK-1775. Although the response was more heterogeneous, on-target Wee1 inhibition led to decreased CDK1 Y15 phosphorylation and increased DNA damage and apoptosis in each line. These results were also validated in vivo, where single-agent MK-1775 demonstrated an antitumor effect on a flank PDX tumor model, increasing mouse survival by 1.74-fold. This study highlights the ability of unbiased quantitative phosphoproteomics to reveal therapeutic targets in tumor models, and the potential for Wee1 inhibition as a treatment approach in preclinical models of GBM. Mol Cancer Ther; 15(6); 1332-43. ©2016 AACR. ©2016 American Association for Cancer Research.

  17. Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.

    Science.gov (United States)

    Campiñez, María Dolores; Caraballo, Isidoro; Puchkov, Maxim; Kuentz, Martin

    2017-07-01

    The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

  18. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    Science.gov (United States)

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-08-18

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

  19. The uncertainty analysis of model results a practical guide

    CERN Document Server

    Hofer, Eduard

    2018-01-01

    This book is a practical guide to the uncertainty analysis of computer model applications. Used in many areas, such as engineering, ecology and economics, computer models are subject to various uncertainties at the level of model formulations, parameter values and input data. Naturally, it would be advantageous to know the combined effect of these uncertainties on the model results as well as whether the state of knowledge should be improved in order to reduce the uncertainty of the results most effectively. The book supports decision-makers, model developers and users in their argumentation for an uncertainty analysis and assists them in the interpretation of the analysis results.

  20. V and V Efforts of Auroral Precipitation Models: Preliminary Results

    Science.gov (United States)

    Zheng, Yihua; Kuznetsova, Masha; Rastaetter, Lutz; Hesse, Michael

    2011-01-01

    Auroral precipitation models have been valuable both in terms of space weather applications and space science research. Yet very limited testing has been performed regarding model performance. A variety of auroral models are available, including empirical models that are parameterized by geomagnetic indices or upstream solar wind conditions, now casting models that are based on satellite observations, or those derived from physics-based, coupled global models. In this presentation, we will show our preliminary results regarding V&V efforts of some of the models.

  1. Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model.

    Science.gov (United States)

    Zeng, Xiaojun; Zhang, Liyun; Xiao, Xiuchan; Jiang, Yuanyuan; Guo, Yanzhi; Yu, Xinyan; Pu, Xuemei; Li, Menglong

    2016-04-05

    Thrombin-binding aptamer (TBA) with the sequence 5'GGTTGGTGTGGTTGG3' could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation.

  2. ExEP yield modeling tool and validation test results

    Science.gov (United States)

    Morgan, Rhonda; Turmon, Michael; Delacroix, Christian; Savransky, Dmitry; Garrett, Daniel; Lowrance, Patrick; Liu, Xiang Cate; Nunez, Paul

    2017-09-01

    EXOSIMS is an open-source simulation tool for parametric modeling of the detection yield and characterization of exoplanets. EXOSIMS has been adopted by the Exoplanet Exploration Programs Standards Definition and Evaluation Team (ExSDET) as a common mechanism for comparison of exoplanet mission concept studies. To ensure trustworthiness of the tool, we developed a validation test plan that leverages the Python-language unit-test framework, utilizes integration tests for selected module interactions, and performs end-to-end crossvalidation with other yield tools. This paper presents the test methods and results, with the physics-based tests such as photometry and integration time calculation treated in detail and the functional tests treated summarily. The test case utilized a 4m unobscured telescope with an idealized coronagraph and an exoplanet population from the IPAC radial velocity (RV) exoplanet catalog. The known RV planets were set at quadrature to allow deterministic validation of the calculation of physical parameters, such as working angle, photon counts and integration time. The observing keepout region was tested by generating plots and movies of the targets and the keepout zone over a year. Although the keepout integration test required the interpretation of a user, the test revealed problems in the L2 halo orbit and the parameterization of keepout applied to some solar system bodies, which the development team was able to address. The validation testing of EXOSIMS was performed iteratively with the developers of EXOSIMS and resulted in a more robust, stable, and trustworthy tool that the exoplanet community can use to simulate exoplanet direct-detection missions from probe class, to WFIRST, up to large mission concepts such as HabEx and LUVOIR.

  3. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses

    DEFF Research Database (Denmark)

    Brok, J.; Thorlund, K.; Gluud, C.

    2008-01-01

    in 80% (insufficient information size). TSA(15%) and TSA(LBHIS) found that 95% and 91% had absence of evidence. The remaining nonsignificant meta-analyses had evidence of lack of effect. CONCLUSION: TSA reveals insufficient information size and potentially false positive results in many meta......OBJECTIVES: To evaluate meta-analyses with trial sequential analysis (TSA). TSA adjusts for random error risk and provides the required number of participants (information size) in a meta-analysis. Meta-analyses not reaching information size are analyzed with trial sequential monitoring boundaries...... analogous to interim monitoring boundaries in a single trial. STUDY DESIGN AND SETTING: We applied TSA on meta-analyses performed in Cochrane Neonatal reviews. We calculated information sizes and monitoring boundaries with three different anticipated intervention effects of 30% relative risk reduction (TSA...

  4. Network modeling reveals prevalent negative regulatory relationships between signaling sectors in Arabidopsis immune signaling.

    Directory of Open Access Journals (Sweden)

    Masanao Sato

    Full Text Available Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2. This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i the components of the network are highly interconnected; and (ii negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a "sector

  5. Verification of aseismic design model by using experimental results

    International Nuclear Information System (INIS)

    Mizuno, N.; Sugiyama, N.; Suzuki, T.; Shibata, Y.; Miura, K.; Miyagawa, N.

    1985-01-01

    A lattice model is applied as an analysis model for an aseismic design of the Hamaoka nuclear reactor building. With object to verify an availability of this design model, two reinforced concrete blocks are constructed on the ground and the forced vibration tests are carried out. The test results are well followed by simulation analysis using the lattice model. Damping value of the ground obtained from the test is more conservative than the design value. (orig.)

  6. Diffusion Modelling Reveals the Decision Making Processes Underlying Negative Judgement Bias in Rats.

    Directory of Open Access Journals (Sweden)

    Claire A Hales

    Full Text Available Human decision making is modified by emotional state. Rodents exhibit similar biases during interpretation of ambiguous cues that can be altered by affective state manipulations. In this study, the impact of negative affective state on judgement bias in rats was measured using an ambiguous-cue interpretation task. Acute treatment with an anxiogenic drug (FG7142, and chronic restraint stress and social isolation both induced a bias towards more negative interpretation of the ambiguous cue. The diffusion model was fit to behavioural data to allow further analysis of the underlying decision making processes. To uncover the way in which parameters vary together in relation to affective state manipulations, independent component analysis was conducted on rate of information accumulation and distances to decision threshold parameters for control data. Results from this analysis were applied to parameters from negative affective state manipulations. These projected components were compared to control components to reveal the changes in decision making processes that are due to affective state manipulations. Negative affective bias in rodents induced by either FG7142 or chronic stress is due to a combination of more negative interpretation of the ambiguous cue, reduced anticipation of the high reward and increased anticipation of the low reward.

  7. Diffusion Modelling Reveals the Decision Making Processes Underlying Negative Judgement Bias in Rats.

    Science.gov (United States)

    Hales, Claire A; Robinson, Emma S J; Houghton, Conor J

    2016-01-01

    Human decision making is modified by emotional state. Rodents exhibit similar biases during interpretation of ambiguous cues that can be altered by affective state manipulations. In this study, the impact of negative affective state on judgement bias in rats was measured using an ambiguous-cue interpretation task. Acute treatment with an anxiogenic drug (FG7142), and chronic restraint stress and social isolation both induced a bias towards more negative interpretation of the ambiguous cue. The diffusion model was fit to behavioural data to allow further analysis of the underlying decision making processes. To uncover the way in which parameters vary together in relation to affective state manipulations, independent component analysis was conducted on rate of information accumulation and distances to decision threshold parameters for control data. Results from this analysis were applied to parameters from negative affective state manipulations. These projected components were compared to control components to reveal the changes in decision making processes that are due to affective state manipulations. Negative affective bias in rodents induced by either FG7142 or chronic stress is due to a combination of more negative interpretation of the ambiguous cue, reduced anticipation of the high reward and increased anticipation of the low reward.

  8. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Directory of Open Access Journals (Sweden)

    Chiao-Ling Lo

    2016-08-01

    Full Text Available Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP. This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross resulted in small haplotype blocks (HB with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS, were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50% of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284 and intronic regions (169 with the least in exon's (4, suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a, excitatory receptors (Grin2a, Gria3, Grip1, neurotransmitters (Pomc, and synapses (Snap29. This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

  9. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Science.gov (United States)

    Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

    2016-08-01

    Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

  10. Asymmetric biotic interactions and abiotic niche differences revealed by a dynamic joint species distribution model.

    Science.gov (United States)

    Lany, Nina K; Zarnetske, Phoebe L; Schliep, Erin M; Schaeffer, Robert N; Orians, Colin M; Orwig, David A; Preisser, Evan L

    2018-05-01

    A species' distribution and abundance are determined by abiotic conditions and biotic interactions with other species in the community. Most species distribution models correlate the occurrence of a single species with environmental variables only, and leave out biotic interactions. To test the importance of biotic interactions on occurrence and abundance, we compared a multivariate spatiotemporal model of the joint abundance of two invasive insects that share a host plant, hemlock woolly adelgid (HWA; Adelges tsugae) and elongate hemlock scale (EHS; Fiorina externa), to independent models that do not account for dependence among co-occurring species. The joint model revealed that HWA responded more strongly to abiotic conditions than EHS. Additionally, HWA appeared to predispose stands to subsequent increase of EHS, but HWA abundance was not strongly dependent on EHS abundance. This study demonstrates how incorporating spatial and temporal dependence into a species distribution model can reveal the dependence of a species' abundance on other species in the community. Accounting for dependence among co-occurring species with a joint distribution model can also improve estimation of the abiotic niche for species affected by interspecific interactions. © 2018 by the Ecological Society of America.

  11. Identifiability Results for Several Classes of Linear Compartment Models.

    Science.gov (United States)

    Meshkat, Nicolette; Sullivant, Seth; Eisenberg, Marisa

    2015-08-01

    Identifiability concerns finding which unknown parameters of a model can be estimated, uniquely or otherwise, from given input-output data. If some subset of the parameters of a model cannot be determined given input-output data, then we say the model is unidentifiable. In this work, we study linear compartment models, which are a class of biological models commonly used in pharmacokinetics, physiology, and ecology. In past work, we used commutative algebra and graph theory to identify a class of linear compartment models that we call identifiable cycle models, which are unidentifiable but have the simplest possible identifiable functions (so-called monomial cycles). Here we show how to modify identifiable cycle models by adding inputs, adding outputs, or removing leaks, in such a way that we obtain an identifiable model. We also prove a constructive result on how to combine identifiable models, each corresponding to strongly connected graphs, into a larger identifiable model. We apply these theoretical results to several real-world biological models from physiology, cell biology, and ecology.

  12. VNIR spectral modeling of Mars analogue rocks: first results

    Science.gov (United States)

    Pompilio, L.; Roush, T.; Pedrazzi, G.; Sgavetti, M.

    a study applying the Modified Gaussian Model [MGM, 13] to solid mafic rock spectral modeling. Reflectance measurements were acquired on rock slabs, rock powder, and mineral separates. The results of spectral modeling were evaluated using compositional data determined from techniques other than reflectance spectroscopy. The rocks studied, melanorite (cumulate analog) and basalt (effusive analog), have different textural characteristics. The modal composition of melanorite includes relatively high opaque content. Opaque minerals strongly affect reflectance 1 spectra of transparent minerals and the criteria for their identification from remotely acquired data are not clearly established. Detailed studies of the melanorite slab spectrum, which includes accounting for the opaque content, can be extended to the basalt spectrum, which must also account for the spectral influence of glass. The spectral analyses reveal the MGM decompositions of solid rock samples can be used to obtain qualitative estimates of the main mineral compositions, for the melanorite, but become more problematic for the basalt. Statistically objective evaluation of the spectral models is complicated by the increased observational error due to the heterogeneity of the rock surfaces relative to mixtures of powders. This suggests additional efforts are required to provide a better understanding regarding the spectral modeling of both laboratory and in-situ measurements of bulk rocks. REFERENCES - [1] Bandfield, J., P. Christensen, and V. Hamilton (2000) Science, 287, 1626-1630. [2] Christensen, P., J. Bandfield, V. Hamilton, and 23 others (2001) J. Geophys. Res.-Planets., 106 (E10), 23823-23871. [3] Wyatt, M. and H. McSween (2002) Nature, 417, 263-266. [4] Hamilton, V. and M. Minitti (2003) Geophys. Res. Lett., 30, PLA 1-1. [5] Bibring, J., Y. Langevin, A. Gendrin, and 9 others (2005) Science, 307, 1576-1581. [6] Mustard, J., F. Poulet, A. Gendrin, and 6 others (2005) Science, 307, 1594-1597. [7] Hapke

  13. Results of the Marine Ice Sheet Model Intercomparison Project, MISMIP

    Directory of Open Access Journals (Sweden)

    F. Pattyn

    2012-05-01

    Full Text Available Predictions of marine ice-sheet behaviour require models that are able to robustly simulate grounding line migration. We present results of an intercomparison exercise for marine ice-sheet models. Verification is effected by comparison with approximate analytical solutions for flux across the grounding line using simplified geometrical configurations (no lateral variations, no effects of lateral buttressing. Unique steady state grounding line positions exist for ice sheets on a downward sloping bed, while hysteresis occurs across an overdeepened bed, and stable steady state grounding line positions only occur on the downward-sloping sections. Models based on the shallow ice approximation, which does not resolve extensional stresses, do not reproduce the approximate analytical results unless appropriate parameterizations for ice flux are imposed at the grounding line. For extensional-stress resolving "shelfy stream" models, differences between model results were mainly due to the choice of spatial discretization. Moving grid methods were found to be the most accurate at capturing grounding line evolution, since they track the grounding line explicitly. Adaptive mesh refinement can further improve accuracy, including fixed grid models that generally perform poorly at coarse resolution. Fixed grid models, with nested grid representations of the grounding line, are able to generate accurate steady state positions, but can be inaccurate over transients. Only one full-Stokes model was included in the intercomparison, and consequently the accuracy of shelfy stream models as approximations of full-Stokes models remains to be determined in detail, especially during transients.

  14. Automatic generation of predictive dynamic models reveals nuclear phosphorylation as the key Msn2 control mechanism.

    Science.gov (United States)

    Sunnåker, Mikael; Zamora-Sillero, Elias; Dechant, Reinhard; Ludwig, Christina; Busetto, Alberto Giovanni; Wagner, Andreas; Stelling, Joerg

    2013-05-28

    Predictive dynamical models are critical for the analysis of complex biological systems. However, methods to systematically develop and discriminate among systems biology models are still lacking. We describe a computational method that incorporates all hypothetical mechanisms about the architecture of a biological system into a single model and automatically generates a set of simpler models compatible with observational data. As a proof of principle, we analyzed the dynamic control of the transcription factor Msn2 in Saccharomyces cerevisiae, specifically the short-term mechanisms mediating the cells' recovery after release from starvation stress. Our method determined that 12 of 192 possible models were compatible with available Msn2 localization data. Iterations between model predictions and rationally designed phosphoproteomics and imaging experiments identified a single-circuit topology with a relative probability of 99% among the 192 models. Model analysis revealed that the coupling of dynamic phenomena in Msn2 phosphorylation and transport could lead to efficient stress response signaling by establishing a rate-of-change sensor. Similar principles could apply to mammalian stress response pathways. Systematic construction of dynamic models may yield detailed insight into nonobvious molecular mechanisms.

  15. Generalised Chou-Yang model and recent results

    International Nuclear Information System (INIS)

    Fazal-e-Aleem; Rashid, H.

    1995-09-01

    It is shown that most recent results of E710 and UA4/2 collaboration for the total cross section and ρ together with earlier measurements give good agreement with measurements for the differential cross section at 546 and 1800 GeV the framework of Generalised Chou-Yang model. These results are also compared with the predictions of other models. (author). 16 refs, 2 figs

  16. Generalised Chou-Yang model and recent results

    Energy Technology Data Exchange (ETDEWEB)

    Fazal-e-Aleem [International Centre for Theoretical Physics, Trieste (Italy); Rashid, H. [Punjab Univ., Lahore (Pakistan). Centre for High Energy Physics

    1996-12-31

    It is shown that most recent results of E710 and UA4/2 collaboration for the total cross section and {rho} together with earlier measurements give good agreement with measurements for the differential cross section at 546 and 1800 GeV within the framework of Generalised Chou-Yang model. These results are also compared with the predictions of other models. (author) 16 refs.

  17. Generalised Chou-Yang model and recent results

    International Nuclear Information System (INIS)

    Fazal-e-Aleem; Rashid, H.

    1996-01-01

    It is shown that most recent results of E710 and UA4/2 collaboration for the total cross section and ρ together with earlier measurements give good agreement with measurements for the differential cross section at 546 and 1800 GeV within the framework of Generalised Chou-Yang model. These results are also compared with the predictions of other models. (author)

  18. 1H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    International Nuclear Information System (INIS)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D.

    2011-01-01

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in 1 H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  19. {sup 1}H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    Energy Technology Data Exchange (ETDEWEB)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D., E-mail: bernard.lemire@ualberta.ca [University of Alberta, Department of Biochemistry, School of Molecular and Systems Medicine (Canada)

    2011-04-15

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in {sup 1}H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  20. A lesion model of envy and Schadenfreude: legal, deservingness and moral dimensions as revealed by neurodegeneration

    Science.gov (United States)

    Santamaría-García, Hernando; Baez, Sandra; Reyes, Pablo; Santamaría-García, José A; Santacruz-Escudero, José M; Matallana, Diana; Arévalo, Analía; Sigman, Mariano; García, Adolfo M; Ibáñez, Agustín

    2017-01-01

    Abstract The study of moral emotions (i.e. Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as unified and monolithic emotional domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested a group of patients with behavioural variant frontotemporal dementia (bvFTD), patients with Alzheimer’s disease, as a contrastive neurodegeneration model, and healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the Alzheimer’s disease and control groups, patients with bvFTD obtained significantly higher scores on all dimensions for both emotions. Correlational analyses revealed an association between envy and Schadenfreude scores and greater deficits in social cognition, inhibitory control, and behaviour disturbances in bvFTD patients. Brain anatomy findings (restricted to bvFTD and controls) confirmed the partially dissociable nature of the moral emotions’ experiences and highlighted the importance of socio-moral brain areas in processing those emotions. In all subjects, an association emerged between Schadenfreude and the ventral striatum, and between envy and the anterior cingulate cortex. In addition, the results supported an association between scores for moral and legal transgression and the morphology of areas implicated in emotional appraisal, including the amygdala and the parahippocampus. By contrast, bvFTD patients exhibited a negative association between increased Schadenfreude and envy across dimensions and critical regions supporting social-value rewards and social-moral processes (dorsolateral prefrontal cortex, angular

  1. A lesion model of envy and Schadenfreude: legal, deservingness and moral dimensions as revealed by neurodegeneration.

    Science.gov (United States)

    Santamaría-García, Hernando; Baez, Sandra; Reyes, Pablo; Santamaría-García, José A; Santacruz-Escudero, José M; Matallana, Diana; Arévalo, Analía; Sigman, Mariano; García, Adolfo M; Ibáñez, Agustín

    2017-12-01

    The study of moral emotions (i.e. Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as unified and monolithic emotional domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested a group of patients with behavioural variant frontotemporal dementia (bvFTD), patients with Alzheimer's disease, as a contrastive neurodegeneration model, and healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the Alzheimer's disease and control groups, patients with bvFTD obtained significantly higher scores on all dimensions for both emotions. Correlational analyses revealed an association between envy and Schadenfreude scores and greater deficits in social cognition, inhibitory control, and behaviour disturbances in bvFTD patients. Brain anatomy findings (restricted to bvFTD and controls) confirmed the partially dissociable nature of the moral emotions' experiences and highlighted the importance of socio-moral brain areas in processing those emotions. In all subjects, an association emerged between Schadenfreude and the ventral striatum, and between envy and the anterior cingulate cortex. In addition, the results supported an association between scores for moral and legal transgression and the morphology of areas implicated in emotional appraisal, including the amygdala and the parahippocampus. By contrast, bvFTD patients exhibited a negative association between increased Schadenfreude and envy across dimensions and critical regions supporting social-value rewards and social-moral processes (dorsolateral prefrontal cortex, angular gyrus and

  2. Analysis of Transcriptional Signatures in Response to Listeria monocytogenes Infection Reveals Temporal Changes That Result from Type I Interferon Signaling

    Science.gov (United States)

    Potempa, Krzysztof; Graham, Christine M.; Moreira-Teixeira, Lucia; McNab, Finlay W.; Howes, Ashleigh; Stavropoulos, Evangelos; Pascual, Virginia; Banchereau, Jacques; Chaussabel, Damien; O’Garra, Anne

    2016-01-01

    Analysis of the mouse transcriptional response to Listeria monocytogenes infection reveals that a large set of genes are perturbed in both blood and tissue and that these transcriptional responses are enriched for pathways of the immune response. Further we identified enrichment for both type I and type II interferon (IFN) signaling molecules in the blood and tissues upon infection. Since type I IFN signaling has been reported widely to impair bacterial clearance we examined gene expression from blood and tissues of wild type (WT) and type I IFNαβ receptor-deficient (Ifnar1-/-) mice at the basal level and upon infection with L. monocytogenes. Measurement of the fold change response upon infection in the absence of type I IFN signaling demonstrated an upregulation of specific genes at day 1 post infection. A less marked reduction of the global gene expression signature in blood or tissues from infected Ifnar1-/- as compared to WT mice was observed at days 2 and 3 after infection, with marked reduction in key genes such as Oasg1 and Stat2. Moreover, on in depth analysis, changes in gene expression in uninfected mice of key IFN regulatory genes including Irf9, Irf7, Stat1 and others were identified, and although induced by an equivalent degree upon infection this resulted in significantly lower final gene expression levels upon infection of Ifnar1-/- mice. These data highlight how dysregulation of this network in the steady state and temporally upon infection may determine the outcome of this bacterial infection and how basal levels of type I IFN-inducible genes may perturb an optimal host immune response to control intracellular bacterial infections such as L. monocytogenes. PMID:26918359

  3. Results from the IAEA benchmark of spallation models

    International Nuclear Information System (INIS)

    Leray, S.; David, J.C.; Khandaker, M.; Mank, G.; Mengoni, A.; Otsuka, N.; Filges, D.; Gallmeier, F.; Konobeyev, A.; Michel, R.

    2011-01-01

    Spallation reactions play an important role in a wide domain of applications. In the simulation codes used in this field, the nuclear interaction cross-sections and characteristics are computed by spallation models. The International Atomic Energy Agency (IAEA) has recently organised a benchmark of the spallation models used or that could be used in the future into high-energy transport codes. The objectives were, first, to assess the prediction capabilities of the different spallation models for the different mass and energy regions and the different exit channels and, second, to understand the reason for the success or deficiency of the models. Results of the benchmark concerning both the analysis of the prediction capabilities of the models and the first conclusions on the physics of spallation models are presented. (authors)

  4. The animal model determines the results of Aeromonas virulence factors

    Directory of Open Access Journals (Sweden)

    Alejandro Romero

    2016-10-01

    demonstrates that zebrafish larvae can be used as a host model to assess the virulence factors of A. hydrophila. This model revealed more differences in pathogenicity than the in vitro models and enabled the detection of slight variations in pathogenesis not observed using intraperitoneal injections of mice or fish.

  5. The effect of bathymetric filtering on nearshore process model results

    Science.gov (United States)

    Plant, N.G.; Edwards, K.L.; Kaihatu, J.M.; Veeramony, J.; Hsu, L.; Holland, K.T.

    2009-01-01

    Nearshore wave and flow model results are shown to exhibit a strong sensitivity to the resolution of the input bathymetry. In this analysis, bathymetric resolution was varied by applying smoothing filters to high-resolution survey data to produce a number of bathymetric grid surfaces. We demonstrate that the sensitivity of model-predicted wave height and flow to variations in bathymetric resolution had different characteristics. Wave height predictions were most sensitive to resolution of cross-shore variability associated with the structure of nearshore sandbars. Flow predictions were most sensitive to the resolution of intermediate scale alongshore variability associated with the prominent sandbar rhythmicity. Flow sensitivity increased in cases where a sandbar was closer to shore and shallower. Perhaps the most surprising implication of these results is that the interpolation and smoothing of bathymetric data could be optimized differently for the wave and flow models. We show that errors between observed and modeled flow and wave heights are well predicted by comparing model simulation results using progressively filtered bathymetry to results from the highest resolution simulation. The damage done by over smoothing or inadequate sampling can therefore be estimated using model simulations. We conclude that the ability to quantify prediction errors will be useful for supporting future data assimilation efforts that require this information.

  6. Circulation in the Gulf of Trieste: measurements and model results

    International Nuclear Information System (INIS)

    Bogunovici, B.; Malacic, V.

    2008-01-01

    The study presents seasonal variability of currents in the southern part of the Gulf of Trieste. A time series analysis of currents and wind stress for the period 2003-2006, which were measured by the coastal oceanographic buoy, was conducted. A comparison between these data and results obtained from a numerical model of circulation in the Gulf was performed to validate model results. Three different approaches were applied to the wind data to determine the wind stress. Similarities were found between Kondo and Smith approaches while the method of Vera shows differences which were particularly noticeable for lower (= 1 m/s) and higher wind speeds (= 15 m/s). Mean currents in the surface layer are generally outflow currents from the Gulf due to wind forcing (bora). However in all other depth layers inflow currents are dominant. With the principal component analysis (Pca) major and minor axes were determined for all seasons. The major axis of maximum variance in years between 2003 and 2006 is prevailing in Ne-Sw direction, which is parallel to the coastline. Comparison of observation and model results is showing that currents are similar (in direction) for the surface and bottom layers but are significantly different for the middle layer (5-13 m). At a depth between 14-21 m velocities are comparable in direction as well as in magnitude even though model values are higher. Higher values of modelled currents at the surface and near the bottom are explained by higher values of wind stress that were used in the model as driving input with respect to the stress calculated from the measured winds. Larger values of modelled currents near the bottom are related to the larger inflow that needs to compensate for the larger modelled outflow at the surface. However, inspection of the vertical structure of temperature, salinity and density shows that the model is reproducing a weaker density gradient which enables the penetration of the outflow surface currents to larger depths.

  7. Melt coolability modeling and comparison to MACE test results

    International Nuclear Information System (INIS)

    Farmer, M.T.; Sienicki, J.J.; Spencer, B.W.

    1992-01-01

    An important question in the assessment of severe accidents in light water nuclear reactors is the ability of water to quench a molten corium-concrete interaction and thereby terminate the accident progression. As part of the Melt Attack and Coolability Experiment (MACE) Program, phenomenological models of the corium quenching process are under development. The modeling approach considers both bulk cooldown and crust-limited heat transfer regimes, as well as criteria for the pool thermal hydraulic conditions which separate the two regimes. The model is then compared with results of the MACE experiments

  8. Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

    Science.gov (United States)

    Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; Du, Niu; Mih, Nathan; Diamond, Spencer; Lee, Jenny J.; Golden, Susan S.; Palsson, Bernhard O.

    2016-01-01

    The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting in the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology. PMID:27911809

  9. Ocular-following responses to white noise stimuli in humans reveal a novel nonlinearity that results from temporal sampling.

    Science.gov (United States)

    Sheliga, Boris M; Quaia, Christian; FitzGibbon, Edmond J; Cumming, Bruce G

    2016-01-01

    White noise stimuli are frequently used to study the visual processing of broadband images in the laboratory. A common goal is to describe how responses are derived from Fourier components in the image. We investigated this issue by recording the ocular-following responses (OFRs) to white noise stimuli in human subjects. For a given speed we compared OFRs to unfiltered white noise with those to noise filtered with band-pass filters and notch filters. Removing components with low spatial frequency (SF) reduced OFR magnitudes, and the SF associated with the greatest reduction matched the SF that produced the maximal response when presented alone. This reduction declined rapidly with SF, compatible with a winner-take-all operation. Removing higher SF components increased OFR magnitudes. For higher speeds this effect became larger and propagated toward lower SFs. All of these effects were quantitatively well described by a model that combined two factors: (a) an excitatory drive that reflected the OFRs to individual Fourier components and (b) a suppression by higher SF channels where the temporal sampling of the display led to flicker. This nonlinear interaction has an important practical implication: Even with high refresh rates (150 Hz), the temporal sampling introduced by visual displays has a significant impact on visual processing. For instance, we show that this distorts speed tuning curves, shifting the peak to lower speeds. Careful attention to spectral content, in the light of this nonlinearity, is necessary to minimize the resulting artifact when using white noise patterns undergoing apparent motion.

  10. Automatic sleep classification using a data-driven topic model reveals latent sleep states

    DEFF Research Database (Denmark)

    Koch, Henriette; Christensen, Julie Anja Engelhard; Frandsen, Rune

    2014-01-01

    Latent Dirichlet Allocation. Model application was tested on control subjects and patients with periodic leg movements (PLM) representing a non-neurodegenerative group, and patients with idiopathic REM sleep behavior disorder (iRBD) and Parkinson's Disease (PD) representing a neurodegenerative group......Background: The golden standard for sleep classification uses manual scoring of polysomnography despite points of criticism such as oversimplification, low inter-rater reliability and the standard being designed on young and healthy subjects. New method: To meet the criticism and reveal the latent...... sleep states, this study developed a general and automatic sleep classifier using a data-driven approach. Spectral EEG and EOG measures and eye correlation in 1 s windows were calculated and each sleep epoch was expressed as a mixture of probabilities of latent sleep states by using the topic model...

  11. Relationship Marketing results: proposition of a cognitive mapping model

    Directory of Open Access Journals (Sweden)

    Iná Futino Barreto

    2015-12-01

    Full Text Available Objective - This research sought to develop a cognitive model that expresses how marketing professionals understand the relationship between the constructs that define relationship marketing (RM. It also tried to understand, using the obtained model, how objectives in this field are achieved. Design/methodology/approach – Through cognitive mapping, we traced 35 individual mental maps, highlighting how each respondent understands the interactions between RM elements. Based on the views of these individuals, we established an aggregate mental map. Theoretical foundation – The topic is based on a literature review that explores the RM concept and its main elements. Based on this review, we listed eleven main constructs. Findings – We established an aggregate mental map that represents the RM structural model. Model analysis identified that CLV is understood as the final result of RM. We also observed that the impact of most of the RM elements on CLV is brokered by loyalty. Personalization and quality, on the other hand, proved to be process input elements, and are the ones that most strongly impact others. Finally, we highlight that elements that punish customers are much less effective than elements that benefit them. Contributions - The model was able to insert core elements of RM, but absent from most formal models: CLV and customization. The analysis allowed us to understand the interactions between the RM elements and how the end result of RM (CLV is formed. This understanding improves knowledge on the subject and helps guide, assess and correct actions.

  12. Functional results-oriented healthcare leadership: a novel leadership model.

    Science.gov (United States)

    Al-Touby, Salem Said

    2012-03-01

    This article modifies the traditional functional leadership model to accommodate contemporary needs in healthcare leadership based on two findings. First, the article argues that it is important that the ideal healthcare leadership emphasizes the outcomes of the patient care more than processes and structures used to deliver such care; and secondly, that the leadership must strive to attain effectiveness of their care provision and not merely targeting the attractive option of efficient operations. Based on these premises, the paper reviews the traditional Functional Leadership Model and the three elements that define the type of leadership an organization has namely, the tasks, the individuals, and the team. The article argues that concentrating on any one of these elements is not ideal and proposes adding a new element to the model to construct a novel Functional Result-Oriented healthcare leadership model. The recommended Functional-Results Oriented leadership model embosses the results element on top of the other three elements so that every effort on healthcare leadership is directed towards attaining excellent patient outcomes.

  13. Value of the distant future: Model-independent results

    Science.gov (United States)

    Katz, Yuri A.

    2017-01-01

    This paper shows that the model-independent account of correlations in an interest rate process or a log-consumption growth process leads to declining long-term tails of discount curves. Under the assumption of an exponentially decaying memory in fluctuations of risk-free real interest rates, I derive the analytical expression for an apt value of the long run discount factor and provide a detailed comparison of the obtained result with the outcome of the benchmark risk-free interest rate models. Utilizing the standard consumption-based model with an isoelastic power utility of the representative economic agent, I derive the non-Markovian generalization of the Ramsey discounting formula. Obtained analytical results allowing simple calibration, may augment the rigorous cost-benefit and regulatory impact analysis of long-term environmental and infrastructure projects.

  14. Storm-time ring current: model-dependent results

    Directory of Open Access Journals (Sweden)

    N. Yu. Ganushkina

    2012-01-01

    Full Text Available The main point of the paper is to investigate how much the modeled ring current depends on the representations of magnetic and electric fields and boundary conditions used in simulations. Two storm events, one moderate (SymH minimum of −120 nT on 6–7 November 1997 and one intense (SymH minimum of −230 nT on 21–22 October 1999, are modeled. A rather simple ring current model is employed, namely, the Inner Magnetosphere Particle Transport and Acceleration model (IMPTAM, in order to make the results most evident. Four different magnetic field and two electric field representations and four boundary conditions are used. We find that different combinations of the magnetic and electric field configurations and boundary conditions result in very different modeled ring current, and, therefore, the physical conclusions based on simulation results can differ significantly. A time-dependent boundary outside of 6.6 RE gives a possibility to take into account the particles in the transition region (between dipole and stretched field lines forming partial ring current and near-Earth tail current in that region. Calculating the model SymH* by Biot-Savart's law instead of the widely used Dessler-Parker-Sckopke (DPS relation gives larger and more realistic values, since the currents are calculated in the regions with nondipolar magnetic field. Therefore, the boundary location and the method of SymH* calculation are of key importance for ring current data-model comparisons to be correctly interpreted.

  15. Systems biology integration of proteomic data in rodent models of depression reveals involvement of the immune response and glutamatergic signaling.

    Science.gov (United States)

    Carboni, Lucia; Nguyen, Thanh-Phuong; Caberlotto, Laura

    2016-12-01

    The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study is to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease. Network analysis is performed integrating preexisting proteomic data from rodent models of depression. The IntAct mouse and the HRPD are used as reference protein-protein interaction databases. The functionality analyses of the networks are then performed by testing overrepresented GO biological process terms and pathways. Functional enrichment analyses of the networks revealed an association with molecular processes related to depression in humans, such as those involved in the immune response. Pathways impacted by clinically effective antidepressants are modulated, including glutamatergic signaling and neurotrophic responses. Moreover, dysregulations of proteins regulating energy metabolism and circadian rhythms are implicated. The comparison with protein pathways modulated in depressive patients revealed significant overlapping. This systems biology study supports the notion that animal models can contribute to the research into the biology and therapeutics of depression. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Analysis of a dynamic model of guard cell signaling reveals the stability of signal propagation

    Science.gov (United States)

    Gan, Xiao; Albert, RéKa

    Analyzing the long-term behaviors (attractors) of dynamic models of biological systems can provide valuable insight into biological phenotypes and their stability. We identified the long-term behaviors of a multi-level, 70-node discrete dynamic model of the stomatal opening process in plants. We reduce the model's huge state space by reducing unregulated nodes and simple mediator nodes, and by simplifying the regulatory functions of selected nodes while keeping the model consistent with experimental observations. We perform attractor analysis on the resulting 32-node reduced model by two methods: 1. converting it into a Boolean model, then applying two attractor-finding algorithms; 2. theoretical analysis of the regulatory functions. We conclude that all nodes except two in the reduced model have a single attractor; and only two nodes can admit oscillations. The multistability or oscillations do not affect the stomatal opening level in any situation. This conclusion applies to the original model as well in all the biologically meaningful cases. We further demonstrate the robustness of signal propagation by showing that a large percentage of single-node knockouts does not affect the stomatal opening level. Thus, we conclude that the complex structure of this signal transduction network provides multiple information propagation pathways while not allowing extensive multistability or oscillations, resulting in robust signal propagation. Our innovative combination of methods offers a promising way to analyze multi-level models.

  17. Principles of proteome allocation are revealed using proteomic data and genome-scale models

    DEFF Research Database (Denmark)

    Yang, Laurence; Yurkovich, James T.; Lloyd, Colton J.

    2016-01-01

    to metabolism and fitness. Using proteomics data, we formulated allocation constraints for key proteome sectors in the ME model. The resulting calibrated model effectively computed the "generalist" (wild-type) E. coli proteome and phenotype across diverse growth environments. Across 15 growth conditions......Integrating omics data to refine or make context-specific models is an active field of constraint-based modeling. Proteomics now cover over 95% of the Escherichia coli proteome by mass. Genome-scale models of Metabolism and macromolecular Expression (ME) compute proteome allocation linked...... of these sectors for the general stress response sigma factor sigma(S). Finally, the sector constraints represent a general formalism for integrating omics data from any experimental condition into constraint-based ME models. The constraints can be fine-grained (individual proteins) or coarse-grained (functionally...

  18. Test results of the SMES model coil. Pulse performance

    International Nuclear Information System (INIS)

    Hamajima, Takataro; Shimada, Mamoru; Ono, Michitaka

    1998-01-01

    A model coil for superconducting magnetic energy storage (SMES model coil) has been developed to establish the component technologies needed for a small-scale 100 kWh SMES device. The SMES model coil was fabricated, and then performance tests were carried out in 1996. The coil was successfully charged up to around 30 kA and down to zero at the same ramp rate of magnetic field experienced in a 100 kWh SMES device. AC loss in the coil was measured by an enthalpy method as parameters of ramp rate and flat top current. The results were evaluated by an analysis and compared with short-sample test results. The measured hysteresis loss is in good agreement with that estimated from the short-sample results. It was found that the coupling loss of the coil consists of two major coupling time constants. One is a short time constant of about 200 ms, which is in agreement with the test results of a short real conductor. The other is a long time constant of about 30 s, which could not be expected from the short sample test results. (author)

  19. Modeling Results For the ITER Cryogenic Fore Pump. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Pfotenhauer, John M. [University of Wisconsin, Madison, WI (United States); Zhang, Dongsheng [University of Wisconsin, Madison, WI (United States)

    2014-03-31

    A numerical model characterizing the operation of a cryogenic fore-pump (CFP) for ITER has been developed at the University of Wisconsin – Madison during the period from March 15, 2011 through June 30, 2014. The purpose of the ITER-CFP is to separate hydrogen isotopes from helium gas, both making up the exhaust components from the ITER reactor. The model explicitly determines the amount of hydrogen that is captured by the supercritical-helium-cooled pump as a function of the inlet temperature of the supercritical helium, its flow rate, and the inlet conditions of the hydrogen gas flow. Furthermore the model computes the location and amount of hydrogen captured in the pump as a function of time. Throughout the model’s development, and as a calibration check for its results, it has been extensively compared with the measurements of a CFP prototype tested at Oak Ridge National Lab. The results of the model demonstrate that the quantity of captured hydrogen is very sensitive to the inlet temperature of the helium coolant on the outside of the cryopump. Furthermore, the model can be utilized to refine those tests, and suggests methods that could be incorporated in the testing to enhance the usefulness of the measured data.

  20. Methodology and Results of Mathematical Modelling of Complex Technological Processes

    Science.gov (United States)

    Mokrova, Nataliya V.

    2018-03-01

    The methodology of system analysis allows us to draw a mathematical model of the complex technological process. The mathematical description of the plasma-chemical process was proposed. The importance the quenching rate and initial temperature decrease time was confirmed for producing the maximum amount of the target product. The results of numerical integration of the system of differential equations can be used to describe reagent concentrations, plasma jet rate and temperature in order to achieve optimal mode of hardening. Such models are applicable both for solving control problems and predicting future states of sophisticated technological systems.

  1. Modeling vertical loads in pools resulting from fluid injection

    International Nuclear Information System (INIS)

    Lai, W.; McCauley, E.W.

    1978-01-01

    Table-top model experiments were performed to investigate pressure suppression pool dynamics effects due to a postulated loss-of-coolant accident (LOCA) for the Peachbottom Mark I boiling water reactor containment system. The results guided subsequent conduct of experiments in the 1 / 5 -scale facility and provided new insight into the vertical load function (VLF). Model experiments show an oscillatory VLF with the download typically double-spiked followed by a more gradual sinusoidal upload. The load function contains a high frequency oscillation superimposed on a low frequency one; evidence from measurements indicates that the oscillations are initiated by fluid dynamics phenomena

  2. The physical model of a terraced plot: first results

    Science.gov (United States)

    Perlotto, Chiara; D'Agostino, Vincenzo; Buzzanca, Giacomo

    2017-04-01

    response have been monitored and analyzed, well corroborating the findings on the kinematics of the terrace plot. Finally, the computation of the specific Curve Number (Soil Conservation Service) of the physical model has revealed values rather large if compared with those reported in the literature. This phenomena was likely caused by the high values of the inflow discharge, the limited cross-width of the model (1 m) and the increasing compactness of the soil owing to the experiment repetition. These pioneering experiments have produced some remarkable outcomes on the important role of lag-times (runoff and groundwater) of a terraced system as well as many ideas on improving the physical model and its setting in a next investigation.

  3. Results of the eruptive column model inter-comparison study

    Science.gov (United States)

    Costa, Antonio; Suzuki, Yujiro; Cerminara, M.; Devenish, Ben J.; Esposti Ongaro, T.; Herzog, Michael; Van Eaton, Alexa; Denby, L.C.; Bursik, Marcus; de' Michieli Vitturi, Mattia; Engwell, S.; Neri, Augusto; Barsotti, Sara; Folch, Arnau; Macedonio, Giovanni; Girault, F.; Carazzo, G.; Tait, S.; Kaminski, E.; Mastin, Larry G.; Woodhouse, Mark J.; Phillips, Jeremy C.; Hogg, Andrew J.; Degruyter, Wim; Bonadonna, Costanza

    2016-01-01

    This study compares and evaluates one-dimensional (1D) and three-dimensional (3D) numerical models of volcanic eruption columns in a set of different inter-comparison exercises. The exercises were designed as a blind test in which a set of common input parameters was given for two reference eruptions, representing a strong and a weak eruption column under different meteorological conditions. Comparing the results of the different models allows us to evaluate their capabilities and target areas for future improvement. Despite their different formulations, the 1D and 3D models provide reasonably consistent predictions of some of the key global descriptors of the volcanic plumes. Variability in plume height, estimated from the standard deviation of model predictions, is within ~ 20% for the weak plume and ~ 10% for the strong plume. Predictions of neutral buoyancy level are also in reasonably good agreement among the different models, with a standard deviation ranging from 9 to 19% (the latter for the weak plume in a windy atmosphere). Overall, these discrepancies are in the range of observational uncertainty of column height. However, there are important differences amongst models in terms of local properties along the plume axis, particularly for the strong plume. Our analysis suggests that the simplified treatment of entrainment in 1D models is adequate to resolve the general behaviour of the weak plume. However, it is inadequate to capture complex features of the strong plume, such as large vortices, partial column collapse, or gravitational fountaining that strongly enhance entrainment in the lower atmosphere. We conclude that there is a need to more accurately quantify entrainment rates, improve the representation of plume radius, and incorporate the effects of column instability in future versions of 1D volcanic plume models.

  4. Initial CGE Model Results Summary Exogenous and Endogenous Variables Tests

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, Brian Keith [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Boero, Riccardo [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rivera, Michael Kelly [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-08-07

    The following discussion presents initial results of tests of the most recent version of the National Infrastructure Simulation and Analysis Center Dynamic Computable General Equilibrium (CGE) model developed by Los Alamos National Laboratory (LANL). The intent of this is to test and assess the model’s behavioral properties. The test evaluated whether the predicted impacts are reasonable from a qualitative perspective. This issue is whether the predicted change, be it an increase or decrease in other model variables, is consistent with prior economic intuition and expectations about the predicted change. One of the purposes of this effort is to determine whether model changes are needed in order to improve its behavior qualitatively and quantitatively.

  5. A model of lipid-free apolipoprotein A-I revealed by iterative molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Xing Zhang

    Full Text Available Apolipoprotein A-I (apo A-I, the major protein component of high-density lipoprotein, has been proven inversely correlated to cardiovascular risk in past decades. The lipid-free state of apo A-I is the initial stage which binds to lipids forming high-density lipoprotein. Molecular models of lipid-free apo A-I have been reported by methods like X-ray crystallography and chemical cross-linking/mass spectrometry (CCL/MS. Through structural analysis we found that those current models had limited consistency with other experimental results, such as those from hydrogen exchange with mass spectrometry. Through molecular dynamics simulations, we also found those models could not reach a stable equilibrium state. Therefore, by integrating various experimental results, we proposed a new structural model for lipid-free apo A-I, which contains a bundled four-helix N-terminal domain (1-192 that forms a variable hydrophobic groove and a mobile short hairpin C-terminal domain (193-243. This model exhibits an equilibrium state through molecular dynamics simulation and is consistent with most of the experimental results known from CCL/MS on lysine pairs, fluorescence resonance energy transfer and hydrogen exchange. This solution-state lipid-free apo A-I model may elucidate the possible conformational transitions of apo A-I binding with lipids in high-density lipoprotein formation.

  6. Revealing topographic lineaments through IHS enhancement of DEM data. [Digital Elevation Model

    Science.gov (United States)

    Murdock, Gary

    1990-01-01

    Intensity-hue-saturation (IHS) processing of slope (dip), aspect (dip direction), and elevation to reveal subtle topographic lineaments which may not be obvious in the unprocessed data are used to enhance digital elevation model (DEM) data from northwestern Nevada. This IHS method of lineament identification was applied to a mosiac of 12 square degrees using a Cray Y-MP8/864. Square arrays from 3 x 3 to 31 x 31 points were tested as well as several different slope enhancements. When relatively few points are used to fit the plane, lineaments of various lengths are observed and a mechanism for lineament classification is described. An area encompassing the gold deposits of the Carlin trend and including the Rain in the southeast to Midas in the northwest is investigated in greater detail. The orientation and density of lineaments may be determined on the gently sloping pediment surface as well as in the more steeply sloping ranges.

  7. First experiments results about the engineering model of Rapsodie

    International Nuclear Information System (INIS)

    Chalot, A.; Ginier, R.; Sauvage, M.

    1964-01-01

    This report deals with the first series of experiments carried out on the engineering model of Rapsodie and on an associated sodium facility set in a laboratory hall of Cadarache. It conveys more precisely: 1/ - The difficulties encountered during the erection and assembly of the engineering model and a compilation of the results of the first series of experiments and tests carried out on this installation (loading of the subassemblies preheating, thermal chocks...). 2/ - The experiments and tests carried out on the two prototypes control rod drive mechanisms which brought to the choice for the design of the definitive drive mechanism. As a whole, the results proved the validity of the general design principles adopted for Rapsodie. (authors) [fr

  8. Meteorological uncertainty of atmospheric dispersion model results (MUD)

    Energy Technology Data Exchange (ETDEWEB)

    Havskov Soerensen, J.; Amstrup, B.; Feddersen, H. [Danish Meteorological Institute, Copenhagen (Denmark)] [and others

    2013-08-15

    The MUD project addresses assessment of uncertainties of atmospheric dispersion model predictions, as well as possibilities for optimum presentation to decision makers. Previously, it has not been possible to estimate such uncertainties quantitatively, but merely to calculate the 'most likely' dispersion scenario. However, recent developments in numerical weather prediction (NWP) include probabilistic forecasting techniques, which can be utilised also for long-range atmospheric dispersion models. The ensemble statistical methods developed and applied to NWP models aim at describing the inherent uncertainties of the meteorological model results. These uncertainties stem from e.g. limits in meteorological observations used to initialise meteorological forecast series. By perturbing e.g. the initial state of an NWP model run in agreement with the available observational data, an ensemble of meteorological forecasts is produced from which uncertainties in the various meteorological parameters are estimated, e.g. probabilities for rain. Corresponding ensembles of atmospheric dispersion can now be computed from which uncertainties of predicted radionuclide concentration and deposition patterns can be derived. (Author)

  9. Meteorological uncertainty of atmospheric dispersion model results (MUD)

    International Nuclear Information System (INIS)

    Havskov Soerensen, J.; Amstrup, B.; Feddersen, H.

    2013-08-01

    The MUD project addresses assessment of uncertainties of atmospheric dispersion model predictions, as well as possibilities for optimum presentation to decision makers. Previously, it has not been possible to estimate such uncertainties quantitatively, but merely to calculate the 'most likely' dispersion scenario. However, recent developments in numerical weather prediction (NWP) include probabilistic forecasting techniques, which can be utilised also for long-range atmospheric dispersion models. The ensemble statistical methods developed and applied to NWP models aim at describing the inherent uncertainties of the meteorological model results. These uncertainties stem from e.g. limits in meteorological observations used to initialise meteorological forecast series. By perturbing e.g. the initial state of an NWP model run in agreement with the available observational data, an ensemble of meteorological forecasts is produced from which uncertainties in the various meteorological parameters are estimated, e.g. probabilities for rain. Corresponding ensembles of atmospheric dispersion can now be computed from which uncertainties of predicted radionuclide concentration and deposition patterns can be derived. (Author)

  10. Acoustic results of the Boeing model 360 whirl tower test

    Science.gov (United States)

    Watts, Michael E.; Jordan, David

    1990-09-01

    An evaluation is presented for whirl tower test results of the Model 360 helicopter's advanced, high-performance four-bladed composite rotor system intended to facilitate over-200-knot flight. During these performance measurements, acoustic data were acquired by seven microphones. A comparison of whirl-tower tests with theory indicate that theoretical prediction accuracies vary with both microphone position and the inclusion of ground reflection. Prediction errors varied from 0 to 40 percent of the measured signal-to-peak amplitude.

  11. Exact results for the one dimensional asymmetric exclusion model

    International Nuclear Information System (INIS)

    Derrida, B.; Evans, M.R.; Pasquier, V.

    1993-01-01

    The asymmetric exclusion model describes a system of particles hopping in a preferred direction with hard core repulsion. These particles can be thought of as charged particles in a field, as steps of an interface, as cars in a queue. Several exact results concerning the steady state of this system have been obtained recently. The solution consists of representing the weights of the configurations in the steady state as products of non-commuting matrices. (author)

  12. Review of Current Standard Model Results in ATLAS

    CERN Document Server

    Brandt, Gerhard; The ATLAS collaboration

    2018-01-01

    This talk highlights results selected from the Standard Model research programme of the ATLAS Collaboration at the Large Hadron Collider. Results using data from $p-p$ collisions at $\\sqrt{s}=7,8$~TeV in LHC Run-1 as well as results using data at $\\sqrt{s}=13$~TeV in LHC Run-2 are covered. The status of cross section measurements from soft QCD processes and jet production as well as photon production are presented. The presentation extends to vector boson production with associated jets. Precision measurements of the production of $W$ and $Z$ bosons, including a first measurement of the mass of the $W$ bosons, $m_W$, are discussed. The programme to measure electroweak processes with di-boson and tri-boson final states is outlined. All presented measurements are compatible with Standard Model descriptions and allow to further constrain it. In addition they allow to probe new physics which would manifest through extra gauge couplings, or Standard Model gauge couplings deviating from their predicted value.

  13. A whole-body model for glycogen regulation reveals a critical role for substrate cycling in maintaining blood glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Xu

    2011-12-01

    Full Text Available Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into "whole-body" contextual models that mimic in vivo conditions.

  14. Comparison of transient PCRV model test results with analysis

    International Nuclear Information System (INIS)

    Marchertas, A.H.; Belytschko, T.B.

    1979-01-01

    Comparisons are made of transient data derived from simple models of a reactor containment vessel with analytical solutions. This effort is a part of the ongoing process of development and testing of the DYNAPCON computer code. The test results used in these comparisons were obtained from scaled models of the British sodium cooled fast breeder program. The test structure is a scaled model of a cylindrically shaped reactor containment vessel made of concrete. This concrete vessel is prestressed axially by holddown bolts spanning the top and bottom slabs along the cylindrical walls, and is also prestressed circumferentially by a number of cables wrapped around the vessel. For test purposes this containment vessel is partially filled with water, which comes in direct contact with the vessel walls. The explosive charge is immersed in the pool of water and is centrally suspended from the top of the vessel. The load history was obtained from an ICECO analysis, using the equations of state for the source and the water. A detailed check of this solution was made to assure that the derived loading did provide the correct input. The DYNAPCON code was then used for the analysis of the prestressed concrete containment model. This analysis required the simulation of prestressing and the response of the model to the applied transient load. The calculations correctly predict the magnitudes of displacements of the PCRV model. In addition, the displacement time histories obtained from the calculations reproduce the general features of the experimental records: the period elongation and amplitude increase as compared to an elastic solution, and also the absence of permanent displacement. However, the period still underestimates the experiment, while the amplitude is generally somewhat large

  15. Thermal-Chemical Model Of Subduction: Results And Tests

    Science.gov (United States)

    Gorczyk, W.; Gerya, T. V.; Connolly, J. A.; Yuen, D. A.; Rudolph, M.

    2005-12-01

    Seismic structures with strong positive and negative velocity anomalies in the mantle wedge above subduction zones have been interpreted as thermally and/or chemically induced phenomena. We have developed a thermal-chemical model of subduction, which constrains the dynamics of seismic velocity structure beneath volcanic arcs. Our simulations have been calculated over a finite-difference grid with (201×101) to (201×401) regularly spaced Eulerian points, using 0.5 million to 10 billion markers. The model couples numerical thermo-mechanical solution with Gibbs energy minimization to investigate the dynamic behavior of partially molten upwellings from slabs (cold plumes) and structures associated with their development. The model demonstrates two chemically distinct types of plumes (mixed and unmixed), and various rigid body rotation phenomena in the wedge (subduction wheel, fore-arc spin, wedge pin-ball). These thermal-chemical features strongly perturb seismic structure. Their occurrence is dependent on the age of subducting slab and the rate of subduction.The model has been validated through a series of test cases and its results are consistent with a variety of geological and geophysical data. In contrast to models that attribute a purely thermal origin for mantle wedge seismic anomalies, the thermal-chemical model is able to simulate the strong variations of seismic velocity existing beneath volcanic arcs which are associated with development of cold plumes. In particular, molten regions that form beneath volcanic arcs as a consequence of vigorous cold wet plumes are manifest by > 20% variations in the local Poisson ratio, as compared to variations of ~ 2% expected as a consequence of temperature variation within the mantle wedge.

  16. Integrative demographic modeling reveals population level impacts of PCB toxicity to juvenile snapping turtles

    International Nuclear Information System (INIS)

    Salice, Christopher J.; Rowe, Christopher L.; Eisenreich, Karen M.

    2014-01-01

    A significant challenge in ecotoxicology and risk assessment lies in placing observed contaminant effects in a meaningful ecological context. Polychlorinated biphenyls (PCBs) have been shown to affect juvenile snapping turtle survival and growth but the ecological significance of these effects is difficult to discern without a formal, population-level assessment. We used a demographic matrix model to explore the potential population-level effects of PCBs on turtles. Our model showed that effects of PCBs on juvenile survival, growth and size at hatching could translate to negative effects at the population level despite the fact that these life cycle components do not typically contribute strongly to population level processes. This research points to the utility of using integrative demographic modeling approaches to better understand contaminant effects in wildlife. The results indicate that population-level effects are only evident after several years, suggesting that for long-lived species, detecting adverse contaminant effects could prove challenging. -- Highlights: • Previous studies have shown the PCBs can impact juvenile snapping turtles. • We used a demographic model of turtles to evaluate population-level PCB effects. • PCB effects on turtles may translate to negative population responses. • Long-term monitoring is needed to detect contaminant effects on natural turtle populations. • Demographic models can improve our understanding contaminant ecotoxicity. -- A demographic model was used to show that PCB induced effects on young snapping turtles can result in adverse effects at the population level

  17. Reduced ENSO Variability at the LGM Revealed by an Isotope-Enabled Earth System Model

    Science.gov (United States)

    Zhu, Jiang; Liu, Zhengyu; Brady, Esther; Otto-Bliesner, Bette; Zhang, Jiaxu; Noone, David; Tomas, Robert; Nusbaumer, Jesse; Wong, Tony; Jahn, Alexandra; hide

    2017-01-01

    Studying the El Nino Southern Oscillation (ENSO) in the past can help us better understand its dynamics and improve its future projections. However, both paleoclimate reconstructions and model simulations of ENSO strength at the Last Glacial Maximum (LGM; 21 ka B.P.) have led to contradicting results. Here we perform model simulations using the recently developed water isotope-enabled Community Earth System Model (iCESM). For the first time, model-simulated oxygen isotopes are directly compared with those from ENSO reconstructions using the individual foraminifera analysis (IFA). We find that the LGM ENSO is most likely weaker comparing with the preindustrial. The iCESM suggests that total variance of the IFA records may only reflect changes in the annual cycle instead of ENSO variability as previously assumed. Furthermore, the interpretation of subsurface IFA records can be substantially complicated by the habitat depth of thermocline-dwelling foraminifera and their vertical migration with a temporally varying thermocline.

  18. Effective Connectivity Reveals Right-Hemisphere Dominance in Audiospatial Perception: Implications for Models of Spatial Neglect

    Science.gov (United States)

    Friston, Karl J.; Mattingley, Jason B.; Roepstorff, Andreas; Garrido, Marta I.

    2014-01-01

    Detecting the location of salient sounds in the environment rests on the brain's ability to use differences in sounds arriving at both ears. Functional neuroimaging studies in humans indicate that the left and right auditory hemispaces are coded asymmetrically, with a rightward attentional bias that reflects spatial attention in vision. Neuropsychological observations in patients with spatial neglect have led to the formulation of two competing models: the orientation bias and right-hemisphere dominance models. The orientation bias model posits a symmetrical mapping between one side of the sensorium and the contralateral hemisphere, with mutual inhibition of the ipsilateral hemisphere. The right-hemisphere dominance model introduces a functional asymmetry in the brain's coding of space: the left hemisphere represents the right side, whereas the right hemisphere represents both sides of the sensorium. We used Dynamic Causal Modeling of effective connectivity and Bayesian model comparison to adjudicate between these alternative network architectures, based on human electroencephalographic data acquired during an auditory location oddball paradigm. Our results support a hemispheric asymmetry in a frontoparietal network that conforms to the right-hemisphere dominance model. We show that, within this frontoparietal network, forward connectivity increases selectively in the hemisphere contralateral to the side of sensory stimulation. We interpret this finding in light of hierarchical predictive coding as a selective increase in attentional gain, which is mediated by feedforward connections that carry precision-weighted prediction errors during perceptual inference. This finding supports the disconnection hypothesis of unilateral neglect and has implications for theories of its etiology. PMID:24695717

  19. Measurement model choice influenced randomized controlled trial results.

    Science.gov (United States)

    Gorter, Rosalie; Fox, Jean-Paul; Apeldoorn, Adri; Twisk, Jos

    2016-11-01

    In randomized controlled trials (RCTs), outcome variables are often patient-reported outcomes measured with questionnaires. Ideally, all available item information is used for score construction, which requires an item response theory (IRT) measurement model. However, in practice, the classical test theory measurement model (sum scores) is mostly used, and differences between response patterns leading to the same sum score are ignored. The enhanced differentiation between scores with IRT enables more precise estimation of individual trajectories over time and group effects. The objective of this study was to show the advantages of using IRT scores instead of sum scores when analyzing RCTs. Two studies are presented, a real-life RCT, and a simulation study. Both IRT and sum scores are used to measure the construct and are subsequently used as outcomes for effect calculation. The bias in RCT results is conditional on the measurement model that was used to construct the scores. A bias in estimated trend of around one standard deviation was found when sum scores were used, where IRT showed negligible bias. Accurate statistical inferences are made from an RCT study when using IRT to estimate construct measurements. The use of sum scores leads to incorrect RCT results. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Local-scale models reveal ecological niche variability in amphibian and reptile communities from two contrasting biogeographic regions

    Directory of Open Access Journals (Sweden)

    Alberto Muñoz

    2016-10-01

    Full Text Available Ecological Niche Models (ENMs are widely used to describe how environmental factors influence species distribution. Modelling at a local scale, compared to a large scale within a high environmental gradient, can improve our understanding of ecological species niches. The main goal of this study is to assess and compare the contribution of environmental variables to amphibian and reptile ENMs in two Spanish national parks located in contrasting biogeographic regions, i.e., the Mediterranean and the Atlantic area. The ENMs were built with maximum entropy modelling using 11 environmental variables in each territory. The contributions of these variables to the models were analysed and classified using various statistical procedures (Mann–Whitney U tests, Principal Components Analysis and General Linear Models. Distance to the hydrological network was consistently the most relevant variable for both parks and taxonomic classes. Topographic variables (i.e., slope and altitude were the second most predictive variables, followed by climatic variables. Differences in variable contribution were observed between parks and taxonomic classes. Variables related to water availability had the larger contribution to the models in the Mediterranean park, while topography variables were decisive in the Atlantic park. Specific response curves to environmental variables were in accordance with the biogeographic affinity of species (Mediterranean and non-Mediterranean species and taxonomy (amphibians and reptiles. Interestingly, these results were observed for species located in both parks, particularly those situated at their range limits. Our findings show that ecological niche models built at local scale reveal differences in habitat preferences within a wide environmental gradient. Therefore, modelling at local scales rather than assuming large-scale models could be preferable for the establishment of conservation strategies for herptile species in natural

  1. Local-scale models reveal ecological niche variability in amphibian and reptile communities from two contrasting biogeographic regions

    Science.gov (United States)

    Santos, Xavier; Felicísimo, Ángel M.

    2016-01-01

    Ecological Niche Models (ENMs) are widely used to describe how environmental factors influence species distribution. Modelling at a local scale, compared to a large scale within a high environmental gradient, can improve our understanding of ecological species niches. The main goal of this study is to assess and compare the contribution of environmental variables to amphibian and reptile ENMs in two Spanish national parks located in contrasting biogeographic regions, i.e., the Mediterranean and the Atlantic area. The ENMs were built with maximum entropy modelling using 11 environmental variables in each territory. The contributions of these variables to the models were analysed and classified using various statistical procedures (Mann–Whitney U tests, Principal Components Analysis and General Linear Models). Distance to the hydrological network was consistently the most relevant variable for both parks and taxonomic classes. Topographic variables (i.e., slope and altitude) were the second most predictive variables, followed by climatic variables. Differences in variable contribution were observed between parks and taxonomic classes. Variables related to water availability had the larger contribution to the models in the Mediterranean park, while topography variables were decisive in the Atlantic park. Specific response curves to environmental variables were in accordance with the biogeographic affinity of species (Mediterranean and non-Mediterranean species) and taxonomy (amphibians and reptiles). Interestingly, these results were observed for species located in both parks, particularly those situated at their range limits. Our findings show that ecological niche models built at local scale reveal differences in habitat preferences within a wide environmental gradient. Therefore, modelling at local scales rather than assuming large-scale models could be preferable for the establishment of conservation strategies for herptile species in natural parks. PMID

  2. SR-Site groundwater flow modelling methodology, setup and results

    International Nuclear Information System (INIS)

    Selroos, Jan-Olof; Follin, Sven

    2010-12-01

    As a part of the license application for a final repository for spent nuclear fuel at Forsmark, the Swedish Nuclear Fuel and Waste Management Company (SKB) has undertaken three groundwater flow modelling studies. These are performed within the SR-Site project and represent time periods with different climate conditions. The simulations carried out contribute to the overall evaluation of the repository design and long-term radiological safety. Three time periods are addressed; the Excavation and operational phases, the Initial period of temperate climate after closure, and the Remaining part of the reference glacial cycle. The present report is a synthesis of the background reports describing the modelling methodology, setup, and results. It is the primary reference for the conclusions drawn in a SR-Site specific context concerning groundwater flow during the three climate periods. These conclusions are not necessarily provided explicitly in the background reports, but are based on the results provided in these reports. The main results and comparisons presented in the present report are summarised in the SR-Site Main report

  3. Geochemical controls on shale groundwaters: Results of reaction path modeling

    International Nuclear Information System (INIS)

    Von Damm, K.L.; VandenBrook, A.J.

    1989-03-01

    The EQ3NR/EQ6 geochemical modeling code was used to simulate the reaction of several shale mineralogies with different groundwater compositions in order to elucidate changes that may occur in both the groundwater compositions, and rock mineralogies and compositions under conditions which may be encountered in a high-level radioactive waste repository. Shales with primarily illitic or smectitic compositions were the focus of this study. The reactions were run at the ambient temperatures of the groundwaters and to temperatures as high as 250/degree/C, the approximate temperature maximum expected in a repository. All modeling assumed that equilibrium was achieved and treated the rock and water assemblage as a closed system. Graphite was used as a proxy mineral for organic matter in the shales. The results show that the presence of even a very small amount of reducing mineral has a large influence on the redox state of the groundwaters, and that either pyrite or graphite provides essentially the same results, with slight differences in dissolved C, Fe and S concentrations. The thermodynamic data base is inadequate at the present time to fully evaluate the speciation of dissolved carbon, due to the paucity of thermodynamic data for organic compounds. In the illitic cases the groundwaters resulting from interaction at elevated temperatures are acid, while the smectitic cases remain alkaline, although the final equilibrium mineral assemblages are quite similar. 10 refs., 8 figs., 15 tabs

  4. Loss of spent fuel pool cooling PRA: Model and results

    International Nuclear Information System (INIS)

    Siu, N.; Khericha, S.; Conroy, S.; Beck, S.; Blackman, H.

    1996-09-01

    This letter report documents models for quantifying the likelihood of loss of spent fuel pool cooling; models for identifying post-boiling scenarios that lead to core damage; qualitative and quantitative results generated for a selected plant that account for plant design and operational practices; a comparison of these results and those generated from earlier studies; and a review of available data on spent fuel pool accidents. The results of this study show that for a representative two-unit boiling water reactor, the annual probability of spent fuel pool boiling is 5 x 10 -5 and the annual probability of flooding associated with loss of spent fuel pool cooling scenarios is 1 x 10 -3 . Qualitative arguments are provided to show that the likelihood of core damage due to spent fuel pool boiling accidents is low for most US commercial nuclear power plants. It is also shown that, depending on the design characteristics of a given plant, the likelihood of either: (a) core damage due to spent fuel pool-associated flooding, or (b) spent fuel damage due to pool dryout, may not be negligible

  5. SR-Site groundwater flow modelling methodology, setup and results

    Energy Technology Data Exchange (ETDEWEB)

    Selroos, Jan-Olof (Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden)); Follin, Sven (SF GeoLogic AB, Taeby (Sweden))

    2010-12-15

    As a part of the license application for a final repository for spent nuclear fuel at Forsmark, the Swedish Nuclear Fuel and Waste Management Company (SKB) has undertaken three groundwater flow modelling studies. These are performed within the SR-Site project and represent time periods with different climate conditions. The simulations carried out contribute to the overall evaluation of the repository design and long-term radiological safety. Three time periods are addressed; the Excavation and operational phases, the Initial period of temperate climate after closure, and the Remaining part of the reference glacial cycle. The present report is a synthesis of the background reports describing the modelling methodology, setup, and results. It is the primary reference for the conclusions drawn in a SR-Site specific context concerning groundwater flow during the three climate periods. These conclusions are not necessarily provided explicitly in the background reports, but are based on the results provided in these reports. The main results and comparisons presented in the present report are summarised in the SR-Site Main report.

  6. Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

    Science.gov (United States)

    2013-01-01

    Background Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1-/Δ progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. Results In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1-/Δ mice showed cluster formation between young WT and Ercc1-/Δ as well as old WT and Ercc1-/Δ samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1-/Δ mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1-/Δ mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies. PMID:23947592

  7. Sexually dimorphic distribution of Prokr2 neurons revealed by the Prokr2-Cre mouse model.

    Science.gov (United States)

    Mohsen, Zaid; Sim, Hosung; Garcia-Galiano, David; Han, Xingfa; Bellefontaine, Nicole; Saunders, Thomas L; Elias, Carol F

    2017-12-01

    Prokineticin receptor 2 (PROKR2) is predominantly expressed in the mammalian central nervous system. Loss-of-function mutations of PROKR2 in humans are associated with Kallmann syndrome due to the disruption of gonadotropin releasing hormone neuronal migration and deficient olfactory bulb morphogenesis. PROKR2 has been also implicated in the neuroendocrine control of GnRH neurons post-migration and other physiological systems. However, the brain circuitry and mechanisms associated with these actions have been difficult to investigate mainly due to the widespread distribution of Prokr2-expressing cells, and the lack of animal models and molecular tools. Here, we describe the generation, validation and characterization of a new mouse model that expresses Cre recombinase driven by the Prokr2 promoter, using CRISPR-Cas9 technology. Cre expression was visualized using reporter genes, tdTomato and GFP, in males and females. Expression of Cre-induced reporter genes was found in brain sites previously described to express Prokr2, e.g., the paraventricular and the suprachiasmatic nuclei, and the area postrema. The Prokr2-Cre mouse model was further validated by colocalization of Cre-induced GFP and Prokr2 mRNA. No disruption of Prokr2 expression, GnRH neuronal migration or fertility was observed. Comparative analysis of Prokr2-Cre expression in male and female brains revealed a sexually dimorphic distribution confirmed by in situ hybridization. In females, higher Cre activity was found in the medial preoptic area, ventromedial nucleus of the hypothalamus, arcuate nucleus, medial amygdala and lateral parabrachial nucleus. In males, Cre was higher in the amygdalo-hippocampal area. The sexually dimorphic pattern of Prokr2 expression indicates differential roles in reproductive function and, potentially, in other physiological systems.

  8. Results of the benchmark for blade structural models, part A

    DEFF Research Database (Denmark)

    Lekou, D.J.; Chortis, D.; Belen Fariñas, A.

    2013-01-01

    A benchmark on structural design methods for blades was performed within the InnWind.Eu project under WP2 “Lightweight Rotor” Task 2.2 “Lightweight structural design”. The present document is describes the results of the comparison simulation runs that were performed by the partners involved within...... Task 2.2 of the InnWind.Eu project. The benchmark is based on the reference wind turbine and the reference blade provided by DTU [1]. "Structural Concept developers/modelers" of WP2 were provided with the necessary input for a comparison numerical simulation run, upon definition of the reference blade...

  9. Preliminary results of steel containment vessel model test

    International Nuclear Information System (INIS)

    Matsumoto, T.; Komine, K.; Arai, S.

    1997-01-01

    A high pressure test of a mixed-scaled model (1:10 in geometry and 1:4 in shell thickness) of a steel containment vessel (SCV), representing an improved boiling water reactor (BWR) Mark II containment, was conducted on December 11-12, 1996 at Sandia National Laboratories. This paper describes the preliminary results of the high pressure test. In addition, the preliminary post-test measurement data and the preliminary comparison of test data with pretest analysis predictions are also presented

  10. Results of the ITER toroidal field model coil project

    International Nuclear Information System (INIS)

    Salpietro, E.; Maix, R.

    2001-01-01

    In the scope of the ITER EDA one of the seven largest projects was devoted to the development, manufacture and testing of a Toroidal Field Model Coil (TFMC). The industry consortium AGAN manufactured the TFMC based on on a conceptual design developed by the ITER EDA EU Home Team. The TFMC was completed and assembled in the test facility TOSKA of the Forschungszentrum Karlsruhe in the first half of 2001. The first testing phase started in June 2001 and lasted till October 2001. The first results have shown that the main goals of the project have been achieved

  11. Opacity and Transport Measurements Reveal That Dilute Plasma Models of Sonoluminescence Are Not Valid

    Science.gov (United States)

    Khalid, Shahzad; Kappus, Brian; Weninger, Keith; Putterman, Seth

    2012-03-01

    A strong interaction between a nanosecond laser and a 70 μm radius sonoluminescing plasma is achieved. The overall response of the system results in a factor of 2 increase in temperature as determined by its spectrum. Images of the interaction reveal that light energy is absorbed and trapped in a region smaller than the sonoluminescence emitting region of the bubble for over 100 ns. We interpret this opacity and transport measurement as demonstrating that sonoluminescencing bubbles can be 1000 times more opaque than what follows from the Saha equation of statistical mechanics in the ideal plasma limit. To address this discrepancy, we suggest that the effects of strong Coulomb interactions are an essential component of a first principles theory of sonoluminescence.

  12. PhyloChip microarray analysis reveals altered gastrointestinal microbial communities in a rat model of colonic hypersensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, T.A.; Holmes, S.; Alekseyenko, A.V.; Shenoy, M.; DeSantis, T.; Wu, C.H.; Andersen, G.L.; Winston, J.; Sonnenburg, J.; Pasricha, P.J.; Spormann, A.

    2010-12-01

    Irritable bowel syndrome (IBS) is a chronic, episodic gastrointestinal disorder that is prevalent in a significant fraction of western human populations; and changes in the microbiota of the large bowel have been implicated in the pathology of the disease. Using a novel comprehensive, high-density DNA microarray (PhyloChip) we performed a phylogenetic analysis of the microbial community of the large bowel in a rat model in which intracolonic acetic acid in neonates was used to induce long lasting colonic hypersensitivity and decreased stool water content and frequency, representing the equivalent of human constipation-predominant IBS. Our results revealed a significantly increased compositional difference in the microbial communities in rats with neonatal irritation as compared with controls. Even more striking was the dramatic change in the ratio of Firmicutes relative to Bacteroidetes, where neonatally irritated rats were enriched more with Bacteroidetes and also contained a different composition of species within this phylum. Our study also revealed differences at the level of bacterial families and species. The PhyloChip is a useful and convenient method to study enteric microflora. Further, this rat model system may be a useful experimental platform to study the causes and consequences of changes in microbial community composition associated with IBS.

  13. Comparison of transient PCRV model test results with analysis

    International Nuclear Information System (INIS)

    Marchertas, A.H.; Belytschko, T.B.

    1979-01-01

    Comparisons are made of transient data derived from simple models of a reactor containment vessel with analytical solutions. This effort is a part of the ongoing process of development and testing of the DYNAPCON computer code. The test results used in these comparisons were obtained from scaled models of the British sodium cooled fast breeder program. The test structure is a scaled model of a cylindrically shaped reactor containment vessel made of concrete. This concrete vessel is prestressed axially by holddown bolts spanning the top and bottom slabs along the cylindrical walls, and is also prestressed circumferentially by a number of cables wrapped around the vessel. For test purposes this containment vessel is partially filled with water, which comes in direct contact with the vessel walls. The explosive charge is immersed in the pool of water and is centrally suspended from the top of the vessel. The tests are very similar to the series of tests made for the COVA experimental program, but the vessel here is the prestressed concrete container. (orig.)

  14. INTRAVAL Finnsjoen Test - modelling results for some tracer experiments

    International Nuclear Information System (INIS)

    Jakob, A.; Hadermann, J.

    1994-09-01

    This report presents the results within Phase II of the INTRAVAL study. Migration experiments performed at the Finnsjoen test site were investigated. The study was done to gain an improved understanding of not only the mechanisms of tracer transport, but also the accuracy and limitations of the model used. The model is based on the concept of a dual porosity medium, taking into account one dimensional advection, longitudinal dispersion, sorption onto the fracture surfaces, diffusion into connected pores of the matrix rock, and sorption onto matrix surfaces. The number of independent water carrying zones, represented either as planar fractures or tubelike veins, may be greater than one, and the sorption processes are described either by linear or non-linear Freundlich isotherms assuming instantaneous sorption equilibrium. The diffusion of the tracer out of the water-carrying zones into connected pore space of the adjacent rock is calculated perpendicular to the direction of the advective/dispersive flow. In the analysis, the fluid flow parameters are calibrated by the measured breakthrough curves for the conservative tracer (iodide). Subsequent fits to the experimental data for the two sorbing tracers strontium and cesium then involve element dependent parameters providing information on the sorption processes and on its representation in the model. The methodology of fixing all parameters except those for sorption with breakthrough curves for non-sorbing tracers generally worked well. The investigation clearly demonstrates the necessity of taking into account pump flow rate variations at both boundaries. If this is not done, reliable conclusions on transport mechanisms or geometrical factors can not be achieved. A two flow path model reproduces the measured data much better than a single flow path concept. (author) figs., tabs., 26 refs

  15. Portfolio Effects of Renewable Energies - Basics, Models, Exemplary Results

    Energy Technology Data Exchange (ETDEWEB)

    Wiese, Andreas; Herrmann, Matthias

    2007-07-01

    The combination of sites and technologies to so-called renewable energy portfolios, which are being developed and implemented under the same financing umbrella, is currently the subject of intense discussion in the finance world. The resulting portfolio effect may allow the prediction of a higher return with the same risk or the same return with a lower risk - always in comparison with the investment in a single project. Models are currently being developed to analyse this subject and derive the portfolio effect. In particular, the effect of the spatial distribution, as well as the effects of using different technologies, suppliers and cost assumptions with different level of uncertainties, are of importance. Wind parks, photovoltaic, biomass, biogas and hydropower are being considered. The status of the model development and first results are being presented in the current paper. In a first example, the portfolio effect has been calculated and analysed using selected parameters for a wind energy portfolio of 39 sites distributed over Europe. Consequently it has been shown that the predicted yield, with the predetermined probabilities between 75 to 90%, is 3 - 8% higher than the sum of the yields for the individual wind parks using the same probabilities. (auth)

  16. Results and Error Estimates from GRACE Forward Modeling over Antarctica

    Science.gov (United States)

    Bonin, Jennifer; Chambers, Don

    2013-04-01

    Forward modeling using a weighted least squares technique allows GRACE information to be projected onto a pre-determined collection of local basins. This decreases the impact of spatial leakage, allowing estimates of mass change to be better localized. The technique is especially valuable where models of current-day mass change are poor, such as over Antarctica. However when tested previously, the least squares technique has required constraints in the form of added process noise in order to be reliable. Poor choice of local basin layout has also adversely affected results, as has the choice of spatial smoothing used with GRACE. To develop design parameters which will result in correct high-resolution mass detection and to estimate the systematic errors of the method over Antarctica, we use a "truth" simulation of the Antarctic signal. We apply the optimal parameters found from the simulation to RL05 GRACE data across Antarctica and the surrounding ocean. We particularly focus on separating the Antarctic peninsula's mass signal from that of the rest of western Antarctica. Additionally, we characterize how well the technique works for removing land leakage signal from the nearby ocean, particularly that near the Drake Passage.

  17. Some exact results for the three-layer Zamolodchikov model

    International Nuclear Information System (INIS)

    Boos, H.E.; Mangazeev, V.V.

    2001-01-01

    In this paper we continue the study of the three-layer Zamolodchikov model started in our previous works (H.E. Boos, V.V. Mangazeev, J. Phys. A 32 (1999) 3041-3054 and H.E. Boos, V.V. Mangazeev, J. Phys. A 32 (1999) 5285-5298). We analyse numerically the solutions to the Bethe ansatz equations obtained in H.E. Boos, V.V. Mangazeev, J. Phys. A 32 (1999) 5285-5298. We consider two regimes I and II which differ by the signs of the spherical sides (a 1 ,a 2 ,a 3 )→(-a 1 ,-a 2 ,-a 3 ). We accept the two-line hypothesis for the regime I and the one-line hypothesis for the regime II. In the thermodynamic limit we derive integral equations for distribution densities and solve them exactly. We calculate the partition function for the three-layer Zamolodchikov model and check a compatibility of this result with the functional relations obtained in H.E. Boos, V.V. Mangazeev, J. Phys. A 32 (1999) 5285-5298. We also do some numeric checkings of our results

  18. Preliminary time-phased TWRS process model results

    International Nuclear Information System (INIS)

    Orme, R.M.

    1995-01-01

    This report documents the first phase of efforts to model the retrieval and processing of Hanford tank waste within the constraints of an assumed tank farm configuration. This time-phased approach simulates a first try at a retrieval sequence, the batching of waste through retrieval facilities, the batching of retrieved waste through enhanced sludge washing, the batching of liquids through pretreatment and low-level waste (LLW) vitrification, and the batching of pretreated solids through high-level waste (HLW) vitrification. The results reflect the outcome of an assumed retrieval sequence that has not been tailored with respect to accepted measures of performance. The batch data, composition variability, and final waste volume projects in this report should be regarded as tentative. Nevertheless, the results provide interesting insights into time-phased processing of the tank waste. Inspection of the composition variability, for example, suggests modifications to the retrieval sequence that will further improve the uniformity of feed to the vitrification facilities. This model will be a valuable tool for evaluating suggested retrieval sequences and establishing a time-phased processing baseline. An official recommendation on tank retrieval sequence will be made in September, 1995

  19. Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during Plasmodium falciparum invasion of erythrocytes.

    Directory of Open Access Journals (Sweden)

    Greta E Weiss

    2015-02-01

    Full Text Available During blood stage Plasmodium falciparum infection, merozoites invade uninfected erythrocytes via a complex, multistep process involving a series of distinct receptor-ligand binding events. Understanding each element in this process increases the potential to block the parasite's life cycle via drugs or vaccines. To investigate specific receptor-ligand interactions, they were systematically blocked using a combination of genetic deletion, enzymatic receptor cleavage and inhibition of binding via antibodies, peptides and small molecules, and the resulting temporal changes in invasion and morphological effects on erythrocytes were filmed using live cell imaging. Analysis of the videos have shown receptor-ligand interactions occur in the following sequence with the following cellular morphologies; 1 an early heparin-blockable interaction which weakly deforms the erythrocyte, 2 EBA and PfRh ligands which strongly deform the erythrocyte, a process dependant on the merozoite's actin-myosin motor, 3 a PfRh5-basigin binding step which results in a pore or opening between parasite and host through which it appears small molecules and possibly invasion components can flow and 4 an AMA1-RON2 interaction that mediates tight junction formation, which acts as an anchor point for internalization. In addition to enhancing general knowledge of apicomplexan biology, this work provides a rational basis to combine sequentially acting merozoite vaccine candidates in a single multi-receptor-blocking vaccine.

  20. Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging.

    Science.gov (United States)

    Schermer, Bernhard; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Braun, Fabian; Schultze, Joachim L; Roodbergen, Marianne; Hoeijmakers, Jan Hj; Schumacher, Björn; Nürnberg, Peter; Dollé, Martijn Et; Benzing, Thomas; Müller, Roman-Ulrich; Kurschat, Christine E

    2013-08-16

    Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1(-/Δ) progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1(-/Δ) mice showed cluster formation between young WT and Ercc1(-/Δ) as well as old WT and Ercc1(-/Δ) samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1(-/Δ) mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1(-/Δ) mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies.

  1. Fourier decomposition of spatial localization errors reveals an idiotropic dominance of an internal model of gravity.

    Science.gov (United States)

    De Sá Teixeira, Nuno Alexandre

    2014-12-01

    Given its conspicuous nature, gravity has been acknowledged by several research lines as a prime factor in structuring the spatial perception of one's environment. One such line of enquiry has focused on errors in spatial localization aimed at the vanishing location of moving objects - it has been systematically reported that humans mislocalize spatial positions forward, in the direction of motion (representational momentum) and downward in the direction of gravity (representational gravity). Moreover, spatial localization errors were found to evolve dynamically with time in a pattern congruent with an anticipated trajectory (representational trajectory). The present study attempts to ascertain the degree to which vestibular information plays a role in these phenomena. Human observers performed a spatial localization task while tilted to varying degrees and referring to the vanishing locations of targets moving along several directions. A Fourier decomposition of the obtained spatial localization errors revealed that although spatial errors were increased "downward" mainly along the body's longitudinal axis (idiotropic dominance), the degree of misalignment between the latter and physical gravity modulated the time course of the localization responses. This pattern is surmised to reflect increased uncertainty about the internal model when faced with conflicting cues regarding the perceived "downward" direction.

  2. Multilayer Stochastic Block Models Reveal the Multilayer Structure of Complex Networks

    Directory of Open Access Journals (Sweden)

    Toni Vallès-Català

    2016-03-01

    Full Text Available In complex systems, the network of interactions we observe between systems components is the aggregate of the interactions that occur through different mechanisms or layers. Recent studies reveal that the existence of multiple interaction layers can have a dramatic impact in the dynamical processes occurring on these systems. However, these studies assume that the interactions between systems components in each one of the layers are known, while typically for real-world systems we do not have that information. Here, we address the issue of uncovering the different interaction layers from aggregate data by introducing multilayer stochastic block models (SBMs, a generalization of single-layer SBMs that considers different mechanisms of layer aggregation. First, we find the complete probabilistic solution to the problem of finding the optimal multilayer SBM for a given aggregate-observed network. Because this solution is computationally intractable, we propose an approximation that enables us to verify that multilayer SBMs are more predictive of network structure in real-world complex systems.

  3. Graph and model transformation tools for model migration : empirical results from the transformation tool contest

    NARCIS (Netherlands)

    Rose, L.M.; Herrmannsdoerfer, M.; Mazanek, S.; Van Gorp, P.M.E.; Buchwald, S.; Horn, T.; Kalnina, E.; Koch, A.; Lano, K.; Schätz, B.; Wimmer, M.

    2014-01-01

    We describe the results of the Transformation Tool Contest 2010 workshop, in which nine graph and model transformation tools were compared for specifying model migration. The model migration problem—migration of UML activity diagrams from version 1.4 to version 2.2—is non-trivial and practically

  4. Negative differential mobility for negative carriers as revealed by space charge measurements on crosslinked polyethylene insulated model cables

    International Nuclear Information System (INIS)

    Teyssedre, G.; Laurent, C.; Vu, T. T. N.

    2015-01-01

    Among features observed in polyethylene materials under relatively high field, space charge packets, consisting in a pulse of net charge that remains in the form of a pulse as it crosses the insulation, are repeatedly observed but without complete theory explaining their formation and propagation. Positive charge packets are more often reported, and the models based on negative differential mobility(NDM) for the transport of holes could account for some charge packets phenomenology. Conversely, NDM for electrons transport has never been reported so far. The present contribution reports space charge measurements by pulsed electroacoustic method on miniature cables that are model of HVDC cables. The measurements were realized at room temperature or with a temperature gradient of 10 °C through the insulation under DC fields on the order 30–60 kV/mm. Space charge results reveal systematic occurrence of a negative front of charges generated at the inner electrode that moves toward the outer electrode at the beginning of the polarization step. It is observed that the transit time of the front of negative charge increases, and therefore the mobility decreases, with the applied voltage. Further, the estimated mobility, in the range 10 −14 –10 −13  m 2  V −1  s −1 for the present results, increases when the temperature increases for the same condition of applied voltage. The features substantiate the hypothesis of negative differential mobility used for modelling space charge packets

  5. Negative differential mobility for negative carriers as revealed by space charge measurements on crosslinked polyethylene insulated model cables

    Science.gov (United States)

    Teyssedre, G.; Vu, T. T. N.; Laurent, C.

    2015-12-01

    Among features observed in polyethylene materials under relatively high field, space charge packets, consisting in a pulse of net charge that remains in the form of a pulse as it crosses the insulation, are repeatedly observed but without complete theory explaining their formation and propagation. Positive charge packets are more often reported, and the models based on negative differential mobility(NDM) for the transport of holes could account for some charge packets phenomenology. Conversely, NDM for electrons transport has never been reported so far. The present contribution reports space charge measurements by pulsed electroacoustic method on miniature cables that are model of HVDC cables. The measurements were realized at room temperature or with a temperature gradient of 10 °C through the insulation under DC fields on the order 30-60 kV/mm. Space charge results reveal systematic occurrence of a negative front of charges generated at the inner electrode that moves toward the outer electrode at the beginning of the polarization step. It is observed that the transit time of the front of negative charge increases, and therefore the mobility decreases, with the applied voltage. Further, the estimated mobility, in the range 10-14-10-13 m2 V-1 s-1 for the present results, increases when the temperature increases for the same condition of applied voltage. The features substantiate the hypothesis of negative differential mobility used for modelling space charge packets.

  6. Integrated Experimental and Model-based Analysis Reveals the Spatial Aspects of EGFR Activation Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Shankaran, Harish; Zhang, Yi; Chrisler, William B.; Ewald, Jonathan A.; Wiley, H. S.; Resat, Haluk

    2012-10-02

    The epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinases, and controls a diverse set of cellular responses relevant to development and tumorigenesis. ErbB activation is a complex process involving receptor-ligand binding, receptor dimerization, phosphorylation, and trafficking (internalization, recycling and degradation), which together dictate the spatio-temporal distribution of active receptors within the cell. The ability to predict this distribution, and elucidation of the factors regulating it, would help to establish a mechanistic link between ErbB expression levels and the cellular response. Towards this end, we constructed mathematical models for deconvolving the contributions of receptor dimerization and phosphorylation to EGFR activation, and to examine the dependence of these processes on sub-cellular location. We collected experimental datasets for EGFR activation dynamics in human mammary epithelial cells, with the specific goal of model parameterization, and used the data to estimate parameters for several alternate models. Model-based analysis indicated that: 1) signal termination via receptor dephosphorylation in late endosomes, prior to degradation, is an important component of the response, 2) less than 40% of the receptors in the cell are phosphorylated at any given time, even at saturating ligand doses, and 3) receptor dephosphorylation rates at the cell surface and early endosomes are comparable. We validated the last finding by measuring EGFR dephosphorylation rates at various times following ligand addition both in whole cells, and in endosomes using ELISAs and fluorescent imaging. Overall, our results provide important information on how EGFR phosphorylation levels are regulated within cells. Further, the mathematical model described here can be extended to determine receptor dimer abundances in cells co-expressing various levels of ErbB receptors. This study demonstrates that an iterative cycle of

  7. Simple analytical model reveals the functional role of embodied sensorimotor interaction in hexapod gaits

    Science.gov (United States)

    Aoi, Shinya; Nachstedt, Timo; Manoonpong, Poramate; Wörgötter, Florentin; Matsuno, Fumitoshi

    2018-01-01

    Insects have various gaits with specific characteristics and can change their gaits smoothly in accordance with their speed. These gaits emerge from the embodied sensorimotor interactions that occur between the insect’s neural control and body dynamic systems through sensory feedback. Sensory feedback plays a critical role in coordinated movements such as locomotion, particularly in stick insects. While many previously developed insect models can generate different insect gaits, the functional role of embodied sensorimotor interactions in the interlimb coordination of insects remains unclear because of their complexity. In this study, we propose a simple physical model that is amenable to mathematical analysis to explain the functional role of these interactions clearly. We focus on a foot contact sensory feedback called phase resetting, which regulates leg retraction timing based on touchdown information. First, we used a hexapod robot to determine whether the distributed decoupled oscillators used for legs with the sensory feedback generate insect-like gaits through embodied sensorimotor interactions. The robot generated two different gaits and one had similar characteristics to insect gaits. Next, we proposed the simple model as a minimal model that allowed us to analyze and explain the gait mechanism through the embodied sensorimotor interactions. The simple model consists of a rigid body with massless springs acting as legs, where the legs are controlled using oscillator phases with phase resetting, and the governed equations are reduced such that they can be explained using only the oscillator phases with some approximations. This simplicity leads to analytical solutions for the hexapod gaits via perturbation analysis, despite the complexity of the embodied sensorimotor interactions. This is the first study to provide an analytical model for insect gaits under these interaction conditions. Our results clarified how this specific foot contact sensory

  8. A high HIV-1 strain variability in London, UK, revealed by full-genome analysis: Results from the ICONIC project

    Science.gov (United States)

    Frampton, Dan; Gallo Cassarino, Tiziano; Raffle, Jade; Hubb, Jonathan; Ferns, R. Bridget; Waters, Laura; Tong, C. Y. William; Kozlakidis, Zisis; Hayward, Andrew; Kellam, Paul; Pillay, Deenan; Clark, Duncan; Nastouli, Eleni; Leigh Brown, Andrew J.

    2018-01-01

    Background & methods The ICONIC project has developed an automated high-throughput pipeline to generate HIV nearly full-length genomes (NFLG, i.e. from gag to nef) from next-generation sequencing (NGS) data. The pipeline was applied to 420 HIV samples collected at University College London Hospitals NHS Trust and Barts Health NHS Trust (London) and sequenced using an Illumina MiSeq at the Wellcome Trust Sanger Institute (Cambridge). Consensus genomes were generated and subtyped using COMET, and unique recombinants were studied with jpHMM and SimPlot. Maximum-likelihood phylogenetic trees were constructed using RAxML to identify transmission networks using the Cluster Picker. Results The pipeline generated sequences of at least 1Kb of length (median = 7.46Kb, IQR = 4.01Kb) for 375 out of the 420 samples (89%), with 174 (46.4%) being NFLG. A total of 365 sequences (169 of them NFLG) corresponded to unique subjects and were included in the down-stream analyses. The most frequent HIV subtypes were B (n = 149, 40.8%) and C (n = 77, 21.1%) and the circulating recombinant form CRF02_AG (n = 32, 8.8%). We found 14 different CRFs (n = 66, 18.1%) and multiple URFs (n = 32, 8.8%) that involved recombination between 12 different subtypes/CRFs. The most frequent URFs were B/CRF01_AE (4 cases) and A1/D, B/C, and B/CRF02_AG (3 cases each). Most URFs (19/26, 73%) lacked breakpoints in the PR+RT pol region, rendering them undetectable if only that was sequenced. Twelve (37.5%) of the URFs could have emerged within the UK, whereas the rest were probably imported from sub-Saharan Africa, South East Asia and South America. For 2 URFs we found highly similar pol sequences circulating in the UK. We detected 31 phylogenetic clusters using the full dataset: 25 pairs (mostly subtypes B and C), 4 triplets and 2 quadruplets. Some of these were not consistent across different genes due to inter- and intra-subtype recombination. Clusters involved 70 sequences, 19.2% of the dataset. Conclusions

  9. Further Results on Dynamic Additive Hazard Rate Model

    Directory of Open Access Journals (Sweden)

    Zhengcheng Zhang

    2014-01-01

    Full Text Available In the past, the proportional and additive hazard rate models have been investigated in the works. Nanda and Das (2011 introduced and studied the dynamic proportional (reversed hazard rate model. In this paper we study the dynamic additive hazard rate model, and investigate its aging properties for different aging classes. The closure of the model under some stochastic orders has also been investigated. Some examples are also given to illustrate different aging properties and stochastic comparisons of the model.

  10. Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

    Science.gov (United States)

    Bolton, Helen; Graham, Sarah J L; Van der Aa, Niels; Kumar, Parveen; Theunis, Koen; Fernandez Gallardo, Elia; Voet, Thierry; Zernicka-Goetz, Magdalena

    2016-03-29

    Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.

  11. Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

    Science.gov (United States)

    Gregory, Elaine K; Vercammen, Janet M; Flynn, Megan E; Kibbe, Melina R

    2016-12-01

    Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species. A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting. We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 μm 2 ; P guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 μm 2 ; P guinea pig, and describe a unique distribution of intimal formation that results in both species

  12. Empirical study of travel mode forecasting improvement for the combined revealed preference/stated preference data–based discrete choice model

    Directory of Open Access Journals (Sweden)

    Yanfu Qiao

    2016-01-01

    Full Text Available The combined revealed preference/stated preference data–based discrete choice model has provided the actual choice-making restraints as well as reduced the prediction errors. But the random error variance of alternatives belonging to different data would impact its universality. In this article, we studied the traffic corridor between Chengdu and Longquan with the revealed preference/stated preference joint model, and the single stated preference data model separately predicted the choice probability of each mode. We found the revealed preference/stated preference joint model is universal only when there is a significant difference between the random error terms in different data. The single stated preference data would amplify the travelers’ preference and cause prediction error. We proposed a universal way that uses revealed preference data to modify the single stated preference data parameter estimation results to achieve the composite utility and reduce the prediction error. And the result suggests that prediction results are more reasonable based on the composite utility than the results based on the single stated preference data, especially forecasting the mode share of bus. The future metro line will be the main travel mode in this corridor, and 45% of passenger flow will transfer to the metro.

  13. Modeling of the Dorsal Gradient across Species Reveals Interaction between Embryo Morphology and Toll Signaling Pathway during Evolution

    Science.gov (United States)

    Koslen, Hannah R.; Chiel, Hillel J.; Mizutani, Claudia Mieko

    2014-01-01

    Morphogenetic gradients are essential to allocate cell fates in embryos of varying sizes within and across closely related species. We previously showed that the maternal NF-κB/Dorsal (Dl) gradient has acquired different shapes in Drosophila species, which result in unequally scaled germ layers along the dorso-ventral axis and the repositioning of the neuroectodermal borders. Here we combined experimentation and mathematical modeling to investigate which factors might have contributed to the fast evolutionary changes of this gradient. To this end, we modified a previously developed model that employs differential equations of the main biochemical interactions of the Toll (Tl) signaling pathway, which regulates Dl nuclear transport. The original model simulations fit well the D. melanogaster wild type, but not mutant conditions. To broaden the applicability of this model and probe evolutionary changes in gradient distributions, we adjusted a set of 19 independent parameters to reproduce three quantified experimental conditions (i.e. Dl levels lowered, nuclear size and density increased or decreased). We next searched for the most relevant parameters that reproduce the species-specific Dl gradients. We show that adjusting parameters relative to morphological traits (i.e. embryo diameter, nuclear size and density) alone is not sufficient to reproduce the species Dl gradients. Since components of the Tl pathway simulated by the model are fast-evolving, we next asked which parameters related to Tl would most effectively reproduce these gradients and identified a particular subset. A sensitivity analysis reveals the existence of nonlinear interactions between the two fast-evolving traits tested above, namely the embryonic morphological changes and Tl pathway components. Our modeling further suggests that distinct Dl gradient shapes observed in closely related melanogaster sub-group lineages may be caused by similar sequence modifications in Tl pathway components, which

  14. Tapering of the CHESS-APS undulator: Results and modelling

    International Nuclear Information System (INIS)

    Lai, B.; Viccaro, P.J.; Dejus, R.; Gluskin, E.; Yun, W.B.; McNulty, I.; Henderson, C.; White, J.; Shen, Q.; Finkelstein, K.

    1992-01-01

    When the magnetic gap of an undulator is tapered along the beam direction, the slowly varying peak field B o introduces a spread in the value of the deflection parameter K. The result is a broad energy-band undulator that still maintains high degree of spatial collimation. These properties are very useful for EXAFS and energy dispersive techniques. We have characterized the CHESS-APS undulator (1 υ = 3.3cm) at one tapered configuration (10% change of the magnetic gap from one end of the undulator to the other). Spatial distribution and energy spectra of the first three harmonics through a pinhole were measured. The on-axis first harmonic width increased from 0.27 keV to 0.61 keV (FWHM) at the central energy of E 1 = 6.6 keV (K average = 0.69). Broadening in the angular distribution due to tapering was minimal. These results will be compared with computer modelling which simulates the actual electron trajectory in the tapered case

  15. Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models

    Directory of Open Access Journals (Sweden)

    Dominik Schreiber

    2017-08-01

    Full Text Available Inflammatory bowel diseases (IBD, which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml, TNF-α (10 ng/ml, and IL-1β (5 ng/ml. Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD.

  16. Statistical modeling reveals the effect of absolute humidity on dengue in Singapore.

    Directory of Open Access Journals (Sweden)

    Hai-Yan Xu

    2014-05-01

    Full Text Available Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM was used to evaluate and compare the impact of weekly Absolute Humidity (AH and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike's Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing

  17. Statistical modeling reveals the effect of absolute humidity on dengue in Singapore.

    Science.gov (United States)

    Xu, Hai-Yan; Fu, Xiuju; Lee, Lionel Kim Hock; Ma, Stefan; Goh, Kee Tai; Wong, Jiancheng; Habibullah, Mohamed Salahuddin; Lee, Gary Kee Khoon; Lim, Tian Kuay; Tambyah, Paul Anantharajah; Lim, Chin Leong; Ng, Lee Ching

    2014-05-01

    Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM) was used to evaluate and compare the impact of weekly Absolute Humidity (AH) and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed) on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike's Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT) also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing factors into

  18. Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

    Science.gov (United States)

    Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

    2016-03-01

    Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood

  19. Agent-based modeling of autophagy reveals emergent regulatory behavior of spatio-temporal autophagy dynamics.

    Science.gov (United States)

    Börlin, Christoph S; Lang, Verena; Hamacher-Brady, Anne; Brady, Nathan R

    2014-09-10

    Autophagy is a vesicle-mediated pathway for lysosomal degradation, essential under basal and stressed conditions. Various cellular components, including specific proteins, protein aggregates, organelles and intracellular pathogens, are targets for autophagic degradation. Thereby, autophagy controls numerous vital physiological and pathophysiological functions, including cell signaling, differentiation, turnover of cellular components and pathogen defense. Moreover, autophagy enables the cell to recycle cellular components to metabolic substrates, thereby permitting prolonged survival under low nutrient conditions. Due to the multi-faceted roles for autophagy in maintaining cellular and organismal homeostasis and responding to diverse stresses, malfunction of autophagy contributes to both chronic and acute pathologies. We applied a systems biology approach to improve the understanding of this complex cellular process of autophagy. All autophagy pathway vesicle activities, i.e. creation, movement, fusion and degradation, are highly dynamic, temporally and spatially, and under various forms of regulation. We therefore developed an agent-based model (ABM) to represent individual components of the autophagy pathway, subcellular vesicle dynamics and metabolic feedback with the cellular environment, thereby providing a framework to investigate spatio-temporal aspects of autophagy regulation and dynamic behavior. The rules defining our ABM were derived from literature and from high-resolution images of autophagy markers under basal and activated conditions. Key model parameters were fit with an iterative method using a genetic algorithm and a predefined fitness function. From this approach, we found that accurate prediction of spatio-temporal behavior required increasing model complexity by implementing functional integration of autophagy with the cellular nutrient state. The resulting model is able to reproduce short-term autophagic flux measurements (up to 3

  20. Demixing in a metal halide lamp, results from modelling

    NARCIS (Netherlands)

    Beks, M.L.; Hartgers, A.; Mullen, van der J.J.A.M.

    2006-01-01

    Convection and diffusion in the discharge region of a metal halide lamp is studied using a computer model built with the plasma modeling package Plasimo. A model lamp contg. mercury and sodium iodide is studied. The effects of the total lamp pressure on the degree of segregation of the light

  1. A Duality Result for the Generalized Erlang Risk Model

    Directory of Open Access Journals (Sweden)

    Lanpeng Ji

    2014-11-01

    Full Text Available In this article, we consider the generalized Erlang risk model and its dual model. By using a conditional measure-preserving correspondence between the two models, we derive an identity for two interesting conditional probabilities. Applications to the discounted joint density of the surplus prior to ruin and the deficit at ruin are also discussed.

  2. Translational rodent models of Korsakoff syndrome reveal the critical neuroanatomical substrates of memory dysfunction and recovery.

    Science.gov (United States)

    Savage, Lisa M; Hall, Joseph M; Resende, Leticia S

    2012-06-01

    Investigation of the amnesic disorder Korsakoff Syndrome (KS) has been vital in elucidating the critical brain regions involved in learning and memory. Although the thalamus and mammillary bodies are the primary sites of neuropathology in KS, functional deactivation of the hippocampus and certain cortical regions also contributes to the chronic cognitive dysfunction reported in KS. The rodent pyrithiamine-induced thiamine deficiency (PTD) model has been used to study the extent of hippocampal and cortical neuroadaptations in KS. In the PTD model, the hippocampus, frontal and retrosplenial cortical regions display loss of cholinergic innervation, decreases in behaviorally stimulated acetylcholine release and reductions in neurotrophins. While PTD treatment results in significant impairment in measures of spatial learning and memory, other cognitive processes are left intact and may be recruited to improve cognitive outcome. In addition, behavioral recovery can be stimulated in the PTD model by increasing acetylcholine levels in the medial septum, hippocampus and frontal cortex, but not in the retrosplenial cortex. These data indicate that although the hippocampus and frontal cortex are involved in the pathogenesis of KS, these regions retain neuroplasticity and may be critical targets for improving cognitive outcome in KS.

  3. Waste glass corrosion modeling: Comparison with experimental results

    International Nuclear Information System (INIS)

    Bourcier, W.L.

    1994-01-01

    Models for borosilicate glass dissolution must account for the processes of (1) kinetically-controlled network dissolution, (2) precipitation of secondary phases, (3) ion exchange, (4) rate-limiting diffusive transport of silica through a hydrous surface reaction layer, and (5) specific glass surface interactions with dissolved cations and anions. Current long-term corrosion models for borosilicate glass employ a rate equation consistent with transition state theory embodied in a geochemical reaction-path modeling program that calculates aqueous phase speciation and mineral precipitation/dissolution. These models are currently under development. Future experimental and modeling work to better quantify the rate-controlling processes and validate these models are necessary before the models can be used in repository performance assessment calculations

  4. Computational modeling reveals dendritic origins of GABA(A-mediated excitation in CA1 pyramidal neurons.

    Directory of Open Access Journals (Sweden)

    Naomi Lewin

    Full Text Available GABA is the key inhibitory neurotransmitter in the adult central nervous system, but in some circumstances can lead to a paradoxical excitation that has been causally implicated in diverse pathologies from endocrine stress responses to diseases of excitability including neuropathic pain and temporal lobe epilepsy. We undertook a computational modeling approach to determine plausible ionic mechanisms of GABA(A-dependent excitation in isolated post-synaptic CA1 hippocampal neurons because it may constitute a trigger for pathological synchronous epileptiform discharge. In particular, the interplay intracellular chloride accumulation via the GABA(A receptor and extracellular potassium accumulation via the K/Cl co-transporter KCC2 in promoting GABA(A-mediated excitation is complex. Experimentally it is difficult to determine the ionic mechanisms of depolarizing current since potassium transients are challenging to isolate pharmacologically and much GABA signaling occurs in small, difficult to measure, dendritic compartments. To address this problem and determine plausible ionic mechanisms of GABA(A-mediated excitation, we built a detailed biophysically realistic model of the CA1 pyramidal neuron that includes processes critical for ion homeostasis. Our results suggest that in dendritic compartments, but not in the somatic compartments, chloride buildup is sufficient to cause dramatic depolarization of the GABA(A reversal potential and dominating bicarbonate currents that provide a substantial current source to drive whole-cell depolarization. The model simulations predict that extracellular K(+ transients can augment GABA(A-mediated excitation, but not cause it. Our model also suggests the potential for GABA(A-mediated excitation to promote network synchrony depending on interneuron synapse location - excitatory positive-feedback can occur when interneurons synapse onto distal dendritic compartments, while interneurons projecting to the perisomatic

  5. Argonne Fuel Cycle Facility ventilation system -- modeling and results

    International Nuclear Information System (INIS)

    Mohr, D.; Feldman, E.E.; Danielson, W.F.

    1995-01-01

    This paper describes an integrated study of the Argonne-West Fuel Cycle Facility (FCF) interconnected ventilation systems during various operations. Analyses and test results include first a nominal condition reflecting balanced pressures and flows followed by several infrequent and off-normal scenarios. This effort is the first study of the FCF ventilation systems as an integrated network wherein the hydraulic effects of all major air systems have been analyzed and tested. The FCF building consists of many interconnected regions in which nuclear fuel is handled, transported and reprocessed. The ventilation systems comprise a large number of ducts, fans, dampers, and filters which together must provide clean, properly conditioned air to the worker occupied spaces of the facility while preventing the spread of airborne radioactive materials to clean am-as or the atmosphere. This objective is achieved by keeping the FCF building at a partial vacuum in which the contaminated areas are kept at lower pressures than the other worker occupied spaces. The ventilation systems of FCF and the EBR-II reactor are analyzed as an integrated totality, as demonstrated. We then developed the network model shown in Fig. 2 for the TORAC code. The scope of this study was to assess the measured results from the acceptance/flow balancing testing and to predict the effects of power failures, hatch and door openings, single-failure faulted conditions, EBR-II isolation, and other infrequent operations. The studies show that the FCF ventilation systems am very controllable and remain stable following off-normal events. In addition, the FCF ventilation system complex is essentially immune to reverse flows and spread of contamination to clean areas during normal and off-normal operation

  6. Computational models reveal a passive mechanism for cell migration in the crypt.

    Directory of Open Access Journals (Sweden)

    Sara-Jane Dunn

    Full Text Available Cell migration in the intestinal crypt is essential for the regular renewal of the epithelium, and the continued upward movement of cells is a key characteristic of healthy crypt dynamics. However, the driving force behind this migration is unknown. Possibilities include mitotic pressure, active movement driven by motility cues, or negative pressure arising from cell loss at the crypt collar. It is possible that a combination of factors together coordinate migration. Here, three different computational models are used to provide insight into the mechanisms that underpin cell movement in the crypt, by examining the consequence of eliminating cell division on cell movement. Computational simulations agree with existing experimental results, confirming that migration can continue in the absence of mitosis. Importantly, however, simulations allow us to infer mechanisms that are sufficient to generate cell movement, which is not possible through experimental observation alone. The results produced by the three models agree and suggest that cell loss due to apoptosis and extrusion at the crypt collar relieves cell compression below, allowing cells to expand and move upwards. This finding suggests that future experiments should focus on the role of apoptosis and cell extrusion in controlling cell migration in the crypt.

  7. Final model independent result of DAMA/LIBRA-phase1

    Energy Technology Data Exchange (ETDEWEB)

    Bernabei, R.; D' Angelo, S.; Di Marco, A. [Universita di Roma ' ' Tor Vergata' ' , Dipartimento di Fisica, Rome (Italy); INFN, sez. Roma ' ' Tor Vergata' ' , Rome (Italy); Belli, P. [INFN, sez. Roma ' ' Tor Vergata' ' , Rome (Italy); Cappella, F.; D' Angelo, A.; Prosperi, D. [Universita di Roma ' ' La Sapienza' ' , Dipartimento di Fisica, Rome (Italy); INFN, sez. Roma, Rome (Italy); Caracciolo, V.; Castellano, S.; Cerulli, R. [INFN, Laboratori Nazionali del Gran Sasso, Assergi (Italy); Dai, C.J.; He, H.L.; Kuang, H.H.; Ma, X.H.; Sheng, X.D.; Wang, R.G. [Chinese Academy, IHEP, Beijing (China); Incicchitti, A. [INFN, sez. Roma, Rome (Italy); Montecchia, F. [INFN, sez. Roma ' ' Tor Vergata' ' , Rome (Italy); Universita di Roma ' ' Tor Vergata' ' , Dipartimento di Ingegneria Civile e Ingegneria Informatica, Rome (Italy); Ye, Z.P. [Chinese Academy, IHEP, Beijing (China); University of Jing Gangshan, Jiangxi (China)

    2013-12-15

    The results obtained with the total exposure of 1.04 ton x yr collected by DAMA/LIBRA-phase1 deep underground at the Gran Sasso National Laboratory (LNGS) of the I.N.F.N. during 7 annual cycles (i.e. adding a further 0.17 ton x yr exposure) are presented. The DAMA/LIBRA-phase1 data give evidence for the presence of Dark Matter (DM) particles in the galactic halo, on the basis of the exploited model independent DM annual modulation signature by using highly radio-pure NaI(Tl) target, at 7.5{sigma} C.L. Including also the first generation DAMA/NaI experiment (cumulative exposure 1.33 ton x yr, corresponding to 14 annual cycles), the C.L. is 9.3{sigma} and the modulation amplitude of the single-hit events in the (2-6) keV energy interval is: (0.0112{+-}0.0012) cpd/kg/keV; the measured phase is (144{+-}7) days and the measured period is (0.998{+-}0.002) yr, values well in agreement with those expected for DM particles. No systematic or side reaction able to mimic the exploited DM signature has been found or suggested by anyone over more than a decade. (orig.)

  8. Innovation ecosystem model for commercialization of research results

    Directory of Open Access Journals (Sweden)

    Vlăduţ Gabriel

    2017-07-01

    Full Text Available Innovation means Creativity and Added value recognise by the market. The first step in creating a sustainable commercialization of research results, Technological Transfer – TT mechanism, on one hand is to define the “technology” which will be transferred and on other hand to define the context in which the TT mechanism work, the ecosystem. The focus must be set on technology as an entity, not as a science or a study of the practical industrial arts and certainly not any specific applied science. The transfer object, the technology, must rely on a subjectively determined but specifiable set of processes and products. Focusing on the product is not sufficient to the transfer and diffusion of technology. It is not merely the product that is transferred but also knowledge of its use and application. The innovation ecosystem model brings together new companies, experienced business leaders, researchers, government officials, established technology companies, and investors. This environment provides those new companies with a wealth of technical expertise, business experience, and access to capital that supports innovation in the early stages of growth.

  9. A model of gene expression based on random dynamical systems reveals modularity properties of gene regulatory networks.

    Science.gov (United States)

    Antoneli, Fernando; Ferreira, Renata C; Briones, Marcelo R S

    2016-06-01

    Here we propose a new approach to modeling gene expression based on the theory of random dynamical systems (RDS) that provides a general coupling prescription between the nodes of any given regulatory network given the dynamics of each node is modeled by a RDS. The main virtues of this approach are the following: (i) it provides a natural way to obtain arbitrarily large networks by coupling together simple basic pieces, thus revealing the modularity of regulatory networks; (ii) the assumptions about the stochastic processes used in the modeling are fairly general, in the sense that the only requirement is stationarity; (iii) there is a well developed mathematical theory, which is a blend of smooth dynamical systems theory, ergodic theory and stochastic analysis that allows one to extract relevant dynamical and statistical information without solving the system; (iv) one may obtain the classical rate equations form the corresponding stochastic version by averaging the dynamic random variables (small noise limit). It is important to emphasize that unlike the deterministic case, where coupling two equations is a trivial matter, coupling two RDS is non-trivial, specially in our case, where the coupling is performed between a state variable of one gene and the switching stochastic process of another gene and, hence, it is not a priori true that the resulting coupled system will satisfy the definition of a random dynamical system. We shall provide the necessary arguments that ensure that our coupling prescription does indeed furnish a coupled regulatory network of random dynamical systems. Finally, the fact that classical rate equations are the small noise limit of our stochastic model ensures that any validation or prediction made on the basis of the classical theory is also a validation or prediction of our model. We illustrate our framework with some simple examples of single-gene system and network motifs. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Seismic tomography model reveals mantle magma sources of recent volcanic activity at El Hierro Island (Canary Islands, Spain)

    Science.gov (United States)

    García-Yeguas, Araceli; Ibáñez, Jesús M.; Koulakov, Ivan; Jakovlev, Andrey; Romero-Ruiz, M. Carmen; Prudencio, Janire

    2014-12-01

    We present a 3-D model of P and S velocities beneath El Hierro Island, constructed using the traveltime data of more than 13 000 local earthquakes recorded by the Instituto Geográfico Nacional (IGN, Spain) in the period from 2011 July to 2012 September. The velocity models were performed using the LOTOS code for iterative passive source tomography. The results of inversion were thoroughly verified using different resolution and robustness tests. The results reveal that the majority of the onshore area of El Hierro is associated with a high-velocity anomaly observed down to 10-12-km depth. This anomaly is interpreted as the accumulation of solid igneous rocks erupted during the last 1 Myr and intrusive magmatic bodies. Below this high-velocity pattern, we observe a low-velocity anomaly, interpreted as a batch of magma coming from the mantle located beneath El Hierro. The boundary between the low- and high-velocity anomalies is marked by a prominent seismicity cluster, thought to represent anomalous stresses due to the interaction of the batch of magma with crust material. The areas of recent eruptions, Orchilla and La Restinga, are associated with low-velocity anomalies surrounding the main high-velocity block. These eruptions took place around the island where the crust is much weaker than the onshore area and where the melted material cannot penetrate. These results put constraints on the geological model that could explain the origin of the volcanism in oceanic islands, such as in the Canaries, which is not yet clearly understood.

  11. Results from the Savannah River Laboratory model validation workshop

    International Nuclear Information System (INIS)

    Pepper, D.W.

    1981-01-01

    To evaluate existing and newly developed air pollution models used in DOE-funded laboratories, the Savannah River Laboratory sponsored a model validation workshop. The workshop used Kr-85 measurements and meteorology data obtained at SRL during 1975 to 1977. Individual laboratories used models to calculate daily, weekly, monthly or annual test periods. Cumulative integrated air concentrations were reported at each grid point and at each of the eight sampler locations

  12. Multi-Analytical Approach Reveals Potential Microbial Indicators in Soil for Sugarcane Model Systems.

    Directory of Open Access Journals (Sweden)

    Acacio Aparecido Navarrete

    Full Text Available This study focused on the effects of organic and inorganic amendments and straw retention on the microbial biomass (MB and taxonomic groups of bacteria in sugarcane-cultivated soils in a greenhouse mesocosm experiment monitored for gas emissions and chemical factors. The experiment consisted of combinations of synthetic nitrogen (N, vinasse (V; a liquid waste from ethanol production, and sugarcane-straw blankets. Increases in CO2-C and N2O-N emissions were identified shortly after the addition of both N and V to the soils, thus increasing MB nitrogen (MB-N and decreasing MB carbon (MB-C in the N+V-amended soils and altering soil chemical factors that were correlated with the MB. Across 57 soil metagenomic datasets, Actinobacteria (31.5%, Planctomycetes (12.3%, Deltaproteobacteria (12.3%, Alphaproteobacteria (12.0% and Betaproteobacteria (11.1% were the most dominant bacterial groups during the experiment. Differences in relative abundance of metagenomic sequences were mainly revealed for Acidobacteria, Actinobacteria, Gammaproteobacteria and Verrucomicrobia with regard to N+V fertilization and straw retention. Differential abundances in bacterial groups were confirmed using 16S rRNA gene-targeted phylum-specific primers for real-time PCR analysis in all soil samples, whose results were in accordance with sequence data, except for Gammaproteobacteria. Actinobacteria were more responsive to straw retention with Rubrobacterales, Bifidobacteriales and Actinomycetales related to the chemical factors of N+V-amended soils. Acidobacteria subgroup 7 and Opitutae, a verrucomicrobial class, were related to the chemical factors of soils without straw retention as a surface blanket. Taken together, the results showed that MB-C and MB-N responded to changes in soil chemical factors and CO2-C and N2O-N emissions, especially for N+V-amended soils. The results also indicated that several taxonomic groups of bacteria, such as Acidobacteria, Actinobacteria and

  13. Multi-Analytical Approach Reveals Potential Microbial Indicators in Soil for Sugarcane Model Systems

    Science.gov (United States)

    Navarrete, Acacio Aparecido; Diniz, Tatiana Rosa; Braga, Lucas Palma Perez; Silva, Genivaldo Gueiros Zacarias; Franchini, Julio Cezar; Rossetto, Raffaella; Edwards, Robert Alan; Tsai, Siu Mui

    2015-01-01

    This study focused on the effects of organic and inorganic amendments and straw retention on the microbial biomass (MB) and taxonomic groups of bacteria in sugarcane-cultivated soils in a greenhouse mesocosm experiment monitored for gas emissions and chemical factors. The experiment consisted of combinations of synthetic nitrogen (N), vinasse (V; a liquid waste from ethanol production), and sugarcane-straw blankets. Increases in CO2-C and N2O-N emissions were identified shortly after the addition of both N and V to the soils, thus increasing MB nitrogen (MB-N) and decreasing MB carbon (MB-C) in the N+V-amended soils and altering soil chemical factors that were correlated with the MB. Across 57 soil metagenomic datasets, Actinobacteria (31.5%), Planctomycetes (12.3%), Deltaproteobacteria (12.3%), Alphaproteobacteria (12.0%) and Betaproteobacteria (11.1%) were the most dominant bacterial groups during the experiment. Differences in relative abundance of metagenomic sequences were mainly revealed for Acidobacteria, Actinobacteria, Gammaproteobacteria and Verrucomicrobia with regard to N+V fertilization and straw retention. Differential abundances in bacterial groups were confirmed using 16S rRNA gene-targeted phylum-specific primers for real-time PCR analysis in all soil samples, whose results were in accordance with sequence data, except for Gammaproteobacteria. Actinobacteria were more responsive to straw retention with Rubrobacterales, Bifidobacteriales and Actinomycetales related to the chemical factors of N+V-amended soils. Acidobacteria subgroup 7 and Opitutae, a verrucomicrobial class, were related to the chemical factors of soils without straw retention as a surface blanket. Taken together, the results showed that MB-C and MB-N responded to changes in soil chemical factors and CO2-C and N2O-N emissions, especially for N+V-amended soils. The results also indicated that several taxonomic groups of bacteria, such as Acidobacteria, Actinobacteria and

  14. Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures

    Directory of Open Access Journals (Sweden)

    Peter A. Bell

    2013-06-01

    Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal diseases resulting from mutations in cartilage structural proteins. Electron microscopy and immunohistochemistry previously showed that the appearance of the cartilage extracellular matrix (ECM in targeted mouse models of these diseases is disrupted; however, the precise changes in ECM organization and the pathological consequences remain unknown. Our aim was to determine the effects of matrilin-3 and COMP mutations on the composition and extractability of ECM components to inform how these detrimental changes might influence cartilage organization and degeneration. Cartilage was sequentially extracted using increasing denaturants and the extraction profiles of specific proteins determined using SDS-PAGE/Western blotting. Furthermore, the relative composition of protein pools was determined using mass spectrometry for a non-biased semi-quantitative analysis. Western blotting revealed changes in the extraction of matrilins, COMP and collagen IX in mutant cartilage. Mass spectrometry confirmed quantitative changes in the extraction of structural and non-structural ECM proteins, including proteins with roles in cellular processes such as protein folding and trafficking. In particular, genotype-specific differences in the extraction of collagens XII and XIV and tenascins C and X were identified; interestingly, increased expression of several of these genes has recently been implicated in susceptibility and/or progression of murine osteoarthritis. We demonstrated that mutation of matrilin-3 and COMP caused changes in the extractability of other cartilage proteins and that proteomic analyses of Matn3 V194D, Comp T585M and Comp DelD469 mouse models revealed both common and discrete disease signatures that provide novel insight into skeletal disease mechanisms and cartilage degradation.

  15. Waste glass corrosion modeling: Comparison with experimental results

    International Nuclear Information System (INIS)

    Bourcier, W.L.

    1993-11-01

    A chemical model of glass corrosion will be used to predict the rates of release of radionuclides from borosilicate glass waste forms in high-level waste repositories. The model will be used both to calculate the rate of degradation of the glass, and also to predict the effects of chemical interactions between the glass and repository materials such as spent fuel, canister and container materials, backfill, cements, grouts, and others. Coupling between the degradation processes affecting all these materials is expected. Models for borosilicate glass dissolution must account for the processes of (1) kinetically-controlled network dissolution, (2) precipitation of secondary phases, (3) ion exchange, (4) rate-limiting diffusive transport of silica through a hydrous surface reaction layer, and (5) specific glass surface interactions with dissolved cations and anions. Current long-term corrosion models for borosilicate glass employ a rate equation consistent with transition state theory embodied in a geochemical reaction-path modeling program that calculates aqueous phase speciation and mineral precipitation/dissolution. These models are currently under development. Future experimental and modeling work to better quantify the rate-controlling processes and validate these models are necessary before the models can be used in repository performance assessment calculations

  16. Regionalization of climate model results for the North Sea

    Energy Technology Data Exchange (ETDEWEB)

    Kauker, F.

    1999-07-01

    A dynamical downscaling is presented that allows an estimation of potential effects of climate change on the North Sea. Therefore, the ocean general circulation model OPYC is adapted for application on a shelf by adding a lateral boundary formulation and a tide model. In this set-up the model is forced, first, with data from the ECMWF reanalysis for model validation and the study of the natural variability, and, second, with data from climate change experiments to estimate the effects of climate change on the North Sea. (orig.)

  17. results

    Directory of Open Access Journals (Sweden)

    Salabura Piotr

    2017-01-01

    Full Text Available HADES experiment at GSI is the only high precision experiment probing nuclear matter in the beam energy range of a few AGeV. Pion, proton and ion beams are used to study rare dielectron and strangeness probes to diagnose properties of strongly interacting matter in this energy regime. Selected results from p + A and A + A collisions are presented and discussed.

  18. Spinal cord stimulation: modeling results and clinical data

    NARCIS (Netherlands)

    Struijk, Johannes J.; Struijk, J.J.; Holsheimer, J.; Barolat, Giancarlo; He, Jiping

    1992-01-01

    The potential distribution in volume couductor models of the spinal cord at cervical, midthoracic and lowthoracic levels, due to epidural stimulation, was calculated. Treshold stimuli of modeled myelhated dorsal column and dorsal root fibers were calculated and were compared with perception

  19. How to: understanding SWAT model uncertainty relative to measured results

    Science.gov (United States)

    Watershed models are being relied upon to contribute to most policy-making decisions of watershed management, and the demand for an accurate accounting of complete model uncertainty is rising. Generalized likelihood uncertainty estimation (GLUE) is a widely used method for quantifying uncertainty i...

  20. Urban traffic noise assessment by combining measurement and model results

    NARCIS (Netherlands)

    Eerden, F.J.M. van der; Graafland, F.; Wessels, P.W.; Basten, T.G.H.

    2013-01-01

    A model based monitoring system is applied on a local scale in an urban area to obtain a better understanding of the traffic noise situation. The system consists of a scalable sensor network and an engineering model. A better understanding is needed to take appropriate and cost efficient measures,

  1. Revealing the regime of shallow coral reefs at patch scale by continuous spatial modeling

    Directory of Open Access Journals (Sweden)

    Antoine eCollin

    2014-11-01

    Full Text Available Reliably translating real-world spatial patterns of ecosystems is critical for understanding processes susceptible to reinforce resilience. However the great majority of studies in spatial ecology use thematic maps to describe habitats and species in a binary scheme. By discretizing the transitional areas and neglecting the gradual replacement across a given space, the thematic approach may suffer from substantial limitations when interpreting patterns created by many continuous variables. Here, local and regional spectral proxies were used to design and spatially map at very fine scale a continuous index dedicated to one of the most complex seascapes, the coral reefscape. Through a groundbreaking merge of bottom-up and top-down approach, we demonstrate that three to seven-habitat continuous indices can be modeled by nine, six, four and three spectral proxies, respectively, at 0.5 m spatial resolution using hand- and spaceborne measurements. We map the seven-habitat continuous index, spanning major Indo-Pacific coral reef habitats through the far red-green normalized difference ratio over the entire lagoon of a low (Tetiaroa atoll and a high volcanic (Moorea island in French Polynesia with 84% and 82% accuracy, respectively. Further examinations of the two resulting spatial models using a customized histoscape (density function of model values distributed on a concentric strip across the reef crest-coastline distance show that Tetiaroa exhibits a greater variety of coral reef habitats than Moorea. By designing such easy-to-implement, transferrable spectral proxies of coral reef regime, this study initiates a framework for spatial ecologists tackling coral reef biodiversity, responses to stresses, perturbations and shifts. We discuss the limitations and contributions of our findings towards the study of worldwide coral reef resilience following stochastic environmental change.

  2. Noise and dose modeling for pediatric CT optimization: preliminary results

    International Nuclear Information System (INIS)

    Miller Clemente, Rafael A.; Perez Diaz, Marlen; Mora Reyes, Yudel; Rodriguez Garlobo, Maikel; Castillo Salazar, Rafael

    2008-01-01

    Full text: A Multiple Linear Regression Model was developed to predict noise and dose in computed tomography pediatric imaging for head and abdominal examinations. Relative values of Noise and Volumetric Computed Tomography Dose Index was used to estimate de model respectively. 54 images of physical phantoms were performed. Independent variables considered included: phantom diameter, tube current and kilovolts, x ray beam collimation, reconstruction diameter and equipment's post processing filters. Predicted values show good agreement with measurements, which were better in noise model (R 2 adjusted =0.953) than the dose model (R 2 adjusted =0.744). Tube current, object diameter, beam collimation and reconstruction filter were identified as the most influencing factors in models. (author)

  3. Comparison of simulation and experimental results for a model aqueous tert-butanol solution

    Science.gov (United States)

    Overduin, S. D.; Patey, G. N.

    2017-07-01

    Molecular dynamics simulations are used to investigate the behavior of aqueous tert-butanol (TBA) solutions for a range of temperatures, using the CHARMM generalized force field (CGenFF) to model TBA and the TIP4P/2005 or TIP4P-Ew water model. Simulation results for the density, isothermal compressibility, constant pressure heat capacity, and self-diffusion coefficients are in good accord with experimental measurements. Agreement with the experiment is particularly good at low TBA concentration, where experiments have revealed anomalies in a number of thermodynamic properties. Importantly, the CGenFF model does not exhibit liquid-liquid demixing at temperatures between 290 and 320 K (for systems of 32 000 molecules), in contrast with the situation for several other common TBA models [R. Gupta and G. N. Patey, J. Chem. Phys. 137, 034509 (2012)]. However, whereas real water and TBA are miscible at all temperatures where the liquid is stable, we observe some evidence of demixing at 340 K and above. To evaluate the structural properties at low concentrations, we compare with both neutron scattering and recent spectroscopic measurements. This reveals that while the CGenFF model is a definite improvement over other models that have been considered, the TBA molecules still exhibit a tendency to associate at low concentrations that is somewhat stronger than that indicated by experiments. Finally, we discuss the range and decay times of the long-range correlations, providing an indication of the system size and simulation times that are necessary in order to obtain reliable results for certain properties.

  4. Multistate models of bigheaded carps in the Illinois River reveal spatial dynamics of invasive species

    Science.gov (United States)

    Coulter, Alison A.; Brey, Marybeth; Lubejko, Matthew; Kallis, Jahn L.; Coulter, David P.; Glover, David C.; Whitledge, Gregory W.; Garvey, James E.

    2018-01-01

    Knowledge of the spatial distributions and dispersal characteristics of invasive species is necessary for managing the spread of highly mobile species, such as invasive bigheaded carps (Bighead Carp [Hypophthalmichthys nobilis] and Silver Carp [H. molitrix]). Management of invasive bigheaded carps in the Illinois River has focused on using human-made barriers and harvest to limit dispersal towards the Laurentian Great Lakes. Acoustic telemetry data were used to parameterize multistate models to examine the spatial dynamics of bigheaded carps in the Illinois River to (1) evaluate the effects of existing dams on movement, (2) identify how individuals distribute among pools, and (3) gauge the effects of reductions in movement towards the invasion front. Multistate models estimated that movement was generally less likely among upper river pools (Starved Rock, Marseilles, and Dresden Island) than the lower river (La Grange and Peoria) which matched the pattern of gated versus wicket style dams. Simulations using estimated movement probabilities indicated that Bighead Carp accumulate in La Grange Pool while Silver Carp accumulate in Alton Pool. Fewer Bighead Carp reached the upper river compared to Silver Carp during simulations. Reducing upstream movement probabilities (e.g., reduced propagule pressure) by ≥ 75% into any of the upper river pools could reduce upper river abundance with similar results regardless of location. Given bigheaded carp reproduction in the upper Illinois River is presently limited, reduced movement towards the invasion front coupled with removal of individuals reaching these areas could limit potential future dispersal towards the Great Lakes.

  5. Dynamic Modelling Reveals 'Hotspots' on the Pathway to Enzyme-Substrate Complex Formation.

    Directory of Open Access Journals (Sweden)

    Shane E Gordon

    2016-03-01

    Full Text Available Dihydrodipicolinate synthase (DHDPS catalyzes the first committed step in the diaminopimelate pathway of bacteria, yielding amino acids required for cell wall and protein biosyntheses. The essentiality of the enzyme to bacteria, coupled with its absence in humans, validates DHDPS as an antibacterial drug target. Conventional drug design efforts have thus far been unsuccessful in identifying potent DHDPS inhibitors. Here, we make use of contemporary molecular dynamics simulation and Markov state models to explore the interactions between DHDPS from the human pathogen Staphylococcus aureus and its cognate substrate, pyruvate. Our simulations recover the crystallographic DHDPS-pyruvate complex without a priori knowledge of the final bound structure. The highly conserved residue Arg140 was found to have a pivotal role in coordinating the entry of pyruvate into the active site from bulk solvent, consistent with previous kinetic reports, indicating an indirect role for the residue in DHDPS catalysis. A metastable binding intermediate characterized by multiple points of intermolecular interaction between pyruvate and key DHDPS residue Arg140 was found to be a highly conserved feature of the binding trajectory when comparing alternative binding pathways. By means of umbrella sampling we show that these binding intermediates are thermodynamically metastable, consistent with both the available experimental data and the substrate binding model presented in this study. Our results provide insight into an important enzyme-substrate interaction in atomistic detail that offers the potential to be exploited for the discovery of more effective DHDPS inhibitors and, in a broader sense, dynamic protein-drug interactions.

  6. Exact results for quantum chaotic systems and one-dimensional fermions from matrix models

    International Nuclear Information System (INIS)

    Simons, B.D.; Lee, P.A.; Altshuler, B.L.

    1993-01-01

    We demonstrate a striking connection between the universal parametric correlations of the spectra of quantum chaotic systems and a class of integrable quantum hamiltonians. We begin by deriving a non-perturbative expression for the universal m-point correlation function of the spectra of random matrix ensembles in terms of a non-linear supermatrix σ-model. These results are shown to coincide with those from previous studies of weakly disordered metallic systems. We then introduce a continuous matrix model which describes the quantum mechanics of the Sutherland hamiltonian describing particles interacting through an inverse-square pairwise potential. We demonstrate that a field theoretic approach can be employed to determine exact analytical expressions for correlations of the quantum hamiltonian. The results, which are expressed in terms of a non-linear σ-model, are shown to coincide with those for analogous correlation functions of random matrix ensembles after an appropriate change of variables. We also discuss possible generalizations of the matrix model to higher dimensions. These results reveal a common mathematical structure which underlies branches of theoretical physics ranging from continuous matrix models to strongly interacting quantum hamiltonians, and universalities in the spectra of quantum chaotic systems. (orig.)

  7. Genome-wide investigation reveals high evolutionary rates in annual model plants.

    Science.gov (United States)

    Yue, Jia-Xing; Li, Jinpeng; Wang, Dan; Araki, Hitoshi; Tian, Dacheng; Yang, Sihai

    2010-11-09

    Rates of molecular evolution vary widely among species. While significant deviations from molecular clock have been found in many taxa, effects of life histories on molecular evolution are not fully understood. In plants, annual/perennial life history traits have long been suspected to influence the evolutionary rates at the molecular level. To date, however, the number of genes investigated on this subject is limited and the conclusions are mixed. To evaluate the possible heterogeneity in evolutionary rates between annual and perennial plants at the genomic level, we investigated 85 nuclear housekeeping genes, 10 non-housekeeping families, and 34 chloroplast genes using the genomic data from model plants including Arabidopsis thaliana and Medicago truncatula for annuals and grape (Vitis vinifera) and popular (Populus trichocarpa) for perennials. According to the cross-comparisons among the four species, 74-82% of the nuclear genes and 71-97% of the chloroplast genes suggested higher rates of molecular evolution in the two annuals than those in the two perennials. The significant heterogeneity in evolutionary rate between annuals and perennials was consistently found both in nonsynonymous sites and synonymous sites. While a linear correlation of evolutionary rates in orthologous genes between species was observed in nonsynonymous sites, the correlation was weak or invisible in synonymous sites. This tendency was clearer in nuclear genes than in chloroplast genes, in which the overall evolutionary rate was small. The slope of the regression line was consistently lower than unity, further confirming the higher evolutionary rate in annuals at the genomic level. The higher evolutionary rate in annuals than in perennials appears to be a universal phenomenon both in nuclear and chloroplast genomes in the four dicot model plants we investigated. Therefore, such heterogeneity in evolutionary rate should result from factors that have genome-wide influence, most likely those

  8. Molecular modelling studies of kdr mutations in voltage gated sodium channel revealed significant conformational variations contributing to insecticide resistance.

    Science.gov (United States)

    Yellapu, Nanda Kumar; Gopal, Jeyakodi; Kasinathan, Gunasekaran; Purushothaman, Jambulingam

    2018-06-01

    Voltage gated sodium channels (VGSC) of mosquito vectors are the primary targets of dichlorodiphenyltrichloroethane (DDT) and other synthetic pyrethroids used in public health programmes. The knockdown resistant (kdr) mutations in VGSC are associated with the insecticide resistance especially in Anophelines. The present study is aimed to emphasize and demarcate the impact of three kdr-mutations such as L1014S, L1014F and L1014H on insecticide resistance. The membrane model of sodium transport domain of VGSC (STD-VGSC) was constructed using de novo approach based on domain and trans-membrane predictions. The comparative molecular modelling studies of wild type and mutant models of STD-VGSC revealed that L1014F mutant was observed to be near native to the wild type model in all the respects, but, L1014S and L1014H mutations showed drastic variations in the energy levels, root mean square fluctuations (RMSF) that resulted in conformational variations. The predicted binding sites also showed variable cavity volumes and RMSF in L1014S and L1014H mutants. Further, DDT also found be bound in near native manner to wild type in L1014F mutant and with variable orientation and affinities in L1014S and L1014H mutants. The variations and fluctuations observed in mutant structures explained that each mutation has its specific impact on the conformation of VGSC and its binding with DDT. The study provides new insights into the structure-function-correlations of mutant STD-VGSC structures and demonstrates the role and effects of kdr mutations on insecticide resistance in mosquito vectors.

  9. Negative differential mobility for negative carriers as revealed by space charge measurements on crosslinked polyethylene insulated model cables

    Energy Technology Data Exchange (ETDEWEB)

    Teyssedre, G., E-mail: gilbert.teyssedre@laplace.univ-tlse.fr; Laurent, C. [Université de Toulouse, UPS, INPT, LAPLACE (Laboratoire Plasma et Conversion d' Energie), 118 route de Narbonne, F-31062 Toulouse cedex 9 (France); CNRS, LAPLACE, F-31062 Toulouse (France); Vu, T. T. N. [Université de Toulouse, UPS, INPT, LAPLACE (Laboratoire Plasma et Conversion d' Energie), 118 route de Narbonne, F-31062 Toulouse cedex 9 (France); Electric Power University, 235 Hoang Quoc Viet, 10000 Hanoi (Viet Nam)

    2015-12-21

    Among features observed in polyethylene materials under relatively high field, space charge packets, consisting in a pulse of net charge that remains in the form of a pulse as it crosses the insulation, are repeatedly observed but without complete theory explaining their formation and propagation. Positive charge packets are more often reported, and the models based on negative differential mobility(NDM) for the transport of holes could account for some charge packets phenomenology. Conversely, NDM for electrons transport has never been reported so far. The present contribution reports space charge measurements by pulsed electroacoustic method on miniature cables that are model of HVDC cables. The measurements were realized at room temperature or with a temperature gradient of 10 °C through the insulation under DC fields on the order 30–60 kV/mm. Space charge results reveal systematic occurrence of a negative front of charges generated at the inner electrode that moves toward the outer electrode at the beginning of the polarization step. It is observed that the transit time of the front of negative charge increases, and therefore the mobility decreases, with the applied voltage. Further, the estimated mobility, in the range 10{sup −14}–10{sup −13} m{sup 2} V{sup −1} s{sup −1} for the present results, increases when the temperature increases for the same condition of applied voltage. The features substantiate the hypothesis of negative differential mobility used for modelling space charge packets.

  10. Results on a Binding Neuron Model and Their Implications for Modified Hourglass Model for Neuronal Network

    Directory of Open Access Journals (Sweden)

    Viswanathan Arunachalam

    2013-01-01

    Full Text Available The classical models of single neuron like Hodgkin-Huxley point neuron or leaky integrate and fire neuron assume the influence of postsynaptic potentials to last till the neuron fires. Vidybida (2008 in a refreshing departure has proposed models for binding neurons in which the trace of an input is remembered only for a finite fixed period of time after which it is forgotten. The binding neurons conform to the behaviour of real neurons and are applicable in constructing fast recurrent networks for computer modeling. This paper develops explicitly several useful results for a binding neuron like the firing time distribution and other statistical characteristics. We also discuss the applicability of the developed results in constructing a modified hourglass network model in which there are interconnected neurons with excitatory as well as inhibitory inputs. Limited simulation results of the hourglass network are presented.

  11. Meteorological Uncertainty of atmospheric Dispersion model results (MUD)

    DEFF Research Database (Denmark)

    Havskov Sørensen, Jens; Amstrup, Bjarne; Feddersen, Henrik

    The MUD project addresses assessment of uncertainties of atmospheric dispersion model predictions, as well as optimum presentation to decision makers. Previously, it has not been possible to estimate such uncertainties quantitatively, but merely to calculate the 'most likely' dispersion scenario....

  12. Verification of Simulation Results Using Scale Model Flight Test Trajectories

    National Research Council Canada - National Science Library

    Obermark, Jeff

    2004-01-01

    .... A second compromise scaling law was investigated as a possible improvement. For ejector-driven events at minimum sideslip, the most important variables for scale model construction are the mass moment of inertia and ejector...

  13. Box photosynthesis modeling results for WRF/CMAQ LSM

    Data.gov (United States)

    U.S. Environmental Protection Agency — Box Photosynthesis model simulations for latent heat and ozone at 6 different FLUXNET sites. This dataset is associated with the following publication: Ran, L., J....

  14. Systems biology modeling reveals a possible mechanism of the tumor cell death upon oncogene inactivation in EGFR addicted cancers.

    Directory of Open Access Journals (Sweden)

    Jian-Ping Zhou

    Full Text Available Despite many evidences supporting the concept of "oncogene addiction" and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK and phosphoinositol-3 kinase (PI3K/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential due to the elevated level of reactive oxygen species (ROS is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers.

  15. Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells

    International Nuclear Information System (INIS)

    Askmyr, M; Ågerstam, H; Lilljebjörn, H; Hansen, N; Karlsson, C; Palffy, S von; Landberg, N; Högberg, C; Lassen, C; Rissler, M; Richter, J; Ehinger, M; Järås, M; Fioretos, T

    2014-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanized CML model, we retrovirally expressed BCR-ABL1 in the cord blood CD34 + cells and transplanted these into NOD-SCID (non-obese diabetic/severe-combined immunodeficient) interleukin-2-receptor γ-deficient mice. In primary mice, BCR-ABL1 expression induced an inflammatory-like state in the bone marrow and spleen, and mast cells were the only myeloid lineage specifically expanded by BCR-ABL1. Upon secondary transplantation, the pronounced inflammatory phenotype was lost and mainly human mast cells and macrophages were found in the bone marrow. Moreover, a striking block at the pre-B-cell stage was observed in primary mice, resulting in an accumulation of pre-B cells. A similar block in B-cell differentiation could be confirmed in primary cells from CML patients. Hence, this humanized mouse model of CML reveals previously unexplored features of CP CML and should be useful for further studies to understand the disease pathogenesis of CML

  16. Some Econometric Results for the Blanchard-Watson Bubble Model

    DEFF Research Database (Denmark)

    Johansen, Soren; Lange, Theis

    The purpose of the present paper is to analyse a simple bubble model suggested by Blanchard and Watson. The model is defined by y(t) =s(t)¿y(t-1)+e(t), t=1,…,n, where s(t) is an i.i.d. binary variable with p=P(s(t)=1), independent of e(t) i.i.d. with mean zero and finite variance. We take ¿>1 so...

  17. The 3D Reference Earth Model: Status and Preliminary Results

    Science.gov (United States)

    Moulik, P.; Lekic, V.; Romanowicz, B. A.

    2017-12-01

    In the 20th century, seismologists constructed models of how average physical properties (e.g. density, rigidity, compressibility, anisotropy) vary with depth in the Earth's interior. These one-dimensional (1D) reference Earth models (e.g. PREM) have proven indispensable in earthquake location, imaging of interior structure, understanding material properties under extreme conditions, and as a reference in other fields, such as particle physics and astronomy. Over the past three decades, new datasets motivated more sophisticated efforts that yielded models of how properties vary both laterally and with depth in the Earth's interior. Though these three-dimensional (3D) models exhibit compelling similarities at large scales, differences in the methodology, representation of structure, and dataset upon which they are based, have prevented the creation of 3D community reference models. As part of the REM-3D project, we are compiling and reconciling reference seismic datasets of body wave travel-time measurements, fundamental mode and overtone surface wave dispersion measurements, and normal mode frequencies and splitting functions. These reference datasets are being inverted for a long-wavelength, 3D reference Earth model that describes the robust long-wavelength features of mantle heterogeneity. As a community reference model with fully quantified uncertainties and tradeoffs and an associated publically available dataset, REM-3D will facilitate Earth imaging studies, earthquake characterization, inferences on temperature and composition in the deep interior, and be of improved utility to emerging scientific endeavors, such as neutrino geoscience. Here, we summarize progress made in the construction of the reference long period dataset and present a preliminary version of REM-3D in the upper-mantle. In order to determine the level of detail warranted for inclusion in REM-3D, we analyze the spectrum of discrepancies between models inverted with different subsets of the

  18. Sparse Modeling Reveals miRNA Signatures for Diagnostics of Inflammatory Bowel Disease.

    Directory of Open Access Journals (Sweden)

    Matthias Hübenthal

    Full Text Available The diagnosis of inflammatory bowel disease (IBD still remains a clinical challenge and the most accurate diagnostic procedure is a combination of clinical tests including invasive endoscopy. In this study we evaluated whether systematic miRNA expression profiling, in conjunction with machine learning techniques, is suitable as a non-invasive test for the major IBD phenotypes (Crohn's disease (CD and ulcerative colitis (UC. Based on microarray technology, expression levels of 863 miRNAs were determined for whole blood samples from 40 CD and 36 UC patients and compared to data from 38 healthy controls (HC. To further discriminate between disease-specific and general inflammation we included miRNA expression data from other inflammatory diseases (inflammation controls (IC: 24 chronic obstructive pulmonary disease (COPD, 23 multiple sclerosis, 38 pancreatitis and 45 sarcoidosis cases as well as 70 healthy controls from previous studies. Classification problems considering 2, 3 or 4 groups were solved using different types of penalized support vector machines (SVMs. The resulting models were assessed regarding sparsity and performance and a subset was selected for further investigation. Measured by the area under the ROC curve (AUC the corresponding median holdout-validated accuracy was estimated as ranging from 0.75 to 1.00 (including IC and 0.89 to 0.98 (excluding IC, respectively. In combination, the corresponding models provide tools for the distinction of CD and UC as well as CD, UC and HC with expected classification error rates of 3.1 and 3.3%, respectively. These results were obtained by incorporating not more than 16 distinct miRNAs. Validated target genes of these miRNAs have been previously described as being related to IBD. For others we observed significant enrichment for IBD susceptibility loci identified in earlier GWAS. These results suggest that the proposed miRNA signature is of relevance for the etiology of IBD. Its diagnostic

  19. Climate model biases in seasonality of continental water storage revealed by satellite gravimetry

    Science.gov (United States)

    Swenson, Sean; Milly, P.C.D.

    2006-01-01

    Satellite gravimetric observations of monthly changes in continental water storage are compared with outputs from five climate models. All models qualitatively reproduce the global pattern of annual storage amplitude, and the seasonal cycle of global average storage is reproduced well, consistent with earlier studies. However, global average agreements mask systematic model biases in low latitudes. Seasonal extrema of low‐latitude, hemispheric storage generally occur too early in the models, and model‐specific errors in amplitude of the low‐latitude annual variations are substantial. These errors are potentially explicable in terms of neglected or suboptimally parameterized water stores in the land models and precipitation biases in the climate models.

  20. Financial analysis and forecasting of the results of small businesses performance based on regression model

    Directory of Open Access Journals (Sweden)

    Svetlana O. Musienko

    2017-03-01

    Full Text Available Objective to develop the economicmathematical model of the dependence of revenue on other balance sheet items taking into account the sectoral affiliation of the companies. Methods using comparative analysis the article studies the existing approaches to the construction of the company management models. Applying the regression analysis and the least squares method which is widely used for financial management of enterprises in Russia and abroad the author builds a model of the dependence of revenue on other balance sheet items taking into account the sectoral affiliation of the companies which can be used in the financial analysis and prediction of small enterprisesrsquo performance. Results the article states the need to identify factors affecting the financial management efficiency. The author analyzed scientific research and revealed the lack of comprehensive studies on the methodology for assessing the small enterprisesrsquo management while the methods used for large companies are not always suitable for the task. The systematized approaches of various authors to the formation of regression models describe the influence of certain factors on the company activity. It is revealed that the resulting indicators in the studies were revenue profit or the company relative profitability. The main drawback of most models is the mathematical not economic approach to the definition of the dependent and independent variables. Basing on the analysis it was determined that the most correct is the model of dependence between revenues and total assets of the company using the decimal logarithm. The model was built using data on the activities of the 507 small businesses operating in three spheres of economic activity. Using the presented model it was proved that there is direct dependence between the sales proceeds and the main items of the asset balance as well as differences in the degree of this effect depending on the economic activity of small

  1. Genetic models reveal historical patterns of sea lamprey population fluctuations within Lake Champlain

    Directory of Open Access Journals (Sweden)

    Cassidy C. D’Aloia

    2015-10-01

    Full Text Available The origin of sea lamprey (Petromyzon marinus in Lake Champlain has been heavily debated over the past decade. Given the lack of historical documentation, two competing hypotheses have emerged in the literature. First, it has been argued that the relatively recent population size increase and concomitant rise in wounding rates on prey populations are indicative of an invasive population that entered the lake through the Champlain Canal. Second, recent genetic evidence suggests a post-glacial colonization at the end of the Pleistocene, approximately 11,000 years ago. One limitation to resolving the origin of sea lamprey in Lake Champlain is a lack of historical and current measures of population size. In this study, the issue of population size was explicitly addressed using nuclear (nDNA and mitochondrial DNA (mtDNA markers to estimate historical demography with genetic models. Haplotype network analysis, mismatch analysis, and summary statistics based on mtDNA noncoding sequences for NCI (479 bp and NCII (173 bp all indicate a recent population expansion. Coalescent models based on mtDNA and nDNA identified two potential demographic events: a population decline followed by a very recent population expansion. The decline in effective population size may correlate with land-use and fishing pressure changes post-European settlement, while the recent expansion may be associated with the implementation of the salmonid stocking program in the 1970s. These results are most consistent with the hypothesis that sea lamprey are native to Lake Champlain; however, the credibility intervals around parameter estimates demonstrate that there is uncertainty regarding the magnitude and timing of past demographic events.

  2. Genome association study through nonlinear mixed models revealed new candidate genes for pig growth curves

    Directory of Open Access Journals (Sweden)

    Fabyano Fonseca e Silva

    Full Text Available ABSTRACT: Genome association analyses have been successful in identifying quantitative trait loci (QTLs for pig body weights measured at a single age. However, when considering the whole weight trajectories over time in the context of genome association analyses, it is important to look at the markers that affect growth curve parameters. The easiest way to consider them is via the two-step method, in which the growth curve parameters and marker effects are estimated separately, thereby resulting in a reduction of the statistical power and the precision of estimates. One efficient solution is to adopt nonlinear mixed models (NMM, which enables a joint modeling of the individual growth curves and marker effects. Our aim was to propose a genome association analysis for growth curves in pigs based on NMM as well as to compare it with the traditional two-step method. In addition, we also aimed to identify the nearest candidate genes related to significant SNP (single nucleotide polymorphism markers. The NMM presented a higher number of significant SNPs for adult weight (A and maturity rate (K, and provided a direct way to test SNP significance simultaneously for both the A and K parameters. Furthermore, all significant SNPs from the two-step method were also reported in the NMM analysis. The ontology of the three candidate genes (SH3BGRL2, MAPK14, and MYL9 derived from significant SNPs (simultaneously affecting A and K allows us to make inferences with regards to their contribution to the pig growth process in the population studied.

  3. A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.

    Science.gov (United States)

    Leacock, Stefanie W; Basse, Audrey N; Chandler, Garvin L; Kirk, Anne M; Rakheja, Dinesh; Amatruda, James F

    2012-01-01

    Ewing's sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing's sarcoma family tumors (ESFTs), which include peripheral primitive neuroectodermal tumors (PNETs), are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing's sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing's sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS-FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing's sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene.

  4. Recent shell-model results for exotic nuclei

    Directory of Open Access Journals (Sweden)

    Utsuno Yusuke

    2014-03-01

    Full Text Available We report on our recent advancement in the shell model and its applications to exotic nuclei, focusing on the shell evolution and large-scale calculations with the Monte Carlo shell model (MCSM. First, we test the validity of the monopole-based universal interaction (VMU as a shell-model interaction by performing large-scale shell-model calculations in two different mass regions using effective interactions which partly comprise VMU. Those calculations are successful and provide a deeper insight into the shell evolution beyond the single-particle model, in particular showing that the evolution of the spin-orbit splitting due to the tensor force plays a decisive role in the structure of the neutron-rich N ∼ 28 region and antimony isotopes. Next, we give a brief overview of recent developments in MCSM, and show that it is applicable to exotic nuclei that involve many valence orbits. As an example of its applications to exotic nuclei, shape coexistence in 32Mg is examined.

  5. A model for hot electron phenomena: Theory and general results

    International Nuclear Information System (INIS)

    Carrillo, J.L.; Rodriquez, M.A.

    1988-10-01

    We propose a model for the description of the hot electron phenomena in semiconductors. Based on this model we are able to reproduce accurately the main characteristics observed in experiments of electric field transport, optical absorption, steady state photoluminescence and relaxation process. Our theory does not contain free nor adjustable parameters, it is very fast computerwise, and incorporates the main collision mechanisms including screening and phonon heating effects. Our description on a set of nonlinear rate equations in which the interactions are represented by coupling coefficients or effective frequencies. We calculate three coefficients from the characteristic constants and the band structure of the material. (author). 22 refs, 5 figs, 1 tab

  6. Results from Development of Model Specifications for Multifamily Energy Retrofits

    Energy Technology Data Exchange (ETDEWEB)

    Brozyna, K.

    2012-08-01

    Specifications, modeled after CSI MasterFormat, provide the trade contractors and builders with requirements and recommendations on specific building materials, components and industry practices that comply with the expectations and intent of the requirements within the various funding programs associated with a project. The goal is to create a greater level of consistency in execution of energy efficiency retrofits measures across the multiple regions a developer may work. IBACOS and Mercy Housing developed sample model specifications based on a common building construction type that Mercy Housing encounters.

  7. Results From Development of Model Specifications for Multifamily Energy Retrofits

    Energy Technology Data Exchange (ETDEWEB)

    Brozyna, Kevin [IBACOS, Inc., Pittsburgh, PA (United States)

    2012-08-01

    Specifications, modeled after CSI MasterFormat, provide the trade contractors and builders with requirements and recommendations on specific building materials, components and industry practices that comply with the expectations and intent of the requirements within the various funding programs associated with a project. The goal is to create a greater level of consistency in execution of energy efficiency retrofits measures across the multiple regions a developer may work. IBACOS and Mercy Housing developed sample model specifications based on a common building construction type that Mercy Housing encounters.

  8. Analytical results for the Sznajd model of opinion formation

    Czech Academy of Sciences Publication Activity Database

    Slanina, František; Lavička, H.

    2003-01-01

    Roč. 35, - (2003), s. 279-288 ISSN 1434-6028 R&D Projects: GA ČR GA202/01/1091 Institutional research plan: CEZ:AV0Z1010914 Keywords : agent models * sociophysics Subject RIV: BE - Theoretical Physics Impact factor: 1.457, year: 2003

  9. Meteorological Uncertainty of atmospheric Dispersion model results (MUD)

    DEFF Research Database (Denmark)

    Havskov Sørensen, Jens; Amstrup, Bjarne; Feddersen, Henrik

    The MUD project addresses assessment of uncertainties of atmospheric dispersion model predictions, as well as possibilities for optimum presentation to decision makers. Previously, it has not been possible to estimate such uncertainties quantitatively, but merely to calculate the ‘most likely’ di...

  10. Some Results On The Modelling Of TSS Manufacturing Lines

    Directory of Open Access Journals (Sweden)

    Viorel MÎNZU

    2000-12-01

    Full Text Available This paper deals with the modelling of a particular class of manufacturing lines, governed by a decentralised control strategy so that they balance themselves. Such lines are known as “bucket brigades” and also as “TSS lines”, after their first implementation, at Toyota, in the 70’s. A first study of their behaviour was based upon modelling as stochastic dynamic systems, which emphasised, in the frame of the so-called “Normative Model”, a sufficient condition for self-balancing, that means for autonomous functioning at a steady production rate (stationary behaviour. Under some particular conditions, a simulation analysis of TSS lines could be made on non-linear block diagrams, showing that the state trajectories are piecewise continuous in between occurrences of certain discrete events, which determine their discontinuity. TSS lines may therefore be modelled as hybrid dynamic systems, more specific, with autonomous switching and autonomous impulses (jumps. A stability analysis of such manufacturing lines is allowed by modelling them as hybrid dynamic systems with discontinuous motions.

  11. Recent numerical results on the two dimensional Hubbard model

    Energy Technology Data Exchange (ETDEWEB)

    Parola, A.; Sorella, S.; Baroni, S.; Car, R.; Parrinello, M.; Tosatti, E. (SISSA, Trieste (Italy))

    1989-12-01

    A new method for simulating strongly correlated fermionic systems, has been applied to the study of the ground state properties of the 2D Hubbard model at various fillings. Comparison has been made with exact diagonalizations in the 4 x 4 lattices where very good agreement has been verified in all the correlation functions which have been studied: charge, magnetization and momentum distribution. (orig.).

  12. Recent numerical results on the two dimensional Hubbard model

    International Nuclear Information System (INIS)

    Parola, A.; Sorella, S.; Baroni, S.; Car, R.; Parrinello, M.; Tosatti, E.

    1989-01-01

    This paper reports a new method for simulating strongly correlated fermionic systems applied to the study of the ground state properties of the 2D Hubbard model at various fillings. Comparison has been made with exact diagonalizations in the 4 x 4 lattices where very good agreement has been verified in all the correlation functions which have been studied: charge, magnetization and momentum distribution

  13. Some rigorous results on the Hopfield neural network model

    International Nuclear Information System (INIS)

    Koch, H.; Piasko, J.

    1989-01-01

    The authors analyze the thermal equilibrium distribution of 2 p mean field variables for the Hopfield model with p stored patterns, in the case where 2 p is small compared to the number of spins. In particular, they give a full description of the free energy density in the thermodynamic limit, and of the so-called symmetric solutions for the mean field equations

  14. Energy consumption and economic growth in New Zealand: Results of trivariate and multivariate models

    International Nuclear Information System (INIS)

    Bartleet, Matthew; Gounder, Rukmani

    2010-01-01

    This study examines the energy consumption-growth nexus in New Zealand. Causal linkages between energy and macroeconomic variables are investigated using trivariate demand-side and multivariate production models. Long run and short run relationships are estimated for the period 1960-2004. The estimated results of demand model reveal a long run relationship between energy consumption, real GDP and energy prices. The short run results indicate that real GDP Granger-causes energy consumption without feedback, consistent with the proposition that energy demand is a derived demand. Energy prices are found to be significant for energy consumption outcomes. Production model results indicate a long run relationship between real GDP, energy consumption and employment. The Granger-causality is found from real GDP to energy consumption, providing additional evidence to support the neoclassical proposition that energy consumption in New Zealand is fundamentally driven by economic activities. Inclusion of capital in the multivariate production model shows short run causality from capital to energy consumption. Also, changes in real GDP and employment have significant predictive power for changes in real capital.

  15. Spatially Explicit Modeling Reveals Cephalopod Distributions Match Contrasting Trophic Pathways in the Western Mediterranean Sea.

    Directory of Open Access Journals (Sweden)

    Patricia Puerta

    Full Text Available Populations of the same species can experience different responses to the environment throughout their distributional range as a result of spatial and temporal heterogeneity in habitat conditions. This highlights the importance of understanding the processes governing species distribution at local scales. However, research on species distribution often averages environmental covariates across large geographic areas, missing variability in population-environment interactions within geographically distinct regions. We used spatially explicit models to identify interactions between species and environmental, including chlorophyll a (Chla and sea surface temperature (SST, and trophic (prey density conditions, along with processes governing the distribution of two cephalopods with contrasting life-histories (octopus and squid across the western Mediterranean Sea. This approach is relevant for cephalopods, since their population dynamics are especially sensitive to variations in habitat conditions and rarely stable in abundance and location. The regional distributions of the two cephalopod species matched two different trophic pathways present in the western Mediterranean Sea, associated with the Gulf of Lion upwelling and the Ebro river discharges respectively. The effects of the studied environmental and trophic conditions were spatially variant in both species, with usually stronger effects along their distributional boundaries. We identify areas where prey availability limited the abundance of cephalopod populations as well as contrasting effects of temperature in the warmest regions. Despite distributional patterns matching productive areas, a general negative effect of Chla on cephalopod densities suggests that competition pressure is common in the study area. Additionally, results highlight the importance of trophic interactions, beyond other common environmental factors, in shaping the distribution of cephalopod populations. Our study presents

  16. A mouse model for Costello syndrome reveals an Ang II–mediated hypertensive condition

    Science.gov (United States)

    Schuhmacher, Alberto J.; Guerra, Carmen; Sauzeau, Vincent; Cañamero, Marta; Bustelo, Xosé R.; Barbacid, Mariano

    2008-01-01

    Germline activation of H-RAS oncogenes is the primary cause of Costello syndrome (CS), a neuro-cardio-facio-cutaneous developmental syndrome. Here we describe the generation of a mouse model of CS by introduction of an oncogenic Gly12Val mutation in the mouse H-Ras locus using homologous recombination in ES cells. Germline expression of the endogenous H-RasG12V oncogene, even in homozygosis, resulted in hyperplasia of the mammary gland. However, development of tumors in these mice was rare. H-RasG12V mutant mice closely phenocopied some of the abnormalities observed in patients with CS, including facial dysmorphia and cardiomyopathies. These mice also displayed alterations in the homeostasis of the cardiovascular system, including development of systemic hypertension, extensive vascular remodeling, and fibrosis in both the heart and the kidneys. This phenotype was age dependent and was a consequence of the abnormal upregulation of the renin–Ang II system. Treatment with captopril, an inhibitor of Ang II biosynthesis, prevented development of the hypertension condition, vascular remodeling, and heart and kidney fibrosis. In addition, it partially alleviated the observed cardiomyopathies. These mice should help in elucidating the etiology of CS symptoms, identifying additional defects, and evaluating potential therapeutic strategies. PMID:18483625

  17. Fortune Favours the Bold: An Agent-Based Model Reveals Adaptive Advantages of Overconfidence in War

    Science.gov (United States)

    Johnson, Dominic D. P.; Weidmann, Nils B.; Cederman, Lars-Erik

    2011-01-01

    Overconfidence has long been considered a cause of war. Like other decision-making biases, overconfidence seems detrimental because it increases the frequency and costs of fighting. However, evolutionary biologists have proposed that overconfidence may also confer adaptive advantages: increasing ambition, resolve, persistence, bluffing opponents, and winning net payoffs from risky opportunities despite occasional failures. We report the results of an agent-based model of inter-state conflict, which allows us to evaluate the performance of different strategies in competition with each other. Counter-intuitively, we find that overconfident states predominate in the population at the expense of unbiased or underconfident states. Overconfident states win because: (1) they are more likely to accumulate resources from frequent attempts at conquest; (2) they are more likely to gang up on weak states, forcing victims to split their defences; and (3) when the decision threshold for attacking requires an overwhelming asymmetry of power, unbiased and underconfident states shirk many conflicts they are actually likely to win. These “adaptive advantages” of overconfidence may, via selection effects, learning, or evolved psychology, have spread and become entrenched among modern states, organizations and decision-makers. This would help to explain the frequent association of overconfidence and war, even if it no longer brings benefits today. PMID:21731627

  18. Can representational trajectory reveal the nature of an internal model of gravity?

    Science.gov (United States)

    De Sá Teixeira, Nuno; Hecht, Heiko

    2014-05-01

    The memory for the vanishing location of a horizontally moving target is usually displaced forward in the direction of motion (representational momentum) and downward in the direction of gravity (representational gravity). Moreover, this downward displacement has been shown to increase with time (representational trajectory). However, the degree to which different kinematic events change the temporal profile of these displacements remains to be determined. The present article attempts to fill this gap. In the first experiment, we replicate the finding that representational momentum for downward-moving targets is bigger than for upward motions, showing, moreover, that it increases rapidly during the first 300 ms, stabilizing afterward. This temporal profile, but not the increased error for descending targets, is shown to be disrupted when eye movements are not allowed. In the second experiment, we show that the downward drift with time emerges even for static targets. Finally, in the third experiment, we report an increased error for upward-moving targets, as compared with downward movements, when the display is compatible with a downward ego-motion by including vection cues. Thus, the errors in the direction of gravity are compatible with the perceived event and do not merely reflect a retinotopic bias. Overall, these results provide further evidence for an internal model of gravity in the visual representational system.

  19. Glioblastoma models reveal the connection between adult glial progenitors and the proneural phenotype.

    Directory of Open Access Journals (Sweden)

    Liang Lei

    Full Text Available Tumor heterogeneity is a major obstacle for finding effective treatment of Glioblastoma (GBM. Based on global expression analysis, GBM can be classified into distinct subtypes: Proneural, Neural, Classical and Mesenchymal. The signatures of these different tumor subtypes may reflect the phenotypes of cells giving rise to them. However, the experimental evidence connecting any specific subtype of GBM to particular cells of origin is lacking. In addition, it is unclear how different genetic alterations interact with cells of origin in determining tumor heterogeneity. This issue cannot be addressed by studying end-stage human tumors.To address this issue, we used retroviruses to deliver transforming genetic lesions to glial progenitors in adult mouse brain. We compared the resulting tumors to human GBM. We found that different initiating genetic lesions gave rise to tumors with different growth rates. However all mouse tumors closely resembled the human Proneural GBM. Comparative analysis of these mouse tumors allowed us to identify a set of genes whose expression in humans with Proneural GBM correlates with survival.This study offers insights into the relationship between adult glial progenitors and Proneural GBM, and allows us to identify molecular alterations that lead to more aggressive tumor growth. In addition, we present a new preclinical model that can be used to test treatments directed at a specific type of GBM in future studies.

  20. Nonmotor symptoms of Parkinson's disease revealed in an animal model with reduced monoamine storage capacity.

    Science.gov (United States)

    Taylor, Tonya N; Caudle, W Michael; Shepherd, Kennie R; Noorian, AliReza; Jackson, Chad R; Iuvone, P Michael; Weinshenker, David; Greene, James G; Miller, Gary W

    2009-06-24

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the loss of dopamine neurons in the substantia nigra pars compacta, culminating in severe motor symptoms, including resting tremor, rigidity, bradykinesia, and postural instability. In addition to motor deficits, there are a variety of nonmotor symptoms associated with PD. These symptoms generally precede the onset of motor symptoms, sometimes by years, and include anosmia, problems with gastrointestinal motility, sleep disturbances, sympathetic denervation, anxiety, and depression. Previously, we have shown that mice with a 95% genetic reduction in vesicular monoamine transporter expression (VMAT2-deficient, VMAT2 LO) display progressive loss of striatal dopamine, L-DOPA-responsive motor deficits, alpha-synuclein accumulation, and nigral dopaminergic cell loss. We hypothesized that since these animals exhibit deficits in other monoamine systems (norepinephrine and serotonin), which are known to regulate some of these behaviors, the VMAT2-deficient mice may display some of the nonmotor symptoms associated with PD. Here we report that the VMAT2-deficient mice demonstrate progressive deficits in olfactory discrimination, delayed gastric emptying, altered sleep latency, anxiety-like behavior, and age-dependent depressive behavior. These results suggest that the VMAT2-deficient mice may be a useful model of the nonmotor symptoms of PD. Furthermore, monoamine dysfunction may contribute to many of the nonmotor symptoms of PD, and interventions aimed at restoring monoamine function may be beneficial in treating the disease.

  1. Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism[S

    Science.gov (United States)

    Palczewski, Grzegorz; Widjaja-Adhi, M. Airanthi K.; Amengual, Jaume; Golczak, Marcin; von Lintig, Johannes

    2016-01-01

    Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health. However, knowledge about their biological action and the consequences of their dietary accumulation in mammals is limited. Progress in this research field is limited by the expeditious metabolism of carotenoids in rodents and the confounding production of apocarotenoid signaling molecules. Herein, we established a mouse model lacking the enzymes responsible for carotenoid catabolism and apocarotenoid production, fed on either a β-carotene- or a zeaxanthin-enriched diet. Applying a genome wide microarray analysis, we assessed the effects of the parent carotenoids on the liver transcriptome. Our analysis documented changes in pathways for liver lipid metabolism and mitochondrial respiration. We biochemically defined these effects, and observed that β-carotene accumulation resulted in an elevation of liver triglycerides and liver cholesterol, while zeaxanthin accumulation increased serum cholesterol levels. We further show that carotenoids were predominantly transported within HDL particles in the serum of mice. Finally, we provide evidence that carotenoid accumulation influenced whole-body respiration and energy expenditure. Thus, we observed that accumulation of parent carotenoids interacts with lipid metabolism and that structurally related carotenoids display distinct biological functions in mammals. PMID:27389691

  2. Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism.

    Science.gov (United States)

    Palczewski, Grzegorz; Widjaja-Adhi, M Airanthi K; Amengual, Jaume; Golczak, Marcin; von Lintig, Johannes

    2016-09-01

    Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health. However, knowledge about their biological action and the consequences of their dietary accumulation in mammals is limited. Progress in this research field is limited by the expeditious metabolism of carotenoids in rodents and the confounding production of apocarotenoid signaling molecules. Herein, we established a mouse model lacking the enzymes responsible for carotenoid catabolism and apocarotenoid production, fed on either a β-carotene- or a zeaxanthin-enriched diet. Applying a genome wide microarray analysis, we assessed the effects of the parent carotenoids on the liver transcriptome. Our analysis documented changes in pathways for liver lipid metabolism and mitochondrial respiration. We biochemically defined these effects, and observed that β-carotene accumulation resulted in an elevation of liver triglycerides and liver cholesterol, while zeaxanthin accumulation increased serum cholesterol levels. We further show that carotenoids were predominantly transported within HDL particles in the serum of mice. Finally, we provide evidence that carotenoid accumulation influenced whole-body respiration and energy expenditure. Thus, we observed that accumulation of parent carotenoids interacts with lipid metabolism and that structurally related carotenoids display distinct biological functions in mammals. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  3. Regionalization of climate model results for the North Sea

    Energy Technology Data Exchange (ETDEWEB)

    Kauker, F. [Alfred-Wegener-Institut fuer Polar- und Meeresforschung, Bremerhaven (Germany); Storch, H. von [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Hydrophysik

    2000-07-01

    A dynamical downscaling for the North Sea is presented. The numerical model used for the study is the coupled ice-ocean model OPYC. In a hindcast of the years 1979 to 1993 it was forced with atmospheric forcing of the ECMWF reanalysis. The models capability in simulating the observed mean state and variability in the North Sea is demonstrated by the hindcast. Two time scale ranges, from weekly to seasonal and the longer-than-seasonal time scales are investigated. Shorter time scales, for storm surges, are not captured by the model formulation. The main modes of variability of sea level, sea-surface circulation, sea-surface temperature, and sea-surface salinity are described and connections to atmospheric phenomena, like the NAO, are discussed. T106 ''time-slice'' simulations with a ''2 x CO{sub 2}'' horizon are used to estimate the effects of a changing climate on the shelf sea ''North Sea''. The ''2 x CO{sub 2}'' changes in the surface forcing are accompanied by changes in the lateral oceanic boundary conditions taken from a global coupled climate model. For ''2 x CO{sub 2}'' the time mean sea level increases up to 25 cm in the German Bight in the winter, where 15 cm are due to the surface forcing and 10 cm due to thermal expansion. This change is compared to the ''natural'' variability as simulated in the ECMWF integration and found to be not outside the range spanned by it. The variability of sea level on the weekly-to-seasonal time-scales is significantly reduced in the scenario integration. The variability on the longer-than-seasonal time-scales in the control and scenario runs is much smaller then in the ECMWF integration. This is traced back to the use of ''time-slice'' experiments. Discriminating between locally forced changes and changes induced at the lateral oceanic boundaries of the model in the circulation and

  4. Guiding center model to interpret neutral particle analyzer results

    Science.gov (United States)

    Englert, G. W.; Reinmann, J. J.; Lauver, M. R.

    1974-01-01

    The theoretical model is discussed, which accounts for drift and cyclotron components of ion motion in a partially ionized plasma. Density and velocity distributions are systematically precribed. The flux into the neutral particle analyzer (NPA) from this plasma is determined by summing over all charge exchange neutrals in phase space which are directed into apertures. Especially detailed data, obtained by sweeping the line of sight of the apertures across the plasma of the NASA Lewis HIP-1 burnout device, are presented. Selection of randomized cyclotron velocity distributions about mean azimuthal drift yield energy distributions which compared well with experiment. Use of data obtained with a bending magnet on the NPA showed that separation between energy distribution curves of various mass species correlate well with a drift divided by mean cyclotron energy parameter of the theory. Use of the guiding center model in conjunction with NPA scans across the plasma aid in estimates of ion density and E field variation with plasma radius.

  5. Use of results from microscopic methods in optical model calculations

    International Nuclear Information System (INIS)

    Lagrange, C.

    1985-11-01

    A concept of vectorization for coupled-channel programs based upon conventional methods is first presented. This has been implanted in our program for its use on the CRAY-1 computer. In a second part we investigate the capabilities of a semi-microscopic optical model involving fewer adjustable parameters than phenomenological ones. The two main ingredients of our calculations are, for spherical or well-deformed nuclei, the microscopic optical-model calculations of Jeukenne, Lejeune and Mahaux and nuclear densities from Hartree-Fock-Bogoliubov calculations using the density-dependent force D1. For transitional nuclei deformation-dependent nuclear structure wave functions are employed to weigh the scattering potentials for different shapes and channels [fr

  6. Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.

    Science.gov (United States)

    Berkes, Pietro; Orbán, Gergo; Lengyel, Máté; Fiser, József

    2011-01-07

    The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.

  7. Non-parametric Bayesian graph models reveal community structure in resting state fMRI

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther; Madsen, Kristoffer H.; Siebner, Hartwig Roman

    2014-01-01

    Modeling of resting state functional magnetic resonance imaging (rs-fMRI) data using network models is of increasing interest. It is often desirable to group nodes into clusters to interpret the communication patterns between nodes. In this study we consider three different nonparametric Bayesian...... models for node clustering in complex networks. In particular, we test their ability to predict unseen data and their ability to reproduce clustering across datasets. The three generative models considered are the Infinite Relational Model (IRM), Bayesian Community Detection (BCD), and the Infinite...... between clusters. BCD restricts the between-cluster link probabilities to be strictly lower than within-cluster link probabilities to conform to the community structure typically seen in social networks. IDM only models a single between-cluster link probability, which can be interpreted as a background...

  8. 1-g model loading tests: methods and results

    Czech Academy of Sciences Publication Activity Database

    Feda, Jaroslav

    1999-01-01

    Roč. 2, č. 4 (1999), s. 371-381 ISSN 1436-6517. [Int.Conf. on Soil - Structure Interaction in Urban Civ. Engineering. Darmstadt, 08.10.1999-09.10.1999] R&D Projects: GA MŠk OC C7.10 Keywords : shallow foundation * model tests * sandy subsoil * bearing capacity * subsoil failure * volume deformation Subject RIV: JM - Building Engineering

  9. Considerations on Modeling Strategies of the Financial Result

    Directory of Open Access Journals (Sweden)

    Lucian Cernuşca

    2012-12-01

    Full Text Available This study's objective is to highlight some of the strategies to maximize or minimize the accounting result, situated un-der the impulse of bad accounting. Although we assist the manipulation of the accounting result, this procedure is done according to the law, been exploited by some entities in knowledge of the lack of justice and accounting regulations.

  10. DISCRETE DEFORMATION WAVE DYNAMICS IN SHEAR ZONES: PHYSICAL MODELLING RESULTS

    Directory of Open Access Journals (Sweden)

    S. A. Bornyakov

    2016-01-01

    Full Text Available Observations of earthquake migration along active fault zones [Richter, 1958; Mogi, 1968] and related theoretical concepts [Elsasser, 1969] have laid the foundation for studying the problem of slow deformation waves in the lithosphere. Despite the fact that this problem has been under study for several decades and discussed in numerous publications, convincing evidence for the existence of deformation waves is still lacking. One of the causes is that comprehensive field studies to register such waves by special tools and equipment, which require sufficient organizational and technical resources, have not been conducted yet.The authors attempted at finding a solution to this problem by physical simulation of a major shear zone in an elastic-viscous-plastic model of the lithosphere. The experiment setup is shown in Figure 1 (A. The model material and boundary conditions were specified in accordance with the similarity criteria (described in detail in [Sherman, 1984; Sherman et al., 1991; Bornyakov et al., 2014]. The montmorillonite clay-and-water paste was placed evenly on two stamps of the installation and subject to deformation as the active stamp (1 moved relative to the passive stamp (2 at a constant speed. The upper model surface was covered with fine sand in order to get high-contrast photos. Photos of an emerging shear zone were taken every second by a Basler acA2000-50gm digital camera. Figure 1 (B shows an optical image of a fragment of the shear zone. The photos were processed by the digital image correlation method described in [Sutton et al., 2009]. This method estimates the distribution of components of displacement vectors and strain tensors on the model surface and their evolution over time [Panteleev et al., 2014, 2015].Strain fields and displacements recorded in the optical images of the model surface were estimated in a rectangular box (220.00×72.17 mm shown by a dot-and-dash line in Fig. 1, A. To ensure a sufficient level of

  11. Analysis of inelastic neutron scattering results on model compounds ...

    Indian Academy of Sciences (India)

    Vibrational spectroscopy; nitrogenous bases; inelastic neutron scattering. PACS No. ... obtain good quality, high resolution results in this region. Here the .... knowledge of the character of each molecular transition as well as the calculated.

  12. Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

    NARCIS (Netherlands)

    B. Schumacher (Björn); V. Bartels (Valerie); P. Frommolt (Peter); B. Habermann (Bianca); F. Braun (Fabian); J.L. Schultze (Joachim); M. Roodbergen (Marianne); J.H.J. Hoeijmakers (Jan); P. Nürnberg (Peter); M.E.T. Dollé (Martijn); T. Benzing (Thomas); R.-U. Müller (Roman-Ulrich); C.E. Kurschat (Christine)

    2013-01-01

    textabstractBackground: Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome

  13. MCNP Modeling Results for Location of Buried TRU Waste Drums

    International Nuclear Information System (INIS)

    Steinman, D K; Schweitzer, J S

    2006-01-01

    In the 1960's, fifty-five gallon drums of TRU waste were buried in shallow pits on remote U.S. Government facilities such as the Idaho National Engineering Laboratory (now split into the Idaho National Laboratory and the Idaho Completion Project [ICP]). Subsequently, it was decided to remove the drums and the material that was in them from the burial pits and send the material to the Waste Isolation Pilot Plant in New Mexico. Several technologies have been tried to locate the drums non-intrusively with enough precision to minimize the chance for material to be spread into the environment. One of these technologies is the placement of steel probe holes in the pits into which wireline logging probes can be lowered to measure properties and concentrations of material surrounding the probe holes for evidence of TRU material. There is also a concern that large quantities of volatile organic compounds (VOC) are also present that would contaminate the environment during removal. In 2001, the Idaho National Engineering and Environmental Laboratory (INEEL) built two pulsed neutron wireline logging tools to measure TRU and VOC around the probe holes. The tools are the Prompt Fission Neutron (PFN) and the Pulsed Neutron Gamma (PNG), respectively. They were tested experimentally in surrogate test holes in 2003. The work reported here estimates the performance of the tools using Monte-Carlo modelling prior to field deployment. A MCNP model was constructed by INEEL personnel. It was modified by the authors to assess the ability of the tools to predict quantitatively the position and concentration of TRU and VOC materials disposed around the probe holes. The model was used to simulate the tools scanning the probe holes vertically in five centimetre increments. A drum was included in the model that could be placed near the probe hole and at other locations out to forty-five centimetres from the probe-hole in five centimetre increments. Scans were performed with no chlorine in the

  14. Delta-tilde interpretation of standard linear mixed model results

    DEFF Research Database (Denmark)

    Brockhoff, Per Bruun; Amorim, Isabel de Sousa; Kuznetsova, Alexandra

    2016-01-01

    effects relative to the residual error and to choose the proper effect size measure. For multi-attribute bar plots of F-statistics this amounts, in balanced settings, to a simple transformation of the bar heights to get them transformed into depicting what can be seen as approximately the average pairwise...... data set and compared to actual d-prime calculations based on Thurstonian regression modeling through the ordinal package. For more challenging cases we offer a generic "plug-in" implementation of a version of the method as part of the R-package SensMixed. We discuss and clarify the bias mechanisms...

  15. Solar activity variations of ionosonde measurements and modeling results

    Czech Academy of Sciences Publication Activity Database

    Altadill, D.; Arrazola, D.; Blanch, E.; Burešová, Dalia

    2008-01-01

    Roč. 42, č. 4 (2008), s. 610-616 ISSN 0273-1177 R&D Projects: GA AV ČR 1QS300120506 Grant - others:MCYT(ES) REN2003-08376-C02-02; CSIC(XE) 2004CZ0002; AGAUR(XE) 2006BE00112; AF Research Laboratory(XE) FA8718-L-0072 Institutional research plan: CEZ:AV0Z30420517 Keywords : mid-latitude ionosphere * bottomside modeling * ionospheric variability Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 0.860, year: 2008 http://www.sciencedirect.com/science/journal/02731177

  16. NASA Air Force Cost Model (NAFCOM): Capabilities and Results

    Science.gov (United States)

    McAfee, Julie; Culver, George; Naderi, Mahmoud

    2011-01-01

    NAFCOM is a parametric estimating tool for space hardware. Uses cost estimating relationships (CERs) which correlate historical costs to mission characteristics to predict new project costs. It is based on historical NASA and Air Force space projects. It is intended to be used in the very early phases of a development project. NAFCOM can be used at the subsystem or component levels and estimates development and production costs. NAFCOM is applicable to various types of missions (crewed spacecraft, uncrewed spacecraft, and launch vehicles). There are two versions of the model: a government version that is restricted and a contractor releasable version.

  17. The calculation of exchange forces: General results and specific models

    International Nuclear Information System (INIS)

    Scott, T.C.; Babb, J.F.; Dalgarno, A.; Morgan, J.D. III

    1993-01-01

    In order to clarify questions about the calculation of the exchange energy of a homonuclear molecular ion, an analysis is carried out of a model problem consisting of the one-dimensional limit of H 2 + . It is demonstrated that the use of the infinite polarization expansion for the localized wave function in the Holstein--Herring formula yields an approximate exchange energy which at large internuclear distances R has the correct leading behavior to O(e -R ) and is close to but not equal to the exact exchange energy. The extension to the n-dimensional double-well problem is presented

  18. Guiding center model to interpret neutral particle analyzer results

    International Nuclear Information System (INIS)

    Englert, G.W.; Reinmann, J.J.; Lauver, M.R.

    1974-01-01

    The theoretical model is discussed, which accounts for drift and cyclotron components of ion motion in a partially ionized plasma. Density and velocity distributions are systematically prescribed. The flux into the neutron particle analyzer (NPA) from this plasma is determined by summing over all charge exchange neutrals in phase space which are directed into apertures. Especially detailed data, obtained by sweeping the line of sight of the apertures across the plasma of the NASA Lewis HIP-1 burnout device, are presented. Selection of randomized cyclotron velocity distributions about mean azimuthal drift yield energy distributions which compared well with experiment. Use of data obtained with a bending magnet on the NPA showed that separation between energy distribution curves of various mass species correlate well with a drift divided by mean cyclotron energy parameter of the theory. Use of the guiding center model in conjunction with NPA scans across the plasma aid in estimates of ion density and E field variation with plasma radius. (U.S.)

  19. First Results of Modeling Radiation Belt Electron Dynamics with the SAMI3 Plasmasphere Model

    Science.gov (United States)

    Komar, C. M.; Glocer, A.; Huba, J.; Fok, M. C. H.; Kang, S. B.; Buzulukova, N.

    2017-12-01

    The radiation belts were one of the first discoveries of the Space Age some sixty years ago and radiation belt models have been improving since the discovery of the radiation belts. The plasmasphere is one region that has been critically important to determining the dynamics of radiation belt populations. This region of space plays a critical role in describing the distribution of chorus and magnetospheric hiss waves throughout the inner magnetosphere. Both of these waves have been shown to interact with energetic electrons in the radiation belts and can result in the energization or loss of radiation belt electrons. However, radiation belt models have been historically limited in describing the distribution of cold plasmaspheric plasma and have relied on empirically determined plasmasphere models. Some plasmasphere models use an azimuthally symmetric distribution of the plasmasphere which can fail to capture important plasmaspheric dynamics such as the development of plasmaspheric drainage plumes. Previous work have coupled the kinetic bounce-averaged Comprehensive Inner Magnetosphere-Ionosphere (CIMI) model used to model ring current and radiation belt populations with the Block-adaptive Tree Solar wind Roe-type Upwind Scheme (BATSRUS) global magnetohydrodynamic model to self-consistently obtain the magnetospheric magnetic field and ionospheric potential. The present work will utilize this previous coupling and will additionally couple the SAMI3 plasmasphere model to better represent the dynamics on the plasmasphere and its role in determining the distribution of waves throughout the inner magnetosphere. First results on the relevance of chorus, hiss, and ultralow frequency waves on radiation belt electron dynamics will be discussed in context of the June 1st, 2013 storm-time dropout event.

  20. Experimental results and modeling of a dynamic hohlraum on SATURN

    International Nuclear Information System (INIS)

    Derzon, M.S.; Allshouse, G.O.; Deeney, C.; Leeper, R.J.; Nash, T.J.; Matuska, W.; Peterson, D.L.; MacFarlane, J.J.; Ryutov, D.D.

    1998-06-01

    Experiments were performed at SATURN, a high current z-pinch, to explore the feasibility of creating a hohlraum by imploding a tungsten wire array onto a low-density foam. Emission measurements in the 200--280 eV energy band were consistent with a 110--135 eV Planckian before the target shock heated, or stagnated, on-axis. Peak pinch radiation temperatures of nominally 160 eV were obtained. Measured early time x-ray emission histories and temperature estimates agree well with modeled performance in the 200--280 eV band using a 2D radiation magneto-hydrodynamics code. However, significant differences are observed in comparisons of the x-ray images and 2D simulations

  1. Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile X syndrome reveals limited, call type specific deficits.

    Directory of Open Access Journals (Sweden)

    Snigdha Roy

    Full Text Available Fragile X syndrome (FXS is a well-recognized form of inherited mental retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1 gene. The gene is located on the long arm of the X chromosome and encodes fragile X mental retardation protein (FMRP. Absence of FMRP in fragile X patients as well as in Fmr1 knockout (KO mice results, among other changes, in abnormal dendritic spine formation and altered synaptic plasticity in the neocortex and hippocampus. Clinical features of FXS include cognitive impairment, anxiety, abnormal social interaction, mental retardation, motor coordination and speech articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs when isolated from their mothers. Whether those social ultrasonic vocalizations are deficient in mouse models of FXS is unknown. Here we compared isolation-induced USVs generated by pups of Fmr1-KO mice with those of their wild type (WT littermates. Though the total number of calls was not significantly different between genotypes, a detailed analysis of 10 different categories of calls revealed that loss of Fmr1 expression in mice causes limited and call-type specific deficits in ultrasonic vocalization: the carrier frequency of flat calls was higher, the percentage of downward calls was lower and that the frequency range of complex calls was wider in Fmr1-KO mice compared to their WT littermates.

  2. Vulnerability of hydropower generation to climate change in China: Results based on Grey forecasting model

    International Nuclear Information System (INIS)

    Wang, Bing; Liang, Xiao-Jie; Zhang, Hao; Wang, Lu; Wei, Yi-Ming

    2014-01-01

    This paper analyzes the long-term relationships between hydropower generation and climate factors (precipitation), hydropower generation capacity (installed capacity of hydropower station) to quantify the vulnerability of renewable energy production in China for the case of hydropower generation. Furthermore, this study applies Grey forecasting model to forecast precipitation in different provinces, and then sets up different scenarios for precipitation based on the IPCC Special Report on Emission Scenarios and results from PRECIS (Providing Regional Climate projections for Impacts Studies) model. The most important result found in this research is the increasing hydropower vulnerability of the poorest regions and the main hydropower generation provinces of China to climate change. Other main empirical results reveal that the impacts of climate change on the supply of hydropower generation in China will be noteworthy for the society. Different scenarios have different effects on hydropower generation, of which A2 scenario (pessimistic, high emission) has the largest. Meanwhile, the impacts of climate change on hydropower generation of every province are distinctly different, of which the Southwest part has the higher vulnerability than the average level while the central part lower. - Highlights: • The hydropower vulnerability will be enlarged with the rapid increase of hydropower capacity. • Modeling the vulnerability of hydropower in different scenarios and different provinces. • The increasing hydropower vulnerability of the poorest regions to climate change. • The increasing hydropower vulnerability of the main hydropower generation provinces. • Rainfall pattern caused by climate change would be the reason for the increasing vulnerability

  3. Results of modeling advanced BWR fuel designs using CASMO-4

    International Nuclear Information System (INIS)

    Knott, D.; Edenius, M.

    1996-01-01

    Advanced BWR fuel designs from General Electric, Siemens and ABB-Atom have been analyzed using CASMO-4 and compared against fission rate distributions and control rod worths from MCNP. Included in the analysis were fuel storage rack configurations and proposed mixed oxide (MOX) designs. Results are also presented from several cycles of SIMULATE-3 core follow analysis, using nodal data generated by CASMO-4, for cycles in transition from 8x8 designs to advanced fuel designs. (author)

  4. Commensurate comparisons of models with energy budget observations reveal consistent climate sensitivities

    Science.gov (United States)

    Armour, K.

    2017-12-01

    Global energy budget observations have been widely used to constrain the effective, or instantaneous climate sensitivity (ICS), producing median estimates around 2°C (Otto et al. 2013; Lewis & Curry 2015). A key question is whether the comprehensive climate models used to project future warming are consistent with these energy budget estimates of ICS. Yet, performing such comparisons has proven challenging. Within models, values of ICS robustly vary over time, as surface temperature patterns evolve with transient warming, and are generally smaller than the values of equilibrium climate sensitivity (ECS). Naively comparing values of ECS in CMIP5 models (median of about 3.4°C) to observation-based values of ICS has led to the suggestion that models are overly sensitive. This apparent discrepancy can partially be resolved by (i) comparing observation-based values of ICS to model values of ICS relevant for historical warming (Armour 2017; Proistosescu & Huybers 2017); (ii) taking into account the "efficacies" of non-CO2 radiative forcing agents (Marvel et al. 2015); and (iii) accounting for the sparseness of historical temperature observations and differences in sea-surface temperature and near-surface air temperature over the oceans (Richardson et al. 2016). Another potential source of discrepancy is a mismatch between observed and simulated surface temperature patterns over recent decades, due to either natural variability or model deficiencies in simulating historical warming patterns. The nature of the mismatch is such that simulated patterns can lead to more positive radiative feedbacks (higher ICS) relative to those engendered by observed patterns. The magnitude of this effect has not yet been addressed. Here we outline an approach to perform fully commensurate comparisons of climate models with global energy budget observations that take all of the above effects into account. We find that when apples-to-apples comparisons are made, values of ICS in models are

  5. A Mouse Model of Visual Perceptual Learning Reveals Alterations in Neuronal Coding and Dendritic Spine Density in the Visual Cortex.

    Science.gov (United States)

    Wang, Yan; Wu, Wei; Zhang, Xian; Hu, Xu; Li, Yue; Lou, Shihao; Ma, Xiao; An, Xu; Liu, Hui; Peng, Jing; Ma, Danyi; Zhou, Yifeng; Yang, Yupeng

    2016-01-01

    Visual perceptual learning (VPL) can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF) for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS) and a 55% gain in visual acuity (VA). Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1) than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL.

  6. A mouse model of visual perceptual learning reveals alterations in neuronal coding and dendritic spine density in the visual cortex

    Directory of Open Access Journals (Sweden)

    Yan eWang

    2016-03-01

    Full Text Available Visual perceptual learning (VPL can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS and a 55% gain in visual acuity (VA. Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1 than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL.

  7. First results from the International Urban Energy Balance Model Comparison: Model Complexity

    Science.gov (United States)

    Blackett, M.; Grimmond, S.; Best, M.

    2009-04-01

    A great variety of urban energy balance models has been developed. These vary in complexity from simple schemes that represent the city as a slab, through those which model various facets (i.e. road, walls and roof) to more complex urban forms (including street canyons with intersections) and features (such as vegetation cover and anthropogenic heat fluxes). Some schemes also incorporate detailed representations of momentum and energy fluxes distributed throughout various layers of the urban canopy layer. The models each differ in the parameters they require to describe the site and the in demands they make on computational processing power. Many of these models have been evaluated using observational datasets but to date, no controlled comparisons have been conducted. Urban surface energy balance models provide a means to predict the energy exchange processes which influence factors such as urban temperature, humidity, atmospheric stability and winds. These all need to be modelled accurately to capture features such as the urban heat island effect and to provide key information for dispersion and air quality modelling. A comparison of the various models available will assist in improving current and future models and will assist in formulating research priorities for future observational campaigns within urban areas. In this presentation we will summarise the initial results of this international urban energy balance model comparison. In particular, the relative performance of the models involved will be compared based on their degree of complexity. These results will inform us on ways in which we can improve the modelling of air quality within, and climate impacts of, global megacities. The methodology employed in conducting this comparison followed that used in PILPS (the Project for Intercomparison of Land-Surface Parameterization Schemes) which is also endorsed by the GEWEX Global Land Atmosphere System Study (GLASS) panel. In all cases, models were run

  8. Exact results for the O( N ) model with quenched disorder

    Science.gov (United States)

    Delfino, Gesualdo; Lamsen, Noel

    2018-04-01

    We use scale invariant scattering theory to exactly determine the lines of renormalization group fixed points for O( N )-symmetric models with quenched disorder in two dimensions. Random fixed points are characterized by two disorder parameters: a modulus that vanishes when approaching the pure case, and a phase angle. The critical lines fall into three classes depending on the values of the disorder modulus. Besides the class corresponding to the pure case, a second class has maximal value of the disorder modulus and includes Nishimori-like multicritical points as well as zero temperature fixed points. The third class contains critical lines that interpolate, as N varies, between the first two classes. For positive N , it contains a single line of infrared fixed points spanning the values of N from √{2}-1 to 1. The symmetry sector of the energy density operator is superuniversal (i.e. N -independent) along this line. For N = 2 a line of fixed points exists only in the pure case, but accounts also for the Berezinskii-Kosterlitz-Thouless phase observed in presence of disorder.

  9. Modeling Framework and Results to Inform Charging Infrastructure Investments

    Energy Technology Data Exchange (ETDEWEB)

    Melaina, Marc W [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Wood, Eric W [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-01

    The plug-in electric vehicle (PEV) market is experiencing rapid growth with dozens of battery electric (BEV) and plug-in hybrid electric (PHEV) models already available and billions of dollars being invested by automotive manufacturers in the PEV space. Electric range is increasing thanks to larger and more advanced batteries and significant infrastructure investments are being made to enable higher power fast charging. Costs are falling and PEVs are becoming more competitive with conventional vehicles. Moreover, new technologies such as connectivity and automation hold the promise of enhancing the value proposition of PEVs. This presentation outlines a suite of projects funded by the U.S. Department of Energy's Vehicle Technology Office to conduct assessments of the economic value and charging infrastructure requirements of the evolving PEV market. Individual assessments include national evaluations of PEV economic value (assuming 73M PEVs on the road in 2035), national analysis of charging infrastructure requirements (with community and corridor level resolution), and case studies of PEV ownership in Columbus, OH and Massachusetts.

  10. The Multipole Plasma Trap-PIC Modeling Results

    Science.gov (United States)

    Hicks, Nathaniel; Bowman, Amanda; Godden, Katarina

    2017-10-01

    A radio-frequency (RF) multipole structure is studied via particle-in-cell computer modeling, to assess the response of quasi-neutral plasma to the imposed RF fields. Several regimes, such as pair plasma, antimatter plasma, and conventional (ion-electron) plasma are considered. In the case of equal charge-to-mass ratio of plasma species, the effects of the multipole field are symmetric between positive and negative particles. In the case of a charge-to-mass disparity, the multipole RF parameters (frequency, voltage, structure size) may be chosen such that the light species (e.g. electrons) is strongly confined, while the heavy species (e.g. positive ions) does not respond to the RF field. In this case, the trapped negative space charge creates a potential well that then traps the positive species. 2D and 3D particle-in-cell simulations of this concept are presented, to assess plasma response and trapping dependences on multipole order, consequences of the formation of an RF plasma sheath, and the effects of an axial magnetic field. The scalings of trapped plasma parameters are explored in each of the mentioned regimes, to guide the design of prospective experiments investigating each. Supported by U.S. NSF/DOE Partnership in Basic Plasma Science and Engineering Grant PHY-1619615.

  11. Systems Perturbation Analysis of a Large-Scale Signal Transduction Model Reveals Potentially Influential Candidates for Cancer Therapeutics

    Science.gov (United States)

    Puniya, Bhanwar Lal; Allen, Laura; Hochfelder, Colleen; Majumder, Mahbubul; Helikar, Tomáš

    2016-01-01

    Dysregulation in signal transduction pathways can lead to a variety of complex disorders, including cancer. Computational approaches such as network analysis are important tools to understand system dynamics as well as to identify critical components that could be further explored as therapeutic targets. Here, we performed perturbation analysis of a large-scale signal transduction model in extracellular environments that stimulate cell death, growth, motility, and quiescence. Each of the model’s components was perturbed under both loss-of-function and gain-of-function mutations. Using 1,300 simulations under both types of perturbations across various extracellular conditions, we identified the most and least influential components based on the magnitude of their influence on the rest of the system. Based on the premise that the most influential components might serve as better drug targets, we characterized them for biological functions, housekeeping genes, essential genes, and druggable proteins. The most influential components under all environmental conditions were enriched with several biological processes. The inositol pathway was found as most influential under inactivating perturbations, whereas the kinase and small lung cancer pathways were identified as the most influential under activating perturbations. The most influential components were enriched with essential genes and druggable proteins. Moreover, known cancer drug targets were also classified in influential components based on the affected components in the network. Additionally, the systemic perturbation analysis of the model revealed a network motif of most influential components which affect each other. Furthermore, our analysis predicted novel combinations of cancer drug targets with various effects on other most influential components. We found that the combinatorial perturbation consisting of PI3K inactivation and overactivation of IP3R1 can lead to increased activity levels of apoptosis

  12. Revealing Business Opportunities in the Norwegian Power Industry: How the implementation of AMR facilitates new business models

    OpenAIRE

    Platou, Rikke Stoud; Sleire, Maren

    2011-01-01

    This thesis aims to map out the current state of the Norwegian power industry and reveal opportunities that can serve as a fundament for the formation of new business models in the industry post AMR implementation.Demand side management (DSM) arouse to include end customers and give them incentives for having a power consumption pattern which also benefits the power system. Market structure; lack of ICT infrastructure and understanding of the solutions; costs and competitiveness, as well as t...

  13. Stirling cryocooler test results and design model verification

    International Nuclear Information System (INIS)

    Shimko, M.A.; Stacy, W.D.; McCormick, J.A.

    1990-01-01

    This paper reports on progress in developing a long-life Stirling cycle cryocooler for space borne applications. It presents the results from tests on a preliminary breadboard version of the cryocooler used to demonstrate the feasibility of the technology and to validate the regenerator design code used in its development. This machine achieved a cold-end temperature of 65 K while carrying a 1/2 Watt cooling load. The basic machine is a double-acting, flexure-bearing, split Stirling design with linear electromagnetic drives for the expander and compressors. Flat metal diaphragms replace pistons for both sweeping and sealing the machine working volumes. In addition, the double-acting expander couples to a laminar-channel counterflow recuperative heat exchanger for regeneration. A PC compatible design code was developed for this design approach that calculates regenerator loss including heat transfer irreversibilities, pressure drop, and axial conduction in the regenerator walls

  14. The similia principle: results obtained in a cellular model system.

    Science.gov (United States)

    Wiegant, Fred; Van Wijk, Roeland

    2010-01-01

    This paper describes the results of a research program focused on the beneficial effect of low dose stress conditions that were applied according to the similia principle to cells previously disturbed by more severe stress conditions. In first instance, we discuss criteria for research on the similia principle at the cellular level. Then, the homologous ('isopathic') approach is reviewed, in which the initial (high dose) stress used to disturb cellular physiology and the subsequent (low dose) stress are identical. Beneficial effects of low dose stress are described in terms of increased cellular survival capacity and at the molecular level as an increase in the synthesis of heat shock proteins (hsps). Both phenomena reflect a stimulation of the endogenous cellular self-recovery capacity. Low dose stress conditions applied in a homologous approach stimulate the synthesis of hsps and enhance survival in comparison with stressed cells that were incubated in the absence of low dose stress conditions. Thirdly, the specificity of the low dose stress condition is described where the initial (high dose) stress is different in nature from the subsequently applied (low dose) stress; the heterologous or 'heteropathic' approach. The results support the similia principle at the cellular level and add to understanding of how low dose stress conditions influence the regulatory processes underlying self-recovery. In addition, the phenomenon of 'symptom aggravation' which is also observed at the cellular level, is discussed in the context of self-recovery. Finally, the difference in efficiency between the homologous and the heterologous approach is discussed; a perspective is indicated for further research; and the relationship between studies on the similia principle and the recently introduced concept of 'postconditioning hormesis' is emphasized. Copyright 2009 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  15. The Formation of the Model of Diagnosing the Results Implementation of of Consulting Projects for Enterprises

    Directory of Open Access Journals (Sweden)

    Kuzmin Oleh Ye.

    2017-11-01

    Full Text Available In the article the graphic-analytical model of diagnostics of results of implementation of consulting projects is formed, which allows to: take into consideration interests of participants to the project on choice of methods and methodologies of diagnosing; allocate alternative sets of business indicators for each object of impact in terms of consulting project; establish economic and non-economic criteria for evaluating the effectiveness of consulting, as well as monitoring of indicators and automated processing of diagnostic results to control deviations from the optimal values of the diagnosed project results. A structural-logical model of formation of alternative sets of indicators and choice of indicators for diagnostics of results of consulting projects has been developed. The elements of the enterprise management system have been codified to harmonize the corresponding indicators with their subsequent combination within the proposed sets. The control system objects and their elements have been allocated. The groups of indicators according to the technology of Balanced Score Card (BSC have been presented. The prospect of further research is the economic assessment of implementation of the diagnosed consulting projects, which will reveal the links between the parameters of production-economic activity and the assessment of projects, and allows choose the most significant ones.

  16. Higher surface mass balance of the Greenland ice sheet revealed by high - resolution climate modeling

    NARCIS (Netherlands)

    Ettema, Janneke; van den Broeke, Michiel R.; van Meijgaard, Erik; van de Berg, Willem Jan; Bamber, Jonathan L.; Box, Jason E.; Bales, Roger C.

    2009-01-01

    High‐resolution (∼11 km) regional climate modeling shows total annual precipitation on the Greenland ice sheet for 1958–2007 to be up to 24% and surface mass balance up to 63% higher than previously thought. The largest differences occur in coastal southeast Greenland, where the much higher

  17. Modeled distribution and abundance of a pelagic seabird reveal trends in relation to fisheries

    Science.gov (United States)

    Renner, Martin; Parrish, Julia K.; Piatt, John F.; Kuletz, Kathy J.; Edwards, Ann E.; Hunt, George L.

    2013-01-01

    The northern fulmar Fulmarus glacialis is one of the most visible and widespread seabirds in the eastern Bering Sea and Aleutian Islands. However, relatively little is known about its abundance, trends, or the factors that shape its distribution. We used a long-term pelagic dataset to model changes in fulmar at-sea distribution and abundance since the mid-1970s. We used an ensemble model, based on a weighted average of generalized additive model (GAM), multivariate adaptive regression splines (MARS), and random forest models to estimate the pelagic distribution and density of fulmars in the waters of the Aleutian Archipelago and Bering Sea. The most important predictor variables were colony effect, sea surface temperature, distribution of fisheries, location, and primary productivity. We calculated a time series from the ratio of observed to predicted values and found that fulmar at-sea abundance declined from the 1970s to the 2000s at a rate of 0.83% (± 0.39% SE) per annum. Interpolating fulmar densities on a spatial grid through time, we found that the center of fulmar distribution in the Bering Sea has shifted north, coinciding with a northward shift in fish catches and a warming ocean. Our study shows that fisheries are an important, but not the only factor, shaping fulmar distribution and abundance trends in the eastern Bering Sea and Aleutian Islands.

  18. Spatial models reveal the microclimatic buffering capacity of old-growth forests.

    Science.gov (United States)

    Frey, Sarah J K; Hadley, Adam S; Johnson, Sherri L; Schulze, Mark; Jones, Julia A; Betts, Matthew G

    2016-04-01

    Climate change is predicted to cause widespread declines in biodiversity, but these predictions are derived from coarse-resolution climate models applied at global scales. Such models lack the capacity to incorporate microclimate variability, which is critical to biodiversity microrefugia. In forested montane regions, microclimate is thought to be influenced by combined effects of elevation, microtopography, and vegetation, but their relative effects at fine spatial scales are poorly known. We used boosted regression trees to model the spatial distribution of fine-scale, under-canopy air temperatures in mountainous terrain. Spatial models predicted observed independent test data well (r = 0.87). As expected, elevation strongly predicted temperatures, but vegetation and microtopography also exerted critical effects. Old-growth vegetation characteristics, measured using LiDAR (light detection and ranging), appeared to have an insulating effect; maximum spring monthly temperatures decreased by 2.5°C across the observed gradient in old-growth structure. These cooling effects across a gradient in forest structure are of similar magnitude to 50-year forecasts of the Intergovernmental Panel on Climate Change and therefore have the potential to mitigate climate warming at local scales. Management strategies to conserve old-growth characteristics and to curb current rates of primary forest loss could maintain microrefugia, enhancing biodiversity persistence in mountainous systems under climate warming.

  19. Valuing snorkeling visits to the Florida Keys with stated and revealed preference models

    Science.gov (United States)

    Timothy Park; J. Michael Bowker; Vernon R. Leeworthy

    2002-01-01

    Coastal coral reefs, especially in the Florida Keys, are declining at a disturbing rate. Marine ecologists and reef scientists have emphasized the importance of establishing nonmarket values of coral reefs to assess the cost effectiveness of coral reef management and remediation programs. The purpose of this paper is to develop a travel cost--contingent valuation model...

  20. The structure of the asteroid 4 Vesta as revealed by models of planet-scale collisions

    Science.gov (United States)

    Jutzi, M.; Asphaug, E.; Gillet, P.; Barrat, J.-A.; Benz, W.

    2013-02-01

    Asteroid 4 Vesta seems to be a major intact protoplanet, with a surface composition similar to that of the HED (howardite-eucrite-diogenite) meteorites. The southern hemisphere is dominated by a giant impact scar, but previous impact models have failed to reproduce the observed topography. The recent discovery that Vesta's southern hemisphere is dominated by two overlapping basins provides an opportunity to model Vesta's topography more accurately. Here we report three-dimensional simulations of Vesta's global evolution under two overlapping planet-scale collisions. We closely reproduce its observed shape, and provide maps of impact excavation and ejecta deposition. Spiral patterns observed in the younger basin Rheasilvia, about one billion years old, are attributed to Coriolis forces during crater collapse. Surface materials exposed in the north come from a depth of about 20 kilometres, according to our models, whereas materials exposed inside the southern double-excavation come from depths of about 60-100 kilometres. If Vesta began as a layered, completely differentiated protoplanet, then our model predicts large areas of pure diogenites and olivine-rich rocks. These are not seen, possibly implying that the outer 100 kilometres or so of Vesta is composed mainly of a basaltic crust (eucrites) with ultramafic intrusions (diogenites).

  1. Dosage and dose schedule screening of drug combinations in agent-based models reveals hidden synergies

    Directory of Open Access Journals (Sweden)

    Lisa Corina Barros de Andrade e Sousa1

    2016-01-01

    Full Text Available The fungus Candida albicans is the most common causative agent of human fungal infections and better drugs or drug combination strategies are urgently needed. Here, we present an agent-based model of the interplay of C. albicans with the host immune system and with the microflora of the host. We took into account the morphological change of C. albicans from the yeast to hyphae form and its dynamics during infection. The model allowed us to follow the dynamics of fungal growth and morphology, of the immune cells and of microflora in different perturbing situations. We specifically focused on the consequences of microflora reduction following antibiotic treatment. Using the agent-based model, different drug types have been tested for their effectiveness, namely drugs that inhibit cell division and drugs that constrain the yeast-to-hyphae transition. Applied individually, the division drug turned out to successfully decrease hyphae while the transition drug leads to a burst in hyphae after the end of the treatment. To evaluate the effect of different drug combinations, doses, and schedules, we introduced a measure for the return to a healthy state, the infection score. Using this measure, we found that the addition of a transition drug to a division drug treatment can improve the treatment reliability while minimizing treatment duration and drug dosage. In this work we present a theoretical study. Although our model has not been calibrated to quantitative experimental data, the technique of computationally identifying synergistic treatment combinations in an agent based model exemplifies the importance of computational techniques in translational research.

  2. Results from an acoustic modelling study of seismic airgun survey noise in Queen Charlotte Basin

    Energy Technology Data Exchange (ETDEWEB)

    MacGillivray, A.O.; Chapman, N.R. [Victoria Univ., BC (Canada). School of Earth and Ocean Sciences

    2005-12-07

    An acoustic modelling study was conducted to examine seismic survey noise propagation in the Queen Charlotte Basin (QCB) and better understand the physical aspects of sound transmission. The study results are intended to help determine the potential physiological and behavioural effects of airgun noise on marine mammals and fish. The scope of the study included a numerical simulation of underwater sound transmission in QCB in areas where oil and gas exploration activities may be conducted; a forecast of received noise levels by combining acoustic transmission loss computations with acoustic source levels representative of seismic exploration activity and, the use of received forecasts to estimate zones of impact for marine mammals. The critical environmental parameters in the QCB are the bathymetry of the ocean, the sound speed profile in the water and the geoacoustic profile of the seabed. The RAM acoustic propagation model developed by the United States Naval Research Laboratory was used to compute acoustic transmission loss in the QCB. The source level and directionality of the seismic array was determined by a full-waveform array source signature model. This modelling study of noise propagation from seismic surveys revealed several key findings. Among them, it showed that received noise levels in the water are affected by the source location, array orientation and the shape of the sound speed profile with respect to water depth. It also showed that noise levels are lowest in shallow bathymetry. 30 refs., 5 tabs., 13 figs.

  3. Modeling results for a linear simulator of a divertor

    International Nuclear Information System (INIS)

    Hooper, E.B.; Brown, M.D.; Byers, J.A.; Casper, T.A.; Cohen, B.I.; Cohen, R.H.; Jackson, M.C.; Kaiser, T.B.; Molvik, A.W.; Nevins, W.M.; Nilson, D.G.; Pearlstein, L.D.; Rognlien, T.D.

    1993-01-01

    A divertor simulator, IDEAL, has been proposed by S. Cohen to study the difficult power-handling requirements of the tokamak program in general and the ITER program in particular. Projections of the power density in the ITER divertor reach ∼ 1 Gw/m 2 along the magnetic fieldlines and > 10 MW/m 2 on a surface inclined at a shallow angle to the fieldlines. These power densities are substantially greater than can be handled reliably on the surface, so new techniques are required to reduce the power density to a reasonable level. Although the divertor physics must be demonstrated in tokamaks, a linear device could contribute to the development because of its flexibility, the easy access to the plasma and to tested components, and long pulse operation (essentially cw). However, a decision to build a simulator requires not just the recognition of its programmatic value, but also confidence that it can meet the required parameters at an affordable cost. Accordingly, as reported here, it was decided to examine the physics of the proposed device, including kinetic effects resulting from the intense heating required to reach the plasma parameters, and to conduct an independent cost estimate. The detailed role of the simulator in a divertor program is not explored in this report

  4. Modelling combustion reactions for gas flaring and its resulting emissions

    Directory of Open Access Journals (Sweden)

    O. Saheed Ismail

    2016-07-01

    Full Text Available Flaring of associated petroleum gas is an age long environmental concern which remains unabated. Flaring of gas maybe a very efficient combustion process especially steam/air assisted flare and more economical than utilization in some oil fields. However, it has serious implications for the environment. This study considered different reaction types and operating conditions for gas flaring. Six combustion equations were generated using the mass balance concept with varying air and combustion efficiency. These equations were coded with a computer program using 12 natural gas samples of different chemical composition and origin to predict the pattern of emission species from gas flaring. The effect of key parameters on the emission output is also shown. CO2, CO, NO, NO2 and SO2 are the anticipated non-hydrocarbon emissions of environmental concern. Results show that the quantity and pattern of these chemical species depended on percentage excess/deficiency of stoichiometric air, natural gas type, reaction type, carbon mass content, impurities, combustion efficiency of the flare system etc. These emissions degrade the environment and human life, so knowing the emission types, pattern and flaring conditions that this study predicts is of paramount importance to governments, environmental agencies and the oil and gas industry.

  5. Environment modelling in near Earth space: Preliminary LDEF results

    Science.gov (United States)

    Coombs, C. R.; Atkinson, D. R.; Wagner, J. D.; Crowell, L. B.; Allbrooks, M.; Watts, A. J.

    1992-01-01

    Hypervelocity impacts by space debris cause not only local cratering or penetrations, but also cause large areas of damage in coated, painted or laminated surfaces. Features examined in these analyses display interesting morphological characteristics, commonly exhibiting a concentric ringed appearance. Virtually all features greater than 0.2 mm in diameter possess a spall zone in which all of the paint was removed from the aluminum surface. These spall zones vary in size from approximately 2 - 5 crater diameters. The actual craters in the aluminum substrate vary from central pits without raised rims, to morphologies more typical of craters formed in aluminum under hypervelocity laboratory conditions for the larger features. Most features also possess what is referred to as a 'shock zone' as well. These zones vary in size from approximately 1 - 20 crater diameters. In most cases, only the outer-most layer of paint was affected by this impact related phenomenon. Several impacts possess ridge-like structures encircling the area in which this outer-most paint layer was removed. In many ways, such features resemble the lunar impact basins, but on an extremely reduced scale. Overall, there were no noticeable penetrations, bulges or spallation features on the backside of the tray. On Row 12, approximately 85 degrees from the leading edge (RAM direction), there was approximately one impact per 15 cm(exp 2). On the trailing edge, there was approximately one impact per 72 cm(exp 2). Currently, craters on four aluminum experiment trays from Bay E09, directly on the leading edge are being measured and analyzed. Preliminary results have produced more than 2200 craters on approximately 1500 cm(exp 2) - or approximately 1 impact per 0.7 cm(exp 2).

  6. A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides.

    Science.gov (United States)

    Voelz, Kerstin; Gratacap, Remi L; Wheeler, Robert T

    2015-11-01

    Mucormycosis is an emerging fungal infection that is clinically difficult to manage, with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity or traumatic injury are at increased risk of developing disease. These individuals often present with defects in phagocytic effector cell function. Research using mammalian models and phagocytic effector cell lines has attempted to decipher the importance of the innate immune system in host defence against mucormycosis. However, these model systems have not been satisfactory for direct analysis of the interaction between innate immune effector cells and infectious sporangiospores in vivo. Here, we report the first real-time in vivo analysis of the early innate immune response to mucormycete infection using a whole-animal zebrafish larval model system. We identified differential host susceptibility, dependent on the site of infection (hindbrain ventricle and swim bladder), as well as differential functions of the two major phagocyte effector cell types in response to viable and non-viable spores. Larval susceptibility to mucormycete spore infection was increased upon immunosuppressant treatment. We showed for the first time that macrophages and neutrophils were readily recruited in vivo to the site of infection in an intact host and that spore phagocytosis can be observed in real-time in vivo. While exploring innate immune effector recruitment dynamics, we discovered the formation of phagocyte clusters in response to fungal spores that potentially play a role in fungal spore dissemination. Spores failed to activate pro-inflammatory gene expression by 6 h post-infection in both infection models. After 24 h, induction of a pro-inflammatory response was observed only in hindbrain ventricle infections. Only a weak pro-inflammatory response was initiated after spore injection into the swim bladder during the same time frame. In the future, the zebrafish larva as a live whole

  7. Chick embryo xenograft model reveals a novel perineural niche for human adipose-derived stromal cells

    Directory of Open Access Journals (Sweden)

    Ingrid R. Cordeiro

    2015-09-01

    Full Text Available Human adipose-derived stromal cells (hADSC are a heterogeneous cell population that contains adult multipotent stem cells. Although it is well established that hADSC have skeletal potential in vivo in adult organisms, in vitro assays suggest further differentiation capacity, such as into glia. Thus, we propose that grafting hADSC into the embryo can provide them with a much more instructive microenvironment, allowing the human cells to adopt diverse fates or niches. Here, hADSC spheroids were grafted into either the presumptive presomitic mesoderm or the first branchial arch (BA1 regions of chick embryos. Cells were identified without previous manipulations via human-specific Alu probes, which allows efficient long-term tracing of heterogeneous primary cultures. When grafted into the trunk, in contrast to previous studies, hADSC were not found in chondrogenic or osteogenic territories up to E8. Surprisingly, 82.5% of the hADSC were associated with HNK1+ tissues, such as peripheral nerves. Human skin fibroblasts showed a smaller tropism for nerves. In line with other studies, hADSC also adopted perivascular locations. When grafted into the presumptive BA1, 74.6% of the cells were in the outflow tract, the final goal of cardiac neural crest cells, and were also associated with peripheral nerves. This is the first study showing that hADSC could adopt a perineural niche in vivo and were able to recognize cues for neural crest cell migration of the host. Therefore, we propose that xenografts of human cells into chick embryos can reveal novel behaviors of heterogeneous cell populations, such as response to migration cues.

  8. Deposition By Turbidity Currents In Intraslope Diapiric Minibasins: Results Of 1-D Experiments And Numerical Modeling

    Science.gov (United States)

    Lamb, M.; Toniolo, H.; Parker, G.

    2001-12-01

    The slope of the continental margin of the northern Gulf of Mexico is riddled with small basins resulting from salt tectonics. Each such minibasin is the result of local subsidence due to salt withdrawal, and is isolated from neighboring basins by ridges formed due to compensational uplift. The minibasins are gradually filled by turbidity currents, which are active at low sea stand. Experiments in a 1-D minibasin reveal that a turbidity current flowing into a deep minibasin must undergo a hydraulic jump and form a muddy pond. This pond may not spill out of the basin even with continuous inflow. The reason for this is the detrainment of water across the settling interface that forms at the top of the muddy pond. Results of both experiments and numerical modeling of the flow and the evolution of the deposit are presented. The numerical model is the first of its kind to capture both the hydraulic jump and the effect of detrainment in ponded turbidity currents.

  9. Mathematical modeling reveals kinetics of lymphocyte recirculation in the whole organism.

    Directory of Open Access Journals (Sweden)

    Vitaly V Ganusov

    2014-05-01

    Full Text Available The kinetics of recirculation of naive lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct lymphocytes (TDLs via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95% of lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5% migrate to secondary lymphoid tissues such as lymph nodes, Peyer's patches, or the spleen. Interestingly, our analysis suggests that lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours and a longer average residence time of TDLs in major lymph nodes and Peyer's patches (10 hours. Surprisingly, we find that the average residence time of lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs or the gut (mesenteric LNs or in Peyer's patches. Applying our model to an additional dataset on lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of recirculation kinetics of thoracic duct lymphocytes in the whole organism.

  10. Tracer simulation using a global general circulation model: Results from a midlatitude instantaneous source experiment

    International Nuclear Information System (INIS)

    Mahlman, J.D.; Moxim, W.J.

    1978-01-01

    An 11-level general circulation model with seasonal variation is used to perform an experiment on the dispersion of passive tracers. Specially constructed time-dependent winds from this model are used as input to a separate tracer model. The methodologies employed to construct the tracer model are described.The experiment presented is the evolution of a hypothetical instantaneous source of tracer on 1 Janaury with maximum initial concentration at 65 mb, 36 0 N, 180 0 E. The tracer is assumed to have no sources or sinks in the stratosphere, but is subject to removal processes in the lower troposphere.The experimental results reveal a number of similarities to observed tracer behavior, including the average poleward-downward slope of mixing ratio isopleths, strong tracer gradients across the tropopause, intrusion of tracer into the Southern Hemisphere lower stratosphere, and the long-term interhemispheric exchange rate. The model residence times show behavior intermediate to those exhibited for particulate radioactive debris and gaseous C 14 O 2 . This suggests that caution should be employed when either radioactive debris or C 14 O 2 data are used to develop empirical models for prediction of gaseous tracers which are efficiently removed in the troposphere.In this experiment, the tracer mixing ratio and potential vorticity evolve to very high correlations. Mechanisms for this correlation are discussed. The zonal mean tracer balances exhibit complex behavior among the various transport terms. At early stages, the tracer evolution is dominated by eddy effects. Later, a very large degree of self-cancellation between mean cell and eddy effects is observed. During seasonal transitions, however, this self-cancellation diminishes markedly, leading to significant changes in the zonal mean tracer distribution. A possible theoretical explanation is presented

  11. Aiptasia sp. larvae as a model to reveal mechanisms of symbiont selection in cnidarians

    KAUST Repository

    Wolfowicz, Iliona

    2016-09-01

    Symbiosis, defined as the persistent association between two distinct species, is an evolutionary and ecologically critical phenomenon facilitating survival of both partners in diverse habitats. The biodiversity of coral reef ecosystems depends on a functional symbiosis with photosynthetic dinoflagellates of the highly diverse genus Symbiodinium, which reside in coral host cells and continuously support their nutrition. The mechanisms underlying symbiont selection to establish a stable endosymbiosis in non-symbiotic juvenile corals are unclear. Here we show for the first time that symbiont selection patterns for larvae of two Acropora coral species and the model anemone Aiptasia are similar under controlled conditions. We find that Aiptasia larvae distinguish between compatible and incompatible symbionts during uptake into the gastric cavity and phagocytosis. Using RNA-Seq, we identify a set of candidate genes potentially involved in symbiosis establishment. Together, our data complement existing molecular resources to mechanistically dissect symbiont phagocytosis in cnidarians under controlled conditions, thereby strengthening the role of Aiptasia larvae as a powerful model for cnidarian endosymbiosis establishment.

  12. Dynamic information processing states revealed through neurocognitive models of object semantics

    Science.gov (United States)

    Clarke, Alex

    2015-01-01

    Recognising objects relies on highly dynamic, interactive brain networks to process multiple aspects of object information. To fully understand how different forms of information about objects are represented and processed in the brain requires a neurocognitive account of visual object recognition that combines a detailed cognitive model of semantic knowledge with a neurobiological model of visual object processing. Here we ask how specific cognitive factors are instantiated in our mental processes and how they dynamically evolve over time. We suggest that coarse semantic information, based on generic shared semantic knowledge, is rapidly extracted from visual inputs and is sufficient to drive rapid category decisions. Subsequent recurrent neural activity between the anterior temporal lobe and posterior fusiform supports the formation of object-specific semantic representations – a conjunctive process primarily driven by the perirhinal cortex. These object-specific representations require the integration of shared and distinguishing object properties and support the unique recognition of objects. We conclude that a valuable way of understanding the cognitive activity of the brain is though testing the relationship between specific cognitive measures and dynamic neural activity. This kind of approach allows us to move towards uncovering the information processing states of the brain and how they evolve over time. PMID:25745632

  13. Dynamic Modeling of GAIT System Reveals Transcriptome Expansion and Translational Trickle Control Device

    Science.gov (United States)

    Yao, Peng; Potdar, Alka A.; Arif, Abul; Ray, Partho Sarothi; Mukhopadhyay, Rupak; Willard, Belinda; Xu, Yichi; Yan, Jun; Saidel, Gerald M.; Fox, Paul L.

    2012-01-01

    SUMMARY Post-transcriptional regulatory mechanisms superimpose “fine-tuning” control upon “on-off” switches characteristic of gene transcription. We have exploited computational modeling with experimental validation to resolve an anomalous relationship between mRNA expression and protein synthesis. Differential GAIT (Gamma-interferon Activated Inhibitor of Translation) complex activation repressed VEGF-A synthesis to a low, constant rate despite high, variable VEGFA mRNA expression. Dynamic model simulations indicated the presence of an unidentified, inhibitory GAIT element-interacting factor. We discovered a truncated form of glutamyl-prolyl tRNA synthetase (EPRS), the GAIT constituent that binds the 3’-UTR GAIT element in target transcripts. The truncated protein, EPRSN1, prevents binding of functional GAIT complex. EPRSN1 mRNA is generated by a remarkable polyadenylation-directed conversion of a Tyr codon in the EPRS coding sequence to a stop codon (PAY*). By low-level protection of GAIT element-bearing transcripts, EPRSN1 imposes a robust “translational trickle” of target protein expression. Genome-wide analysis shows PAY* generates multiple truncated transcripts thereby contributing to transcriptome expansion. PMID:22386318

  14. Active Tension Network model reveals an exotic mechanical state realized in epithelial tissues

    Science.gov (United States)

    Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streicha, Sebastian; Shraiman, Boris

    Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that mechanical balance of cells is dominated by cortical tension and introduces tension dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties: i) ATN behaves as a fluid at short times, but at long times it supports external tension, like a solid; ii) its mechanical equilibrium state has extensive degeneracy associated with a discrete conformal - ''isogonal'' - deformation of cells. ATN model predicts a constraint on equilibrium cell geometry, which we demonstrate to hold in certain epithelial tissues. We further show that isogonal modes are observed in a fruit fly embryo, accounting for the striking variability of apical area of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, understanding which helps understand biological phenomena.

  15. Revealing transboundary and local air pollutant sources affecting Metro Manila through receptor modeling studies

    International Nuclear Information System (INIS)

    Pabroa, Preciosa Corazon B.; Bautista VII, Angel T.; Santos, Flora L.; Racho, Joseph Michael D.

    2011-01-01

    Ambient fine particulate matter (PM 2 .5) levels at the Metro Manila air sampling stations of the Philippine Nuclear Research Research Institute were found to be above the WHO guideline value of 10 μg m 3 indicating, in general, very poor air quality in the area. The elemental components of the fine particulate matter were obtained using the energy-dispersive x-ray fluorescence spectrometry. Positive matrix factorization, a receptor modelling tool, was used to identify and apportion air pollution sources. Location of probable transboundary air pollutants were evaluated using HYSPLIT (Hybrid Single Particle Lagrangian Integrated Trajectory Model) while location of probable local air pollutant sources were determined using the conditional probability function (CPF). Air pollutant sources can either be natural or anthropogenic. This study has shown natural air pollutant sources such as volcanic eruptions from Bulusan volcano in 2006 and from Anatahan volcano in 2005 to have impacted on the region. Fine soils was shown to have originated from China's Mu US Desert some time in 2004. Smoke in the fine fraction in 2006 show indications of coming from forest fires in Sumatra and Borneo. Fine particulate Pb in Valenzuela was shown to be coming from the surrounding area. Many more significant air pollution impacts can be evaluated with the identification of probable air pollutant sources with the use of elemental fingerprints and locating these sources with the use of HYSPLIT and CPF. (author)

  16. Aiptasia sp. larvae as a model to reveal mechanisms of symbiont selection in cnidarians

    KAUST Repository

    Wolfowicz, Iliona; Baumgarten, Sebastian; Voss, Philipp A.; Hambleton, Elizabeth A.; Voolstra, Christian R.; Hatta, Masayuki; Guse, Annika

    2016-01-01

    Symbiosis, defined as the persistent association between two distinct species, is an evolutionary and ecologically critical phenomenon facilitating survival of both partners in diverse habitats. The biodiversity of coral reef ecosystems depends on a functional symbiosis with photosynthetic dinoflagellates of the highly diverse genus Symbiodinium, which reside in coral host cells and continuously support their nutrition. The mechanisms underlying symbiont selection to establish a stable endosymbiosis in non-symbiotic juvenile corals are unclear. Here we show for the first time that symbiont selection patterns for larvae of two Acropora coral species and the model anemone Aiptasia are similar under controlled conditions. We find that Aiptasia larvae distinguish between compatible and incompatible symbionts during uptake into the gastric cavity and phagocytosis. Using RNA-Seq, we identify a set of candidate genes potentially involved in symbiosis establishment. Together, our data complement existing molecular resources to mechanistically dissect symbiont phagocytosis in cnidarians under controlled conditions, thereby strengthening the role of Aiptasia larvae as a powerful model for cnidarian endosymbiosis establishment.

  17. How causal analysis can reveal autonomy in models of biological systems

    Science.gov (United States)

    Marshall, William; Kim, Hyunju; Walker, Sara I.; Tononi, Giulio; Albantakis, Larissa

    2017-11-01

    Standard techniques for studying biological systems largely focus on their dynamical or, more recently, their informational properties, usually taking either a reductionist or holistic perspective. Yet, studying only individual system elements or the dynamics of the system as a whole disregards the organizational structure of the system-whether there are subsets of elements with joint causes or effects, and whether the system is strongly integrated or composed of several loosely interacting components. Integrated information theory offers a theoretical framework to (1) investigate the compositional cause-effect structure of a system and to (2) identify causal borders of highly integrated elements comprising local maxima of intrinsic cause-effect power. Here we apply this comprehensive causal analysis to a Boolean network model of the fission yeast (Schizosaccharomyces pombe) cell cycle. We demonstrate that this biological model features a non-trivial causal architecture, whose discovery may provide insights about the real cell cycle that could not be gained from holistic or reductionist approaches. We also show how some specific properties of this underlying causal architecture relate to the biological notion of autonomy. Ultimately, we suggest that analysing the causal organization of a system, including key features like intrinsic control and stable causal borders, should prove relevant for distinguishing life from non-life, and thus could also illuminate the origin of life problem. This article is part of the themed issue 'Reconceptualizing the origins of life'.

  18. Reconstructing Holocene climate using a climate model: Model strategy and preliminary results

    Science.gov (United States)

    Haberkorn, K.; Blender, R.; Lunkeit, F.; Fraedrich, K.

    2009-04-01

    An Earth system model of intermediate complexity (Planet Simulator; PlaSim) is used to reconstruct Holocene climate based on proxy data. The Planet Simulator is a user friendly general circulation model (GCM) suitable for palaeoclimate research. Its easy handling and the modular structure allow for fast and problem dependent simulations. The spectral model is based on the moist primitive equations conserving momentum, mass, energy and moisture. Besides the atmospheric part, a mixed layer-ocean with sea ice and a land surface with biosphere are included. The present-day climate of PlaSim, based on an AMIP II control-run (T21/10L resolution), shows reasonable agreement with ERA-40 reanalysis data. Combining PlaSim with a socio-technological model (GLUES; DFG priority project INTERDYNAMIK) provides improved knowledge on the shift from hunting-gathering to agropastoral subsistence societies. This is achieved by a data assimilation approach, incorporating proxy time series into PlaSim to initialize palaeoclimate simulations during the Holocene. For this, the following strategy is applied: The sensitivities of the terrestrial PlaSim climate are determined with respect to sea surface temperature (SST) anomalies. Here, the focus is the impact of regionally varying SST both in the tropics and the Northern Hemisphere mid-latitudes. The inverse of these sensitivities is used to determine the SST conditions necessary for the nudging of land and coastal proxy climates. Preliminary results indicate the potential, the uncertainty and the limitations of the method.

  19. Higher plant modelling for life support applications: first results of a simple mechanistic model

    Science.gov (United States)

    Hezard, Pauline; Dussap, Claude-Gilles; Sasidharan L, Swathy

    2012-07-01

    In the case of closed ecological life support systems, the air and water regeneration and food production are performed using microorganisms and higher plants. Wheat, rice, soybean, lettuce, tomato or other types of eatable annual plants produce fresh food while recycling CO2 into breathable oxygen. Additionally, they evaporate a large quantity of water, which can be condensed and used as potable water. This shows that recycling functions of air revitalization and food production are completely linked. Consequently, the control of a growth chamber for higher plant production has to be performed with efficient mechanistic models, in order to ensure a realistic prediction of plant behaviour, water and gas recycling whatever the environmental conditions. Purely mechanistic models of plant production in controlled environments are not available yet. This is the reason why new models must be developed and validated. This work concerns the design and test of a simplified version of a mathematical model coupling plant architecture and mass balance purposes in order to compare its results with available data of lettuce grown in closed and controlled chambers. The carbon exchange rate, water absorption and evaporation rate, biomass fresh weight as well as leaf surface are modelled and compared with available data. The model consists of four modules. The first one evaluates plant architecture, like total leaf surface, leaf area index and stem length data. The second one calculates the rate of matter and energy exchange depending on architectural and environmental data: light absorption in the canopy, CO2 uptake or release, water uptake and evapotranspiration. The third module evaluates which of the previous rates is limiting overall biomass growth; and the last one calculates biomass growth rate depending on matter exchange rates, using a global stoichiometric equation. All these rates are a set of differential equations, which are integrated with time in order to provide

  20. MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models.

    Science.gov (United States)

    Hoye, Mariah L; Koval, Erica D; Wegener, Amy J; Hyman, Theodore S; Yang, Chengran; O'Brien, David R; Miller, Rebecca L; Cole, Tracy; Schoch, Kathleen M; Shen, Tao; Kunikata, Tomonori; Richard, Jean-Philippe; Gutmann, David H; Maragakis, Nicholas J; Kordasiewicz, Holly B; Dougherty, Joseph D; Miller, Timothy M

    2017-05-31

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining the in vivo miRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents. SIGNIFICANCE STATEMENT Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease

  1. Model-based traction force microscopy reveals differential tension in cellular actin bundles.

    Science.gov (United States)

    Soiné, Jérôme R D; Brand, Christoph A; Stricker, Jonathan; Oakes, Patrick W; Gardel, Margaret L; Schwarz, Ulrich S

    2015-03-01

    Adherent cells use forces at the cell-substrate interface to sense and respond to the physical properties of their environment. These cell forces can be measured with traction force microscopy which inverts the equations of elasticity theory to calculate them from the deformations of soft polymer substrates. We introduce a new type of traction force microscopy that in contrast to traditional methods uses additional image data for cytoskeleton and adhesion structures and a biophysical model to improve the robustness of the inverse procedure and abolishes the need for regularization. We use this method to demonstrate that ventral stress fibers of U2OS-cells are typically under higher mechanical tension than dorsal stress fibers or transverse arcs.

  2. Mixture models reveal multiple positional bias types in RNA-Seq data and lead to accurate transcript concentration estimates.

    Directory of Open Access Journals (Sweden)

    Andreas Tuerk

    2017-05-01

    Full Text Available Accuracy of transcript quantification with RNA-Seq is negatively affected by positional fragment bias. This article introduces Mix2 (rd. "mixquare", a transcript quantification method which uses a mixture of probability distributions to model and thereby neutralize the effects of positional fragment bias. The parameters of Mix2 are trained by Expectation Maximization resulting in simultaneous transcript abundance and bias estimates. We compare Mix2 to Cufflinks, RSEM, eXpress and PennSeq; state-of-the-art quantification methods implementing some form of bias correction. On four synthetic biases we show that the accuracy of Mix2 overall exceeds the accuracy of the other methods and that its bias estimates converge to the correct solution. We further evaluate Mix2 on real RNA-Seq data from the Microarray and Sequencing Quality Control (MAQC, SEQC Consortia. On MAQC data, Mix2 achieves improved correlation to qPCR measurements with a relative increase in R2 between 4% and 50%. Mix2 also yields repeatable concentration estimates across technical replicates with a relative increase in R2 between 8% and 47% and reduced standard deviation across the full concentration range. We further observe more accurate detection of differential expression with a relative increase in true positives between 74% and 378% for 5% false positives. In addition, Mix2 reveals 5 dominant biases in MAQC data deviating from the common assumption of a uniform fragment distribution. On SEQC data, Mix2 yields higher consistency between measured and predicted concentration ratios. A relative error of 20% or less is obtained for 51% of transcripts by Mix2, 40% of transcripts by Cufflinks and RSEM and 30% by eXpress. Titration order consistency is correct for 47% of transcripts for Mix2, 41% for Cufflinks and RSEM and 34% for eXpress. We, further, observe improved repeatability across laboratory sites with a relative increase in R2 between 8% and 44% and reduced standard deviation.

  3. Observations and operational model simulations reveal the impact of Hurricane Matthew (2016) on the Gulf Stream and coastal sea level

    Science.gov (United States)

    Ezer, Tal; Atkinson, Larry P.; Tuleya, Robert

    2017-12-01

    In October 7-9, 2016, Hurricane Matthew moved along the southeastern coast of the U.S., causing major flooding and significant damage, even to locations farther north well away from the storm's winds. Various observations, such as tide gauge data, cable measurements of the Florida Current (FC) transport, satellite altimeter data and high-frequency radar data, were analyzed to evaluate the impact of the storm. The data show a dramatic decline in the FC flow and increased coastal sea level along the U.S. coast. Weakening of the Gulf Stream (GS) downstream from the storm's area contributed to high coastal sea levels farther north. Analyses of simulations of an operational hurricane-ocean coupled model reveal the disruption that the hurricane caused to the GS flow, including a decline in transport of ∼20 Sv (1 Sv = 106 m3 s-1). In comparison, the observed FC reached a maximum transport of ∼40 Sv before the storm on September 10 and a minimum of ∼20 Sv after the storm on October 12. The hurricane impacts both the geostrophic part of the GS and the wind-driven currents, generating inertial oscillations with velocities of up to ±1 m s-1. Analysis of the observed FC transport since 1982 indicated that the magnitude of the current weakening in October 2016 was quite rare (outside 3 standard deviations from the mean). Such a large FC weakening in the past occurred more often in October and November, but is extremely rare in June-August. Similar impacts on the FC from past tropical storms and hurricanes suggest that storms may contribute to seasonal and interannual variations in the FC. The results also demonstrated the extended range of coastal impacts that remote storms can cause through their influence on ocean currents.

  4. PV Performance Modeling Methods and Practices: Results from the 4th PV Performance Modeling Collaborative Workshop.

    Energy Technology Data Exchange (ETDEWEB)

    Stein, Joshua [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-03-01

    In 2014, the IEA PVPS Task 13 added the PVPMC as a formal activity to its technical work plan for 2014-2017. The goal of this activity is to expand the reach of the PVPMC to a broader international audience and help to reduce PV performance modeling uncertainties worldwide. One of the main deliverables of this activity is to host one or more PVPMC workshops outside the US to foster more international participation within this collaborative group. This report reviews the results of the first in a series of these joint IEA PVPS Task 13/PVPMC workshops. The 4th PV Performance Modeling Collaborative Workshop was held in Cologne, Germany at the headquarters of TÜV Rheinland on October 22-23, 2015.

  5. Ecological niche models reveal the importance of climate variability for the biogeography of protosteloid amoebae.

    Science.gov (United States)

    Aguilar, María; Lado, Carlos

    2012-08-01

    Habitat availability and environmental preferences of species are among the most important factors in determining the success of dispersal processes and therefore in shaping the distribution of protists. We explored the differences in fundamental niches and potential distributions of an ecological guild of slime moulds-protosteloid amoebae-in the Iberian Peninsula. A large set of samples collected in a north-east to south-west transect of approximately 1000 km along the peninsula was used to test the hypothesis that, together with the existence of suitable microhabitats, climate conditions may determine the probability of survival of species. Although protosteloid amoebae share similar morphologies and life history strategies, canonical correspondence analyses showed that they have varied ecological optima, and that climate conditions have an important effect in niche differentiation. Maxent environmental niche models provided consistent predictions of the probability of presence of the species based on climate data, and they were used to generate maps of potential distribution in an 'everything is everywhere' scenario. The most important climatic factors were, in both analyses, variables that measure changes in conditions throughout the year, confirming that the alternation of fruiting bodies, cysts and amoeboid stages in the life cycles of protosteloid amoebae constitutes an advantage for surviving in a changing environment. Microhabitat affinity seems to be influenced by climatic conditions, which suggests that the micro-environment may vary at a local scale and change together with the external climate at a larger scale.

  6. Tropical-extratropical climate interaction as revealed in idealized coupled climate model experiments

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Haijun [Peking University, Department of Atmospheric Science and Laboratory for Severe Storm and Flood Disasters, School of Physics, Beijing (China); Liu, Zhengyu [University of Wisconsin-Madison, Center for Climatic Research and Department of the Atmospheric and Oceanic Sciences, Madison, WI (United States)

    2005-06-01

    Tropical-extratropical climate interactions are studied by idealized experiments with a prescribed 2 C SST anomaly at different latitude bands in a coupled climate model. Instead of focusing on intrinsic climate variability, this work investigates the mean climate adjustment to remote external forcing. The extratropical impact on tropical climate can be as strong as the tropical impact on extratropical climate, with the remote sea surface temperature (SST) response being about half the magnitude of the imposed SST change in the forcing region. The equatorward impact of extratropical climate is accomplished by both the atmospheric bridge and the oceanic tunnel. About two-thirds of the tropical SST change comes from the atmospheric bridge, while the remaining one-third comes from the oceanic tunnel. The equatorial SST increase is first driven by the reduced latent heat flux and the weakened poleward surface Ekman transport, and then enhanced by the decrease in subtropical cells' strength and the equatorward subduction of warm anomalies. In contrast, the poleward impact of tropical climate is accomplished mainly by the atmospheric bridge, which is responsible for extratropical temperature changes in both the surface and subsurface. Sensitivity experiments also show the dominant role of the Southern Hemisphere oceans in the tropical climate change. (orig.)

  7. Dynamic occupancy modelling reveals a hierarchy of competition among fishers, grey foxes and ringtails.

    Science.gov (United States)

    Green, David S; Matthews, Sean M; Swiers, Robert C; Callas, Richard L; Scott Yaeger, J; Farber, Stuart L; Schwartz, Michael K; Powell, Roger A

    2018-05-01

    Determining how species coexist is critical for understanding functional diversity, niche partitioning and interspecific interactions. Identifying the direct and indirect interactions among sympatric carnivores that enable their coexistence is particularly important to elucidate because they are integral for maintaining ecosystem function. We studied the effects of removing nine fishers (Pekania pennanti) on their population dynamics and used this perturbation to elucidate the interspecific interactions among fishers, grey foxes (Urocyon cinereoargenteus) and ringtails (Bassariscus astutus). Grey foxes (family: Canidae) are likely to compete with fishers due to their similar body sizes and dietary overlap, and ringtails (family: Procyonidae), like fishers, are semi-arboreal species of conservation concern. We used spatial capture-recapture to investigate fisher population numbers and dynamic occupancy models that incorporated interspecific interactions to investigate the effects members of these species had on the colonization and persistence of each other's site occupancy. The fisher population showed no change in density for up to 3 years following the removals of fishers for translocations. In contrast, fisher site occupancy decreased in the years immediately following the translocations. During this same time period, site occupancy by grey foxes increased and remained elevated through the end of the study. We found a complicated hierarchy among fishers, foxes and ringtails. Fishers affected grey fox site persistence negatively but had a positive effect on their colonization. Foxes had a positive effect on ringtail site colonization. Thus, fishers were the dominant small carnivore where present and negatively affected foxes directly and ringtails indirectly. Coexistence among the small carnivores we studied appears to reflect dynamic spatial partitioning. Conservation and management efforts should investigate how intraguild interactions may influence the

  8. Reconstructing dynamic mental models of facial expressions in prosopagnosia reveals distinct representations for identity and expression.

    Science.gov (United States)

    Richoz, Anne-Raphaëlle; Jack, Rachael E; Garrod, Oliver G B; Schyns, Philippe G; Caldara, Roberto

    2015-04-01

    The human face transmits a wealth of signals that readily provide crucial information for social interactions, such as facial identity and emotional expression. Yet, a fundamental question remains unresolved: does the face information for identity and emotional expression categorization tap into common or distinct representational systems? To address this question we tested PS, a pure case of acquired prosopagnosia with bilateral occipitotemporal lesions anatomically sparing the regions that are assumed to contribute to facial expression (de)coding (i.e., the amygdala, the insula and the posterior superior temporal sulcus--pSTS). We previously demonstrated that PS does not use information from the eye region to identify faces, but relies on the suboptimal mouth region. PS's abnormal information use for identity, coupled with her neural dissociation, provides a unique opportunity to probe the existence of a dichotomy in the face representational system. To reconstruct the mental models of the six basic facial expressions of emotion in PS and age-matched healthy observers, we used a novel reverse correlation technique tracking information use on dynamic faces. PS was comparable to controls, using all facial features to (de)code facial expressions with the exception of fear. PS's normal (de)coding of dynamic facial expressions suggests that the face system relies either on distinct representational systems for identity and expression, or dissociable cortical pathways to access them. Interestingly, PS showed a selective impairment for categorizing many static facial expressions, which could be accounted for by her lesion in the right inferior occipital gyrus. PS's advantage for dynamic facial expressions might instead relate to a functionally distinct and sufficient cortical pathway directly connecting the early visual cortex to the spared pSTS. Altogether, our data provide critical insights on the healthy and impaired face systems, question evidence of deficits

  9. Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model.

    Science.gov (United States)

    Besson, Marie Thérèse; Alegría, Karin; Garrido-Gerter, Pamela; Barros, Luis Felipe; Liévens, Jean-Charles

    2015-01-01

    Huntington's disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93). We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP) impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK) which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the PPP, extended significantly the lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to synthesize NADPH involved in cell survival by maintenance of the redox state, we showed that tolerance to experimental oxidative stress was enhanced in flies co-expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK were able to circumvent mitochondrial deficits induced by specific silencing of genes necessary for mitochondrial homeostasis. Our study confirms the involvement of bioenergetic deficits in HD course; they can be rescued by specific expression of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent, the glycolysis seem to mediate the hGluT3

  10. Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model.

    Directory of Open Access Journals (Sweden)

    Marie Thérèse Besson

    Full Text Available Huntington's disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93. We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydrogenase (G6PD, the key enzyme of the PPP, extended significantly the lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to synthesize NADPH involved in cell survival by maintenance of the redox state, we showed that tolerance to experimental oxidative stress was enhanced in flies co-expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK were able to circumvent mitochondrial deficits induced by specific silencing of genes necessary for mitochondrial homeostasis. Our study confirms the involvement of bioenergetic deficits in HD course; they can be rescued by specific expression of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent, the glycolysis seem to

  11. Location of persisting mycobacteria in a Guinea pig model of tuberculosis revealed by r207910.

    Science.gov (United States)

    Lenaerts, Anne J; Hoff, Donald; Aly, Sahar; Ehlers, Stefan; Andries, Koen; Cantarero, Luis; Orme, Ian M; Basaraba, Randall J

    2007-09-01

    The lengthy chemotherapy of tuberculosis reflects the ability of a small subpopulation of Mycobacterium tuberculosis bacteria to persist in infected individuals. To date, the exact location of these persisting bacteria is not known. Lung lesions in guinea pigs infected with M. tuberculosis have striking similarities, such as necrosis, mineralization, and hypoxia, to natural infections in humans. Guinea pigs develop necrotic primary lesions after aerosol infection that differ in their morphology compared to secondary lesions resulting from hematogenous dissemination. In infected guinea pigs conventional therapy for tuberculosis during 6 weeks reduced the bacterial load by 1.7 logs in the lungs and, although this completely reversed lung inflammation associated with secondary lesions, the primary granulomas remained largely unaffected. Treatment of animals with the experimental drug R207910 (TMC207) for 6 weeks was highly effective with almost complete eradication of the bacteria throughout both the primary and the secondary lesions. Most importantly, the few remnants of acid-fast bacilli remaining after R207910 treatment were to be found extracellular, in a microenvironment of residual primary lesion necrosis with incomplete dystrophic calcification. This zone of the primary granuloma is hypoxic and is morphologically similar to what has been described for human lung lesions. These results show that this acellular rim may, therefore, be a primary location of persisting bacilli withstanding drug treatment.

  12. Location of Persisting Mycobacteria in a Guinea Pig Model of Tuberculosis Revealed by R207910▿

    Science.gov (United States)

    Lenaerts, Anne J.; Hoff, Donald; Aly, Sahar; Ehlers, Stefan; Andries, Koen; Cantarero, Luis; Orme, Ian M.; Basaraba, Randall J.

    2007-01-01

    The lengthy chemotherapy of tuberculosis reflects the ability of a small subpopulation of Mycobacterium tuberculosis bacteria to persist in infected individuals. To date, the exact location of these persisting bacteria is not known. Lung lesions in guinea pigs infected with M. tuberculosis have striking similarities, such as necrosis, mineralization, and hypoxia, to natural infections in humans. Guinea pigs develop necrotic primary lesions after aerosol infection that differ in their morphology compared to secondary lesions resulting from hematogenous dissemination. In infected guinea pigs conventional therapy for tuberculosis during 6 weeks reduced the bacterial load by 1.7 logs in the lungs and, although this completely reversed lung inflammation associated with secondary lesions, the primary granulomas remained largely unaffected. Treatment of animals with the experimental drug R207910 (TMC207) for 6 weeks was highly effective with almost complete eradication of the bacteria throughout both the primary and the secondary lesions. Most importantly, the few remnants of acid-fast bacilli remaining after R207910 treatment were to be found extracellular, in a microenvironment of residual primary lesion necrosis with incomplete dystrophic calcification. This zone of the primary granuloma is hypoxic and is morphologically similar to what has been described for human lung lesions. These results show that this acellular rim may, therefore, be a primary location of persisting bacilli withstanding drug treatment. PMID:17517834

  13. A Dynamic Bayesian Observer Model Reveals Origins of Bias in Visual Path Integration.

    Science.gov (United States)

    Lakshminarasimhan, Kaushik J; Petsalis, Marina; Park, Hyeshin; DeAngelis, Gregory C; Pitkow, Xaq; Angelaki, Dora E

    2018-06-20

    Path integration is a strategy by which animals track their position by integrating their self-motion velocity. To identify the computational origins of bias in visual path integration, we asked human subjects to navigate in a virtual environment using optic flow and found that they generally traveled beyond the goal location. Such a behavior could stem from leaky integration of unbiased self-motion velocity estimates or from a prior expectation favoring slower speeds that causes velocity underestimation. Testing both alternatives using a probabilistic framework that maximizes expected reward, we found that subjects' biases were better explained by a slow-speed prior than imperfect integration. When subjects integrate paths over long periods, this framework intriguingly predicts a distance-dependent bias reversal due to buildup of uncertainty, which we also confirmed experimentally. These results suggest that visual path integration in noisy environments is limited largely by biases in processing optic flow rather than by leaky integration. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Catchment tracers reveal discharge, recharge and sources of groundwater-borne pollutants in a novel lake modelling approach

    Directory of Open Access Journals (Sweden)

    E. Kristensen

    2018-02-01

    , the CATS model isolated groundwater discharge sites located mainly in the eastern part of the lake with a single site in the southern part. Observations from the eastern part of the lake revealed an impermeable clay layer that promotes discharge during heavy precipitation events, which would otherwise be difficult to identify using traditional hydrological methods. In comparison to the lake concentrations, high tracer concentrations in the southern part showed that only a smaller fraction of water could originate from this area, thereby confirming the model results. A Euclidean cluster analysis of δ18O isotopes identified recharge sites corresponding to areas adjacent to drainage channels, and a cluster analysis of the microbially influenced FDOM component C4 further identified five sites that showed a tendency towards high groundwater recharge rate. In conclusion, it was found that this methodology can be applied to smaller lakes within a short time frame, providing useful information regarding the WRT of the lake and more importantly the groundwater recharge and discharge sites around the lake. Thus, it is a tool for specific management of the catchment.

  15. Catchment tracers reveal discharge, recharge and sources of groundwater-borne pollutants in a novel lake modelling approach

    Science.gov (United States)

    Kristensen, Emil; Madsen-Østerbye, Mikkel; Massicotte, Philippe; Pedersen, Ole; Markager, Stiig; Kragh, Theis

    2018-02-01

    groundwater discharge sites located mainly in the eastern part of the lake with a single site in the southern part. Observations from the eastern part of the lake revealed an impermeable clay layer that promotes discharge during heavy precipitation events, which would otherwise be difficult to identify using traditional hydrological methods. In comparison to the lake concentrations, high tracer concentrations in the southern part showed that only a smaller fraction of water could originate from this area, thereby confirming the model results. A Euclidean cluster analysis of δ18O isotopes identified recharge sites corresponding to areas adjacent to drainage channels, and a cluster analysis of the microbially influenced FDOM component C4 further identified five sites that showed a tendency towards high groundwater recharge rate. In conclusion, it was found that this methodology can be applied to smaller lakes within a short time frame, providing useful information regarding the WRT of the lake and more importantly the groundwater recharge and discharge sites around the lake. Thus, it is a tool for specific management of the catchment.

  16. Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis.

    Science.gov (United States)

    Ananieva, Elitsa A; Van Horn, Cynthia G; Jones, Meghan R; Hutson, Susan M

    2017-02-01

    Unlike other amino acids, the branched-chain amino acids (BCAAs) largely bypass first-pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched-chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart and kidney were impacted. Expression of the hepatic BCATm transgene lowered the concentrations of hepatic BCAAs while enhancing the concentrations of some nonessential amino acids. Extrahepatic BCAA metabolic enzymes and plasma amino acids were largely unaffected, and no growth rate or body composition differences were observed in the transgenic animals as compared to wild-type mice. Feeding the transgenic animals a high-fat diet did not reverse the effect of the BCATm transgene on the hepatic BCAA catabolism, nor did the high-fat diet cause elevation in plasma BCAAs. However, the high-fat-diet-fed BCATm transgenic animals experienced attenuation in the mammalian target of rapamycin (mTOR) pathway in the liver and had impaired blood glucose tolerance. These results suggest that complete liver BCAA metabolism influences the regulation of glucose utilization during diet-induced obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Modeling learning and memory using verbal learning tests: results from ACTIVE.

    Science.gov (United States)

    Gross, Alden L; Rebok, George W; Brandt, Jason; Tommet, Doug; Marsiske, Michael; Jones, Richard N

    2013-03-01

    To investigate the influence of memory training on initial recall and learning. The Advanced Cognitive Training for Independent and Vital Elderly study of community-dwelling adults older than age 65 (n = 1,401). We decomposed trial-level recall in the Auditory Verbal Learning Test (AVLT) and Hopkins Verbal Learning Test (HVLT) into initial recall and learning across trials using latent growth models. Trial-level increases in words recalled in the AVLT and HVLT at each follow-up visit followed an approximately logarithmic shape. Over the 5-year study period, memory training was associated with slower decline in Trial 1 AVLT recall (Cohen's d = 0.35, p = .03) and steep pre- and posttraining acceleration in learning (d = 1.56, p learning, d = 3.10, p memory-trained group had a higher level of recall than the control group through the end of the 5-year study period despite faster decline in learning. This study contributes to the understanding of the mechanisms by which training benefits memory and expands current knowledge by reporting long-term changes in initial recall and learning, as measured from growth models and by characterization of the impact of memory training on these components. Results reveal that memory training delays the worsening of memory span and boosts learning.

  18. Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost Advantages for Continuous Methods for a Broad Range of Manufacturing Scales.

    Science.gov (United States)

    Hummel, Jonathan; Pagkaliwangan, Mark; Gjoka, Xhorxhi; Davidovits, Terence; Stock, Rick; Ransohoff, Thomas; Gantier, Rene; Schofield, Mark

    2018-01-17

    The biopharmaceutical industry is evolving in response to changing market conditions, including increasing competition and growing pressures to reduce costs. Single-use (SU) technologies and continuous bioprocessing have attracted attention as potential facilitators of cost-optimized manufacturing for monoclonal antibodies. While disposable bioprocessing has been adopted at many scales of manufacturing, continuous bioprocessing has yet to reach the same level of implementation. In this study, the cost of goods of Pall Life Science's integrated, continuous bioprocessing (ICB) platform is modeled, along with that of purification processes in stainless-steel and SU batch formats. All three models include costs associated with downstream processing only. Evaluation of the models across a broad range of clinical and commercial scenarios reveal that the cost savings gained by switching from stainless-steel to SU batch processing are often amplified by continuous operation. The continuous platform exhibits the lowest cost of goods across 78% of all scenarios modeled here, with the SU batch process having the lowest costs in the rest of the cases. The relative savings demonstrated by the continuous process are greatest at the highest feed titers and volumes. These findings indicate that existing and imminent continuous technologies and equipment can become key enablers for more cost effective manufacturing of biopharmaceuticals. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. The geography of demography: long-term demographic studies and species distribution models reveal a species border limited by adaptation.

    Science.gov (United States)

    Eckhart, V M; Geber, M A; Morris, W F; Fabio, E S; Tiffin, P; Moeller, D A

    2011-10-01

    Potential causes of species' geographic distribution limits fall into two broad classes: (1) limited adaptation across spatially variable environments and (2) limited opportunities to colonize unoccupied areas. Combining demographic studies, analyses of demographic responses to environmental variation, and species distribution models, we investigated the causes of range limits in a model system, the eastern border of the California annual plant Clarkia xantiana ssp. xantiana. Vital rates of 20 populations varied with growing season temperature and precipitation: fruit number and overwinter survival of 1-year-old seeds declined steeply, while current-year seed germination increased modestly along west-to-east gradients in decreasing temperature, decreasing mean precipitation, and increasing variation in precipitation. Long-term stochastic finite rate of increase, λ(s), exhibited a fourfold range and varied among geologic surface materials as well as with temperature and precipitation. Growth rate declined significantly toward the eastern border, falling below 1 in three of the five easternmost populations. Distribution models employing demographically important environmental variables predicted low habitat favorability beyond the eastern border. Models that filtered or weighted population presences by λ(s) predicted steeper eastward declines in favorability and assigned greater roles in setting the distribution to among-year variation in precipitation and to geologic surface material. These analyses reveal a species border likely set by limited adaptation to declining environmental quality.

  20. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms

    Science.gov (United States)

    Widdows, Kate L.; Panitchob, Nuttanont; Crocker, Ian P.; Please, Colin P.; Hanson, Mark A.; Sibley, Colin P.; Johnstone, Edward D.; Sengers, Bram G.; Lewis, Rohan M.; Glazier, Jocelyn D.

    2015-01-01

    Uptake of system L amino acid substrates into isolated placental plasma membrane vesicles in the absence of opposing side amino acid (zero-trans uptake) is incompatible with the concept of obligatory exchange, where influx of amino acid is coupled to efflux. We therefore hypothesized that system L amino acid exchange transporters are not fully obligatory and/or that amino acids are initially present inside the vesicles. To address this, we combined computational modeling with vesicle transport assays and transporter localization studies to investigate the mechanisms mediating [14C]l-serine (a system L substrate) transport into human placental microvillous plasma membrane (MVM) vesicles. The carrier model provided a quantitative framework to test the 2 hypotheses that l-serine transport occurs by either obligate exchange or nonobligate exchange coupled with facilitated transport (mixed transport model). The computational model could only account for experimental [14C]l-serine uptake data when the transporter was not exclusively in exchange mode, best described by the mixed transport model. MVM vesicle isolates contained endogenous amino acids allowing for potential contribution to zero-trans uptake. Both L-type amino acid transporter (LAT)1 and LAT2 subtypes of system L were distributed to MVM, with l-serine transport attributed to LAT2. These findings suggest that exchange transporters do not function exclusively as obligate exchangers.—Widdows, K. L., Panitchob, N., Crocker, I. P., Please, C. P., Hanson, M. A., Sibley, C. P., Johnstone, E. D., Sengers, B. G., Lewis, R. M., Glazier, J. D. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms. PMID:25761365

  1. Long-term results of 2 adjuvant trials reveal differences in chemosensitivity and the pattern of metastases between colon cancer and rectal cancer.

    Science.gov (United States)

    Kornmann, Marko; Staib, Ludger; Wiegel, Thomas; Kron, Martina; Henne-Bruns, Doris; Link, Karl-Heinrich; Formentini, Andrea

    2013-03-01

    Two identical randomized controlled trials designed to optimize adjuvant treatment of colon cancer (CC) (n =855) and rectal cancer (RC) (n = 796) were performed. Long-term evaluation confirmed that the addition of folinic acid (FA) to 5-fluorouracil (5-FU) improved 7-year overall survival (OS) in CC but not in RC and revealed different patterns of recurrence in patients with CC and those with RC. Our aim was to compare long-term results of adjuvant treatment of colon cancer (CC) and rectal cancer (RC). Adjuvant chemotherapy of CC improved overall survival (OS), whereas that of RC remained at the level achieved by 5-fluorouracil (5-FU). We separately conducted 2 identically designed adjuvant trials in CC and RC. Patients were assigned to adjuvant chemotherapy with 5-FU alone, 5-FU + folinic acid (FA), or 5-FU + interferon-alfa. The first study enrolled patients with stage IIb/III CC, and the second study enrolled patients with stage II/III RC. All patients with RC received postoperative irradiation. Median follow-up for all patients with CC (n = 855) and RC (n = 796) was 4.9 years. The pattern and frequency of recurrence differed significantly, especially lung metastases, which occurred more frequently in RC (12.7%) than in CC (7.3%; P < .001). Seven-year OS rates for 5-FU, 5-FU + FA, and 5-FU + IFN-alfa were 54.1% (95% confidence interval [CI], 46.5-61.0), 66.8% (95% CI, 59.4-73.1), and 56.7% (95% CI, 49.3-63.4) in CC and 50.6% (95% CI, 43.0-57.7), 56.3% (95% CI, 49.4-62.7), and 54.8% (95% CI, 46.7-62.2) in RC, respectively. A subgroup analysis pointed to a reduced local recurrence (LR) rate and an increased OS by the addition of FA in stage II RC (n = 271) but not in stage III RC (n = 525). FA increased 7-year OS by 12.7 percentage points in CC but was not effective in RC. Based on these results and the pattern of metastases, our results suggest that the chemosensitivity of CC and RC may be different. Strategies different from those used in CC may be successful to

  2. Uncertainty in parameterisation and model structure affect simulation results in coupled ecohydrological models

    Directory of Open Access Journals (Sweden)

    S. Arnold

    2009-10-01

    Full Text Available In this paper we develop and apply a conceptual ecohydrological model to investigate the effects of model structure and parameter uncertainty on the simulation of vegetation structure and hydrological dynamics. The model is applied for a typical water limited riparian ecosystem along an ephemeral river: the middle section of the Kuiseb River in Namibia. We modelled this system by coupling an ecological model with a conceptual hydrological model. The hydrological model is storage based with stochastical forcing from the flood. The ecosystem is modelled with a population model, and represents three dominating riparian plant populations. In appreciation of uncertainty about population dynamics, we applied three model versions with increasing complexity. Population parameters were found by Latin hypercube sampling of the parameter space and with the constraint that three species should coexist as observed. Two of the three models were able to reproduce the observed coexistence. However, both models relied on different coexistence mechanisms, and reacted differently to change of long term memory in the flood forcing. The coexistence requirement strongly constrained the parameter space for both successful models. Only very few parameter sets (0.5% of 150 000 samples allowed for coexistence in a representative number of repeated simulations (at least 10 out of 100 and the success of the coexistence mechanism was controlled by the combination of population parameters. The ensemble statistics of average values of hydrologic variables like transpiration and depth to ground water were similar for both models, suggesting that they were mainly controlled by the applied hydrological model. The ensemble statistics of the fluctuations of depth to groundwater and transpiration, however, differed significantly, suggesting that they were controlled by the applied ecological model and coexistence mechanisms. Our study emphasizes that uncertainty about ecosystem

  3. Constraining performance assessment models with tracer test results: a comparison between two conceptual models

    Science.gov (United States)

    McKenna, Sean A.; Selroos, Jan-Olof

    Tracer tests are conducted to ascertain solute transport parameters of a single rock feature over a 5-m transport pathway. Two different conceptualizations of double-porosity solute transport provide estimates of the tracer breakthrough curves. One of the conceptualizations (single-rate) employs a single effective diffusion coefficient in a matrix with infinite penetration depth. However, the tracer retention between different flow paths can vary as the ratio of flow-wetted surface to flow rate differs between the path lines. The other conceptualization (multirate) employs a continuous distribution of multiple diffusion rate coefficients in a matrix with variable, yet finite, capacity. Application of these two models with the parameters estimated on the tracer test breakthrough curves produces transport results that differ by orders of magnitude in peak concentration and time to peak concentration at the performance assessment (PA) time and length scales (100,000 years and 1,000 m). These differences are examined by calculating the time limits for the diffusive capacity to act as an infinite medium. These limits are compared across both conceptual models and also against characteristic times for diffusion at both the tracer test and PA scales. Additionally, the differences between the models are examined by re-estimating parameters for the multirate model from the traditional double-porosity model results at the PA scale. Results indicate that for each model the amount of the diffusive capacity that acts as an infinite medium over the specified time scale explains the differences between the model results and that tracer tests alone cannot provide reliable estimates of transport parameters for the PA scale. Results of Monte Carlo runs of the transport models with varying travel times and path lengths show consistent results between models and suggest that the variation in flow-wetted surface to flow rate along path lines is insignificant relative to variability in

  4. Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Xiaojun [The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Park, Eunmi [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Fischer, Susan M. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78967 (United States); Hu, Yinling, E-mail: huy2@mail.nih.gov [Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701 (United States)

    2013-02-15

    Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside.

  5. The elastic network model reveals a consistent picture on intrinsic functional dynamics of type II restriction endonucleases

    International Nuclear Information System (INIS)

    Uyar, A; Kurkcuoglu, O; Doruker, P; Nilsson, L

    2011-01-01

    The vibrational dynamics of various type II restriction endonucleases, in complex with cognate/non-cognate DNA and in the apo form, are investigated with the elastic network model in order to reveal common functional mechanisms in this enzyme family. Scissor-like and tong-like motions observed in the slowest modes of all enzymes and their complexes point to common DNA recognition and cleavage mechanisms. Normal mode analysis further points out that the scissor-like motion has an important role in differentiating between cognate and non-cognate sequences at the recognition site, thus implying its catalytic relevance. Flexible regions observed around the DNA-binding site of the enzyme usually concentrate on the highly conserved β-strands, especially after DNA binding. These β-strands may have a structurally stabilizing role in functional dynamics for target site recognition and cleavage. In addition, hot spot residues based on high-frequency modes reveal possible communication pathways between the two distant cleavage sites in the enzyme family. Some of these hot spots also exist on the shortest path between the catalytic sites and are highly conserved

  6. Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

    International Nuclear Information System (INIS)

    Xia, Xiaojun; Park, Eunmi; Fischer, Susan M.; Hu, Yinling

    2013-01-01

    Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside

  7. MSFC Stream Model Preliminary Results: Modeling Recent Leonid and Perseid Encounters

    Science.gov (United States)

    Cooke, William J.; Moser, Danielle E.

    2004-01-01

    The cometary meteoroid ejection model of Jones and Brown (1996b) was used to simulate ejection from comets 55P/Tempel-Tuttle during the last 12 revolutions, and the last 9 apparitions of 109P/Swift-Tuttle. Using cometary ephemerides generated by the Jet Propulsion Laboratory s (JPL) HORIZONS Solar System Data and Ephemeris Computation Service, two independent ejection schemes were simulated. In the first case, ejection was simulated in 1 hour time steps along the comet s orbit while it was within 2.5 AU of the Sun. In the second case, ejection was simulated to occur at the hour the comet reached perihelion. A 4th order variable step-size Runge-Kutta integrator was then used to integrate meteoroid position and velocity forward in time, accounting for the effects of radiation pressure, Poynting-Robertson drag, and the gravitational forces of the planets, which were computed using JPL s DE406 planetary ephemerides. An impact parameter was computed for each particle approaching the Earth to create a flux profile, and the results compared to observations of the 1998 and 1999 Leonid showers, and the 1993 and 2004 Perseids.

  8. The ATLAS3D project - IX. The merger origin of a fast- and a slow-rotating early-type galaxy revealed with deep optical imaging: first results

    Science.gov (United States)

    Duc, Pierre-Alain; Cuillandre, Jean-Charles; Serra, Paolo; Michel-Dansac, Leo; Ferriere, Etienne; Alatalo, Katherine; Blitz, Leo; Bois, Maxime; Bournaud, Frédéric; Bureau, Martin; Cappellari, Michele; Davies, Roger L.; Davis, Timothy A.; de Zeeuw, P. T.; Emsellem, Eric; Khochfar, Sadegh; Krajnović, Davor; Kuntschner, Harald; Lablanche, Pierre-Yves; McDermid, Richard M.; Morganti, Raffaella; Naab, Thorsten; Oosterloo, Tom; Sarzi, Marc; Scott, Nicholas; Weijmans, Anne-Marie; Young, Lisa M.

    2011-10-01

    The mass assembly of galaxies leaves imprints in their outskirts, such as shells and tidal tails. The frequency and properties of such fine structures depend on the main acting mechanisms - secular evolution, minor or major mergers - and on the age of the last substantial accretion event. We use this to constrain the mass assembly history of two apparently relaxed nearby early-type galaxies (ETGs) selected from the ATLAS3D sample, NGC 680 and 5557. Our ultra-deep optical images obtained with MegaCam on the Canada-France-Hawaii Telescope reach 29 mag arcsec-2 in the g band. They reveal very low surface brightness (LSB) filamentary structures around these ellipticals. Among them, a gigantic 160 kpc long, narrow, tail east of NGC 5557 hosts three gas-rich star-forming objects, previously detected in H I with the Westerbork Synthesis Radio Telescope and in UV with GALEX. NGC 680 exhibits two major diffuse plumes apparently connected to extended H I tails, as well as a series of arcs and shells. Comparing the outer stellar and gaseous morphology of the two ellipticals with that predicted from models of colliding galaxies, we argue that the LSB features are tidal debris and that each of these two ETGs was assembled during a relatively recent, major wet merger, which most likely occurred after the redshift z ≃ 0.5 epoch. Had these mergers been older, the tidal features should have already fallen back or be destroyed by more recent accretion events. However, the absence of molecular gas and of a prominent young stellar population in the core region of the galaxies indicates that the merger is at least 1-2 Gyr old: the memory of any merger-triggered nuclear starburst has indeed been lost. The star-forming objects found towards the collisional debris of NGC 5557 are then likely tidal dwarf galaxies. Such recycled galaxies here appear to be long-lived and continue to form stars while any star formation activity has stopped in their parent galaxy. The inner kinematics of NGC

  9. RNA Virus Evolution via a Quasispecies-Based Model Reveals a Drug Target with a High Barrier to Resistance

    Directory of Open Access Journals (Sweden)

    Richard J. Bingham

    2017-11-01

    Full Text Available The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly. We introduce here a quasispecies-based model of a viral infection that incorporates structural and mechanistic knowledge of packaging signal function in assembly to construct a phenotype-fitness map, capturing the impact of this RNA code on assembly yield and efficiency. Details of viral replication and assembly inside an infected host cell are coupled with a population model of a viral infection, allowing the occurrence of therapy resistance to be assessed in response to drugs inhibiting packaging signal recognition. Stochastic simulations of viral quasispecies evolution in chronic HCV infection under drug action and/or immune clearance reveal that drugs targeting all RNA signals in the assembly code collectively have a high barrier to drug resistance, even though each packaging signal in isolation has a lower barrier than conventional drugs. This suggests that drugs targeting the RNA signals in the assembly code could be promising routes for exploitation in anti-viral drug design.

  10. RNA Virus Evolution via a Quasispecies-Based Model Reveals a Drug Target with a High Barrier to Resistance.

    Science.gov (United States)

    Bingham, Richard J; Dykeman, Eric C; Twarock, Reidun

    2017-11-17

    The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly. We introduce here a quasispecies-based model of a viral infection that incorporates structural and mechanistic knowledge of packaging signal function in assembly to construct a phenotype-fitness map, capturing the impact of this RNA code on assembly yield and efficiency. Details of viral replication and assembly inside an infected host cell are coupled with a population model of a viral infection, allowing the occurrence of therapy resistance to be assessed in response to drugs inhibiting packaging signal recognition. Stochastic simulations of viral quasispecies evolution in chronic HCV infection under drug action and/or immune clearance reveal that drugs targeting all RNA signals in the assembly code collectively have a high barrier to drug resistance, even though each packaging signal in isolation has a lower barrier than conventional drugs. This suggests that drugs targeting the RNA signals in the assembly code could be promising routes for exploitation in anti-viral drug design.

  11. Analysis of the fibroblast growth factor system reveals alterations in a mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Hensel, Niko; Ratzka, Andreas; Brinkmann, Hella; Klimaschewski, Lars; Grothe, Claudia; Claus, Peter

    2012-01-01

    The monogenetic disease Spinal Muscular Atrophy (SMA) is characterized by a progressive loss of motoneurons leading to muscle weakness and atrophy due to severe reduction of the Survival of Motoneuron (SMN) protein. Several models of SMA show deficits in neurite outgrowth and maintenance of neuromuscular junction (NMJ) structure. Survival of motoneurons, axonal outgrowth and formation of NMJ is controlled by neurotrophic factors such as the Fibroblast Growth Factor (FGF) system. Besides their classical role as extracellular ligands, some FGFs exert also intracellular functions controlling neuronal differentiation. We have previously shown that intracellular FGF-2 binds to SMN and regulates the number of a subtype of nuclear bodies which are reduced in SMA patients. In the light of these findings, we systematically analyzed the FGF-system comprising five canonical receptors and 22 ligands in a severe mouse model of SMA. In this study, we demonstrate widespread alterations of the FGF-system in both muscle and spinal cord. Importantly, FGF-receptor 1 is upregulated in spinal cord at a pre-symptomatic stage as well as in a mouse motoneuron-like cell-line NSC34 based model of SMA. Consistent with that, phosphorylations of FGFR-downstream targets Akt and ERK are increased. Moreover, ERK hyper-phosphorylation is functionally linked to FGFR-1 as revealed by receptor inhibition experiments. Our study shows that the FGF system is dysregulated at an early stage in SMA and may contribute to the SMA pathogenesis.

  12. Modeling reveals bistability and low-pass filtering in the network module determining blood stem cell fate.

    Directory of Open Access Journals (Sweden)

    Jatin Narula

    2010-05-01

    Full Text Available Combinatorial regulation of gene expression is ubiquitous in eukaryotes with multiple inputs converging on regulatory control elements. The dynamic properties of these elements determine the functionality of genetic networks regulating differentiation and development. Here we propose a method to quantitatively characterize the regulatory output of distant enhancers with a biophysical approach that recursively determines free energies of protein-protein and protein-DNA interactions from experimental analysis of transcriptional reporter libraries. We apply this method to model the Scl-Gata2-Fli1 triad-a network module important for cell fate specification of hematopoietic stem cells. We show that this triad module is inherently bistable with irreversible transitions in response to physiologically relevant signals such as Notch, Bmp4 and Gata1 and we use the model to predict the sensitivity of the network to mutations. We also show that the triad acts as a low-pass filter by switching between steady states only in response to signals that persist for longer than a minimum duration threshold. We have found that the auto-regulation loops connecting the slow-degrading Scl to Gata2 and Fli1 are crucial for this low-pass filtering property. Taken together our analysis not only reveals new insights into hematopoietic stem cell regulatory network functionality but also provides a novel and widely applicable strategy to incorporate experimental measurements into dynamical network models.

  13. Data-driven modeling of sleep EEG and EOG reveals characteristics indicative of pre-Parkinson's and Parkinson's disease.

    Science.gov (United States)

    Christensen, Julie A E; Zoetmulder, Marielle; Koch, Henriette; Frandsen, Rune; Arvastson, Lars; Christensen, Søren R; Jennum, Poul; Sorensen, Helge B D

    2014-09-30

    Manual scoring of sleep relies on identifying certain characteristics in polysomnograph (PSG) signals. However, these characteristics are disrupted in patients with neurodegenerative diseases. This study evaluates sleep using a topic modeling and unsupervised learning approach to identify sleep topics directly from electroencephalography (EEG) and electrooculography (EOG). PSG data from control subjects were used to develop an EOG and an EEG topic model. The models were applied to PSG data from 23 control subjects, 25 patients with periodic leg movements (PLMs), 31 patients with idiopathic REM sleep behavior disorder (iRBD) and 36 patients with Parkinson's disease (PD). The data were divided into training and validation datasets and features reflecting EEG and EOG characteristics based on topics were computed. The most discriminative feature subset for separating iRBD/PD and PLM/controls was estimated using a Lasso-regularized regression model. The features with highest discriminability were the number and stability of EEG topics linked to REM and N3, respectively. Validation of the model indicated a sensitivity of 91.4% and a specificity of 68.8% when classifying iRBD/PD patients. The topics showed visual accordance with the manually scored sleep stages, and the features revealed sleep characteristics containing information indicative of neurodegeneration. This study suggests that the amount of N3 and the ability to maintain NREM and REM sleep have potential as early PD biomarkers. Data-driven analysis of sleep may contribute to the evaluation of neurodegenerative patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Fibrillation mechanism of a model intrinsically disordered protein revealed by 2D correlation deep UV resonance Raman spectroscopy.

    Science.gov (United States)

    Sikirzhytski, Vitali; Topilina, Natalya I; Takor, Gaius A; Higashiya, Seiichiro; Welch, John T; Uversky, Vladimir N; Lednev, Igor K

    2012-05-14

    Understanding of numerous biological functions of intrinsically disordered proteins (IDPs) is of significant interest to modern life science research. A large variety of serious debilitating diseases are associated with the malfunction of IDPs including neurodegenerative disorders and systemic amyloidosis. Here we report on the molecular mechanism of amyloid fibrillation of a model IDP (YE8) using 2D correlation deep UV resonance Raman spectroscopy. YE8 is a genetically engineered polypeptide, which is completely unordered at neutral pH yet exhibits all properties of a fibrillogenic protein at low pH. The very first step of the fibrillation process involves structural rearrangements of YE8 at the global structure level without the detectable appearance of secondary structural elements. The formation of β-sheet species follows the global structural changes and proceeds via the simultaneous formation of turns and β-strands. The kinetic mechanism revealed is an important new contribution to understanding of the general fibrillation mechanism proposed for IDP.

  15. Numerical model of the lowermost Mississippi River as an alluvial-bedrock reach: preliminary results

    Science.gov (United States)

    Viparelli, E.; Nittrouer, J. A.; Mohrig, D. C.; Parker, G.

    2012-12-01

    Recent field studies reveal that the river bed of the Lower Mississippi River is characterized by a transition from alluvium (upstream) to bedrock (downstream). In particular, in the downstream 250 km of the river, fields of actively migrating bedforms alternate with deep zones where a consolidated substratum is exposed. Here we present a first version of a one-dimensional numerical model able to capture the alluvial-bedrock transition in the lowermost Mississippi River, defined herein as the 500-km reach between the Old River Control Structure and the Gulf of Mexico. The flow is assumed to be steady, and the cross-section is divided in two regions, the river channel and the floodplain. The streamwise variation of channel and floodplain geometry is described with synthetic relations derived from field observations. Flow resistance in the river channel is computed with the formulation for low-slope, large sand bed rivers due to Wright and Parker, while a Chezy-type formulation is implemented on the floodplain. Sediment is modeled in terms of bed material and wash load. Suspended load is computed with the Wright-Parker formulation. This treatment allows either uniform sediment or a mixture of different grain sizes, and accounts for stratification effects. Bedload transport rates are estimated with the relation for sediment mixtures of Ashida and Michiue. Previous work documents reasonable agreement between these load relations and field measurements. Washload is routed through the system solving the equation of mass conservation of sediment in suspension in the water column. The gradual transition from the alluvial reach to the bedrock reach is modeled in terms of a "mushy" layer of specified thickness overlying the non-erodible substrate. In the case of a fully alluvial reach, the channel bed elevation is above this mushy layer, while in the case of partial alluvial cover of the substratum, the channel bed elevation is within the mushy layer. Variations in base

  16. Dermal uptake of phthalates from clothing: Comparison of model to human participant results

    DEFF Research Database (Denmark)

    Morrison, G. C.; Weschler, Charles J.; Beko, G.

    2017-01-01

    In this research, we extend a model of transdermal uptake of phthalates to include a layer of clothing. When compared with experimental results, this model better estimates dermal uptake of diethylphthalate and di-n-butylphthalate (DnBP) than a previous model. The model predictions are consistent...

  17. A Reformulation of the Dual Career Conceptual Model for Analysis in an Organizational Scope: Revealing new Aspects

    Directory of Open Access Journals (Sweden)

    Heliani Berlato

    2017-01-01

    Full Text Available Couples who live a dual career, in general, are characterized by their continuing professional engagement and their desire for personal growth together. It is a synergy between career aspirations and family sphere, so that they co-exist; reflecting nowadays, a challenge for people who seek to live this duality. Not exempt from it, it is possible to understand the need for management models of people who are in harmony with the desires of dual career couples who are part of organizations. If in the 1980s the existence of dual career couples was not so common in Brazil, nowadays organizations increasingly receive these couples, which impacts the need for people management models to keep up with these social changes. Therefore, the model recognizes that the personal dimension (impacts on the organizational context cannot be avoided, and also that other factors affect both spheres (personal and organizational when referring to the normative roles that permeate these areas. The main intention of this essay is to construct a theoretical model of dual career to consider the factor - organization, as vital to understand (and accept the need to consider other dimensions on the dual career analytical perspective. The first evidences of dual career studies in Brazil revealed that the look at this movement only from the individual's margin is limited. This way, to consider the existence of other dimensions and consequently the influences they may cause, favors an expansion of the perspective, and also brings a detailing about the external factors (organization, society and culture that influence the dual career couple. To consider that this couple, as well as having personal challenges in the relationship between work and family, is subject to the culture that regulates their roles (men and women and that directly influences how organizations will handle that topic reveals the merit of this study. This, in turn, draws attention to the organizational sphere

  18. Mitochondrial dysfunction, oxidative stress and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson’s disease

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Mark H.; Qian, Weijun; Wang, Haixing; Petyuk, Vladislav A.; Bloom, Joshua S.; Sforza, Daniel M.; Lacan, Goran; Liu, Dahai; Khan, Arshad H.; Cantor, Rita M.; Bigelow, Diana J.; Melega, William P.; Camp, David G.; Smith, Richard D.; Smith, Desmond J.

    2008-02-10

    The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson disease (PD) are not completely understood. Here we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 85 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response and apoptosis. Additionally, codon usage and miRNAs may play an important role in translational control in the striatum. These results constitute one of the largest datasets integrating protein and transcript changes for these neurotoxin models with many similar endpoint phenotypes but distinct mechanisms.

  19. Participatory Water Resources Modeling in a Water-Scarce Basin (Rio Sonora, Mexico) Reveals Uncertainty in Decision-Making

    Science.gov (United States)

    Mayer, A. S.; Vivoni, E. R.; Halvorsen, K. E.; Kossak, D.

    2014-12-01

    The Rio Sonora Basin (RSB) in northwest Mexico has a semi-arid and highly variable climate along with urban and agricultural pressures on water resources. Three participatory modeling workshops were held in the RSB in spring 2013. A model of the water resources system, consisting of a watershed hydrology model, a model of the water infrastructure, and groundwater models, was developed deliberatively in the workshops, along with scenarios of future climate and development. Participants were asked to design water resources management strategies by choosing from a range of supply augmentation and demand reduction measures associated with water conservation. Participants assessed water supply reliability, measured as the average daily supply divided by daily demand for historical and future periods, by probing with the climate and development scenarios. Pre- and post-workshop-surveys were developed and administered, based on conceptual models of workshop participants' beliefs regarding modeling and local water resources. The survey results indicate that participants believed their modeling abilities increased and beliefs in the utility of models increased as a result of the workshops. The selected water resources strategies varied widely among participants. Wastewater reuse for industry and aquifer recharge were popular options, but significant numbers of participants thought that inter-basin transfers and desalination were viable. The majority of participants indicated that substantial increases in agricultural water efficiency could be achieved. On average, participants chose strategies that produce reliabilities over the historical and future periods of 95%, but more than 20% of participants were apparently satisfied with reliabilities lower than 80%. The wide range of strategies chosen and associated reliabilities indicate that there is a substantial degree of uncertainty in how future water resources decisions could be made in the region.

  20. Comparison of model results obtained with several European regional air quality models

    NARCIS (Netherlands)

    Hass, H.; Builtjes, P.J.H.; Simpson, D.; Stern, R.

    1997-01-01

    An intercomparison study has been performed with four photo-oxidant dispersion models (EMEP, EURAD, LOTOS and REM3) which are currently capable of performing photo-oxidant formation calculations over larger path of Europe. The models, in principle, were run in the mode in which they are normally

  1. The Criticality of Connecting People to Financial Results ‒ an ROI Calculation Model for Romanian FSOs

    Directory of Open Access Journals (Sweden)

    Daniela Niculescu

    2016-02-01

    Full Text Available Organisational culture and employee engagement have been the focus of recent broad-based research efforts. Adding this concern to the revealed importance of performance indicators on human capital, and that their use is getting momentum, in order to attach financial values to knowledge management assets, it becomes more and more critical to measure human capital value. Key for Romanian FSO’s managers becomes to consider that both human and financial values have a focus on adding value in every process and function in the organisation, and to perpetuate organisational profitability by the corporate culture, on the one hand, where culture is a powerful factor that helps a company to engage, on the other hand, talented people. There is a substantial concern on using ROI on Learning and Development programmes, but whilst this is still declared, Romanian FSOs do not yet have a consistent method to measure it. This study is showing the criticality of connecting people to financial results and data analysis suggests that ROI calculation has a positive impact on creating and fostering a powerful organisational culture and that employees’ awareness of ROI values within their organisation has a powerful effect on their sense of engagement. Our findings have a more practical implication for the analysed industry by shaping a formal ROI measurement mechanisms blueprint, an ROI calculation model for the Romanian FSOs, in the form of a mechanism that could be employed when considering the design of an ROI Methodology for Romanian FSOs.

  2. Comparison of Computational and Experimental Microphone Array Results for an 18%-Scale Aircraft Model

    Science.gov (United States)

    Lockard, David P.; Humphreys, William M.; Khorrami, Mehdi R.; Fares, Ehab; Casalino, Damiano; Ravetta, Patricio A.

    2015-01-01

    An 18%-scale, semi-span model is used as a platform for examining the efficacy of microphone array processing using synthetic data from numerical simulations. Two hybrid RANS/LES codes coupled with Ffowcs Williams-Hawkings solvers are used to calculate 97 microphone signals at the locations of an array employed in the NASA LaRC 14x22 tunnel. Conventional, DAMAS, and CLEAN-SC array processing is applied in an identical fashion to the experimental and computational results for three different configurations involving deploying and retracting the main landing gear and a part span flap. Despite the short time records of the numerical signals, the beamform maps are able to isolate the noise sources, and the appearance of the DAMAS synthetic array maps is generally better than those from the experimental data. The experimental CLEAN-SC maps are similar in quality to those from the simulations indicating that CLEAN-SC may have less sensitivity to background noise. The spectrum obtained from DAMAS processing of synthetic array data is nearly identical to the spectrum of the center microphone of the array, indicating that for this problem array processing of synthetic data does not improve spectral comparisons with experiment. However, the beamform maps do provide an additional means of comparison that can reveal differences that cannot be ascertained from spectra alone.

  3. Complex network models reveal correlations among network metrics, exercise intensity and role of body changes in the fatigue process

    Science.gov (United States)

    Pereira, Vanessa Helena; Gama, Maria Carolina Traina; Sousa, Filipe Antônio Barros; Lewis, Theodore Gyle; Gobatto, Claudio Alexandre; Manchado-Gobatto, Fúlvia Barros

    2015-05-01

    The aims of the present study were analyze the fatigue process at distinct intensity efforts and to investigate its occurrence as interactions at distinct body changes during exercise, using complex network models. For this, participants were submitted to four different running intensities until exhaustion, accomplished in a non-motorized treadmill using a tethered system. The intensities were selected according to critical power model. Mechanical (force, peak power, mean power, velocity and work) and physiological related parameters (heart rate, blood lactate, time until peak blood lactate concentration (lactate time), lean mass, anaerobic and aerobic capacities) and IPAQ score were obtained during exercises and it was used to construction of four complex network models. Such models have both, theoretical and mathematical value, and enables us to perceive new insights that go beyond conventional analysis. From these, we ranked the influences of each node at the fatigue process. Our results shows that nodes, links and network metrics are sensibility according to increase of efforts intensities, been the velocity a key factor to exercise maintenance at models/intensities 1 and 2 (higher time efforts) and force and power at models 3 and 4, highlighting mechanical variables in the exhaustion occurrence and even training prescription applications.

  4. An empirical model of the Baltic Sea reveals the importance of social dynamics for ecological regime shifts.

    Science.gov (United States)

    Lade, Steven J; Niiranen, Susa; Hentati-Sundberg, Jonas; Blenckner, Thorsten; Boonstra, Wiebren J; Orach, Kirill; Quaas, Martin F; Österblom, Henrik; Schlüter, Maja

    2015-09-01

    Regime shifts triggered by human activities and environmental changes have led to significant ecological and socioeconomic consequences in marine and terrestrial ecosystems worldwide. Ecological processes and feedbacks associated with regime shifts have received considerable attention, but human individual and collective behavior is rarely treated as an integrated component of such shifts. Here, we used generalized modeling to develop a coupled social-ecological model that integrated rich social and ecological data to investigate the role of social dynamics in the 1980s Baltic Sea cod boom and collapse. We showed that psychological, economic, and regulatory aspects of fisher decision making, in addition to ecological interactions, contributed both to the temporary persistence of the cod boom and to its subsequent collapse. These features of the social-ecological system also would have limited the effectiveness of stronger fishery regulations. Our results provide quantitative, empirical evidence that incorporating social dynamics into models of natural resources is critical for understanding how resources can be managed sustainably. We also show that generalized modeling, which is well-suited to collaborative model development and does not require detailed specification of causal relationships between system variables, can help tackle the complexities involved in creating and analyzing social-ecological models.

  5. In vivo imaging reveals rapid astrocyte depletion and axon damage in a model of neuromyelitis optica-related pathology

    DEFF Research Database (Denmark)

    Herwerth, Marina; Kalluri, Sudhakar Reddy; Srivastava, Rajneesh

    2016-01-01

    IgG autoantibodies against aquaporin-4 (AQP4), an astrocytic water channel. Antibodies against AQP4 can damage astrocytes via complement, but NMO histopathology also shows demyelination, and - importantly - axon injury, which may determine permanent deficits following NMO relapses. The dynamics...... antibodies in mice. RESULTS: We found that human AQP4 antibodies caused acute astrocyte depletion with initial oligodendrocyte survival. Within two hours of antibody application, we observed secondary axon injury in the form of progressive swellings. Astrocyte toxicity and axon damage were dependent on AQP4...... antibody concentration and complement, specifically C1q. INTERPRETATION: In vivo imaging of the spinal cord reveals the swift development of NMO-related acute axon injury following AQP4 antibody-mediated astrocyte depletion. This approach will be useful in studying the mechanisms underlying the spread...

  6. Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord.

    KAUST Repository

    Lovrics, Anna

    2014-11-14

    We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.

  7. An evolutionary-network model reveals stratified interactions in the V3 loop of the HIV-1 envelope.

    Directory of Open Access Journals (Sweden)

    Art F Y Poon

    2007-11-01

    Full Text Available The third variable loop (V3 of the human immunodeficiency virus type 1 (HIV-1 envelope is a principal determinant of antibody neutralization and progression to AIDS. Although it is undoubtedly an important target for vaccine research, extensive genetic variation in V3 remains an obstacle to the development of an effective vaccine. Comparative methods that exploit the abundance of sequence data can detect interactions between residues of rapidly evolving proteins such as the HIV-1 envelope, revealing biological constraints on their variability. However, previous studies have relied implicitly on two biologically unrealistic assumptions: (1 that founder effects in the evolutionary history of the sequences can be ignored, and; (2 that statistical associations between residues occur exclusively in pairs. We show that comparative methods that neglect the evolutionary history of extant sequences are susceptible to a high rate of false positives (20%-40%. Therefore, we propose a new method to detect interactions that relaxes both of these assumptions. First, we reconstruct the evolutionary history of extant sequences by maximum likelihood, shifting focus from extant sequence variation to the underlying substitution events. Second, we analyze the joint distribution of substitution events among positions in the sequence as a Bayesian graphical model, in which each branch in the phylogeny is a unit of observation. We perform extensive validation of our models using both simulations and a control case of known interactions in HIV-1 protease, and apply this method to detect interactions within V3 from a sample of 1,154 HIV-1 envelope sequences. Our method greatly reduces the number of false positives due to founder effects, while capturing several higher-order interactions among V3 residues. By mapping these interactions to a structural model of the V3 loop, we find that the loop is stratified into distinct evolutionary clusters. We extend our model to

  8. Revealing the burden of maternal mortality: a probabilistic model for determining pregnancy-related causes of death from verbal autopsies

    Directory of Open Access Journals (Sweden)

    Desta Teklay

    2007-02-01

    Full Text Available Abstract Background Substantial reductions in maternal mortality are called for in Millennium Development Goal 5 (MDG-5, thus assuming that maternal mortality is measurable. A key difficulty is attributing causes of death for the many women who die unaided in developing countries. Verbal autopsy (VA can elicit circumstances of death, but data need to be interpreted reliably and consistently to serve as global indicators. Recent developments in probabilistic modelling of VA interpretation are adapted and assessed here for the specific circumstances of pregnancy-related death. Methods A preliminary version of the InterVA-M probabilistic VA interpretation model was developed and refined with adult female VA data from several sources, and then assessed against 258 additional VA interviews from Burkina Faso. Likely causes of death produced by the model were compared with causes previously determined by local physicians. Distinction was made between free-text and closed-question data in the VA interviews, to assess the added value of free-text material on the model's output. Results Following rationalisation between the model and physician interpretations, cause-specific mortality fractions were broadly similar. Case-by-case agreement between the model and any of the reviewing physicians reached approximately 60%, rising to approximately 80% when cases with a discrepancy were reviewed by an additional physician. Cardiovascular disease and malaria showed the largest differences between the methods, and the attribution of infections related to pregnancy also varied. The model estimated 30% of deaths to be pregnancy-related, of which half were due to direct causes. Data derived from free-text made no appreciable difference. Conclusion InterVA-M represents a potentially valuable new tool for measuring maternal mortality in an efficient, consistent and standardised way. Further development, refinement and validation are planned. It could become a routine

  9. Genome-wide allelotyping of a new in vitro model system reveals early events in breast cancer progression.

    Science.gov (United States)

    Li, Zheng; Meng, Zhen Hang; Sayeed, Aejaz; Shalaby, Refaat; Ljung, Britt-Marie; Dairkee, Shanaz H

    2002-10-15

    Toward the goal of identifying early genetic losses, which mediate the release of human breast epithelium from replicative suppression leading to cellular immortalization, we have used a newly developed in vitro model system. This system consists of epithelial cultures derived from noncancerous breast tissue, treated with the chemical carcinogen N-ethyl-N-nitrosourea, and continuously passaged to yield cell populations culminating in the immortal phenotype. Genome-wide allelotyping of early passage N-ethyl-N-nitrosourea-exposed cell populations revealed aberrations at >10% (18 of 169) loci examined. Allelic losses encompassing chromosomes 6q24-6q27, implicating immortalization-associated candidate genes, hZAC and SEN6, occurred in two independently derived cell lines before the Hayflick limit. Additional LOH sites were present in one cell line at 3p11-3p26, 11p15, and 20p12-13. Allelic losses reported in this cell line preceded detectable levels of telomerase activity and the occurrence of p53-related aberrations. Information gained from the search for early immortalization-associated genetic deletions in cultured cells was applied in a novel approach toward the analysis of morphologically normal terminal ductal lobular units microdissected from 20 cases of ductal carcinoma in situ. Notably, clonal allelic losses at chromosome 3p24 and 6q24 were an early occurrence in adjoining terminal ductal lobular units of a proportion of primary tumors, which displayed loss of heterozygosity (3 of 11 and 3 of 6, respectively). The biological insights provided by the new model system reported here strongly suggest that early allelic losses delineated in immortalized cultures and validated in vivo could serve as surrogate endpoints to assist in the identification and intervention of high-risk benign breast tissue, which sustains the potential for continuous proliferation.

  10. Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism

    Directory of Open Access Journals (Sweden)

    Camilla Ceccatelli Berti

    2015-04-01

    Full Text Available Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA, namely PKAN and CoPAN. PKAN are defined by mutations in PANK2, encoding the pantothenate kinase 2 enzyme, that account for about 50% of cases of NBIA, whereas mutations in CoA synthase COASY have been recently reported as the second inborn error of CoA synthesis leading to CoPAN. As reported previously, yeast cells expressing the pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.

  11. Results on neutrinoless double beta decay search in GERDA. Background modeling and limit setting

    Energy Technology Data Exchange (ETDEWEB)

    Becerici Schmidt, Neslihan

    2014-07-22

    The search for the neutrinoless double beta decay (0νββ) process is primarily motivated by its potential of revealing the possible Majorana nature of the neutrino, in which the neutrino is identical to its antiparticle. It has also the potential to yield information on the intrinsic properties of neutrinos, if the underlying mechanism is the exchange of a light Majorana neutrino. The Gerda experiment is searching for 0νββ decay of {sup 76}Ge by operating high purity germanium (HPGe) detectors enriched in the isotope {sup 76}Ge (∝ 87%), directly in ultra-pure liquid argon (LAr). The first phase of physics data taking (Phase I) was completed in 2013 and has yielded 21.6 kg.yr of data. A background index of B∼10{sup -2} cts/(keV.kg.yr) at Q{sub ββ}=2039 keV has been achieved. A comprehensive background model of the Phase I energy spectrum is presented as the major topic of this dissertation. Decomposition of the background energy spectrum into the individual contributions from different processes provides many interesting physics results. The specific activity of {sup 39}Ar has been determined. The obtained result, A=(1.15±0.11) Bq/kg, is in good agreement with the values reported in literature. The contribution from {sup 42}K decays in LAr to the background spectrum has yielded a {sup 42}K({sup 42}Ar) specific activity of A=(106.2{sub -19.2}{sup +12.7}) μBq/kg, for which only upper limits exist in literature. The analysis of high energy events induced by α decays in the {sup 226}Ra chain indicated a total {sup 226}Ra activity of (3.0±0.9) μBq and a total initial {sup 210}Po activity of (0.18±0.01) mBq on the p{sup +} surfaces of the enriched semi-coaxial HPGe detectors. The half life of the two-neutrino double beta (2νββ) decay of {sup 76}Ge has been determined as T{sub 1/2}{sup 2ν}=(1.926±0.094).10{sup 21} yr, which is in good agreement with the result that was obtained with lower exposure and has been published by the Gerda collaboration

  12. Results on neutrinoless double beta decay search in GERDA. Background modeling and limit setting

    International Nuclear Information System (INIS)

    Becerici Schmidt, Neslihan

    2014-01-01

    The search for the neutrinoless double beta decay (0νββ) process is primarily motivated by its potential of revealing the possible Majorana nature of the neutrino, in which the neutrino is identical to its antiparticle. It has also the potential to yield information on the intrinsic properties of neutrinos, if the underlying mechanism is the exchange of a light Majorana neutrino. The Gerda experiment is searching for 0νββ decay of 76 Ge by operating high purity germanium (HPGe) detectors enriched in the isotope 76 Ge (∝ 87%), directly in ultra-pure liquid argon (LAr). The first phase of physics data taking (Phase I) was completed in 2013 and has yielded 21.6 kg.yr of data. A background index of B∼10 -2 cts/(keV.kg.yr) at Q ββ =2039 keV has been achieved. A comprehensive background model of the Phase I energy spectrum is presented as the major topic of this dissertation. Decomposition of the background energy spectrum into the individual contributions from different processes provides many interesting physics results. The specific activity of 39 Ar has been determined. The obtained result, A=(1.15±0.11) Bq/kg, is in good agreement with the values reported in literature. The contribution from 42 K decays in LAr to the background spectrum has yielded a 42 K( 42 Ar) specific activity of A=(106.2 -19.2 +12.7 ) μBq/kg, for which only upper limits exist in literature. The analysis of high energy events induced by α decays in the 226 Ra chain indicated a total 226 Ra activity of (3.0±0.9) μBq and a total initial 210 Po activity of (0.18±0.01) mBq on the p + surfaces of the enriched semi-coaxial HPGe detectors. The half life of the two-neutrino double beta (2νββ) decay of 76 Ge has been determined as T 1/2 2ν =(1.926±0.094).10 21 yr, which is in good agreement with the result that was obtained with lower exposure and has been published by the Gerda collaboration. According to the model, the background in Q ββ ±5 keV window is resulting from close

  13. Effect of Estimated Daily Global Solar Radiation Data on the Results of Crop Growth Models

    Directory of Open Access Journals (Sweden)

    Herbert Formayer

    2007-10-01

    Full Text Available The results of previous studies have suggested that estimated daily globalradiation (RG values contain an error that could compromise the precision of subsequentcrop model applications. The following study presents a detailed site and spatial analysis ofthe RG error propagation in CERES and WOFOST crop growth models in Central Europeanclimate conditions. The research was conducted i at the eight individual sites in Austria andthe Czech Republic where measured daily RG values were available as a reference, withseven methods for RG estimation being tested, and ii for the agricultural areas of the CzechRepublic using daily data from 52 weather stations, with five RG estimation methods. In thelatter case the RG values estimated from the hours of sunshine using the ångström-Prescottformula were used as the standard method because of the lack of measured RG data. At thesite level we found that even the use of methods based on hours of sunshine, which showedthe lowest bias in RG estimates, led to a significant distortion of the key crop model outputs.When the ångström-Prescott method was used to estimate RG, for example, deviationsgreater than ±10 per cent in winter wheat and spring barley yields were noted in 5 to 6 percent of cases. The precision of the yield estimates and other crop model outputs was lowerwhen RG estimates based on the diurnal temperature range and cloud cover were used (mean bias error 2.0 to 4.1 per cent. The methods for estimating RG from the diurnal temperature range produced a wheat yield bias of more than 25 per cent in 12 to 16 per cent of the seasons. Such uncertainty in the crop model outputs makes the reliability of any seasonal yield forecasts or climate change impact assessments questionable if they are based on this type of data. The spatial assessment of the RG data uncertainty propagation over the winter wheat yields also revealed significant differences within the study area. We

  14. Photovoltaic Grid-Connected Modeling and Characterization Based on Experimental Results

    Science.gov (United States)

    Humada, Ali M.; Hojabri, Mojgan; Sulaiman, Mohd Herwan Bin; Hamada, Hussein M.; Ahmed, Mushtaq N.

    2016-01-01

    A grid-connected photovoltaic (PV) system operates under fluctuated weather condition has been modeled and characterized based on specific test bed. A mathematical model of a small-scale PV system has been developed mainly for residential usage, and the potential results have been simulated. The proposed PV model based on three PV parameters, which are the photocurrent, IL, the reverse diode saturation current, Io, the ideality factor of diode, n. Accuracy of the proposed model and its parameters evaluated based on different benchmarks. The results showed that the proposed model fitting the experimental results with high accuracy compare to the other models, as well as the I-V characteristic curve. The results of this study can be considered valuable in terms of the installation of a grid-connected PV system in fluctuated climatic conditions. PMID:27035575

  15. Photovoltaic Grid-Connected Modeling and Characterization Based on Experimental Results.

    Science.gov (United States)

    Humada, Ali M; Hojabri, Mojgan; Sulaiman, Mohd Herwan Bin; Hamada, Hussein M; Ahmed, Mushtaq N

    2016-01-01

    A grid-connected photovoltaic (PV) system operates under fluctuated weather condition has been modeled and characterized based on specific test bed. A mathematical model of a small-scale PV system has been developed mainly for residential usage, and the potential results have been simulated. The proposed PV model based on three PV parameters, which are the photocurrent, IL, the reverse diode saturation current, Io, the ideality factor of diode, n. Accuracy of the proposed model and its parameters evaluated based on different benchmarks. The results showed that the proposed model fitting the experimental results with high accuracy compare to the other models, as well as the I-V characteristic curve. The results of this study can be considered valuable in terms of the installation of a grid-connected PV system in fluctuated climatic conditions.

  16. [Computer optical topography: a study of the repeatability of the results of human body model examination].

    Science.gov (United States)

    Sarnadskiĭ, V N

    2007-01-01

    The problem of repeatability of the results of examination of a plastic human body model is considered. The model was examined in 7 positions using an optical topograph for kyphosis diagnosis. The examination was performed under television camera monitoring. It was shown that variation of the model position in the camera view affected the repeatability of the results of topographic examination, especially if the model-to-camera distance was changed. A study of the repeatability of the results of optical topographic examination can help to increase the reliability of the topographic method, which is widely used for medical screening of children and adolescents.

  17. Separating foliar physiology from morphology reveals the relative roles of vertically structured transpiration factors within red maple crowns and limitations of larger scale models

    Science.gov (United States)

    Bauerle, William L.; Bowden, Joseph D.

    2011-01-01

    A spatially explicit mechanistic model, MAESTRA, was used to separate key parameters affecting transpiration to provide insights into the most influential parameters for accurate predictions of within-crown and within-canopy transpiration. Once validated among Acer rubrum L. genotypes, model responses to different parameterization scenarios were scaled up to stand transpiration (expressed per unit leaf area) to assess how transpiration might be affected by the spatial distribution of foliage properties. For example, when physiological differences were accounted for, differences in leaf width among A. rubrum L. genotypes resulted in a 25% difference in transpiration. An in silico within-canopy sensitivity analysis was conducted over the range of genotype parameter variation observed and under different climate forcing conditions. The analysis revealed that seven of 16 leaf traits had a ≥5% impact on transpiration predictions. Under sparse foliage conditions, comparisons of the present findings with previous studies were in agreement that parameters such as the maximum Rubisco-limited rate of photosynthesis can explain ∼20% of the variability in predicted transpiration. However, the spatial analysis shows how such parameters can decrease or change in importance below the uppermost canopy layer. Alternatively, model sensitivity to leaf width and minimum stomatal conductance was continuous along a vertical canopy depth profile. Foremost, transpiration sensitivity to an observed range of morphological and physiological parameters is examined and the spatial sensitivity of transpiration model predictions to vertical variations in microclimate and foliage density is identified to reduce the uncertainty of current transpiration predictions. PMID:21617246

  18. A dynamic bivariate Poisson model for analysing and forecasting match results in the English Premier League

    NARCIS (Netherlands)

    Koopman, S.J.; Lit, R.

    2015-01-01

    Summary: We develop a statistical model for the analysis and forecasting of football match results which assumes a bivariate Poisson distribution with intensity coefficients that change stochastically over time. The dynamic model is a novelty in the statistical time series analysis of match results

  19. Revealing Rembrandt

    Directory of Open Access Journals (Sweden)

    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  20. Seeking for the rational basis of the Median Model: the optimal combination of multi-model ensemble results

    Directory of Open Access Journals (Sweden)

    A. Riccio

    2007-12-01

    Full Text Available In this paper we present an approach for the statistical analysis of multi-model ensemble results. The models considered here are operational long-range transport and dispersion models, also used for the real-time simulation of pollutant dispersion or the accidental release of radioactive nuclides.

    We first introduce the theoretical basis (with its roots sinking into the Bayes theorem and then apply this approach to the analysis of model results obtained during the ETEX-1 exercise. We recover some interesting results, supporting the heuristic approach called "median model", originally introduced in Galmarini et al. (2004a, b.

    This approach also provides a way to systematically reduce (and quantify model uncertainties, thus supporting the decision-making process and/or regulatory-purpose activities in a very effective manner.

  1. Computational Fluid Dynamics Modeling Of Scaled Hanford Double Shell Tank Mixing - CFD Modeling Sensitivity Study Results

    International Nuclear Information System (INIS)

    Jackson, V.L.

    2011-01-01

    The primary purpose of the tank mixing and sampling demonstration program is to mitigate the technical risks associated with the ability of the Hanford tank farm delivery and celtification systems to measure and deliver a uniformly mixed high-level waste (HLW) feed to the Waste Treatment and Immobilization Plant (WTP) Uniform feed to the WTP is a requirement of 24590-WTP-ICD-MG-01-019, ICD-19 - Interface Control Document for Waste Feed, although the exact definition of uniform is evolving in this context. Computational Fluid Dynamics (CFD) modeling has been used to assist in evaluating scaleup issues, study operational parameters, and predict mixing performance at full-scale.

  2. A general model of distant hybridization reveals the conditions for extinction in Atlantic salmon and brown trout.

    Science.gov (United States)

    Quilodrán, Claudio S; Currat, Mathias; Montoya-Burgos, Juan I

    2014-01-01

    Interspecific hybridization is common in nature but can be increased in frequency or even originated by human actions, such as species introduction or habitat modification, which may threaten species persistence. When hybridization occurs between distantly related species, referred to as "distant hybridization," the resulting hybrids are generally infertile or fertile but do not undergo chromosomal recombination during gametogenesis. Here, we present a model describing this frequent but poorly studied interspecific hybridization to assess its consequences on parental species and to anticipate the conditions under which they can reach extinction. Our general model fully incorporates three important processes: density-dependent competition, dominance/recessivity inheritance of traits and assortative mating. We demonstrate its use and flexibility by assessing population extinction risk between Atlantic salmon and brown trout in Norway, whose interbreeding has recently increased due to farmed fish releases into the wild. We identified the set of conditions under which hybridization may threaten salmonid species. Thanks to the flexibility of our model, we evaluated the effect of an additional risk factor, a parasitic disease, and showed that the cumulative effects dramatically increase the extinction risk. The consequences of distant hybridization are not genetically, but demographically mediated. Our general model is useful to better comprehend the evolution of such hybrid systems and we demonstrated its importance in the field of conservation biology to set up management recommendations when this increasingly frequent type of hybridization is in action.

  3. Rat models of 17β-estradiol-induced mammary cancer reveal novel insights into breast cancer etiology and prevention.

    Science.gov (United States)

    Shull, James D; Dennison, Kirsten L; Chack, Aaron C; Trentham-Dietz, Amy

    2018-03-01

    Numerous laboratory and epidemiologic studies strongly implicate endogenous and exogenous estrogens in the etiology of breast cancer. Data summarized herein suggest that the ACI rat model of 17β-estradiol (E2)-induced mammary cancer is unique among rodent models in the extent to which it faithfully reflects the etiology and biology of luminal types of breast cancer, which together constitute ~70% of all breast cancers. E2 drives cancer development in this model through mechanisms that are largely dependent upon estrogen receptors and require progesterone and its receptors. Moreover, mammary cancer development appears to be associated with generation of oxidative stress and can be modified by multiple dietary factors, several of which may attenuate the actions of reactive oxygen species. Studies of susceptible ACI rats and resistant COP or BN rats provide novel insights into the genetic bases of susceptibility and the biological processes regulated by genetic determinants of susceptibility. This review summarizes research progress resulting from use of these physiologically relevant rat models to advance understanding of breast cancer etiology and prevention.

  4. A General Model of Distant Hybridization Reveals the Conditions for Extinction in Atlantic Salmon and Brown Trout

    Science.gov (United States)

    Quilodrán, Claudio S.; Currat, Mathias; Montoya-Burgos, Juan I.

    2014-01-01

    Interspecific hybridization is common in nature but can be increased in frequency or even originated by human actions, such as species introduction or habitat modification, which may threaten species persistence. When hybridization occurs between distantly related species, referred to as “distant hybridization,” the resulting hybrids are generally infertile or fertile but do not undergo chromosomal recombination during gametogenesis. Here, we present a model describing this frequent but poorly studied interspecific hybridization to assess its consequences on parental species and to anticipate the conditions under which they can reach extinction. Our general model fully incorporates three important processes: density-dependent competition, dominance/recessivity inheritance of traits and assortative mating. We demonstrate its use and flexibility by assessing population extinction risk between Atlantic salmon and brown trout in Norway, whose interbreeding has recently increased due to farmed fish releases into the wild. We identified the set of conditions under which hybridization may threaten salmonid species. Thanks to the flexibility of our model, we evaluated the effect of an additional risk factor, a parasitic disease, and showed that the cumulative effects dramatically increase the extinction risk. The consequences of distant hybridization are not genetically, but demographically mediated. Our general model is useful to better comprehend the evolution of such hybrid systems and we demonstrated its importance in the field of conservation biology to set up management recommendations when this increasingly frequent type of hybridization is in action. PMID:25003336

  5. A general model of distant hybridization reveals the conditions for extinction in Atlantic salmon and brown trout.

    Directory of Open Access Journals (Sweden)

    Claudio S Quilodrán

    Full Text Available Interspecific hybridization is common in nature but can be increased in frequency or even originated by human actions, such as species introduction or habitat modification, which may threaten species persistence. When hybridization occurs between distantly related species, referred to as "distant hybridization," the resulting hybrids are generally infertile or fertile but do not undergo chromosomal recombination during gametogenesis. Here, we present a model describing this frequent but poorly studied interspecific hybridization to assess its consequences on parental species and to anticipate the conditions under which they can reach extinction. Our general model fully incorporates three important processes: density-dependent competition, dominance/recessivity inheritance of traits and assortative mating. We demonstrate its use and flexibility by assessing population extinction risk between Atlantic salmon and brown trout in Norway, whose interbreeding has recently increased due to farmed fish releases into the wild. We identified the set of conditions under which hybridization may threaten salmonid species. Thanks to the flexibility of our model, we evaluated the effect of an additional risk factor, a parasitic disease, and showed that the cumulative effects dramatically increase the extinction risk. The consequences of distant hybridization are not genetically, but demographically mediated. Our general model is useful to better comprehend the evolution of such hybrid systems and we demonstrated its importance in the field of conservation biology to set up management recommendations when this increasingly frequent type of hybridization is in action.

  6. Comparative analyses reveal potential uses of Brachypodium distachyon as a model for cold stress responses in temperate grasses

    Directory of Open Access Journals (Sweden)

    Li Chuan

    2012-05-01

    Full Text Available Abstract Background Little is known about the potential of Brachypodium distachyon as a model for low temperature stress responses in Pooideae. The ice recrystallization inhibition protein (IRIP genes, fructosyltransferase (FST genes, and many C-repeat binding factor (CBF genes are Pooideae specific and important in low temperature responses. Here we used comparative analyses to study conservation and evolution of these gene families in B. distachyon to better understand its potential as a model species for agriculturally important temperate grasses. Results Brachypodium distachyon contains cold responsive IRIP genes which have evolved through Brachypodium specific gene family expansions. A large cold responsive CBF3 subfamily was identified in B. distachyon, while CBF4 homologs are absent from the genome. No B. distachyon FST gene homologs encode typical core Pooideae FST-motifs and low temperature induced fructan accumulation was dramatically different in B. distachyon compared to core Pooideae species. Conclusions We conclude that B. distachyon can serve as an interesting model for specific molecular mechanisms involved in low temperature responses in core Pooideae species. However, the evolutionary history of key genes involved in low temperature responses has been different in Brachypodium and core Pooideae species. These differences limit the use of B. distachyon as a model for holistic studies relevant for agricultural core Pooideae species.

  7. Disentangling and modeling interactions in fish with burst-and-coast swimming reveal distinct alignment and attraction behaviors

    Science.gov (United States)

    Calovi, Daniel S.; Litchinko, Alexandra; Lopez, Ugo; Chaté, Hugues; Sire, Clément

    2018-01-01

    The development of tracking methods for automatically quantifying individual behavior and social interactions in animal groups has open up new perspectives for building quantitative and predictive models of collective behavior. In this work, we combine extensive data analyses with a modeling approach to measure, disentangle, and reconstruct the actual functional form of interactions involved in the coordination of swimming in Rummy-nose tetra (Hemigrammus rhodostomus). This species of fish performs burst-and-coast swimming behavior that consists of sudden heading changes combined with brief accelerations followed by quasi-passive, straight decelerations. We quantify the spontaneous stochastic behavior of a fish and the interactions that govern wall avoidance and the reaction to a neighboring fish, the latter by exploiting general symmetry constraints for the interactions. In contrast with previous experimental works, we find that both attraction and alignment behaviors control the reaction of fish to a neighbor. We then exploit these results to build a model of spontaneous burst-and-coast swimming and interactions of fish, with all parameters being estimated or directly measured from experiments. This model quantitatively reproduces the key features of the motion and spatial distributions observed in experiments with a single fish and with two fish. This demonstrates the power of our method that exploits large amounts of data for disentangling and fully characterizing the interactions that govern collective behaviors in animals groups. PMID:29324853

  8. Recent progress in econophysics: Chaos, leverage, and business cycles as revealed by agent-based modeling and human experiments

    Science.gov (United States)

    Xin, Chen; Huang, Ji-Ping

    2017-12-01

    Agent-based modeling and controlled human experiments serve as two fundamental research methods in the field of econophysics. Agent-based modeling has been in development for over 20 years, but how to design virtual agents with high levels of human-like "intelligence" remains a challenge. On the other hand, experimental econophysics is an emerging field; however, there is a lack of experience and paradigms related to the field. Here, we review some of the most recent research results obtained through the use of these two methods concerning financial problems such as chaos, leverage, and business cycles. We also review the principles behind assessments of agents' intelligence levels, and some relevant designs for human experiments. The main theme of this review is to show that by combining theory, agent-based modeling, and controlled human experiments, one can garner more reliable and credible results on account of a better verification of theory; accordingly, this way, a wider range of economic and financial problems and phenomena can be studied.

  9. Recent progress in econophysics: Chaos, leverage,and business cycles as revealed by agent-based modeling and human experiments

    Institute of Scientific and Technical Information of China (English)

    Chen Xin; Ji-Ping Huang

    2017-01-01

    Agent-based modeling and controlled human experiments serve as two fundamental research methods in the field of econophysics.Agent-based modeling has been in development for over 20 years,but how to design virtual agents with high levels of human-like "intelligence" remains a challenge.On the other hand,experimental econophysics is an emerging field;however,there is a lack of experience and paradigms related to the field.Here,we review some of the most recent research results obtained through the use of these two methods concerning financial problems such as chaos,leverage,and business cycles.We also review the principles behind assessments of agents' intelligence levels,and some relevant designs for human experiments.The main theme of this review is to show that by combining theory,agent-based modeling,and controlled human experiments,one can garner more reliable and credible results on account of a better verification of theory;accordingly,this way,a wider range of economic and financial problems and phenomena can be studied.

  10. Numerical modelling of radon-222 entry into houses: An outline of techniques and results

    DEFF Research Database (Denmark)

    Andersen, C.E.

    2001-01-01

    Numerical modelling is a powerful tool for studies of soil gas and radon-222 entry into houses. It is the purpose of this paper to review some main techniques and results. In the past, modelling has focused on Darcy flow of soil gas (driven by indoor–outdoor pressure differences) and combined...... diffusive and advective transport of radon. Models of different complexity have been used. The simpler ones are finite-difference models with one or two spatial dimensions. The more complex models allow for full three-dimensional and time dependency. Advanced features include: soil heterogeneity, anisotropy......, fractures, moisture, non-uniform soil temperature, non-Darcy flow of gas, and flow caused by changes in the atmospheric pressure. Numerical models can be used to estimate the importance of specific factors for radon entry. Models are also helpful when results obtained in special laboratory or test structure...

  11. Updating the CHAOS series of field models using Swarm data and resulting candidate models for IGRF-12

    DEFF Research Database (Denmark)

    Finlay, Chris; Olsen, Nils; Tøffner-Clausen, Lars

    th order spline representation with knot points spaced at 0.5 year intervals. The resulting field model is able to consistently fit data from six independent low Earth orbit satellites: Oersted, CHAMP, SAC-C and the three Swarm satellites. As an example, we present comparisons of the excellent model...... therefore conclude that Swarm data is suitable for building high-resolution models of the large-scale internal field, and proceed to extract IGRF-12 candidate models for the main field in epochs 2010 and 2015, as well as the predicted linear secular variarion for 2015-2020. The properties of these IGRF...... candidate models are briefly presented....

  12. A regional climate model for northern Europe: model description and results from the downscaling of two GCM control simulations

    Science.gov (United States)

    Rummukainen, M.; Räisänen, J.; Bringfelt, B.; Ullerstig, A.; Omstedt, A.; Willén, U.; Hansson, U.; Jones, C.

    This work presents a regional climate model, the Rossby Centre regional Atmospheric model (RCA1), recently developed from the High Resolution Limited Area Model (HIRLAM). The changes in the HIRLAM parametrizations, necessary for climate-length integrations, are described. A regional Baltic Sea ocean model and a modeling system for the Nordic inland lake systems have been coupled with RCA1. The coupled system has been used to downscale 10-year time slices from two different general circulation model (GCM) simulations to provide high-resolution regional interpretation of large-scale modeling. A selection of the results from the control runs, i.e. the present-day climate simulations, are presented: large-scale free atmospheric fields, the surface temperature and precipitation results and results for the on-line simulated regional ocean and lake surface climates. The regional model modifies the surface climate description compared to the GCM simulations, but it is also substantially affected by the biases in the GCM simulations. The regional model also improves the representation of the regional ocean and the inland lakes, compared to the GCM results.

  13. A regional climate model for northern Europe: model description and results from the downscaling of two GCM control simulations

    Energy Technology Data Exchange (ETDEWEB)

    Rummukainen, M.; Raeisaenen, J.; Bringfelt, B.; Ullerstig, A.; Omstedt, A.; Willen, U.; Hansson, U.; Jones, C. [Rossby Centre, Swedish Meteorological and Hydrological Inst., Norrkoeping (Sweden)

    2001-03-01

    This work presents a regional climate model, the Rossby Centre regional Atmospheric model (RCA1), recently developed from the High Resolution Limited Area Model (HIRLAM). The changes in the HIRLAM parametrizations, necessary for climate-length integrations, are described. A regional Baltic Sea ocean model and a modeling system for the Nordic inland lake systems have been coupled with RCA1. The coupled system has been used to downscale 10-year time slices from two different general circulation model (GCM) simulations to provide high-resolution regional interpretation of large-scale modeling. A selection of the results from the control runs, i.e. the present-day climate simulations, are presented: large-scale free atmospheric fields, the surface temperature and precipitation results and results for the on-line simulated regional ocean and lake surface climates. The regional model modifies the surface climate description compared to the GCM simulations, but it is also substantially affected by the biases in the GCM simulations. The regional model also improves the representation of the regional ocean and the inland lakes, compared to the GCM results. (orig.)

  14. Revealing Interactions between Human Resources, Quality of Life and Environmental Changes within Socially-oriented Observations : Results from the IPY PPS Arctic Project in the Russian North

    Science.gov (United States)

    Vlasova, Tatiana

    2010-05-01

    Socially-oriented Observations (SOO) in the Russian North have been carried out within multidisciplinary IPY PPS Arctic project under the leadership of Norway and supported by the Research Council of Norway as well as Russian Academy of Sciences. The main objective of SOO is to increase knowledge and observation of changes in quality of life conditions (state of natural environment including climate and biota, safe drinking water and foods, well-being, employment, social relations, access to health care and high quality education, etc.) and - to reveal trends in human capital and capacities (health, demography, education, creativity, spiritual-cultural characteristics and diversity, participation in decision making, etc.). SOO have been carried out in industrial cities as well as sparsely populated rural and nature protection areas in observation sites situated in different bioms (from coastal tundra to southern taiga zone) of Murmansk, Arkhangelsk Oblast and Republic of Komi. SOO were conducted according to the international protocol included in PPS Arctic Manual. SOO approaches based both on local people's perceptions and statistics help to identify main issues and targets for life quality, human capital and environment improvement and thus to distinguish leading SOO indicators for further monitoring. SOO have revealed close interaction between human resources, quality of life and environmental changes. Negative changes in human capital (depopulation, increasing unemployment, aging, declining physical and mental health, quality of education, loss of traditional knowledge, marginalization etc.), despite peoples' high creativity and optimism are becoming the major driving force effecting both the quality of life and the state of environment and overall sustainability. Human induced disturbances such as uncontrolled forests cuttings and poaching are increasing. Observed rapid changes in climate and biota (ice and permafrost melting, tundra shrubs getting taller and

  15. Study on driver model for hybrid truck based on driving simulator experimental results

    Directory of Open Access Journals (Sweden)

    Dam Hoang Phuc

    2018-04-01

    Full Text Available In this paper, a proposed car-following driver model taking into account some features of both the compensatory and anticipatory model representing the human pedal operation has been verified by driving simulator experiments with several real drivers. The comparison between computer simulations performed by determined model parameters with the experimental results confirm the correctness of this mathematical driver model and identified model parameters. Then the driver model is joined to a hybrid vehicle dynamics model and the moderate car following maneuver simulations with various driver parameters are conducted to investigate influences of driver parameters on vehicle dynamics response and fuel economy. Finally, major driver parameters involved in the longitudinal control of drivers are clarified. Keywords: Driver model, Driver-vehicle closed-loop system, Car Following, Driving simulator/hybrid electric vehicle (B1

  16. Atomic force microscopy reveals multiple patterns of antenna organization in purple bacteria: implications for energy transduction mechanisms and membrane modeling.

    Science.gov (United States)

    Sturgis, James N; Niederman, Robert A

    2008-01-01

    Recent topographs of the intracytoplasmic membrane (ICM) of purple bacteria obtained by atomic force microscopy (AFM) have provided the first surface views of the native architecture of a multicomponent biological membrane at submolecular resolution, representing an important landmark in structural biology. A variety of species-dependent, closely packed arrangements of light-harvesting (LH) complexes was revealed: the most highly organized was found in Rhodobacter sphaeroides in which the peripheral LH2 antenna was seen either in large clusters or in fixed rows interspersed among ordered arrays of dimeric LH1-reaction center (RC) core complexes. A more random organization was observed in other species containing both the LH1 and LH2 complexes, as typified by Rhododspirillum photometricum with randomly packed monomeric LH1-RC core complexes intermingled with large, paracrystalline domains of LH2 antenna. Surprisingly, no structures that could be identified as the ATP synthase or cytochrome bc (1) complexes were observed, which may reflect their localization at ICM vesicle poles or in curved membrane areas, out of view from the flat regions imaged by AFM. This possible arrangement of energy transducing complexes has required a reassessment of energy tranduction mechanisms which place the cytochrome bc (1) complex in close association with the RC. Instead, more plausible proposals must account for the movement of quinone redox species over considerable membrane distances on appropriate time scales. AFM, together with atomic resolution structures are also providing the basis for molecular modeling of the ICM that is leading to an improved picture of the supramolecular organization of photosynthetic complexes, as well as the forces that drive their segregation into distinct domains.

  17. Effects of clinically relevant MPL mutations in the transmembrane domain revealed at the atomic level through computational modeling.

    Science.gov (United States)

    Lee, Tai-Sung; Kantarjian, Hagop; Ma, Wanlong; Yeh, Chen-Hsiung; Giles, Francis; Albitar, Maher

    2011-01-01

    Mutations in the thrombopoietin receptor (MPL) may activate relevant pathways and lead to chronic myeloproliferative neoplasms (MPNs). The mechanisms of MPL activation remain elusive because of a lack of experimental structures. Modern computational biology techniques were utilized to explore the mechanisms of MPL protein activation due to various mutations. Transmembrane (TM) domain predictions, homology modeling, ab initio protein structure prediction, and molecular dynamics (MD) simulations were used to build structural dynamic models of wild-type and four clinically observed mutants of MPL. The simulation results suggest that S505 and W515 are important in keeping the TM domain in its correct position within the membrane. Mutations at either of these two positions cause movement of the TM domain, altering the conformation of the nearby intracellular domain in unexpected ways, and may cause the unwanted constitutive activation of MPL's kinase partner, JAK2. Our findings represent the first full-scale molecular dynamics simulations of the wild-type and clinically observed mutants of the MPL protein, a critical element of the MPL-JAK2-STAT signaling pathway. In contrast to usual explanations for the activation mechanism that are based on the relative translational movement between rigid domains of MPL, our results suggest that mutations within the TM region could result in conformational changes including tilt and rotation (azimuthal) angles along the membrane axis. Such changes may significantly alter the conformation of the adjacent and intrinsically flexible intracellular domain. Hence, caution should be exercised when interpreting experimental evidence based on rigid models of cytokine receptors or similar systems.

  18. Epidemiological Characteristics and Clinical Treatment Outcome of Typhoid Fever in Ningbo, China, 2005-2014: Pulsed-Field Gel Electorophoresis Results Revealing Great Proportion of Common Transmission Sources.

    Science.gov (United States)

    Song, Qifa; Yang, Yuanbin; Lin, Wenping; Yi, Bo; Xu, Guozhang

    2017-09-25

    We aimed to describe the molecular epidemiological characteristics and clinical treatment outcome of typhoid fever in Ningbo, China during 2005-2014. Eighty-eight Salmonella Typhi isolates were obtained from 307 hospitalized patients. Three prevalent pulsed-field gel electrophoresis (PFGE) patterns of 54 isolates from 3 outbreaks were identified. Overall, there were 64 (72.7%) isolates from clustered cases and 24 (27.3%) isolates from sporadic cases. Resistance to nalidixic acid (NAL) (n = 47; 53.4%) and ampicillin (AMP) (n = 40; 45.4%) and rare resistance to tetracycline (TET) (n = 2; 2.3%) and gentamicin (GEN) (n = 2; 2.3%) were observed. No isolates resistant to cefotaxime (CTX), chloramphenicol (CL), ciprofloxacin (CIP), and trimethoprim-sulfamethoxazole (SXT) were found. The occurrence of reduced sensitivity to CIP was 52.3% (n = 46). The medians of fever clearance time in cases with and without complications were 7 (interquartile range (IQR): 4-10) and 5 (IQR: 3-7) days (P = 0.001), respectively, when patients were treated with CIP or levofloxacin (LEV) and/or third-generation cephalosporins (CEP). Rates of serious complications were at low levels: peritonitis (2.3%), intestinal hemorrhage (6.8%), and intestinal perforation (1.1%). The present study revealed a long-term clustering trend with respect to PFGE patterns, occasional outbreaks, and the rapid spread of AMP resistance and decreased CIP susceptibility among S. Typhi isolates in recent years.

  19. Noninvasive monitoring of treatment response in a rabbit cyanide toxicity model reveals differences in brain and muscle metabolism

    Science.gov (United States)

    Kim, Jae G.; Lee, Jangwoen; Mahon, Sari B.; Mukai, David; Patterson, Steven E.; Boss, Gerry R.; Tromberg, Bruce J.; Brenner, Matthew

    2012-10-01

    Noninvasive near infrared spectroscopy measurements were performed to monitor cyanide (CN) poisoning and recovery in the brain region and in foreleg muscle simultaneously, and the effects of a novel CN antidote, sulfanegen sodium, on tissue hemoglobin oxygenation changes were compared using a sub-lethal rabbit model. The results demonstrated that the brain region is more susceptible to CN poisoning and slower in endogenous CN detoxification following exposure than peripheral muscles. However, sulfanegen sodium rapidly reversed CN toxicity, with brain region effects reversing more quickly than muscle. In vivo monitoring of multiple organs may provide important clinical information regarding the extent of CN toxicity and subsequent recovery, and facilitate antidote drug development.

  20. Influence of Various Irradiance Models and Their Combination on Simulation Results of Photovoltaic Systems

    Directory of Open Access Journals (Sweden)

    Martin Hofmann

    2017-09-01

    Full Text Available We analyze the output of various state-of-the-art irradiance models for photovoltaic systems. The models include two sun position algorithms, three types of input data time series, nine diffuse fraction models and five transposition models (for tilted surfaces, resulting in 270 different model chains for the photovoltaic (PV system simulation. These model chains are applied to 30 locations worldwide and three different module tracking types, totaling in 24,300 simulations. We show that the simulated PV yearly energy output varies between −5% and +8% for fixed mounted PV modules and between −26% and +14% for modules with two-axis tracking. Model quality varies strongly between locations; sun position algorithms have negligible influence on the simulation results; diffuse fraction models add a lot of variability; and transposition models feature the strongest influence on the simulation results. To highlight the importance of irradiance with high temporal resolution, we present an analysis of the influence of input temporal resolution and simulation models on the inverter clipping losses at varying PV system sizing factors for Lindenberg, Germany. Irradiance in one-minute resolution is essential for accurately calculating inverter clipping losses.

  1. Multi-omics reveal the lifestyle of the acidophilic, mineral-oxidizing model species Leptospirillum ferriphilumT.

    Science.gov (United States)

    Christel, Stephan; Herold, Malte; Bellenberg, Sören; El Hajjami, Mohamed; Buetti-Dinh, Antoine; Pivkin, Igor V; Sand, Wolfgang; Wilmes, Paul; Poetsch, Ansgar; Dopson, Mark

    2017-11-17

    Leptospirillum ferriphilum plays a major role in acidic, metal rich environments where it represents one of the most prevalent iron oxidizers. These milieus include acid rock and mine drainage as well as biomining operations. Despite its perceived importance, no complete genome sequence of this model species' type strain is available, limiting the possibilities to investigate the strategies and adaptations Leptospirillum ferriphilum T applies to survive and compete in its niche. This study presents a complete, circular genome of Leptospirillum ferriphilum T DSM 14647 obtained by PacBio SMRT long read sequencing for use as a high quality reference. Analysis of the functionally annotated genome, mRNA transcripts, and protein concentrations revealed a previously undiscovered nitrogenase cluster for atmospheric nitrogen fixation and elucidated metabolic systems taking part in energy conservation, carbon fixation, pH homeostasis, heavy metal tolerance, oxidative stress response, chemotaxis and motility, quorum sensing, and biofilm formation. Additionally, mRNA transcript counts and protein concentrations were compared between cells grown in continuous culture using ferrous iron as substrate and bioleaching cultures containing chalcopyrite (CuFeS 2 ). Leptospirillum ferriphilum T adaptations to growth on chalcopyrite included a possibly enhanced production of reducing power, reduced carbon dioxide fixation, as well as elevated RNA transcripts and proteins involved in heavy metal resistance, with special emphasis on copper efflux systems. Finally, expression and translation of genes responsible for chemotaxis and motility were enhanced. IMPORTANCE Leptospirillum ferriphilum is one of the most important iron-oxidizers in the context of acidic and metal rich environments during moderately thermophilic biomining. A high-quality circular genome of Leptospirillum ferriphilum T coupled with functional omics data provides new insights into its metabolic properties, such as the

  2. Demographic models reveal the shape of density dependence for a specialist insect herbivore on variable host plants.

    Science.gov (United States)

    Miller, Tom E X

    2007-07-01

    1. It is widely accepted that density-dependent processes play an important role in most natural populations. However, persistent challenges in our understanding of density-dependent population dynamics include evaluating the shape of the relationship between density and demographic rates (linear, concave, convex), and identifying extrinsic factors that can mediate this relationship. 2. I studied the population dynamics of the cactus bug Narnia pallidicornis on host plants (Opuntia imbricata) that varied naturally in relative reproductive effort (RRE, the proportion of meristems allocated to reproduction), an important plant quality trait. I manipulated per-plant cactus bug densities, quantified subsequent dynamics, and fit stage-structured models to the experimental data to ask if and how density influences demographic parameters. 3. In the field experiment, I found that populations with variable starting densities quickly converged upon similar growth trajectories. In the model-fitting analyses, the data strongly supported a model that defined the juvenile cactus bug retention parameter (joint probability of surviving and not dispersing) as a nonlinear decreasing function of density. The estimated shape of this relationship shifted from concave to convex with increasing host-plant RRE. 4. The results demonstrate that host-plant traits are critical sources of variation in the strength and shape of density dependence in insects, and highlight the utility of integrated experimental-theoretical approaches for identifying processes underlying patterns of change in natural populations.

  3. Fibre recruitment and shape changes of knee ligaments during motion: as revealed by a computer graphics-based model.

    Science.gov (United States)

    Lu, T W; O'Connor, J J

    1996-01-01

    A computer graphics-based model of the knee ligaments in the sagittal plane was developed for the simulation and visualization of the shape changes and fibre recruitment process of the ligaments during motion under unloaded and loaded conditions. The cruciate and collateral ligaments were modelled as ordered arrays of fibres which link attachment areas on the tibia and femur. Fibres slacken and tighten as the ligament attachment areas on the bones rotate and translate relative to each other. A four-bar linkage, composed of the femur, tibia and selected isometric fibres of the two cruciates, was used to determine the motion of the femur relative to the tibia during passive (unloaded) movement. Fibres were assumed to slacken in a Euler buckling mode when the distances between their attachments are less than chosen reference lengths. The ligament shape changes and buckling patterns are demonstrated with computer graphics. When the tibia is translated anteriorly or posteriorly relative to the femur by muscle forces and external loads, some ligament fibres tighten and are recruited progressively to transmit increasing shear forces. The shape changes and fibre recruitment patterns predicted by the model compare well qualitatively with experimental results reported in the literature. The computer graphics approach provides insight into the micro behaviour of the knee ligaments. It may help to explain ligament injury mechanisms and provide useful information to guide the design of ligament replacements.

  4. Factors affecting stream nutrient loads: A synthesis of regional SPARROW model results for the continental United States

    Science.gov (United States)

    Preston, Stephen D.; Alexander, Richard B.; Schwarz, Gregory E.; Crawford, Charles G.

    2011-01-01

    We compared the results of 12 recently calibrated regional SPARROW (SPAtially Referenced Regressions On Watershed attributes) models covering most of the continental United States to evaluate the consistency and regional differences in factors affecting stream nutrient loads. The models - 6 for total nitrogen and 6 for total phosphorus - all provide similar levels of prediction accuracy, but those for major river basins in the eastern half of the country were somewhat more accurate. The models simulate long-term mean annual stream nutrient loads as a function of a wide range of known sources and climatic (precipitation, temperature), landscape (e.g., soils, geology), and aquatic factors affecting nutrient fate and transport. The results confirm the dominant effects of urban and agricultural sources on stream nutrient loads nationally and regionally, but reveal considerable spatial variability in the specific types of sources that control water quality. These include regional differences in the relative importance of different types of urban (municipal and industrial point vs. diffuse urban runoff) and agriculture (crop cultivation vs. animal waste) sources, as well as the effects of atmospheric deposition, mining, and background (e.g., soil phosphorus) sources on stream nutrients. Overall, we found that the SPARROW model results provide a consistent set of information for identifying the major sources and environmental factors affecting nutrient fate and transport in United States watersheds at regional and subregional scales. ?? 2011 American Water Resources Association. This article is a U.S. Government work and is in the public domain in the USA.

  5. iTRAQ-based proteomic analysis reveals alterations in the liver induced by restricted meal frequency in a pig model.

    Science.gov (United States)

    Liu, Jingbo; Liu, Zhengqun; Chen, Liang; Zhang, Hongfu

    2016-01-01

    The present study was conducted to investigate the effects of meal frequency on metabolite levels in pig plasma and hepatic proteome by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Twenty-four pigs (60.7 ± 1.0 kg) consumed the same amount of feed either in 2 (M2, n = 12) or 12 (M12, n = 12) meals per day. After an 8-wk feeding period, plasma concentrations of metabolites and hormones, hepatic biochemical traits, and proteome (n = 4 per group) were measured. Pigs on the M12 regimen had lower average daily gain and gain-to-feed ratio than pigs fed the M2 regimen. The M2 regimen resulted in lower total lipid, glycogen, and triacylglycerol content in the liver and circulating triacylglycerol concentration than that in the M12 pigs. The metabolic hormone concentrations were not affected by meal frequency, with the exception of elevated fibroblast growth factor 21 concentrations in the M2 regimen compared with the M12 regimen. The iTRAQ-based proteomic analysis revealed 35 differentially expressed proteins in the liver between pigs fed two and 12 meals per day, and these differentially expressed proteins were involved in the regulation of general biological process such as glucose and energy metabolism, lipid metabolism, protein and amino acid metabolism, stress response, and cell redox homeostasis. Altogether, the proteomic results provide insights into the mechanism mediating the beneficial effects of restricted meal frequency on the metabolic fitness. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Some important results from the air pollution distribution model STACKS (1988-1992)

    International Nuclear Information System (INIS)

    Erbrink, J.J.

    1993-01-01

    Attention is paid to the results of the study on the distribution of air pollutants by high chimney-stacks of electric power plants. An important product of the study is the integrated distribution model STACKS (Short Term Air-pollutant Concentrations Kema modelling System). The improvements and the extensions of STACKS are described in relation to the National Model, which has been used to estimate the environmental effects of individual chimney-stacks. The National Model shows unacceptable variations for high pollutant sources. Based on the results of STACKS revision of the National model has been taken into consideration. By means of the revised National Model a more realistic estimation of the environmental effects of electric power plants can be carried out

  7. Modelling of plasma-based dry reforming: how do uncertainties in the input data affect the calculation results?

    Science.gov (United States)

    Wang, Weizong; Berthelot, Antonin; Zhang, Quanzhi; Bogaerts, Annemie

    2018-05-01

    One of the main issues in plasma chemistry modeling is that the cross sections and rate coefficients are subject to uncertainties, which yields uncertainties in the modeling results and hence hinders the predictive capabilities. In this paper, we reveal the impact of these uncertainties on the model predictions of plasma-based dry reforming in a dielectric barrier discharge. For this purpose, we performed a detailed uncertainty analysis and sensitivity study. 2000 different combinations of rate coefficients, based on the uncertainty from a log-normal distribution, are used to predict the uncertainties in the model output. The uncertainties in the electron density and electron temperature are around 11% and 8% at the maximum of the power deposition for a 70% confidence level. Still, this can have a major effect on the electron impact rates and hence on the calculated conversions of CO2 and CH4, as well as on the selectivities of CO and H2. For the CO2 and CH4 conversion, we obtain uncertainties of 24% and 33%, respectively. For the CO and H2 selectivity, the corresponding uncertainties are 28% and 14%, respectively. We also identify which reactions contribute most to the uncertainty in the model predictions. In order to improve the accuracy and reliability of plasma chemistry models, we recommend using only verified rate coefficients, and we point out the need for dedicated verification experiments.

  8. Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Torrealdea Javier

    2011-07-01

    Full Text Available Abstract Background The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS. Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e.g. failure in central tolerance, activation by pathogens that are able to trigger the immune system. Results The model represents five concepts: central tolerance (T-cell generation by the thymus, T-cell activation, T-cell memory, cross-regulation (negative feedback between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system. Conclusion The relapsing dynamic in MS

  9. Terrane-Scale Metastability in Subducted Himalayan Continental Crust as Revealed by Integrated Petrological and Geodynamic Modeling

    Science.gov (United States)

    Palin, R. M.; Reuber, G. S.; White, R. W.; Kaus, B. J. P.; Weller, O. M.

    2017-12-01

    The Tso Morari massif, northwest India, is one of only two regions in the Himalayan Range that exposes subduction-related ultrahigh-pressure (UHP) metamorphic rocks. The tectonic evolution of the massif is strongly debated, however, as reported pressure estimates for peak metamorphism range between 2.4 GPa and 4.8 GPa. Such ambiguity hinders effective lithospheric-scale modeling of the early stages of the orogen's evolution. We present the results of integrated petrological and geodynamic modeling (Palin et al., 2017, EPSL) that provide new quantitative constraints on the prograde-to-peak pressure-temperature-time (P-T-t) path, and predict the parageneses that felsic and mafic components of the massif crust should have formed under equilibrium conditions. Our model shows that peak P-T conditions of 2.6-2.8 GPa and 600-620 °C, representative of subduction to 90-100 km depth (assuming lithostatic pressure), were reached just 3 Myr after the onset of collision. These P-T-t constraints correlate well with those reported for similar UHP eclogite in the along-strike Kaghan Valley, Pakistan, suggesting that the northwest Himalaya contains dismembered remnants of a 400-km long UHP terrane comparable in size to the Western Gneiss Region, Norway, and the Dabie-Sulu belt, China. The extremely high pressures (up to 4.8 GPa) for peak metamorphism reported by some workers are likely to be unreliable due to thermobarometry having been performed on minerals that did not represent equilibrium assemblages. Furthermore, key high-P minerals predicted to form in subducted Tso Morari continental crust (e.g. jadeite, Mg-rich garnet) are absent from natural samples in the region, reflecting the widespread metastable preservation of lower-pressure protolith assemblages during subduction and exhumation. This result questions the reliability of geodynamic simulations of orogenesis that are commonly predicated on equilibrium metamorphism operating continuously throughout tectonic cycles.

  10. Planck intermediate results XXIX. All-sky dust modelling with Planck, IRAS, and WISE observations

    DEFF Research Database (Denmark)

    Ade, P. A. R.; Aghanim, N.; Alves, M. I. R.

    2016-01-01

    We present all-sky modelling of the high resolution Planck, IRAS, andWISE infrared (IR) observations using the physical dust model presented by Draine & Li in 2007 (DL, ApJ, 657, 810). We study the performance and results of this model, and discuss implications for future dust modelling....... The present work extends the DL dust modelling carried out on nearby galaxies using Herschel and Spitzer data to Galactic dust emission. We employ the DL dust model to generate maps of the dust mass surface density Sigma(Md), the dust optical extinction A(V), and the starlight intensity heating the bulk...... of the dust, parametrized by U-min. The DL model reproduces the observed spectral energy distribution (SED) satisfactorily over most of the sky, with small deviations in the inner Galactic disk and in low ecliptic latitude areas, presumably due to zodiacal light contamination. In the Andromeda galaxy (M31...

  11. GENERAL APROACH TO MODELING NONLINEAR AMPLITUDE AND FREQUENCY DEPENDENT HYSTERESIS EFFECTS BASED ON EXPERIMENTAL RESULTS

    Directory of Open Access Journals (Sweden)

    Christopher Heine

    2014-08-01

    Full Text Available A detailed description of the rubber parts’ properties is gaining in importance in the current simulation models of multi-body simulation. One application example is a multi-body simulation of the washing machine movement. Inside the washing machine, there are different force transmission elements, which consist completely or partly of rubber. Rubber parts or, generally, elastomers usually have amplitude-dependant and frequency-dependent force transmission properties. Rheological models are used to describe these properties. A method for characterization of the amplitude and frequency dependence of such a rheological model is presented within this paper. Within this method, the used rheological model can be reduced or expanded in order to illustrate various non-linear effects. An original result is given with the automated parameter identification. It is fully implemented in Matlab. Such identified rheological models are intended for subsequent implementation in a multi-body model. This allows a significant enhancement of the overall model quality.

  12. Linear regression metamodeling as a tool to summarize and present simulation model results.

    Science.gov (United States)

    Jalal, Hawre; Dowd, Bryan; Sainfort, François; Kuntz, Karen M

    2013-10-01

    Modelers lack a tool to systematically and clearly present complex model results, including those from sensitivity analyses. The objective was to propose linear regression metamodeling as a tool to increase transparency of decision analytic models and better communicate their results. We used a simplified cancer cure model to demonstrate our approach. The model computed the lifetime cost and benefit of 3 treatment options for cancer patients. We simulated 10,000 cohorts in a probabilistic sensitivity analysis (PSA) and regressed the model outcomes on the standardized input parameter values in a set of regression analyses. We used the regression coefficients to describe measures of sensitivity analyses, including threshold and parameter sensitivity analyses. We also compared the results of the PSA to deterministic full-factorial and one-factor-at-a-time designs. The regression intercept represented the estimated base-case outcome, and the other coefficients described the relative parameter uncertainty in the model. We defined simple relationships that compute the average and incremental net benefit of each intervention. Metamodeling produced outputs similar to traditional deterministic 1-way or 2-way sensitivity analyses but was more reliable since it used all parameter values. Linear regression metamodeling is a simple, yet powerful, tool that can assist modelers in communicating model characteristics and sensitivity analyses.

  13. The Plumbing of Land Surface Models: Is Poor Performance a Result of Methodology or Data Quality?

    Science.gov (United States)

    Haughton, Ned; Abramowitz, Gab; Pitman, Andy J.; Or, Dani; Best, Martin J.; Johnson, Helen R.; Balsamo, Gianpaolo; Boone, Aaron; Cuntz, Matthais; Decharme, Bertrand; hide

    2016-01-01

    The PALS Land sUrface Model Benchmarking Evaluation pRoject (PLUMBER) illustrated the value of prescribing a priori performance targets in model intercomparisons. It showed that the performance of turbulent energy flux predictions from different land surface models, at a broad range of flux tower sites using common evaluation metrics, was on average worse than relatively simple empirical models. For sensible heat fluxes, all land surface models were outperformed by a linear regression against downward shortwave radiation. For latent heat flux, all land surface models were outperformed by a regression against downward shortwave, surface air temperature and relative humidity. These results are explored here in greater detail and possible causes are investigated. We examine whether particular metrics or sites unduly influence the collated results, whether results change according to time-scale aggregation and whether a lack of energy conservation in fluxtower data gives the empirical models an unfair advantage in the intercomparison. We demonstrate that energy conservation in the observational data is not responsible for these results. We also show that the partitioning between sensible and latent heat fluxes in LSMs, rather than the calculation of available energy, is the cause of the original findings. Finally, we present evidence suggesting that the nature of this partitioning problem is likely shared among all contributing LSMs. While we do not find a single candidate explanation forwhy land surface models perform poorly relative to empirical benchmarks in PLUMBER, we do exclude multiple possible explanations and provide guidance on where future research should focus.

  14. Predicting ecosystem functioning from plant traits: Results from a multi-scale ecophsiological modeling approach

    NARCIS (Netherlands)

    Wijk, van M.T.

    2007-01-01

    Ecosystem functioning is the result of processes working at a hierarchy of scales. The representation of these processes in a model that is mathematically tractable and ecologically meaningful is a big challenge. In this paper I describe an individual based model (PLACO¿PLAnt COmpetition) that

  15. User's guide to Model Viewer, a program for three-dimensional visualization of ground-water model results

    Science.gov (United States)

    Hsieh, Paul A.; Winston, Richard B.

    2002-01-01

    Model Viewer is a computer program that displays the results of three-dimensional groundwater models. Scalar data (such as hydraulic head or solute concentration) may be displayed as a solid or a set of isosurfaces, using a red-to-blue color spectrum to represent a range of scalar values. Vector data (such as velocity or specific discharge) are represented by lines oriented to the vector direction and scaled to the vector magnitude. Model Viewer can also display pathlines, cells or nodes that represent model features such as streams and wells, and auxiliary graphic objects such as grid lines and coordinate axes. Users may crop the model grid in different orientations to examine the interior structure of the data. For transient simulations, Model Viewer can animate the time evolution of the simulated quantities. The current version (1.0) of Model Viewer runs on Microsoft Windows 95, 98, NT and 2000 operating systems, and supports the following models: MODFLOW-2000, MODFLOW-2000 with the Ground-Water Transport Process, MODFLOW-96, MOC3D (Version 3.5), MODPATH, MT3DMS, and SUTRA (Version 2D3D.1). Model Viewer is designed to directly read input and output files from these models, thus minimizing the need for additional postprocessing. This report provides an overview of Model Viewer. Complete instructions on how to use the software are provided in the on-line help pages.

  16. AFSC/RACE/GAP/Laman: Model Results of Aleutian Island POP distributions

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The data supporting the "Model Results of Aleutian Island POP distributions" manuscript are distribution and abundance of Pacific ocean perch from RACEBase,...

  17. First results with the general equilibrium model GEM-E3 Switzerland

    International Nuclear Information System (INIS)

    Bahn, O.; Frei, C.

    2000-01-01

    The GEM-E3 model has been implemented and applied for Switzerland. It has been in particular used to assess an ecological tax reform in Switzerland. Results of this analysis are presented here. (author)

  18. Removal of arsenic from wastewaters by cryptocrystalline magnesite: complimenting experimental results with modelling

    CSIR Research Space (South Africa)

    Masindi, Vhahangwele

    2016-02-01

    Full Text Available -1 Journal of Cleaner Production Removal of arsenic from wastewaters by cryptocrystalline magnesite: complimenting experimental results with modelling Vhahangwele Masindi W. Mugera Gitari Keywords: Arsenic Mine leachates Cryptocrystalline...

  19. Experimental and modelling results of a parallel-plate based active magnetic regenerator

    DEFF Research Database (Denmark)

    Tura, A.; Nielsen, Kaspar Kirstein; Rowe, A.

    2012-01-01

    The performance of a permanent magnet magnetic refrigerator (PMMR) using gadolinium parallel plates is described. The configuration and operating parameters are described in detail. Experimental results are compared to simulations using an established twodimensional model of an active magnetic...

  20. Modeling the radiation transfer of discontinuous canopies: results for gap probability and single-scattering contribution

    Science.gov (United States)

    Zhao, Feng; Zou, Kai; Shang, Hong; Ji, Zheng; Zhao, Huijie; Huang, Wenjiang; Li, Cunjun

    2010-10-01

    In this paper we present an analytical model for the computation of radiation transfer of discontinuous vegetation canopies. Some initial results of gap probability and bidirectional gap probability of discontinuous vegetation canopies, which are important parameters determining the radiative environment of the canopies, are given and compared with a 3- D computer simulation model. In the model, negative exponential attenuation of light within individual plant canopies is assumed. Then the computation of gap probability is resolved by determining the entry points and exiting points of the ray with the individual plants via their equations in space. For the bidirectional gap probability, which determines the single-scattering contribution of the canopy, a gap statistical analysis based model was adopted to correct the dependence of gap probabilities for both solar and viewing directions. The model incorporates the structural characteristics, such as plant sizes, leaf size, row spacing, foliage density, planting density, leaf inclination distribution. Available experimental data are inadequate for a complete validation of the model. So it was evaluated with a three dimensional computer simulation model for 3D vegetative scenes, which shows good agreement between these two models' results. This model should be useful to the quantification of light interception and the modeling of bidirectional reflectance distributions of discontinuous canopies.

  1. Computation and experiment results of the grounding model of Three Gorges Power Plant

    Energy Technology Data Exchange (ETDEWEB)

    Wen Xishan; Zhang Yuanfang; Yu Jianhui; Chen Cixuan [Wuhan University of Hydraulic and Electrical Engineering (China); Qin Liming; Xu Jun; Shu Lianfu [Yangtze River Water Resources Commission, Wuhan (China)

    1999-07-01

    A model for the computation of the grounding parameters of the grids of Three Gorges Power Plant (TGPP) on the Yangtze River is presented in this paper. Using this model computation and analysis of grounding grids is carried out. The results show that reinforcing the grid of the dam is the main body of current dissipation. It must be reliably welded to form a good grounding grid. The experimental results show that the method and program of the computations are correct. (UK)

  2. Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion

    Directory of Open Access Journals (Sweden)

    He Xianghuo

    2010-07-01

    Full Text Available Abstract Background The formation of metastasis is the most common cause of death in patients with lung cancer. A major implement to understand the molecular mechanisms involved in lung cancer metastasis has been the lack of suitable models to address it. In this study, we aimed at establishing a highly metastatic model of human lung cancer and characterizing its metastatic properties and underlying mechanisms. Methods The human lung adeno-carcinoma SPC-A-1 cell line was used as parental cells for developing of highly metastatic cells by in vivo selection in NOD/SCID mice. After three rounds of selection, a new SPC-A-1sci cell line was established from pulmonary metastatic lesions. Subsequently, the metastatic properties of this cell line were analyzed, including optical imaging of in vivo metastasis, immunofluorescence and immunohistochemical analysis of several epithelial mesenchymal transition (EMT makers and trans-well migration and invasion assays. Finally, the functional roles of fibronectin in the invasive and metastatic potentials of SPC-A-1sci cells were determined by shRNA analysis. Results A spontaneously pulmonary metastatic model of human lung adeno-carcinoma was established in NOD/SCID mice, from which a new lung cancer cell line, designated SPC-A-1sci, was isolated. Initially, the highly metastatic behavior of this cell line was validated by optical imaging in mice models. Further analyses showed that this cell line exhibit phenotypic and molecular alterations consistent with EMT. Compared with its parent cell line SPC-A-1, SPC-A-1sci was more aggressive in vitro, including increased potentials for cell spreading, migration and invasion. Importantly, fibronectin, a mesenchymal maker of EMT, was found to be highly expressed in SPC-A-1sci cells and down-regulation of it can decrease the in vitro and in vivo metastatic abilities of this cell line. Conclusions We have successfully established a new human lung cancer cell line with

  3. More performance results and implementation of an object oriented track reconstruction model in different OO frameworks

    International Nuclear Information System (INIS)

    Gaines, Irwin; Qian Sijin

    2001-01-01

    This is an update of the report about an Object Oriented (OO) track reconstruction model, which was presented in the previous AIHENP'99 at Crete, Greece. The OO model for the Kalman filtering method has been designed for high energy physics experiments at high luminosity hadron colliders. It has been coded in the C++ programming language and successfully implemented into a few different OO computing environments of the CMS and ATLAS experiments at the future Large Hadron Collider at CERN. We shall report: (1) more performance result: (2) implementing the OO model into the new SW OO framework 'Athena' of ATLAS experiment and some upgrades of the OO model itself

  4. New Results on Robust Model Predictive Control for Time-Delay Systems with Input Constraints

    Directory of Open Access Journals (Sweden)

    Qing Lu

    2014-01-01

    Full Text Available This paper investigates the problem of model predictive control for a class of nonlinear systems subject to state delays and input constraints. The time-varying delay is considered with both upper and lower bounds. A new model is proposed to approximate the delay. And the uncertainty is polytopic type. For the state-feedback MPC design objective, we formulate an optimization problem. Under model transformation, a new model predictive controller is designed such that the robust asymptotical stability of the closed-loop system can be guaranteed. Finally, the applicability of the presented results are demonstrated by a practical example.

  5. Modelling of tracer-kinetic results using xylene isomerization as an example

    International Nuclear Information System (INIS)

    Bauer, F.J.; Dermietzel, J.; Roesseler, M.; Koch, H.

    1976-01-01

    The analysis of results from differential or/and integral reactor experiments often admits the interpretation of a chemical reaction in several ways. In addition, the use of mathematical methods for the model selection and planning of experiments is rendered more difficult by great confidence intervals of the ascertained model parameters. The application of radioactively labelled molecules results in improving the knowledge of reaction mechanisms as well as the assessment of parameters obtained. This is shown on the basis of modelling the isomerization of xylene. (author)

  6. Theoretical results on the tandem junction solar cell based on its Ebers-Moll transistor model

    Science.gov (United States)

    Goradia, C.; Vaughn, J.; Baraona, C. R.

    1980-01-01

    A one-dimensional theoretical model of the tandem junction solar cell (TJC) with base resistivity greater than about 1 ohm-cm and under low level injection has been derived. This model extends a previously published conceptual model which treats the TJC as an npn transistor. The model gives theoretical expressions for each of the Ebers-Moll type currents of the illuminated TJC and allows for the calculation of the spectral response, I(sc), V(oc), FF and eta under variation of one or more of the geometrical and material parameters and 1MeV electron fluence. Results of computer calculations based on this model are presented and discussed. These results indicate that for space applications, both a high beginning of life efficiency, greater than 15% AM0, and a high radiation tolerance can be achieved only with thin (less than 50 microns) TJC's with high base resistivity (greater than 10 ohm-cm).

  7. Modelling lung cancer due to radon and smoking in WISMUT miners: Preliminary results

    International Nuclear Information System (INIS)

    Bijwaard, H.; Dekkers, F.; Van Dillen, T.

    2011-01-01

    A mechanistic two-stage carcinogenesis model has been applied to model lung-cancer mortality in the largest uranium-miner cohort available. Models with and without smoking action both fit the data well. As smoking information is largely missing from the cohort data, a method has been devised to project this information from a case-control study onto the cohort. Model calculations using 256 projections show that the method works well. Preliminary results show that if an explicit smoking action is absent in the model, this is compensated by the values of the baseline parameters. This indicates that in earlier studies performed without smoking information, the results obtained for the radiation parameters are still valid. More importantly, the inclusion of smoking-related parameters shows that these mainly influence the later stages of lung-cancer development. (authors)

  8. A new in vivo model of pantothenate kinase-associated neurodegeneration reveals a surprising role for transcriptional regulation in pathogenesis.

    Directory of Open Access Journals (Sweden)

    Varun ePandey

    2013-09-01

    Full Text Available Pantothenate Kinase-Associated Neurodegeneration (PKAN is a neurodegenerative disorder with a poorly understood molecular mechanism. It is caused by mutations in Pantothenate Kinase, the first enzyme in the Coenzyme A (CoA biosynthetic pathway. Here, we developed a Drosophila model of PKAN (tim-fbl flies that allows us to continuously monitor the modeled disease in the brain. In tim-fbl flies, downregulation of fumble, the Drosophila PanK homologue in the cells containing a circadian clock results in characteristic features of PKAN such as developmental lethality, hypersensitivity to oxidative stress, and diminished life span. Despite quasi-normal circadian transcriptional rhythms, tim-fbl flies display brain-specific aberrant circadian locomotor rhythms, and a unique transcriptional signature. Comparison with expression data from flies exposed to paraquat demonstrates that, as previously suggested, pathways others than oxidative stress are affected by PANK downregulation. Surprisingly we found a significant decrease in the expression of key components of the photoreceptor recycling pathways, which could lead to retinal degeneration, a hallmark of PKAN. Importantly, these defects are not accompanied by changes in structural components in eye genes suggesting that changes in gene expression in the eye precede and may cause the retinal degeneration. Indeed tim-fbl flies have diminished response to light transitions, and their altered day/night patterns of activity demonstrates defects in light perception. This suggest that retinal lesions are not solely due to oxidative stress and demonstrates a role for the transcriptional response to CoA deficiency underlying the defects observed in dPanK deficient flies. Moreover, in the present study we developed a new fly model that can be applied to other diseases and that allows the assessment of neurodegeneration in the brains of living flies.

  9. Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor

    Directory of Open Access Journals (Sweden)

    Hong-en Qu

    2017-01-01

    Full Text Available Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.

  10. Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor.

    Science.gov (United States)

    Qu, Hong-En; Niu, Chuanxin M; Li, Si; Hao, Man-Zhao; Hu, Zi-Xiang; Xie, Qing; Lan, Ning

    2017-12-01

    Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.

  11. Investigation into diffusion induced plastic deformation behavior in hollow lithium ion battery electrode revealed by analytical model and atomistic simulation

    International Nuclear Information System (INIS)

    Li, Jia; Fang, Qihong; Wu, Hong; Liu, Youwen; Wen, Pihua

    2015-01-01

    Highlights: • Diffusion induced stress is established. • Yield stress is dependent upon concentration. • Plastic deformation induced stress lowers tensile stress. • Plastic deformation suppresses crack nucleation. • Plastic deformation occurs not only at lithiated phase but also at electrode interior. - Abstract: This paper is theoretically suggested to describe diffusion induced stress in the elastoplastic hollow spherical silicon electrode for plastic deformation using both analytical model and molecular simulation. Based on the plastic deformation and the yield criterion, we develop this model accounting for the lithium-ion diffusion effect in hollow electrode, focusing on the concentration and stress distributions undergoing lithium-ion insertion. The results show that the two ways, applied compressive stress to inner surface or limited inner surface with higher concentration using biological membranes maintaining concentration difference, lead to the compressive stress induced by the lithium-ion diffusion effect. Hollow spherical electrode reduces effectively diffusion induced stress through controlling and tuning electrode parameters to obtain the reasonably low yield strength. According to MD simulations, plastic deformation phenomenon not only occurs at interface layer of lithiated phase, but also penetrates at electrode interior owning to confinement imposed by lithiated phase. These criteria that radial and hoop stresses reduce dramatically when plastic deformation occurs near the end faces of hollow electrode, may help guide development of new materials for lithium-ion batteries with enhanced mechanical durability, by means of reasonable designing yield strength to maintain mechanical stress below fracture strength, thereby increasing battery life.

  12. Influence of delayed neutron parameter calculation accuracy on results of modeled WWER scram experiments

    International Nuclear Information System (INIS)

    Artemov, V.G.; Gusev, V.I.; Zinatullin, R.E.; Karpov, A.S.

    2007-01-01

    Using modeled WWER cram rod drop experiments, performed at the Rostov NPP, as an example, the influence of delayed neutron parameters on the modeling results was investigated. The delayed neutron parameter values were taken from both domestic and foreign nuclear databases. Numerical modeling was carried out on the basis of SAPFIR 9 5andWWERrogram package. Parameters of delayed neutrons were acquired from ENDF/B-VI and BNAB-78 validated data files. It was demonstrated that using delay fraction data from different databases in reactivity meters led to significantly different reactivity results. Based on the results of numerically modeled experiments, delayed neutron parameters providing the best agreement between calculated and measured data were selected and recommended for use in reactor calculations (Authors)

  13. Gaze patterns reveal how texts are remembered: A mental model of what was described is favored over the text itself

    DEFF Research Database (Denmark)

    Traub, Franziska; Johansson, Roger; Holmqvist, Kenneth

    or incongruent with the spatial layout of the text itself. 28 participants read and recalled three texts: (1) a scene description congruent with the spatial layout of the text; (2) a scene description incongruent with the spatial layout of the text; and (3) a control text without any spatial scene content....... Recollection was performed orally while gazing at a blank screen. 
Results demonstrate that participant’s gaze patterns during recall more closely reflect the spatial layout of the scene than the physical locations of the text. We conclude that participants formed a mental model that represents the content...... of what was described, i.e., visuospatial information of the scene, which then guided the retrieval process. During their retellings, they moved the eyes across the blank screen as if they saw the scene in front of them. Whereas previous studies on the involvement of eye movements in mental imagery tasks...

  14. Hidden Markov model analysis reveals the advantage of analytic eye movement patterns in face recognition across cultures.

    Science.gov (United States)

    Chuk, Tim; Crookes, Kate; Hayward, William G; Chan, Antoni B; Hsiao, Janet H

    2017-12-01

    It remains controversial whether culture modulates eye movement behavior in face recognition. Inconsistent results have been reported regarding whether cultural differences in eye movement patterns exist, whether these differences affect recognition performance, and whether participants use similar eye movement patterns when viewing faces from different ethnicities. These inconsistencies may be due to substantial individual differences in eye movement patterns within a cultural group. Here we addressed this issue by conducting individual-level eye movement data analysis using hidden Markov models (HMMs). Each individual's eye movements were modeled with an HMM. We clustered the individual HMMs according to their similarities and discovered three common patterns in both Asian and Caucasian participants: holistic (looking mostly at the face center), left-eye-biased analytic (looking mostly at the two individual eyes in addition to the face center with a slight bias to the left eye), and right-eye-based analytic (looking mostly at the right eye in addition to the face center). The frequency of participants adopting the three patterns did not differ significantly between Asians and Caucasians, suggesting little modulation from culture. Significantly more participants (75%) showed similar eye movement patterns when viewing own- and other-race faces than different patterns. Most importantly, participants with left-eye-biased analytic patterns performed significantly better than those using either holistic or right-eye-biased analytic patterns. These results suggest that active retrieval of facial feature information through an analytic eye movement pattern may be optimal for face recognition regardless of culture. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. A hierarchy of models for simulating experimental results from a 3D heterogeneous porous medium

    Science.gov (United States)

    Vogler, Daniel; Ostvar, Sassan; Paustian, Rebecca; Wood, Brian D.

    2018-04-01

    In this work we examine the dispersion of conservative tracers (bromide and fluorescein) in an experimentally-constructed three-dimensional dual-porosity porous medium. The medium is highly heterogeneous (σY2 = 5.7), and consists of spherical, low-hydraulic-conductivity inclusions embedded in a high-hydraulic-conductivity matrix. The bimodal medium was saturated with tracers, and then flushed with tracer-free fluid while the effluent breakthrough curves were measured. The focus for this work is to examine a hierarchy of four models (in the absence of adjustable parameters) with decreasing complexity to assess their ability to accurately represent the measured breakthrough curves. The most information-rich model was (1) a direct numerical simulation of the system in which the geometry, boundary and initial conditions, and medium properties were fully independently characterized experimentally with high fidelity. The reduced-information models included; (2) a simplified numerical model identical to the fully-resolved direct numerical simulation (DNS) model, but using a domain that was one-tenth the size; (3) an upscaled mobile-immobile model that allowed for a time-dependent mass-transfer coefficient; and, (4) an upscaled mobile-immobile model that assumed a space-time constant mass-transfer coefficient. The results illustrated that all four models provided accurate representations of the experimental breakthrough curves as measured by global RMS error. The primary component of error induced in the upscaled models appeared to arise from the neglect of convection within the inclusions. We discuss the necessity to assign value (via a utility function or other similar method) to outcomes if one is to further select from among model options. Interestingly, these results suggested that the conventional convection-dispersion equation, when applied in a way that resolves the heterogeneities, yields models with high fidelity without requiring the imposition of a more

  16. A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization.

    Science.gov (United States)

    Jao, Li-En; Appel, Bruce; Wente, Susan R

    2012-04-01

    In humans, GLE1 is mutated in lethal congenital contracture syndrome 1 (LCCS1) leading to prenatal death of all affected fetuses. Although the molecular roles of Gle1 in nuclear mRNA export and translation have been documented, no animal models for this disease have been reported. To elucidate the function of Gle1 in vertebrate development, we used the zebrafish (Danio rerio) model system. gle1 mRNA is maternally deposited and widely expressed. Altering Gle1 using an insertional mutant or antisense morpholinos results in multiple defects, including immobility, small eyes, diminished pharyngeal arches, curved body axis, edema, underdeveloped intestine and cell death in the central nervous system. These phenotypes parallel those observed in LCCS1 human fetuses. Gle1 depletion also results in reduction of motoneurons and aberrant arborization of motor axons. Unexpectedly, the motoneuron deficiency results from apoptosis of neural precursors, not of differentiated motoneurons. Mosaic analyses further indicate that Gle1 activity is required extrinsically in the environment for normal motor axon arborization. Importantly, the zebrafish phenotypes caused by Gle1 deficiency are only rescued by expressing wild-type human GLE1 and not by the disease-linked Fin(Major) mutant form of GLE1. Together, our studies provide the first functional characterization of Gle1 in vertebrate development and reveal its essential role in actively dividing cells. We propose that defective GLE1 function in human LCCS1 results in both neurogenic and non-neurogenic defects linked to the apoptosis of proliferative organ precursors.

  17. Imaging mass spectrometry reveals elevated nigral levels of dynorphin neuropeptides in L-DOPA-induced dyskinesia in rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Anna Ljungdahl

    Full Text Available L-DOPA-induced dyskinesia is a troublesome complication of L-DOPA pharmacotherapy of Parkinson's disease and has been associated with disturbed brain opioid transmission. However, so far the results of clinical and preclinical studies on the effects of opioids agonists and antagonists have been contradictory at best. Prodynorphin mRNA levels correlate well with the severity of dyskinesia in animal models of Parkinson's disease; however the identities of the actual neuroactive opioid effectors in their target basal ganglia output structures have not yet been determined. For the first time MALDI-TOF imaging mass spectrometry (IMS was used for unbiased assessment and topographical elucidation of prodynorphin-derived peptides in the substantia nigra of a unilateral rat model of Parkinson's disease and L-DOPA induced dyskinesia. Nigral levels of dynorphin B and alpha-neoendorphin strongly correlated with the severity of dyskinesia. Even if dynorphin peptide levels were elevated in both the medial and lateral part of the substantia nigra, MALDI IMS analysis revealed that the most prominent changes were localized to the lateral part of the substantia nigra. MALDI IMS is advantageous compared with traditional molecular methods, such as radioimmunoassay, in that neither the molecular identity analyzed, nor the specific localization needs to be predetermined. Indeed, MALDI IMS revealed that the bioconverted metabolite leu-enkephalin-arg also correlated positively with severity of dyskinesia. Multiplexing DynB and leu-enkephalin-arg ion images revealed small (0.25 by 0.5 mm nigral subregions with complementing ion intensities, indicating localized peptide release followed by bioconversion. The nigral dynorphins associated with L-DOPA-induced dyskinesia were not those with high affinity to kappa opioid receptors, but consisted of shorter peptides, mainly dynorphin B and alpha-neoendorphin that are known to bind and activate mu and delta opioid receptors

  18. Ex-plant consequence assessment for NUREG-1150: models, typical results, uncertainties

    International Nuclear Information System (INIS)

    Sprung, J.L.

    1988-01-01

    The assessment of ex-plant consequences for NUREG-1150 source terms was performed using the MELCOR Accident Consequence Code System (MACCS). This paper briefly discusses the following elements of MACCS consequence calculations: input data, phenomena modeled, computational framework, typical results, controlling phenomena, and uncertainties. Wherever possible, NUREG-1150 results will be used to illustrate the discussion. 28 references

  19. Equation-free analysis of two-component system signalling model reveals the emergence of co-existing phenotypes in the absence of multistationarity.

    Directory of Open Access Journals (Sweden)

    Rebecca B Hoyle

    Full Text Available Phenotypic differences of genetically identical cells under the same environmental conditions have been attributed to the inherent stochasticity of biochemical processes. Various mechanisms have been suggested, including the existence of alternative steady states in regulatory networks that are reached by means of stochastic fluctuations, long transient excursions from a stable state to an unstable excited state, and the switching on and off of a reaction network according to the availability of a constituent chemical species. Here we analyse a detailed stochastic kinetic model of two-component system signalling in bacteria, and show that alternative phenotypes emerge in the absence of these features. We perform a bifurcation analysis of deterministic reaction rate equations derived from the model, and find that they cannot reproduce the whole range of qualitative responses to external signals demonstrated by direct stochastic simulations. In particular, the mixed mode, where stochastic switching and a graded response are seen simultaneously, is absent. However, probabilistic and equation-free analyses of the stochastic model that calculate stationary states for the mean of an ensemble of stochastic trajectories reveal that slow transcription of either response regulator or histidine kinase leads to the coexistence of an approximate basal solution and a graded response that combine to produce the mixed mode, thus establishing its essential stochastic nature. The same techniques also show that stochasticity results in the observation of an all-or-none bistable response over a much wider range of external signals than would be expected on deterministic grounds. Thus we demonstrate the application of numerical equation-free methods to a detailed biochemical reaction network model, and show that it can provide new insight into the role of stochasticity in the emergence of phenotypic diversity.

  20. Empirical Results of Modeling EUR/RON Exchange Rate using ARCH, GARCH, EGARCH, TARCH and PARCH models

    Directory of Open Access Journals (Sweden)

    Andreea – Cristina PETRICĂ

    2017-03-01

    Full Text Available The aim of this study consists in examining the changes in the volatility of daily returns of EUR/RON exchange rate using on the one hand symmetric GARCH models (ARCH and GARCH and on the other hand the asymmetric GARCH models (EGARCH, TARCH and PARCH, since the conditional variance is time-varying. The analysis takes into account daily quotations of EUR/RON exchange rate over the period of 04th January 1999 to 13th June 2016. Thus, we are modeling heteroscedasticity by applying different specifications of GARCH models followed by looking for significant parameters and low information criteria (minimum Akaike Information Criterion. All models are estimated using the maximum likelihood method under the assumption of several distributions of the innovation terms such as: Normal (Gaussian distribution, Student’s t distribution, Generalized Error distribution (GED, Student’s with fixed df. Distribution, and GED with fixed parameter distribution. The predominant models turned out to be EGARCH and PARCH models, and the empirical results point out that the best model for estimating daily returns of EUR/RON exchange rate is EGARCH(2,1 with Asymmetric order 2 under the assumption of Student’s t distributed innovation terms. This can be explained by the fact that in case of EGARCH model, the restriction regarding the positivity of the conditional variance is automatically satisfied.

  1. Analytical results for a stochastic model of gene expression with arbitrary partitioning of proteins

    Science.gov (United States)

    Tschirhart, Hugo; Platini, Thierry

    2018-05-01

    In biophysics, the search for analytical solutions of stochastic models of cellular processes is often a challenging task. In recent work on models of gene expression, it was shown that a mapping based on partitioning of Poisson arrivals (PPA-mapping) can lead to exact solutions for previously unsolved problems. While the approach can be used in general when the model involves Poisson processes corresponding to creation or degradation, current applications of the method and new results derived using it have been limited to date. In this paper, we present the exact solution of a variation of the two-stage model of gene expression (with time dependent transition rates) describing the arbitrary partitioning of proteins. The methodology proposed makes full use of the PPA-mapping by transforming the original problem into a new process describing the evolution of three biological switches. Based on a succession of transformations, the method leads to a hierarchy of reduced models. We give an integral expression of the time dependent generating function as well as explicit results for the mean, variance, and correlation function. Finally, we discuss how results for time dependent parameters can be extended to the three-stage model and used to make inferences about models with parameter fluctuations induced by hidden stochastic variables.

  2. Deriving user-informed climate information from climate model ensemble results

    Science.gov (United States)

    Huebener, Heike; Hoffmann, Peter; Keuler, Klaus; Pfeifer, Susanne; Ramthun, Hans; Spekat, Arne; Steger, Christian; Warrach-Sagi, Kirsten

    2017-07-01

    Communication between providers and users of climate model simulation results still needs to be improved. In the German regional climate modeling project ReKliEs-De a midterm user workshop was conducted to allow the intended users of the project results to assess the preliminary results and to streamline the final project results to their needs. The user feedback highlighted, in particular, the still considerable gap between climate research output and user-tailored input for climate impact research. Two major requests from the user community addressed the selection of sub-ensembles and some condensed, easy to understand information on the strengths and weaknesses of the climate models involved in the project.

  3. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  4. Assessing flood risk at the global scale: model setup, results, and sensitivity

    International Nuclear Information System (INIS)

    Ward, Philip J; Jongman, Brenden; Weiland, Frederiek Sperna; Winsemius, Hessel C; Bouwman, Arno; Ligtvoet, Willem; Van Beek, Rens; Bierkens, Marc F P

    2013-01-01

    Globally, economic losses from flooding exceeded $19 billion in 2012, and are rising rapidly. Hence, there is an increasing need for global-scale flood risk assessments, also within the context of integrated global assessments. We have developed and validated a model cascade for producing global flood risk maps, based on numerous flood return-periods. Validation results indicate that the model simulates interannual fluctuations in flood impacts well. The cascade involves: hydrological and hydraulic modelling; extreme value statistics; inundation modelling; flood impact modelling; and estimating annual expected impacts. The initial results estimate global impacts for several indicators, for example annual expected exposed population (169 million); and annual expected exposed GDP ($1383 billion). These results are relatively insensitive to the extreme value distribution employed to estimate low frequency flood volumes. However, they are extremely sensitive to the assumed flood protection standard; developing a database of such standards should be a research priority. Also, results are sensitive to the use of two different climate forcing datasets. The impact model can easily accommodate new, user-defined, impact indicators. We envisage several applications, for example: identifying risk hotspots; calculating macro-scale risk for the insurance industry and large companies; and assessing potential benefits (and costs) of adaptation measures. (letter)

  5. Comparison of the 1981 INEL dispersion data with results from a number of different models

    Energy Technology Data Exchange (ETDEWEB)

    Lewellen, W S; Sykes, R I; Parker, S F

    1985-05-01

    The results from simulations by 12 different dispersion models are compared with observations from an extensive field experiment conducted by the Nuclear Regulatory Commission at the Idaho National Engineering Laboratory in July, 1981. Comparisons were made on the bases of hourly SF/sub 6/ samples taken at the surface, out to approximately 10 km from the 46 m release tower, both during and following 7 different 8-hour releases. Comparisons are also made for total integrated doses collected out to approximately 40 km. Three classes of models are used. Within the limited range appropriate for Class A models this data comparison shows that neither the puff models or the transport and diffusion models agree with the data any better than the simple Gaussian plume models. The puff and transport and diffusion models do show a slight edge in performance in comparison with the total dose over the extended range approximate for class B models. The best model results for the hourly samples show approximately 40% calculated within a factor of two when a 15/sup 0/ uncertainty in plume position is permitted and it is assumed that higher data samples may occur at stations between the actual sample sites. This is increased to 60% for the 12 hour integrated dose and 70% for the total integrated dose when the same performance measure is used. None of the models reproduce the observed patchy dose patterns. This patchiness is consistent with the discussion of the inherent uncertainty associated with time averaged plume observations contained in our companion reports on the scientific critique of available models.

  6. The use of the k - {epsilon} turbulence model within the Rossby Centre regional ocean climate model: parameterization development and results

    Energy Technology Data Exchange (ETDEWEB)

    Markus Meier, H.E. [Swedish Meteorological and Hydrological Inst., Norrkoeping (Sweden). Rossby Centre

    2000-09-01

    As mixing plays a dominant role for the physics of an estuary like the Baltic Sea (seasonal heat storage, mixing in channels, deep water mixing), different mixing parameterizations for use in 3D Baltic Sea models are discussed and compared. For this purpose two different OGCMs of the Baltic Sea are utilized. Within the Swedish regional climate modeling program, SWECLIM, a 3D coupled ice-ocean model for the Baltic Sea has been coupled with an improved version of the two-equation k - {epsilon} turbulence model with corrected dissipation term, flux boundary conditions to include the effect of a turbulence enhanced layer due to breaking surface gravity waves and a parameterization for breaking internal waves. Results of multi-year simulations are compared with observations. The seasonal thermocline is simulated satisfactory and erosion of the halocline is avoided. Unsolved problems are discussed. To replace the controversial equation for dissipation the performance of a hierarchy of k-models has been tested and compared with the k - {epsilon} model. In addition, it is shown that the results of the mixing parameterization depend very much on the choice of the ocean model. Finally, the impact of two mixing parameterizations on Baltic Sea climate is investigated. In this case the sensitivity of mean SST, vertical temperature and salinity profiles, ice season and seasonal cycle of heat fluxes is quite large.

  7. Landscape genetics reveals inbreeding and genetic bottlenecks in the extremely rare short-globose cacti Mammillaria pectinifera (Cactaceae as a result of habitat fragmentation

    Directory of Open Access Journals (Sweden)

    Reyna Maya-García

    2017-02-01

    Full Text Available Mammillaria pectinifera is an endemic, short-globose cactus species, included in the IUCN list as a threatened species with only 18 remaining populations in the Tehuacán-Cuicatlán Valley in central Mexico. We evaluated the population genetic diversity and structure, connectivity, recent bottlenecks and population size, using nuclear microsatellites. M. pectinifera showed high genetic diversity but some evidence of heterozygote deficiency (FIS, recent bottlenecks in some populations and reductions in population size. Also, we found low population genetic differentiation and high values of connectivity for M. pectinifera, as the result of historical events of gene flow through pollen and seed dispersal. M. pectinifera occurs in sites with some degree of disturbance leading to the isolation of its populations and decreasing the levels of gene flow among them. Excessive deforestation also changes the original vegetation damaging the natural habitats. This species will become extinct if it is not properly preserved. Furthermore, this species has some ecological features that make them more vulnerable to disturbance such as a very low growth rates and long life cycles. We suggest in situ conservation to prevent the decrease of population sizes and loss of genetic diversity in the natural protected areas such as the Tehuacán-Cuicatlán Biosphere Reserve. In addition, a long-term ex situ conservation program is need to construct seed banks, and optimize seed germination and plant establishment protocols that restore disturbed habitats. Furthermore, creating a supply of living plants for trade is critical to avoid further extraction of plants from nature.

  8. Pilot Study on Folate Bioavailability from a Camembert Cheese Reveals Contradictory Findings to Recent Results from a Human Short-term Study.

    Science.gov (United States)

    Mönch, Sabine; Netzel, Michael; Netzel, Gabriele; Ott, Undine; Frank, Thomas; Rychlik, Michael

    2016-01-01

    Different dietary sources of folate have differing bioavailabilities, which may affect their nutritional "value." In order to examine if these differences also occur within the same food products, a short-term human pilot study was undertaken as a follow-up study to a previously published human trial to evaluate the relative native folate bioavailabilities from low-fat Camembert cheese compared to pteroylmonoglutamic acid as the reference dose. Two healthy human subjects received the test foods in a randomized cross-over design separated by a 14-day equilibrium phase. Folate body pools were saturated with a pteroylmonoglutamic acid supplement before the first testing and between the testings. Folates in test foods and blood plasma were analyzed by stable isotope dilution assays. The biokinetic parameters C max, t max, and area under the curve (AUC) were determined in plasma within the interval of 0-12 h. When comparing the ratio estimates of AUC and C max for the different Camembert cheeses, a higher bioavailability was found for the low-fat Camembert assessed in the present study (≥64%) compared to a different brand in our previous investigation (8.8%). It is suggested that these differences may arise from the different folate distribution in the soft dough and firm rind as well as differing individual folate vitamer proportions. The results clearly underline the importance of the food matrix, even within the same type of food product, in terms of folate bioavailability. Moreover, our findings add to the increasing number of studies questioning the general assumption of 50% bioavailability as the rationale behind the definition of folate equivalents. However, more research is needed to better understand the interactions between individual folate vitamers and other food components and the potential impact on folate bioavailability and metabolism.

  9. Pilot Study on Folate Bioavailability from A Camembert Cheese reveals contradictory findings to recent results from a Human Short-term study

    Directory of Open Access Journals (Sweden)

    Sabine eMönch

    2016-04-01

    Full Text Available Different dietary sources of folate have differing bioavailabilities which may affect their nutritional value. In order to examine if these differences also occur within the same food products, a short term human pilot study was undertaken as a follow-up study to a previously published human trial to evaluate the relative native folate bioavailabilities from low-fat Camembert cheese compared to pteroylmonoglutamic acid as the reference dose. Two healthy human subjects received the test foods in a randomized cross-over design separated by a 14-day equilibrium phase. Folate body pools were saturated with a pteroylmonoglutamic acid supplement before the first testing and between the testings. Folates in test foods and blood plasma were analysed by stable isotope dilution assays. The biokinetic parameters Cmax, tmax and AUC were determined in plasma within the interval of 0 to 12 hours. When comparing the ratio estimates of AUC and Cmax for the different Camembert cheeses, a higher bioavailability was found for the low-fat Camembert assessed in the present study (≥64% compared to a different brand in our previous investigation (8.8%. It is suggested that these differences may arise from the different folate distribution in the soft dough and firm rind as well as differing individual folate vitamer proportions. The results clearly underline the importance of the food matrix, even within the same type of food product, in terms of folate bioavailability. Moreover, our findings add to the increasing number of studies questioning the general assumption of 50 % bioavailability as the rationale behind the definition of folate equivalents. However, more research is needed to better understand the interactions between individual folate vitamers and other food components and the potential impact on folate bioavailability and metabolism.

  10. Modeling autosomal recessive cutis laxa type 1C in mice reveals distinct functions for Ltbp-4 isoforms

    DEFF Research Database (Denmark)

    Bultmann-Mellin, Insa; Conradi, Anne; Maul, Alexandra C

    2015-01-01

    Recent studies have revealed an important role for LTBP-4 in elastogenesis. Its mutational inactivation in humans causes autosomal recessive cutis laxa type 1C (ARCL1C), which is a severe disorder caused by defects of the elastic fiber network. Although the human gene involved in ARCL1C has been ...

  11. A computer model to forecast wetland vegetation changes resulting from restoration and protection in coastal Louisiana

    Science.gov (United States)

    Visser, Jenneke M.; Duke-Sylvester, Scott M.; Carter, Jacoby; Broussard, Whitney P.

    2013-01-01

    The coastal wetlands of Louisiana are a unique ecosystem that supports a diversity of wildlife as well as a diverse community of commercial interests of both local and national importance. The state of Louisiana has established a 5-year cycle of scientific investigation to provide up-to-date information to guide future legislation and regulation aimed at preserving this critical ecosystem. Here we report on a model that projects changes in plant community distribution and composition in response to environmental conditions. This model is linked to a suite of other models and requires input from those that simulate the hydrology and morphology of coastal Louisiana. Collectively, these models are used to assess how alternative management plans may affect the wetland ecosystem through explicit spatial modeling of the physical and biological processes affected by proposed modifications to the ecosystem. We have also taken the opportunity to advance the state-of-the-art in wetland plant community modeling by using a model that is more species-based in its description of plant communities instead of one based on aggregated community types such as brackish marsh and saline marsh. The resulting model provides an increased level of ecological detail about how wetland communities are expected to respond. In addition, the output from this model provides critical inputs for estimating the effects of management on higher trophic level species though a more complete description of the shifts in habitat.

  12. Probabilistic Modeling of Updating Epistemic Uncertainty In Pile Capacity Prediction With a Single Failure Test Result

    Directory of Open Access Journals (Sweden)

    Indra Djati Sidi

    2017-12-01

    Full Text Available The model error N has been introduced to denote the discrepancy between measured and predicted capacity of pile foundation. This model error is recognized as epistemic uncertainty in pile capacity prediction. The statistics of N have been evaluated based on data gathered from various sites and may be considered only as a eneral-error trend in capacity prediction, providing crude estimates of the model error in the absence of more specific data from the site. The results of even a single load test to failure, should provide direct evidence of the pile capacity at a given site. Bayes theorem has been used as a rational basis for combining new data with previous data to revise assessment of uncertainty and reliability. This study is devoted to the development of procedures for updating model error (N, and subsequently the predicted pile capacity with a results of single failure test.

  13. Soil gas and radon entry into a simple test structure: Comparison of experimental and modelling results

    DEFF Research Database (Denmark)

    Andersen, C.E.; Søgaard-Hansen, J.; Majborn, B.

    1994-01-01

    A radon test structure has been established at a field site at Riso National Laboratory. Measurements have been made of soil gas entry rates, pressure couplings and radon depletion. The experimental results have been compared with results obtained from measured soil parameters and a two......-dimensional steady-state numerical model of Darcy flow and combined diffusive and advective transport of radon. For most probe locations, the calculated values of the pressure couplings and the radon depletion agree well with the measured values, thus verifying important elements of the Darcy flow approximation......, and the ability of the model to treat combined diffusive and advective transport of radon. However, the model gives an underestimation of the soil gas entry rate. Even if it is assumed that the soil has a permeability equal to the highest of the measured values, the model underestimates the soil gas entry rate...

  14. Zebrafish model of tuberous sclerosis complex reveals cell-autonomous and non-cell-autonomous functions of mutant tuberin

    Directory of Open Access Journals (Sweden)

    Seok-Hyung Kim

    2011-03-01

    Tuberous sclerosis complex (TSC is an autosomal dominant disease caused by mutations in either the TSC1 (encodes hamartin or TSC2 (encodes tuberin genes. Patients with TSC have hamartomas in various organs throughout the whole body, most notably in the brain, skin, eye, heart, kidney and lung. To study the development of hamartomas, we generated a zebrafish model of TSC featuring a nonsense mutation (vu242 in the tsc2 gene. This tsc2vu242 allele encodes a truncated Tuberin protein lacking the GAP domain, which is required for inhibition of Rheb and of the TOR kinase within TORC1. We show that tsc2vu242 is a recessive larval-lethal mutation that causes increased cell size in the brain and liver. Greatly elevated TORC1 signaling is observed in tsc2vu242/vu242 homozygous zebrafish, and is moderately increased in tsc2vu242/+ heterozygotes. Forebrain neurons are poorly organized in tsc2vu242/vu242 homozygous mutants, which have extensive gray and white matter disorganization and ectopically positioned cells. Genetic mosaic analyses demonstrate that tsc2 limits TORC1 signaling in a cell-autonomous manner. However, in chimeric animals, tsc2vu242/vu242 mutant cells also mislocalize wild-type host cells in the forebrain in a non-cell-autonomous manner. These results demonstrate a highly conserved role of tsc2 in zebrafish and establish a new animal model for studies of TSC. The finding of a non-cell-autonomous function of mutant cells might help explain the formation of brain hamartomas and cortical malformations in human TSC.

  15. The initiation and tectonic regimes of the Cenozoic extension in the Bohai Bay Basin, North China revealed by numerical modelling

    Science.gov (United States)

    Li, Lu; Qiu, Nansheng

    2017-06-01

    In this study the dynamic aspects of the Cenozoic extension in the Bohai Bay Basin are considered in the context of initial thickness of the crust and lithosphere, tectonic force, strain rate and thermal rheology, which are directly or indirectly estimated from a pure shear extensional model. It is accordingly reasonable to expect that, in the Bohai Bay Basin, the thickness variation could be present prior to the initiation of extension. The extensional deformation is localized by a thickness variation of the crust and lithosphere and the heterogeneity of the initial thickness plays an important role in rifting dynamics. The onset of rifting requires a critical tectonic force (initial tectonic force) to be applied, which then immediately begins to decay gradually. Rifting will only occur when the total effective buoyancy force of the subducting slab reaches a critical level, after a certain amount of subduction taking place. The magnitude of the tectonic force decreases with time in the early phase of rifting, which indicates the weakening due to the increase in geothermal gradient. In order to deform the continental lithosphere within the currently accepted maximum magnitude of the force derived from subducted slab roll-back, the following conditions should be satisfied: (1) the thickness of the continental lithosphere is significantly thin and less than 125 km and (2) the lithosphere has a wet and hot rheology, which provides implications for rheological layering in continental lithosphere. Our results are strongly supported by the ;crème brûlée; model, in which the lower crust and mantle are relatively ductile.

  16. A zebrafish transgenic model of Ewing’s sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis

    Directory of Open Access Journals (Sweden)

    Stefanie W. Leacock

    2012-01-01

    Ewing’s sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing’s sarcoma family tumors (ESFTs, which include peripheral primitive neuroectodermal tumors (PNETs, are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing’s sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing’s sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS-FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing’s sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene.

  17. Ecosystem Model Performance at Wetlands: Results from the North American Carbon Program Site Synthesis

    Science.gov (United States)

    Sulman, B. N.; Desai, A. R.; Schroeder, N. M.; NACP Site Synthesis Participants

    2011-12-01

    Northern peatlands contain a significant fraction of the global carbon pool, and their responses to hydrological change are likely to be important factors in future carbon cycle-climate feedbacks. Global-scale carbon cycle modeling studies typically use general ecosystem models with coarse spatial resolution, often without peatland-specific processes. Here, seven ecosystem models were used to simulate CO2 fluxes at three field sites in Canada and the northern United States, including two nutrient-rich fens and one nutrient-poor, sphagnum-dominated bog, from 2002-2006. Flux residuals (simulated - observed) were positively correlated with measured water table for both gross ecosystem productivity (GEP) and ecosystem respiration (ER) at the two fen sites for all models, and were positively correlated with water table at the bog site for the majority of models. Modeled diurnal cycles at fen sites agreed well with eddy covariance measurements overall. Eddy covariance GEP and ER were higher during dry periods than during wet periods, while model results predicted either the opposite relationship or no significant difference. At the bog site, eddy covariance GEP had no significant dependence on water table, while models predicted higher GEP during wet periods. All models significantly over-estimated GEP at the bog site, and all but one over-estimated ER at the bog site. Carbon cycle models in peatland-rich regions could be improved by incorporating better models or measurements of hydrology and by inhibiting GEP and ER rates under saturated conditions. Bogs and fens likely require distinct treatments in ecosystem models due to differences in nutrients, peat properties, and plant communities.

  18. Dermal uptake of phthalates from clothing: comparison of model to human participant results

    DEFF Research Database (Denmark)

    Morrison, Glenn; Weschler, Charles J.; Bekö, Gabriel

    2016-01-01

    In this research, we extend a model of transdermal uptake of phthalates to include a layer of clothing. When compared with experimental results, this model better estimates dermal uptake of diethylphthalate (DEP) and di-n-butylphthalate (DnBP) than a previous model. It also demonstrates that uptake...... is sensitive to both the gap between skin and clothing and the time clothing is allowed to adsorb phthalates. The model predictions are consistent with the observation that exposed clothing increases dermal uptake when compared with uptake observed in bare-skin participants. Extension of this model beyond...... the cotton-phthalate system will be challenging until data on partition coefficients are quantified for other combinations of SVOCs, fabric materials and environmental conditions....

  19. Insight into collision zone dynamics from topography: numerical modelling results and observations

    OpenAIRE

    A. D. Bottrill; J. van Hunen; M. B. Allen

    2012-01-01

    Dynamic models of subduction and continental collision are used to predict dynamic topography changes on the overriding plate. The modelling results show a distinct evolution of topography on the overriding plate, during subduction, continental collision and slab break-off. A prominent topographic feature is a temporary (few Myrs) deepening in the area of the back arc-basin after initial collision. This collisional mantle dynamic basin (CMDB) is caused by slab steepening drawing material away...

  20. Conditional Tests of Factor Augmented Asset Pricing Models with Human Capital and Housing: Some New Results

    OpenAIRE

    Olga Klinkowska

    2009-01-01

    In this paper I develop the asset pricing model in which the wealth portfolio is enriched with human capital and housing capital. These two types of capital account for a significant portion of the total wealth. Additionally I introduce dynamics into the model and represent conditioning information by common factors estimated with dynamic factor methodology. In this way I can use more accurate representative of the unobservable information set of the investors. Obtained results prove that ind...

  1. Results of a feasibility study: barriers and facilitators in implementing the Sherbrooke model in France.

    Science.gov (United States)

    Fassier, Jean-Baptiste; Durand, Marie-José; Caillard, Jean-François; Roquelaure, Yves; Loisel, Patrick

    2015-05-01

    Return-to-work interventions associated with the workplace environment are often more effective than conventional care. The Sherbrooke model is an integrated intervention that has proved successful in preventing work disability due to low-back pain. Implementation, however, runs up against many obstacles, and failure has been reported in many countries. The present study sought to identify barriers to and facilitators of the implementation of the Sherbrooke model within the French health system. A multiple case study with nested levels of analysis was performed in two regions of France. A conceptual framework was designed and refined to identify barriers and facilitators at the individual, organizational and contextual levels. Qualitative data were collected via semi-structured interview (N=22), focus groups (N=7), and observation and from the gray literature. Participants (N=61) belonged to three fields: healthcare, social insurance, and the workplace. Numerous barriers and facilitators were identified in each field and at each level, some specific and others common to workers in all fields. Individual and organizational barriers comprised lack of time and resources, discordant professional values, and perceived risk. Legal barriers comprised medical confidentiality, legal complexity, and priority given to primary prevention. Individual-level facilitators comprised needs and perceived benefits. Some organizations had concordant values and practices. Legal facilitators comprised possibilities of collaboration and gradual return to work. The present feasibility analysis of implementing the Sherbrooke model revealed numerous barriers and facilitators suggesting a new implementation strategy be drawn up if failure is to be avoided.

  2. Research on PCPV for BWR - physical model as design tool - main results

    International Nuclear Information System (INIS)

    Fumagalli, E.; Verdelli, G.

    1975-01-01

    ISMES (Experimental Institute for Models and Structures) is now carrying out a series of tests on physical models as a part of a research programme sponsored by DSR (Studies and Research Direction) of ENEL (Italian State Electricity Board) on behalf of CPN (Nuclear Design and Construction Centre) of ENEL with the aim to experience a 'Thin'-walled PCPV for 'BWR'. The physical model, together with the mathematical model and the rheological model of the materials, is intended as a meaningful design tool. The mathematical model covers the overall structural design phase, (geometries) and the linear behaviour, whereas the physical model, besides of a global information to be compared with the results of the mathematical model, supplies a number of data as the non-linear behaviour up to failure and local conditions (penetration area etc.) are concerned. The aim of the first phase of this research programme is to make a comparison between the calculation and experiment tests as the thicknesses of the wall and the bottom slab are concerned, whereas the second phase of the research deals with the behaviour of the removable lid and its connection with the main structure. To do this, a model in scale 1:10 has been designed which symmetrically reproduces with respect to the equator, the bottom part of the structure. In the bottom slab the penetrations of the prototype design are reproduced, whereas the upper slab is plain. This paper describes the model, and illustrates the main results, underlining the different behaviour of the upper and bottom slabs up to collapse

  3. [DESCRIPTION AND PRESENTATION OF THE RESULTS OF ELECTROENCEPHALOGRAM PROCESSING USING AN INFORMATION MODEL].

    Science.gov (United States)

    Myznikov, I L; Nabokov, N L; Rogovanov, D Yu; Khankevich, Yu R

    2016-01-01

    The paper proposes to apply the informational modeling of correlation matrix developed by I.L. Myznikov in early 1990s in neurophysiological investigations, such as electroencephalogram recording and analysis, coherence description of signals from electrodes on the head surface. The authors demonstrate information models built using the data from studies of inert gas inhalation by healthy human subjects. In the opinion of the authors, information models provide an opportunity to describe physiological processes with a high level of generalization. The procedure of presenting the EEG results holds great promise for the broad application.

  4. The design, results and future development of the National Energy Strategy Environmental Analysis Model (NESEAM)

    International Nuclear Information System (INIS)

    Fisher, R.E.; Boyd, G.A.; Breed, W.S.

    1991-01-01

    The National Energy Strategy Environmental Model (NESEAM) has been developed to project emissions for the National Energy Strategy (NES). Two scenarios were evaluated for the NES, a Current Policy Base Case and a NES Action Case. The results from the NES Actions Case project much lower emissions than the Current Policy Base Case. Future enhancements to NESEAM will focus on fuel cycle analysis, including future technologies and additional pollutants to model. NESEAM's flexibility will allow it to model other future legislative issues. 7 refs., 4 figs., 2 tabs

  5. Multistate Models Reveal Long-Term Trends of Northern Spotted Owls in the Absence of a Novel Competitor.

    Directory of Open Access Journals (Sweden)

    Andrew J Kroll

    Full Text Available Quantifying spatial and temporal variability in population trends is a critical aspect of successful management of imperiled species. We evaluated territory occupancy dynamics of northern spotted owls (Strix occidentalis caurina, California, USA, 1990-2014. The study area possessed two unique aspects. First, timber management has occurred for over 100 years, resulting in dramatically different forest successional and structural conditions compared to other areas. Second, the barred owl (Strix varia, an exotic congener known to exert significant negative effects on spotted owls, has not colonized the study area. We used a Bayesian dynamic multistate model to evaluate if territory occupancy of reproductive spotted owls has declined as in other study areas. The state-space approach for dynamic multistate modeling imputes the number of territories for each nesting state and allows for the estimation of longer-term trends in occupied or reproductive territories from longitudinal studies. The multistate approach accounts for different detection probabilities by nesting state (to account for either inherent differences in detection or for the use of different survey methods for different occupancy states and reduces bias in state assignment. Estimated linear trends in the number of reproductive territories suggested an average loss of approximately one half territory per year (-0.55, 90% CRI: -0.76, -0.33, in one management block and a loss of 0.15 per year (-0.15, 90% CRI: -0.24, -0.07, in another management block during the 25 year observation period. Estimated trends in the third management block were also negative, but substantial uncertainty existed in the estimate (-0.09, 90% CRI: -0.35, 0.17. Our results indicate that the number of territories occupied by northern spotted owl pairs remained relatively constant over a 25 year period (-0.07, 90% CRI: -0.20, 0.05; -0.01, 90% CRI: -0.19, 0.16; -0.16, 90% CRI: -0.40, 0.06. However, we cannot exclude

  6. Multistate Models Reveal Long-Term Trends of Northern Spotted Owls in the Absence of a Novel Competitor.

    Science.gov (United States)

    Kroll, Andrew J; Jones, Jay E; Stringer, Angela B; Meekins, Douglas J

    2016-01-01

    Quantifying spatial and temporal variability in population trends is a critical aspect of successful management of imperiled species. We evaluated territory occupancy dynamics of northern spotted owls (Strix occidentalis caurina), California, USA, 1990-2014. The study area possessed two unique aspects. First, timber management has occurred for over 100 years, resulting in dramatically different forest successional and structural conditions compared to other areas. Second, the barred owl (Strix varia), an exotic congener known to exert significant negative effects on spotted owls, has not colonized the study area. We used a Bayesian dynamic multistate model to evaluate if territory occupancy of reproductive spotted owls has declined as in other study areas. The state-space approach for dynamic multistate modeling imputes the number of territories for each nesting state and allows for the estimation of longer-term trends in occupied or reproductive territories from longitudinal studies. The multistate approach accounts for different detection probabilities by nesting state (to account for either inherent differences in detection or for the use of different survey methods for different occupancy states) and reduces bias in state assignment. Estimated linear trends in the number of reproductive territories suggested an average loss of approximately one half territory per year (-0.55, 90% CRI: -0.76, -0.33), in one management block and a loss of 0.15 per year (-0.15, 90% CRI: -0.24, -0.07), in another management block during the 25 year observation period. Estimated trends in the third management block were also negative, but substantial uncertainty existed in the estimate (-0.09, 90% CRI: -0.35, 0.17). Our results indicate that the number of territories occupied by northern spotted owl pairs remained relatively constant over a 25 year period (-0.07, 90% CRI: -0.20, 0.05; -0.01, 90% CRI: -0.19, 0.16; -0.16, 90% CRI: -0.40, 0.06). However, we cannot exclude small

  7. Results and Error Estimates from GRACE Forward Modeling over Greenland, Canada, and Alaska

    Science.gov (United States)

    Bonin, J. A.; Chambers, D. P.

    2012-12-01

    Forward modeling using a weighted least squares technique allows GRACE information to be projected onto a pre-determined collection of local basins. This decreases the impact of spatial leakage, allowing estimates of mass change to be better localized. The technique is especially valuable where models of current-day mass change are poor, such as over Greenland and Antarctica. However, the accuracy of the forward model technique has not been determined, nor is it known how the distribution of the local basins affects the results. We use a "truth" model composed of hydrology and ice-melt slopes as an example case, to estimate the uncertainties of this forward modeling method and expose those design parameters which may result in an incorrect high-resolution mass distribution. We then apply these optimal parameters in a forward model estimate created from RL05 GRACE data. We compare the resulting mass slopes with the expected systematic errors from the simulation, as well as GIA and basic trend-fitting uncertainties. We also consider whether specific regions (such as Ellesmere Island and Baffin Island) can be estimated reliably using our optimal basin layout.

  8. Exploring the uncertainties of early detection results: model-based interpretation of mayo lung project

    Directory of Open Access Journals (Sweden)

    Berman Barbara

    2011-03-01

    Full Text Available Abstract Background The Mayo Lung Project (MLP, a randomized controlled clinical trial of lung cancer screening conducted between 1971 and 1986 among male smokers aged 45 or above, demonstrated an increase in lung cancer survival since the time of diagnosis, but no reduction in lung cancer mortality. Whether this result necessarily indicates a lack of mortality benefit for screening remains controversial. A number of hypotheses have been proposed to explain the observed outcome, including over-diagnosis, screening sensitivity, and population heterogeneity (initial difference in lung cancer risks between the two trial arms. This study is intended to provide model-based testing for some of these important arguments. Method Using a micro-simulation model, the MISCAN-lung model, we explore the possible influence of screening sensitivity, systematic error, over-diagnosis and population heterogeneity. Results Calibrating screening sensitivity, systematic error, or over-diagnosis does not noticeably improve the fit of the model, whereas calibrating population heterogeneity helps the model predict lung cancer incidence better. Conclusions Our conclusion is that the hypothesized imperfection in screening sensitivity, systematic error, and over-diagnosis do not in themselves explain the observed trial results. Model fit improvement achieved by accounting for population heterogeneity suggests a higher risk of cancer incidence in the intervention group as compared with the control group.

  9. Comparison of analytical models and experimental results for single-event upset in CMOS SRAMs

    International Nuclear Information System (INIS)

    Mnich, T.M.; Diehl, S.E.; Shafer, B.D.

    1983-01-01

    In an effort to design fully radiation-hardened memories for satellite and deep-space applications, a 16K and a 2K CMOS static RAM were modeled for single-particle upset during the design stage. The modeling resulted in the addition of a hardening feedback resistor in the 16K remained tentatively unaltered. Subsequent experiments, using the Lawrence Berkeley Laboratories' 88-inch cyclotron to accelerate krypton and oxygen ions, established an upset threshold for the 2K and the 16K without resistance added, as well as a hardening threshold for the 16K with feedback resistance added. Results for the 16K showed it to be hardenable to the higher level than previously published data for other unhardened 16K RAMs. The data agreed fairly well with the modeling results; however, a close look suggests that modification of the simulation methodology is required to accurately predict the resistance necessary to harden the RAM cell

  10. Statistical methods applied to the study of opinion formation models: a brief overview and results of a numerical study of a model based on the social impact theory

    Science.gov (United States)

    Bordogna, Clelia María; Albano, Ezequiel V.

    2007-02-01

    The aim of this paper is twofold. On the one hand we present a brief overview on the application of statistical physics methods to the modelling of social phenomena focusing our attention on models for opinion formation. On the other hand, we discuss and present original results of a model for opinion formation based on the social impact theory developed by Latané. The presented model accounts for the interaction among the members of a social group under the competitive influence of a strong leader and the mass media, both supporting two different states of opinion. Extensive simulations of the model are presented, showing that they led to the observation of a rich scenery of complex behaviour including, among others, critical behaviour and phase transitions between a state of opinion dominated by the leader and another dominated by the mass media. The occurrence of interesting finite-size effects reveals that, in small communities, the opinion of the leader may prevail over that of the mass media. This observation is relevant for the understanding of social phenomena involving a finite number of individuals, in contrast to actual physical phase transitions that take place in the thermodynamic limit. Finally, we give a brief outlook of open questions and lines for future work.

  11. Statistical methods applied to the study of opinion formation models: a brief overview and results of a numerical study of a model based on the social impact theory

    International Nuclear Information System (INIS)

    Bordogna, Clelia Maria; Albano, Ezequiel V

    2007-01-01

    The aim of this paper is twofold. On the one hand we present a brief overview on the application of statistical physics methods to the modelling of social phenomena focusing our attention on models for opinion formation. On the other hand, we discuss and present original results of a model for opinion formation based on the social impact theory developed by Latane. The presented model accounts for the interaction among the members of a social group under the competitive influence of a strong leader and the mass media, both supporting two different states of opinion. Extensive simulations of the model are presented, showing that they led to the observation of a rich scenery of complex behaviour including, among others, critical behaviour and phase transitions between a state of opinion dominated by the leader and another dominated by the mass media. The occurrence of interesting finite-size effects reveals that, in small communities, the opinion of the leader may prevail over that of the mass media. This observation is relevant for the understanding of social phenomena involving a finite number of individuals, in contrast to actual physical phase transitions that take place in the thermodynamic limit. Finally, we give a brief outlook of open questions and lines for future work

  12. An analytical model for backscattered luminance in fog: comparisons with Monte Carlo computations and experimental results

    International Nuclear Information System (INIS)

    Taillade, Frédéric; Dumont, Eric; Belin, Etienne

    2008-01-01

    We propose an analytical model for backscattered luminance in fog and derive an expression for the visibility signal-to-noise ratio as a function of meteorological visibility distance. The model uses single scattering processes. It is based on the Mie theory and the geometry of the optical device (emitter and receiver). In particular, we present an overlap function and take the phase function of fog into account. The results of the backscattered luminance obtained with our analytical model are compared to simulations made using the Monte Carlo method based on multiple scattering processes. An excellent agreement is found in that the discrepancy between the results is smaller than the Monte Carlo standard uncertainties. If we take no account of the geometry of the optical device, the results of the model-estimated backscattered luminance differ from the simulations by a factor 20. We also conclude that the signal-to-noise ratio computed with the Monte Carlo method and our analytical model is in good agreement with experimental results since the mean difference between the calculations and experimental measurements is smaller than the experimental uncertainty

  13. Vacuum evaporation of KCl-NaCl salts. Part 2: Vaporization-rate model and experimental results

    International Nuclear Information System (INIS)

    Wang, L.L.; Wallace, T.C. Sr.; Hampel, F.G.; Steele, J.H.

    1996-01-01

    Separation of chloride salts from the actinide residue by vacuum evaporation is a promising method of treating wastes from the pyrochemical plutonium processes. A model based on the Hertz-Langmuir relation is used to describe how evaporation rates of the binary KCl-NaCl system change with time. The effective evaporation coefficient (α), which is a ratio of the actual evaporation rate to the theoretical maximum, was obtained for the KCl-NaCl system using this model. In the temperature range of 640 C to 760 C, the effective evaporation coefficient ranges from ∼0.4 to 0.1 for evaporation experiments conducted at 0.13 Pa. At temperatures below the melting point, the lower evaporation coefficients are suggested to result from the more complex path that a molecule needs to follow before escaping to the gas phase. At the higher liquid temperatures, the decreasing evaporation coefficients result from a combination of the increasing vapor-flow resistances and the heat-transfer effects at the evaporation surface and the condensate layer. The microanalysis of the condensate verified that composition of the condensate changes with time, consistent with the model calculation. The microstructural examination revealed that the vaporate may have condensed as a single solution phase, which upon cooling forms fine lamellar structures of the equilibrium KCl and NaCl phases. In conclusion, the optimum design of the evaporation process and equipment must take the mass and heat transfer factors and equipment materials issues into consideration

  14. THE EFFECTS OF COOPERATIVE LEARNING MODEL GROUP INVESTIGATION AND MOTIVATION TOWARD PHYSICS LEARNING RESULTS MAN TANJUNGBALAI

    Directory of Open Access Journals (Sweden)

    Amalia Febri Aristi

    2014-12-01

    Full Text Available This study aimed to determine: (1 Is there a difference in student's learning outcomes with the application of learning models Investigation Group and Direct Instruction teaching model. (2 Is there a difference in students' motivation with the application of learning models Investigation Group and Direct Instruction teaching model, (3 Is there an interaction between learning models Investigation Group and Direct Instruction to improve students' motivation in learning outcomes Physics. This research is a quasi experimental. The study population was a student of class XII Tanjung Balai MAN. Random sample selection is done by randomizing the class. The instrument used consisted of: (1 achievement test (2 students' motivation questionnaire. The tests are used to obtain the data is shaped essay. The data in this study were analyzed using ANOVA analysis of two paths. The results showed that: (1 there were differences in learning outcomes between students who used the physics model of Group Investigation learning compared with students who used the Direct Instruction teaching model. (2 There was a difference in student's learning outcomes that had a low learning motivation and high motivation to learn both in the classroom and in the classroom Investigation Group Direct Instruction. (3 There was interaction between learning models Instruction Direct Group Investigation and motivation to learn in improving learning outcomes Physics.

  15. Comparison of inverse modeling results with measured and interpolated hydraulic head data

    International Nuclear Information System (INIS)

    Jacobson, E.A.

    1986-12-01

    Inverse modeling of aquifers involves identification of effective parameters, such as transmissivities, based on hydraulic head data. The result of inverse modeling is a calibrated ground water flow model that reproduces the measured hydraulic head data as closely as is statistically possible. An inverse method that includes prior information about the parameters (i.e., kriged log transmissivity) was applied to the Avra Valley aquifer of southern Arizona using hydraulic heads obtained in three ways: measured at well locations, estimated at nodes by hand contouring, and estimated at nodes by kriging. Hand contouring yields only estimates of hydraulic head at node points, whereas kriging yields hydraulic head estimates at node points and their corresponding estimation errors. A comparison of the three inverse applications indicates the variations in the ground water flow model caused by the different treatments of the hydraulic head data. Estimates of hydraulic head computed by all three inverse models were more representative of the measured or interpolated hydraulic heads than those computed using the kriged estimates of log transmissivity. The large-scale trends in the estimates of log transmissivity determined by the three inverse models were generally similar except in the southern portion of the study area. The hydraulic head values and gradients produced by the three inverse models were similar in the interior of the study area, while the major differences between the inverse models occurred along the boundaries. 17 refs., 18 figs., 1 tab

  16. Microstructure evolution during homogenization of Al–Mn–Fe–Si alloys: Modeling and experimental results

    International Nuclear Information System (INIS)

    Du, Q.; Poole, W.J.; Wells, M.A.; Parson, N.C.

    2013-01-01

    Microstructure evolution during the homogenization heat treatment of Al–Mn–Fe–Si, or AA3xxx, alloys has been investigated using a combination of modeling and experimental studies. The model is fully coupled to CALculation PHAse Diagram (CALPHAD) software and has explicitly taken into account the two different length scales for diffusion encountered in modeling the homogenization process. The model is able to predict the evolution of all the important microstructural features during homogenization, including the inhomogeneous spatial distribution of dispersoids and alloying elements in solution, the dispersoid number density and the size distribution, and the type and fraction of intergranular constituent particles. Experiments were conducted using four direct chill (DC) cast AA3xxx alloys subjected to various homogenization treatments. The resulting microstructures were then characterized using a range of characterization techniques, including optical and electron microscopy, electron micro probe analysis, field emission gun scanning electron microscopy, and electrical resistivity measurements. The model predictions have been compared with the experimental measurements to validate the model. Further, it has been demonstrated that the validated model is able to predict the effects of alloying elements (e.g. Si and Mn) on microstructure evolution. It is concluded that the model provides a time and cost effective tool in optimizing and designing industrial AA3xxx alloy chemistries and homogenization heat treatments

  17. STRUCTURAL GLITCHES NEAR THE CORES OF RED GIANTS REVEALED BY OSCILLATIONS IN G-MODE PERIOD SPACINGS FROM STELLAR MODELS

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, M. S.; Avelino, P. P. [Instituto de Astrofísica e Ciências do Espaço, Universidade do Porto, CAUP, Rua das Estrelas, 4150-762 Porto (Portugal); Stello, D. [Sydney Institute for Astronomy (SIfA), School of Physics, University of Sydney, NSW 2006 (Australia); Christensen-Dalsgaard, J. [Stellar Astrophysics Centre, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, DK-8000 Aarhus C (Denmark); Townsend, R. H. D., E-mail: mcunha@astro.up.pt [Department of Astronomy, University of Wisconsin–Madison, 2535 Sterling Hall, 475 N. Charter Street, Madison, WI 53706 (United States)

    2015-06-01

    With recent advances in asteroseismology it is now possible to peer into the cores of red giants, potentially providing a way to study processes such as nuclear burning and mixing through their imprint as sharp structural variations—glitches—in the stellar cores. Here we show how such core glitches can affect the oscillations we observe in red giants. We derive an analytical expression describing the expected frequency pattern in the presence of a glitch. This formulation also accounts for the coupling between acoustic and gravity waves. From an extensive set of canonical stellar models we find glitch-induced variation in the period spacing and inertia of non-radial modes during several phases of red giant evolution. Significant changes are seen in the appearance of mode amplitude and frequency patterns in asteroseismic diagrams such as the power spectrum and the échelle diagram. Interestingly, along the red giant branch glitch-induced variation occurs only at the luminosity bump, potentially providing a direct seismic indicator of stars in that particular evolution stage. Similarly, we find the variation at only certain post-helium-ignition evolution stages, namely, in the early phases of helium core burning and at the beginning of helium shell burning, signifying the asymptotic giant branch bump. Based on our results, we note that assuming stars to be glitch-free, while they are not, can result in an incorrect estimate of the period spacing. We further note that including diffusion and mixing beyond classical Schwarzschild could affect the characteristics of the glitches, potentially providing a way to study these physical processes.

  18. A zebrafish model of congenital disorders of glycosylation with phosphomannose isomerase deficiency reveals an early opportunity for corrective mannose supplementation

    Directory of Open Access Journals (Sweden)

    Jaime Chu

    2013-01-01

    Individuals with congenital disorders of glycosylation (CDG have recessive mutations in genes required for protein N-glycosylation, resulting in multi-systemic disease. Despite the well-characterized biochemical consequences in these individuals, the underlying cellular defects that contribute to CDG are not well understood. Synthesis of the lipid-linked oligosaccharide (LLO, which serves as the sugar donor for the N-glycosylation of secretory proteins, requires conversion of fructose-6-phosphate to mannose-6-phosphate via the phosphomannose isomerase (MPI enzyme. Individuals who are deficient in MPI present with bleeding, diarrhea, edema, gastrointestinal bleeding and liver fibrosis. MPI-CDG patients can be treated with oral mannose supplements, which is converted to mannose-6-phosphate through a minor complementary metabolic pathway, restoring protein glycosylation and ameliorating most symptoms, although liver disease continues to progress. Because Mpi deletion in mice causes early embryonic lethality and thus is difficult to study, we used zebrafish to establish a model of MPI-CDG. We used a morpholino to block mpi mRNA translation and established a concentration that consistently yielded 13% residual Mpi enzyme activity at 4 days post-fertilization (dpf, which is within the range of MPI activity detected in fibroblasts from MPI-CDG patients. Fluorophore-assisted carbohydrate electrophoresis detected decreased LLO and N-glycans in mpi morphants. These deficiencies resulted in 50% embryonic lethality by 4 dpf. Multi-systemic abnormalities, including small eyes, dysmorphic jaws, pericardial edema, a small liver and curled tails, occurred in 82% of the surviving larvae. Importantly, these phenotypes could be rescued with mannose supplementation. Thus, parallel processes in fish and humans contribute to the phenotypes caused by Mpi depletion. Interestingly, mannose was only effective if provided prior to 24 hpf. These data provide insight into treatment efficacy

  19. Results of the first tests of the SIDRA satellite-borne instrument breadboard model

    International Nuclear Information System (INIS)

    Dudnik, O.V.; Kurbatov, E.V.; Avilov, A.M.; Titov, K.G.; Prieto, M; Sanchez, S.; Spassky, A.V.; Sylwester, J.; Gburek, S.; Podgorski, P.

    2013-01-01

    In this work, the results of the calibration of the solid-state detectors and electronic channels of the SIDRA satellite borne energetic charged particle spectrometer-telescope breadboard model are presented. The block schemes and experimental equipment used to conduct the thermal vacuum and electromagnetic compatibility tests of the assemblies and modules of the compact satellite equipment are described. The results of the measured thermal conditions of operation of the signal analog and digital processing critical modules of the SIDRA instrument prototype are discussed. Finally, the levels of conducted interference generated by the instrument model in the primary vehicle-borne power circuits are presented.

  20. Lattice Hamiltonian approach to the Schwinger model. Further results from the strong coupling expansion

    International Nuclear Information System (INIS)

    Szyniszewski, Marcin; Manchester Univ.; Cichy, Krzysztof; Poznan Univ.; Kujawa-Cichy, Agnieszka

    2014-10-01

    We employ exact diagonalization with strong coupling expansion to the massless and massive Schwinger model. New results are presented for the ground state energy and scalar mass gap in the massless model, which improve the precision to nearly 10 -9 %. We also investigate the chiral condensate and compare our calculations to previous results available in the literature. Oscillations of the chiral condensate which are present while increasing the expansion order are also studied and are shown to be directly linked to the presence of flux loops in the system.

  1. Modelled and Observed Diurnal SST Signals: "SSTDV:R.EX.-IM.A.M." Project Preliminary Results

    DEFF Research Database (Denmark)

    Karagali, Ioanna; Høyer, Jacob; LeBorgne, Pierre

    2013-01-01

    This study presents some of the preliminary results from the ESA Support To Science Element (STSE) funded project on the Diurnal Variability of the Sea Surface Temperature, regarding its Regional Extend and Implications in Atmospheric Modelling (SSTDV:R.EX.–IM.A.M.). During this phase of the proj......This study presents some of the preliminary results from the ESA Support To Science Element (STSE) funded project on the Diurnal Variability of the Sea Surface Temperature, regarding its Regional Extend and Implications in Atmospheric Modelling (SSTDV:R.EX.–IM.A.M.). During this phase...

  2. Revealing additional preference heterogeneity with an extended random parameter logit model: the case of extra virgin olive oil

    Directory of Open Access Journals (Sweden)

    Ahmed Yangui

    2014-07-01

    Full Text Available Methods that account for preference heterogeneity have received a significant amount of attention in recent literature. Most of them have focused on preference heterogeneity around the mean of the random parameters, which has been specified as a function of socio-demographic characteristics. This paper aims at analyzing consumers’ preferences towards extra-virgin olive oil in Catalonia using a methodological framework with two novelties over past studies: 1 it accounts for both preference heterogeneity around the mean and the variance; and 2 it considers both socio-demographic characteristics of consumers as well as their attitudinal factors. Estimated coefficients and moments of willingness to pay (WTP distributions are compared with those obtained from alternative Random Parameter Logit (RPL models. Results suggest that the proposed framework increases the goodness-of-fit and provides more useful insights for policy analysis. The most important attributes affecting consumers’ preferences towards extra virgin olive oil are the price and the product’s origin. The consumers perceive the organic olive oil attribute negatively, as they think that it is not worth paying a premium for a product that is healthy in nature.

  3. A spatially resolved network spike in model neuronal cultures reveals nucleation centers, circular traveling waves and drifting spiral waves.

    Science.gov (United States)

    Paraskevov, A V; Zendrikov, D K

    2017-03-23

    We show that in model neuronal cultures, where the probability of interneuronal connection formation decreases exponentially with increasing distance between the neurons, there exists a small number of spatial nucleation centers of a network spike, from where the synchronous spiking activity starts propagating in the network typically in the form of circular traveling waves. The number of nucleation centers and their spatial locations are unique and unchanged for a given realization of neuronal network but are different for different networks. In contrast, if the probability of interneuronal connection formation is independent of the distance between neurons, then the nucleation centers do not arise and the synchronization of spiking activity during a network spike occurs spatially uniform throughout the network. Therefore one can conclude that spatial proximity of connections between neurons is important for the formation of nucleation centers. It is also shown that fluctuations of the spatial density of neurons at their random homogeneous distribution typical for the experiments in vitro do not determine the locations of the nucleation centers. The simulation results are qualitatively consistent with the experimental observations.

  4. Comparison of Experimental Surface and Flow Field Measurements to Computational Results of the Juncture Flow Model

    Science.gov (United States)

    Roozeboom, Nettie H.; Lee, Henry C.; Simurda, Laura J.; Zilliac, Gregory G.; Pulliam, Thomas H.

    2016-01-01

    Wing-body juncture flow fields on commercial aircraft configurations are challenging to compute accurately. The NASA Advanced Air Vehicle Program's juncture flow committee is designing an experiment to provide data to improve Computational Fluid Dynamics (CFD) modeling in the juncture flow region. Preliminary design of the model was done using CFD, yet CFD tends to over-predict the separation in the juncture flow region. Risk reduction wind tunnel tests were requisitioned by the committee to obtain a better understanding of the flow characteristics of the designed models. NASA Ames Research Center's Fluid Mechanics Lab performed one of the risk reduction tests. The results of one case, accompanied by CFD simulations, are presented in this paper. Experimental results suggest the wall mounted wind tunnel model produces a thicker boundary layer on the fuselage than the CFD predictions, resulting in a larger wing horseshoe vortex suppressing the side of body separation in the juncture flow region. Compared to experimental results, CFD predicts a thinner boundary layer on the fuselage generates a weaker wing horseshoe vortex resulting in a larger side of body separation.

  5. Conversion of IVA Human Computer Model to EVA Use and Evaluation and Comparison of the Result to Existing EVA Models

    Science.gov (United States)

    Hamilton, George S.; Williams, Jermaine C.

    1998-01-01

    This paper describes the methods, rationale, and comparative results of the conversion of an intravehicular (IVA) 3D human computer model (HCM) to extravehicular (EVA) use and compares the converted model to an existing model on another computer platform. The task of accurately modeling a spacesuited human figure in software is daunting: the suit restricts the human's joint range of motion (ROM) and does not have joints collocated with human joints. The modeling of the variety of materials needed to construct a space suit (e. g. metal bearings, rigid fiberglass torso, flexible cloth limbs and rubber coated gloves) attached to a human figure is currently out of reach of desktop computer hardware and software. Therefore a simplified approach was taken. The HCM's body parts were enlarged and the joint ROM was restricted to match the existing spacesuit model. This basic approach could be used to model other restrictive environments in industry such as chemical or fire protective clothing. In summary, the approach provides a moderate fidelity, usable tool which will run on current notebook computers.

  6. Preliminary results of Physiological plant growth modelling for human life support in space

    Science.gov (United States)

    Sasidharan L, Swathy; Dussap, Claude-Gilles; Hezard, Pauline

    2012-07-01

    physiological plant model, in the case of lettuce (since the leaf metabolic model predominates), the developed model was verified with the carbon consumption of plant, as input. The model predicts the biomass production (as output) with respect to the quantum of light absorbed by the plant. The obtained result was found satisfying for the first initiation in the physiological plant modelling.

  7. Robustness of life cycle assessment results : influence of data variation and modelling choices on results for beverage packaging materials

    NARCIS (Netherlands)

    Harst-Wintraecken, van der E.J.M.

    2015-01-01

    Life cycle assessment (LCA) is a well-established method to evaluate the potential environmental impacts of product and service systems throughout their life cycles. However, it can happen that LCAs for the same product have different and even conflicting outcomes. LCA results need to be robust

  8. A quantitative multiplex nuclease protection assay reveals immunotoxicity gene expression profiles in the rabbit model for vaginal drug safety evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Fichorova, Raina N., E-mail: rfichorova@rics.bwh.harvard.edu [Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Mendonca, Kevin; Yamamoto, Hidemi S.; Murray, Ryan [Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Chandra, Neelima; Doncel, Gustavo F. [CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA (United States)

    2015-06-15

    Any vaginal product that alters the mucosal environment and impairs the immune barrier increases the risk of sexually transmitted infections, especially HIV infection, which thrives on mucosal damage and inflammation. The FDA-recommended rabbit vaginal irritation (RVI) model serves as a first line selection tool for vaginal products; however, for decades it has been limited to histopathology scoring, insufficient to select safe anti-HIV microbicides. In this study we incorporate to the RVI model a novel quantitative nuclease protection assay (qNPA) to quantify mRNA levels of 25 genes representing leukocyte differentiation markers, toll-like receptors (TLR), cytokines, chemokines, epithelial repair, microbicidal and vascular markers, by designing two multiplex arrays. Tissue sections were obtained from 36 rabbits (6 per treatment arm) after 14 daily applications of a placebo gel, saline, 4% nonoxynol-9 (N-9), and three combinations of the anti-HIV microbicides tenofovir (TFV) and UC781 in escalating concentrations (highest: 10% TFV + 2.5%UC781). Results showed that increased expression levels of toll-like receptor (TLR)-4, interleukin (IL)-1β, CXCL8, epithelial membrane protein (EMP)-1 (P < 0.05), and decreased levels of TLR2 (P < 0.05), TLR3 and bactericidal permeability increasing protein (BPI) (P < 0.001) were associated with cervicovaginal mucosal alteration (histopathology). Seven markers showed a significant linear trend predicting epithelial damage (up with CD4, IL-1β, CXCL8, CCL2, CCL21, EMP1 and down with BPI). Despite the low tissue damage RVI scores, the high-dose microbicide combination gel caused activation of HIV host cells (SLC and CD4) while N-9 caused proinflammatory gene upregulation (IL-8 and TLR4) suggesting a potential for increasing risk of HIV via different mechanisms depending on the chemical nature of the test product. - Highlights: • A transcriptome nuclease protection assay assessed microbicides for vaginal safety. • Biomarkers were

  9. A quantitative multiplex nuclease protection assay reveals immunotoxicity gene expression profiles in the rabbit model for vaginal drug safety evaluation

    International Nuclear Information System (INIS)

    Fichorova, Raina N.; Mendonca, Kevin; Yamamoto, Hidemi S.; Murray, Ryan; Chandra, Neelima; Doncel, Gustavo F.

    2015-01-01

    Any vaginal product that alters the mucosal environment and impairs the immune barrier increases the risk of sexually transmitted infections, especially HIV infection, which thrives on mucosal damage and inflammation. The FDA-recommended rabbit vaginal irritation (RVI) model serves as a first line selection tool for vaginal products; however, for decades it has been limited to histopathology scoring, insufficient to select safe anti-HIV microbicides. In this study we incorporate to the RVI model a novel quantitative nuclease protection assay (qNPA) to quantify mRNA levels of 25 genes representing leukocyte differentiation markers, toll-like receptors (TLR), cytokines, chemokines, epithelial repair, microbicidal and vascular markers, by designing two multiplex arrays. Tissue sections were obtained from 36 rabbits (6 per treatment arm) after 14 daily applications of a placebo gel, saline, 4% nonoxynol-9 (N-9), and three combinations of the anti-HIV microbicides tenofovir (TFV) and UC781 in escalating concentrations (highest: 10% TFV + 2.5%UC781). Results showed that increased expression levels of toll-like receptor (TLR)-4, interleukin (IL)-1β, CXCL8, epithelial membrane protein (EMP)-1 (P < 0.05), and decreased levels of TLR2 (P < 0.05), TLR3 and bactericidal permeability increasing protein (BPI) (P < 0.001) were associated with cervicovaginal mucosal alteration (histopathology). Seven markers showed a significant linear trend predicting epithelial damage (up with CD4, IL-1β, CXCL8, CCL2, CCL21, EMP1 and down with BPI). Despite the low tissue damage RVI scores, the high-dose microbicide combination gel caused activation of HIV host cells (SLC and CD4) while N-9 caused proinflammatory gene upregulation (IL-8 and TLR4) suggesting a potential for increasing risk of HIV via different mechanisms depending on the chemical nature of the test product. - Highlights: • A transcriptome nuclease protection assay assessed microbicides for vaginal safety. • Biomarkers were

  10. Trial-by-Trial Modulation of Associative Memory Formation by Reward Prediction Error and Reward Anticipation as Revealed by a Biologically Plausible Computational Model.

    Science.gov (United States)

    Aberg, Kristoffer C; Müller, Julia; Schwartz, Sophie

    2017-01-01

    Anticipation and delivery of rewards improves memory formation, but little effort has been made to disentangle their respective contributions to memory enhancement. Moreover, it has been suggested that the effects of reward on memory are mediated by dopaminergic influences on hippocampal plasticity. Yet, evidence linking memory improvements to actual reward computations reflected in the activity of the dopaminergic system, i.e., prediction errors and expected values, is scarce and inconclusive. For example, different previous studies reported that the magnitude of prediction errors during a reinforcement learning task was a positive, negative, or non-significant predictor of successfully encoding simultaneously presented images. Individual sensitivities to reward and punishment have been found to influence the activation of the dopaminergic reward system and could therefore help explain these seemingly discrepant results. Here, we used a novel associative memory task combined with computational modeling and showed independent effects of reward-delivery and reward-anticipation on memory. Strikingly, the computational approach revealed positive influences from both reward delivery, as mediated by prediction error magnitude, and reward anticipation, as mediated by magnitude of expected value, even in the absence of behavioral effects when analyzed using standard methods, i.e., by collapsing memory performance across trials within conditions. We additionally measured trait estimates of reward and punishment sensitivity and found that individuals with increased reward (vs. punishment) sensitivity had better memory for associations encoded during positive (vs. negative) prediction errors when tested after 20 min, but a negative trend when tested after 24 h. In conclusion, modeling trial-by-trial fluctuations in the magnitude of reward, as we did here for prediction errors and expected value computations, provides a comprehensive and biologically plausible description of

  11. An integrated Drosophila model system reveals unique properties for F14512, a novel polyamine-containing anticancer drug that targets topoisomerase II.

    Directory of Open Access Journals (Sweden)

    Sonia Chelouah

    Full Text Available F14512 is a novel anti-tumor molecule based on an epipodophyllotoxin core coupled to a cancer-cell vectoring spermine moiety. This polyamine linkage is assumed to ensure the preferential uptake of F14512 by cancer cells, strong interaction with DNA and potent inhibition of topoisomerase II (Topo II. The antitumor activity of F14512 in human tumor models is significantly higher than that of other epipodophyllotoxins in spite of a lower induction of DNA breakage. Hence, the demonstrated superiority of F14512 over other Topo II poisons might not result solely from its preferential uptake by cancer cells, but could also be due to unique effects on Topo II interactions with DNA. To further dissect the mechanism of action of F14512, we used Drosophila melanogaster mutants whose genetic background leads to an easily scored phenotype that is sensitive to changes in Topo II activity and/or localization. F14512 has antiproliferative properties in Drosophila cells and stabilizes ternary Topo II/DNA cleavable complexes at unique sites located in moderately repeated sequences, suggesting that the drug specifically targets a select and limited subset of genomic sequences. Feeding F14512 to developing mutant Drosophila larvae led to the recovery of flies expressing a striking phenotype, "Eye wide shut," where one eye is replaced by a first thoracic segment. Other recovered F14512-induced gain- and loss-of-function phenotypes similarly correspond to precise genetic dysfunctions. These complex in vivo results obtained in a whole developing organism can be reconciled with known genetic anomalies and constitute a remarkable instance of specific alterations of gene expression by ingestion of a drug. "Drosophila-based anticancer pharmacology" hence reveals unique properties for F14512, demonstrating the usefulness of an assay system that provides a low-cost, rapid and effective complement to mammalian models and permits the elucidation of fundamental mechanisms of

  12.  Functional Results-Oriented Healthcare Leadership: A Novel Leadership Model

    Directory of Open Access Journals (Sweden)

    Salem Said Al-Touby

    2012-03-01

    Full Text Available  This article modifies the traditional functional leadership model to accommodate contemporary needs in healthcare leadership based on two findings. First, the article argues that it is important that the ideal healthcare leadership emphasizes the outcomes of the patient care more than processes and structures used to deliver such care; and secondly, that the leadership must strive to attain effectiveness of their care provision and not merely targeting the attractive option of efficient operations. Based on these premises, the paper reviews the traditional Functional Leadership Model and the three elements that define the type of leadership an organization has namely, the tasks, the individuals, and the team. The article argues that concentrating on any one of these elements is not ideal and proposes adding a new element to the model to construct a novel Functional Result-Oriented healthcare leadership model. The recommended Functional-Results Oriented leadership model embosses the results element on top of the other three elements so that every effort on healthcare leadership is directed towards attaining excellent patient outcomes.

  13. Computations for the 1:5 model of the THTR pressure vessel compared with experimental results

    International Nuclear Information System (INIS)

    Stangenberg, F.

    1972-01-01

    In this report experimental results measured at the 1:5-model of the prestressed concrete pressure vessel of the THTR-nuclear power station Schmehausen in 1971, are compared with the results of axis-symmetrical computations. Linear-elastic computations were performed as well as approximate computations for overload pressures taking into consideration the influences of the load history (prestressing, temperature, creep) and the effects of the steel components. (orig.) [de

  14. Comparison of vibration test results for Atucha II NPP and large scale concrete block models

    International Nuclear Information System (INIS)

    Iizuka, S.; Konno, T.; Prato, C.A.

    2001-01-01

    In order to study the soil structure interaction of reactor building that could be constructed on a Quaternary soil, a comparison study of the soil structure interaction springs was performed between full scale vibration test results of Atucha II NPP and vibration test results of large scale concrete block models constructed on Quaternary soil. This comparison study provides a case data of soil structure interaction springs on Quaternary soil with different foundation size and stiffness. (author)

  15. Models of Automation Surprise: Results of a Field Survey in Aviation

    Directory of Open Access Journals (Sweden)

    Robert De Boer

    2017-09-01

    Full Text Available Automation surprises in aviation continue to be a significant safety concern and the community’s search for effective strategies to mitigate them are ongoing. The literature has offered two fundamentally divergent directions, based on different ideas about the nature of cognition and collaboration with automation. In this paper, we report the results of a field study that empirically compared and contrasted two models of automation surprises: a normative individual-cognition model and a sensemaking model based on distributed cognition. Our data prove a good fit for the sense-making model. This finding is relevant for aviation safety, since our understanding of the cognitive processes that govern human interaction with automation drive what we need to do to reduce the frequency of automation-induced events.

  16. Results on Standard Model Higgs Boson searches at high mass at the LHC

    International Nuclear Information System (INIS)

    Gao, Yanyan

    2014-01-01

    We present results from searches for the standard model Higgs boson with a mass greater than 200 GeV in pp collisions at √(s)=7 TeV. The data are collected at the LHC with both ATLAS and CMS detectors, and correspond to integrated luminosity of 5 fb -1 each. Searches are performed in the 2 main decay modes WW and ZZ. No significant excess of events above the standard model background expectations is observed, and upper limits on the Higgs boson production relative to the standard model expectation are derived. A standard model Higgs boson is excluded in the mass range up to 539 GeV or 600 GeV at 95% confidence level by the ATLAS or CMS experiments respectively. (author)

  17. Model unspecific search in CMS. Results at 8 TeV

    Energy Technology Data Exchange (ETDEWEB)

    Albert, Andreas; Duchardt, Deborah; Hebbeker, Thomas; Knutzen, Simon; Lieb, Jonas; Meyer, Arnd; Pook, Tobias; Roemer, Jonas [III. Physikalisches Institut A, RWTH Aachen University (Germany)

    2016-07-01

    In the year 2012, CMS collected a total data set of approximately 20 fb{sup -1} in proton-proton collisions at √(s)=8 TeV. Dedicated searches for physics beyond the standard model are commonly designed with the signatures of a given theoretical model in mind. While this approach allows for an optimised sensitivity to the sought-after signal, it may cause unexpected phenomena to be overlooked. In a complementary approach, the Model Unspecific Search in CMS (MUSiC) analyses CMS data in a general way. Depending on the reconstructed final state objects (e.g. electrons), collision events are sorted into classes. In each of the classes, the distributions of selected kinematic variables are compared to standard model simulation. An automated statistical analysis is performed to quantify the agreement between data and prediction. In this talk, the analysis concept is introduced and selected results of the analysis of the 2012 CMS data set are presented.

  18. Global Monthly CO2 Flux Inversion Based on Results of Terrestrial Ecosystem Modeling

    Science.gov (United States)

    Deng, F.; Chen, J.; Peters, W.; Krol, M.

    2008-12-01

    Most of our understanding of the sources and sinks of atmospheric CO2 has come from inverse studies of atmospheric CO2 concentration measurements. However, the number of currently available observation stations and our ability to simulate the diurnal planetary boundary layer evolution over continental regions essentially limit the number of regions that can be reliably inverted globally, especially over continental areas. In order to overcome these restrictions, a nested inverse modeling system was developed based on the Bayesian principle for estimating carbon fluxes of 30 regions in North America and 20 regions for the rest of the globe. Inverse modeling was conducted in monthly steps using CO2 concentration measurements of 5 years (2000 - 2005) with the following two models: (a) An atmospheric transport model (TM5) is used to generate the transport matrix where the diurnal variation n of atmospheric CO2 concentration is considered to enhance the use of the afternoon-hour average CO2 concentration measurements over the continental sites. (b) A process-based terrestrial ecosystem model (BEPS) is used to produce hourly step carbon fluxes, which could minimize the limitation due to our inability to solve the inverse problem in a high resolution, as the background of our inversion. We will present our recent results achieved through a combination of the bottom-up modeling with BEPS and the top-down modeling based on TM5 driven by offline meteorological fields generated by the European Centre for Medium Range Weather Forecast (ECMFW).

  19. Comparison of results of experimental research with numerical calculations of a model one-sided seal

    Directory of Open Access Journals (Sweden)

    Joachimiak Damian

    2015-06-01

    Full Text Available Paper presents the results of experimental and numerical research of a model segment of a labyrinth seal for a different wear level. The analysis covers the extent of leakage and distribution of static pressure in the seal chambers and the planes upstream and downstream of the segment. The measurement data have been compared with the results of numerical calculations obtained using commercial software. Based on the flow conditions occurring in the area subjected to calculations, the size of the mesh defined by parameter y+ has been analyzed and the selection of the turbulence model has been described. The numerical calculations were based on the measurable thermodynamic parameters in the seal segments of steam turbines. The work contains a comparison of the mass flow and distribution of static pressure in the seal chambers obtained during the measurement and calculated numerically in a model segment of the seal of different level of wear.

  20. Technogenic Rock Dumps Physical Properties' Prognosis via Results of the Structure Numerical Modeling

    Directory of Open Access Journals (Sweden)

    Markov Sergey

    2017-01-01

    Full Text Available Understanding of internal structure of the technogenic rock dumps (gob dumps is required condition for estimation of using ones as filtration massifs for treatment of mine wastewater. Internal structure of gob piles greatly depends on dumping technology to applying restrictions for use them as filtration massifs. Numerical modelling of gob dumps allows adequately estimate them physical parameters, as a filtration coefficient, density, etc. The gob dumps numerical modelling results given in this article, in particular was examined grain size distribution of determined fractions depend on dump height. Shown, that filtration coefficient is in a nonlinear dependence on amount of several fractions of rock in gob dump. The numerical model adequacy both the gob structure and the dependence of filtration coefficient from gob height acknowledged equality of calculated and real filtration coefficient values. The results of this research can be apply to peripheral dumping technology.

  1. Extending positive CLASS results across multiple instructors and multiple classes of Modeling Instruction

    Science.gov (United States)

    Brewe, Eric; Traxler, Adrienne; de la Garza, Jorge; Kramer, Laird H.

    2013-12-01

    We report on a multiyear study of student attitudes measured with the Colorado Learning Attitudes about Science Survey in calculus-based introductory physics taught with the Modeling Instruction curriculum. We find that five of six instructors and eight of nine sections using Modeling Instruction showed significantly improved attitudes from pre- to postcourse. Cohen’s d effect sizes range from 0.08 to 0.95 for individual instructors. The average effect was d=0.45, with a 95% confidence interval of (0.26-0.64). These results build on previously published results showing positive shifts in attitudes from Modeling Instruction classes. We interpret these data in light of other published positive attitudinal shifts and explore mechanistic explanations for similarities and differences with other published positive shifts.

  2. Extending positive CLASS results across multiple instructors and multiple classes of Modeling Instruction

    Directory of Open Access Journals (Sweden)

    Eric Brewe

    2013-10-01

    Full Text Available We report on a multiyear study of student attitudes measured with the Colorado Learning Attitudes about Science Survey in calculus-based introductory physics taught with the Modeling Instruction curriculum. We find that five of six instructors and eight of nine sections using Modeling Instruction showed significantly improved attitudes from pre- to postcourse. Cohen’s d effect sizes range from 0.08 to 0.95 for individual instructors. The average effect was d=0.45, with a 95% confidence interval of (0.26–0.64. These results build on previously published results showing positive shifts in attitudes from Modeling Instruction classes. We interpret these data in light of other published positive attitudinal shifts and explore mechanistic explanations for similarities and differences with other published positive shifts.

  3. Results of an interactively coupled atmospheric chemistry - general circulation model. Comparison with observations

    Energy Technology Data Exchange (ETDEWEB)

    Hein, R.; Dameris, M.; Schnadt, C. [and others

    2000-01-01

    An interactively coupled climate-chemistry model which enables a simultaneous treatment of meteorology and atmospheric chemistry and their feedbacks is presented. This is the first model, which interactively combines a general circulation model based on primitive equations with a rather complex model of stratospheric and tropospheric chemistry, and which is computational efficient enough to allow long-term integrations with currently available computer resources. The applied model version extends from the Earth's surface up to 10 hPa with a relatively high number (39) of vertical levels. We present the results of a present-day (1990) simulation and compare it to available observations. We focus on stratospheric dynamics and chemistry relevant to describe the stratospheric ozone layer. The current model version ECHAM4.L39(DLR)/CHEM can realistically reproduce stratospheric dynamics in the Arctic vortex region, including stratospheric warming events. This constitutes a major improvement compared to formerly applied model versions. However, apparent shortcomings in Antarctic circulation and temperatures persist. The seasonal and interannual variability of the ozone layer is simulated in accordance with observations. Activation and deactivation of chlorine in the polar stratospheric vortices and their interhemispheric differences are reproduced. The consideration of the chemistry feedback on dynamics results in an improved representation of the spatial distribution of stratospheric water vapor concentrations, i.e., the simulated meriodional water vapor gradient in the stratosphere is realistic. The present model version constitutes a powerful tool to investigate, for instance, the combined direct and indirect effects of anthropogenic trace gas emissions, and the future evolution of the ozone layer. (orig.)

  4. From sub-source to source: Interpreting results of biological trace investigations using probabilistic models

    NARCIS (Netherlands)

    Oosterman, W.T.; Kokshoorn, B.; Maaskant-van Wijk, P.A.; de Zoete, J.

    2015-01-01

    The current method of reporting a putative cell type is based on a non-probabilistic assessment of test results by the forensic practitioner. Additionally, the association between donor and cell type in mixed DNA profiles can be exceedingly complex. We present a probabilistic model for

  5. An Associative Index Model for the Results List Based on Vannevar Bush's Selection Concept

    Science.gov (United States)

    Cole, Charles; Julien, Charles-Antoine; Leide, John E.

    2010-01-01

    Introduction: We define the results list problem in information search and suggest the "associative index model", an ad-hoc, user-derived indexing solution based on Vannevar Bush's description of an associative indexing approach for his memex machine. We further define what selection means in indexing terms with reference to Charles…

  6. SNP discovery and chromosome anchoring provide the first physically-anchored hexaploid oat map and reveal synteny with model species.

    Directory of Open Access Journals (Sweden)

    Rebekah E Oliver

    Full Text Available A physically anchored consensus map is foundational to modern genomics research; however, construction of such a map in oat (Avena sativa L., 2n = 6x = 42 has been hindered by the size and complexity of the genome, the scarcity of robust molecular markers, and the lack of aneuploid stocks. Resources developed in this study include a modified SNP discovery method for complex genomes, a diverse set of oat SNP markers, and a novel chromosome-deficient SNP anchoring strategy. These resources were applied to build the first complete, physically-anchored consensus map of hexaploid oat. Approximately 11,000 high-confidence in silico SNPs were discovered based on nine million inter-varietal sequence reads of genomic and cDNA origin. GoldenGate genotyping of 3,072 SNP assays yielded 1,311 robust markers, of which 985 were mapped in 390 recombinant-inbred lines from six bi-parental mapping populations ranging in size from 49 to 97 progeny. The consensus map included 985 SNPs and 68 previously-published markers, resolving 21 linkage groups with a total map distance of 1,838.8 cM. Consensus linkage groups were assigned to 21 chromosomes using SNP deletion analysis of chromosome-deficient monosomic hybrid stocks. Alignments with sequenced genomes of rice and Brachypodium provide evidence for extensive conservation of genomic regions, and renewed encouragement for orthology-based genomic discovery in this important hexaploid species. These results also provide a framework for high-resolution genetic analysis in oat, and a model for marker development and map construction in other species with complex genomes and limited resources.

  7. Improved ability of biological and previous caries multimarkers to predict caries disease as revealed by multivariate PLS modelling

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    Ericson Thorild

    2009-11-01

    Full Text Available Abstract Background Dental caries is a chronic disease with plaque bacteria, diet and saliva modifying disease activity. Here we have used the PLS method to evaluate a multiplicity of such biological variables (n = 88 for ability to predict caries in a cross-sectional (baseline caries and prospective (2-year caries development setting. Methods Multivariate PLS modelling was used to associate the many biological variables with caries recorded in thirty 14-year-old children by measuring the numbers of incipient and manifest caries lesions at all surfaces. Results A wide but shallow gliding scale of one fifth caries promoting or protecting, and four fifths non-influential, variables occurred. The influential markers behaved in the order of plaque bacteria > diet > saliva, with previously known plaque bacteria/diet markers and a set of new protective diet markers. A differential variable patterning appeared for new versus progressing lesions. The influential biological multimarkers (n = 18 predicted baseline caries better (ROC area 0.96 than five markers (0.92 and a single lactobacilli marker (0.7 with sensitivity/specificity of 1.87, 1.78 and 1.13 at 1/3 of the subjects diagnosed sick, respectively. Moreover, biological multimarkers (n = 18 explained 2-year caries increment slightly better than reported before but predicted it poorly (ROC area 0.76. By contrast, multimarkers based on previous caries predicted alone (ROC area 0.88, or together with biological multimarkers (0.94, increment well with a sensitivity/specificity of 1.74 at 1/3 of the subjects diagnosed sick. Conclusion Multimarkers behave better than single-to-five markers but future multimarker strategies will require systematic searches for improved saliva and plaque bacteria markers.

  8. Dissociable mechanisms of speed-accuracy tradeoff during visual perceptual learning are revealed by a hierarchical drift diffusion model

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    Jiaxiang eZhang

    2014-04-01

    Full Text Available Two phenomena are commonly observed in decision-making. First, there is a speed-accuracy tradeoff such that decisions are slower and more accurate when instructions emphasize accuracy over speed, and vice versa. Second, decision performance improves with practice, as a task is learnt. The speed-accuracy tradeoff and learning effects have been explained under a well-established evidence-accumulation framework for decision-making, which suggests that evidence supporting each choice is accumulated over time, and a decision is committed to when the accumulated evidence reaches a decision boundary. This framework suggests that changing the decision boundary creates the tradeoff between decision speed and accuracy, while increasing the rate of accumulation leads to more accurate and faster decisions after learning. However, recent studies challenged the view that speed-accuracy tradeoff and learning are associated with changes in distinct, single decision parameters. Further, the influence of speed-accuracy instructions over the course of learning remains largely unknown. Here, we used a hierarchical drift-diffusion model to examine the speed-accuracy tradeoff during learning of a coherent motion discrimination task across multiple training sessions, and a transfer test session. The influence of speed-accuracy instructions was robust over training and generalized across untrained stimulus features. Emphasizing decision accuracy rather than speed was associated with increased boundary separation, drift rate and non-decision time at the beginning of training. However, after training, an emphasis on decision accuracy was only associated with increased boundary separation. In addition, faster and more accurate decisions after learning were due to a gradual decrease in boundary separation and an increase in drift rate. The results suggest that speed-accuracy instructions and learning differentially shape decision-making processes at different time scales.

  9. A zebrafish model for Waardenburg syndrome type IV reveals diverse roles for Sox10 in the otic vesicle.

    Science.gov (United States)

    Dutton, Kirsten; Abbas, Leila; Spencer, Joanne; Brannon, Claire; Mowbray, Catriona; Nikaido, Masataka; Kelsh, Robert N; Whitfield, Tanya T

    2009-01-01

    In humans, mutations in the SOX10 gene are a cause of the auditory-pigmentary disorder Waardenburg syndrome type IV (WS4) and related variants. SOX10 encodes an Sry-related HMG box protein essential for the development of the neural crest; deafness in WS4 and other Waardenburg syndromes is usually attributed to loss of neural-crest-derived melanocytes in the stria vascularis of the cochlea. However, SOX10 is strongly expressed in the developing otic vesicle and so direct roles for SOX10 in the otic epithelium might also be important. Here, we examine the otic phenotype of zebrafish sox10 mutants, a model for WS4. As a cochlea is not present in the fish ear, the severe otic phenotype in these mutants cannot be attributed to effects on this tissue. In zebrafish sox10 mutants, we see abnormalities in all otic placodal derivatives. Gene expression studies indicate deregulated expression of several otic genes, including fgf8, in sox10 mutants. Using a combination of mutant and morphant data, we show that the three sox genes belonging to group E (sox9a, sox9b and sox10) provide a link between otic induction pathways and subsequent otic patterning: they act redundantly to maintain sox10 expression throughout otic tissue and to restrict fgf8 expression to anterior macula regions. Single-cell labelling experiments indicate a small and transient neural crest contribution to the zebrafish ear during normal development, but this is unlikely to account for the strong defects seen in the sox10 mutant. We discuss the implication that the deafness in WS4 patients with SOX10 mutations might reflect a haploinsufficiency for SOX10 in the otic epithelium, resulting in patterning and functional abnormalities in the inner ear.

  10. The landscape of chromosomal aberrations in breast cancer mouse models reveals driver-specific routes to tumorigenesis

    NARCIS (Netherlands)

    Ben-David, Uri; Ha, Gavin; Khadka, Prasidda; Jin, Xin; Wong, Bang; Franke, Lude; Golub, Todd R.

    Aneuploidy and copy-number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) are commonly used to model human cancer, their chromosomal landscapes remain underexplored. Here we use gene expression profiles to infer CNAs in 3,108 samples from 45

  11. A Geometrically-Constrained Mathematical Model of Mammary Gland Ductal Elongation Reveals Novel Cellular Dynamics within the Terminal End Bud.

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    Ingrid Paine

    2016-04-01

    Full Text Available Mathematics is often used to model biological systems. In mammary gland development, mathematical modeling has been limited to acinar and branching morphogenesis and breast cancer, without reference to normal duct formation. We present a model of ductal elongation that exploits the geometrically-constrained shape of the terminal end bud (TEB, the growing tip of the duct, and incorporates morphometrics, region-specific proliferation and apoptosis rates. Iterative model refinement and behavior analysis, compared with biological data, indicated that the traditional metric of nipple to the ductal front distance, or percent fat pad filled to evaluate ductal elongation rate can be misleading, as it disregards branching events that can reduce its magnitude. Further, model driven investigations of the fates of specific TEB cell types confirmed migration of cap cells into the body cell layer, but showed their subsequent preferential elimination by apoptosis, thus minimizing their contribution to the luminal lineage and the mature duct.

  12. One- and multi-segment foot models lead to opposite results on ankle joint kinematics during gait: Implications for clinical assessment.

    Science.gov (United States)

    Pothrat, Claude; Authier, Guillaume; Viehweger, Elke; Berton, Eric; Rao, Guillaume

    2015-06-01

    Biomechanical models representing the foot as a single rigid segment are commonly used in clinical or sport evaluations. However, neglecting internal foot movements could lead to significant inaccuracies on ankle joint kinematics. The present study proposed an assessment of 3D ankle kinematic outputs using two distinct biomechanical models and their application in the clinical flat foot case. Results of the Plug in Gait (one segment foot model) and the Oxford Foot Model (multisegment foot model) were compared for normal children (9 participants) and flat feet children (9 participants). Repeated measures of Analysis of Variance have been performed to assess the Foot model and Group effects on ankle joint kinematics. Significant differences were observed between the two models for each group all along the gait cycle. In particular for the flat feet group, opposite results between the Oxford Foot Model and the Plug in Gait were revealed at heelstrike, with the Plug in Gait showing a 4.7° ankle dorsal flexion and 2.7° varus where the Oxford Foot Model showed a 4.8° ankle plantar flexion and 1.6° valgus. Ankle joint kinematics of the flat feet group was more affected by foot modeling than normal group. Foot modeling appeared to have a strong influence on resulting ankle kinematics. Moreover, our findings showed that this influence could vary depending on the population. Studies involving ankle joint kinematic assessment should take foot modeling with caution. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Predictive Modeling of a Paradigm Mechanical Cooling Tower Model: II. Optimal Best-Estimate Results with Reduced Predicted Uncertainties

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    Ruixian Fang

    2016-09-01

    Full Text Available This work uses the adjoint sensitivity model of the counter-flow cooling tower derived in the accompanying PART I to obtain the expressions and relative numerical rankings of the sensitivities, to all model parameters, of the following model responses: (i outlet air temperature; (ii outlet water temperature; (iii outlet water mass flow rate; and (iv air outlet relative humidity. These sensitivities are subsequently used within the “predictive modeling for coupled multi-physics systems” (PM_CMPS methodology to obtain explicit formulas for the predicted optimal nominal values for the model responses and parameters, along with reduced predicted standard deviations for the predicted model parameters and responses. These explicit formulas embody the assimilation of experimental data and the “calibration” of the model’s parameters. The results presented in this work demonstrate that the PM_CMPS methodology reduces the predicted standard deviations to values that are smaller than either the computed or the experimentally measured ones, even for responses (e.g., the outlet water flow rate for which no measurements are available. These improvements stem from the global characteristics of the PM_CMPS methodology, which combines all of the available information simultaneously in phase-space, as opposed to combining it sequentially, as in current data assimilation procedures.